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1. Early detection of diabetic macular oedema

Author

Ku, Jae Yee

Abstract

Background: Diabetic retinopathy (DR) is the second leading cause of visual loss in working-age adults in the United Kingdom (UK) after inherited eye disease, and is asymptomatic in its early stages. Visual loss from DR is commonly due to diabetic macular oedema (DMO) which current screening methods cannot detect directly. The handheld radial shape discrimination (hRSD) test, has been approved by the US Food and Drug Administration (FDA) as a means of detecting metamorphopsia, and therefore maculopathy. There is also emerging evidence that DR is a neurodegenerative disease resulting in thinning of the ganglion cell complex detected by optical coherence tomography (OCT) in early DR. This thesis describes studies of people with diabetes (PWD) and healthy controls (HC) investigating two emerging approaches, namely hRSD and OCT in the early detection of DMO. Methods: Macular function was measured using hRSD, distance and near visual acuity (VA) and macular structure was assessed using Heidelberg Spectralis OCT. Retinal layers segmentation and mean thicknesses were measured across all Early Treatment Diabetic Retinopathy Study (ETDRS) subfields using the Heidelberg auto-segmentation software with manual adjustment as needed. One eye from each participant was randomly selected for analysis. Results: 292 PWD (mean±SD 54±14 years, 175 males) referred from the local screening programme to hospital clinics as being at risk of DMO were recruited. 229 healthy participants (age 44±18 years; 94 males) were also recruited, of whom 50 (55±14 years, 26 males) were used as age-matched controls for the PWD. Compared to HC, hRSD performance and distance VA were progressively worse in PWD with no or minimal DR, (hRSD logMAR: HC -0.77±0.11, no DR -0.68±0.18, minimal DR -0.61±0.25, ANOVA p<0.001; distance VA logMAR: HC -0.08±0.12, no DR 0.03±0.15, minimal DR 0.06±0.16, ANOVA p<0.001). Compared to HC there was a reduction in full retinal thickness across most subfields in PWD with no or minimal DR. This reduction was driven by thinning in the outer nuclear layer (ONL) in the central subfield (CSF), ganglion cell layer (GCL) and inner plexiform layer (IPL) in the inner subfields and retinal nerve fibre layer (RNFL) in the outer subfields compared to HC. In the outer subfields, there was also thinning in the retinal pigment epithelium (RPE) in PWD with no DR and thinning in the GCL and IPL in PWD with minimal DR. Longitudinal data were available for 159 PWD (54±15 years, 97 males) who attended for a second visit after 191±86 days. In PWD with no or minimal DR, there was a significant decrease in GCL (visit 1 37.73±3.56µm, visit 2 37.27±3.84µm, t=2.523, p=0.020), IPL (visit 1 31.98±2.48µm, visit 2 31.61±2.69µm, t=2.517, p=0.020) and inner nuclear layer (INL) (visit 1 33.89±1.92µm, visit 2 32.96±1.11µm, t=3.129, p=0.005) between visits. Conclusions: Functional and structural changes are detectable in the early pathogenesis of DR, consistent with neuroretinal thinning developing before microvascular abnormalities. Functional changes detected by the hRSD test in PWD with early DR have not been previously demonstrated. Findings from the Early Detection of Diabetic Macular Oedema (EDDMO) study add further support to the concept of pre-clinical retinopathy.

Published
2022
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2. The right to cultural participation, public access to, and enjoyment of museum collections in the English and Taiwanese museums

Author

Ku, Hsiao-Mei

Subjects
Museum Collections, Taiwanese Museums, English Museums, Cultural Participation, Thesis
Abstract

Museums are spaces in which people, culture and collections are woven together. In the 21st century, the museum sector has been encountering demands for transformation, stemming from societal change, contributing to individual and societal well‐being. Of the various contemporary missions, the role of museums and collections in contribution to human rights have come to the fore. The thesis seeks to investigate the public's right to take part in cultural life enshrined in Article 15(1)(a) of the International Covenant on Economic, Social and Cultural Rights, 1966 ('ICESCR'), in the context of museums and their collections. The UK and Taiwan are bound to respect, protect and fulfil the right to cultural participation under the ICESCR. On this ground, this thesis engages in comparative legal research to look at legal and ethical guidance provided for the English and Taiwanese museums. It takes a socio‐legal approach to the discussion of Article 15(1)(a) of the ICESCR, the English charity law, museum ethics (including the ethical codes for museums published by ICOM and the Museums Association in the UK), and Taiwanese laws, including the Two Covenants Implementation Act in 2009 and the Cultural Fundamental Act in 2019.

Published
2021
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3. Development of encapsulated air microparticles using spray drying and sessile single droplet drying

Author

Che Ku Jusoh, Tengku Farizan Izzi

Subjects
TP 368 Food processing and manufacture
Abstract

The aim of this research was to produce spray dried particles with one large vacuole and controlled surface wettability, also known as encapsulated air microparticles, to be potentially applied as the dispersed gas phase in foam-based processed foods. Droplets containing a mixture of the slightly hydrophobic and thus surface active gum Arabic (GA) and the hydrophilic maltodextrin (MD) was selected for the development of encapsulated air microparticles based on literature reports of hollow spray dried particles. A sessile single droplet drying (SDD) on a hydrophobic surface and spray drying with a two-fluid atomiser were employed to evaluate the impact of droplet compositions (ratio of GA:MD, solids concentration and DE-value of MD) and processing conditions (drying temperature and droplet size) on the particle formation and the wetting properties of the particles. The sessile SDD study revealed that the mechanical strength of the skin and the drying rate were the key determining factors for the development of particles with one large vacuole. These particles were also characterised by a smooth surface appearance. The formation of one large vacuole (and a smooth surface) required the droplet to withstand surface collapse during drying. These conditions were fulfilled for droplets containing a higher proportion of GA than MD, for a higher solids concentration (40% w/v) and for the MD with the lowest dextrose equivalent (DE 7) of two MDs included in this research. A high drying rate constant at higher drying temperature (120 °C) and smaller initial droplet volume (1 µl) resulted in an earlier onset of bubble nucleation, and thus were more likely to lead to the formation of a large vacuole. Particle morphologies produced by spray drying were comparable to those produced in the SDD experiments. The highest fraction of smooth-surface hollow particles (15%) was achieved by spray drying the feed that contained high solids (40% w/v) at high inlet temperature (220 °C) and slow feed rate (300 ml/h), whereas the opposite conditions resulted in the lowest percentage of hollow particles (2%). The wetting behaviour of spray dried powders was found to be identical to SDD particles, wherein particles higher in GA showed poorer wetting (by water) due to the enrichment of the more hydrophobic GA at the surface of the particles. Likewise, the dissolution time increased with an increasing amount of GA in the particles due to the ability to hold higher amount of water (swelling) before the onset of collapse. The increasing dissolution time is advantageous in certain applications such as ice cream manufacture. Overall, this research has provided insight into fundamental aspects of encapsulated air microparticles, whereby GA has demonstrated convincing encapsulating material for the development of hollow particles, as well as in the control of particle wettability. The re-design SDD set-up developed in this research can be used as a design tool to achieve specific particle morphology and thus particle functionality for processing using spray drying.

Published
2021

4. Hybrid Real-Value-Genetic-Algorithm and Extended-Nelder- Mead Algorithm for Short Term Energy Demand Prediction

Author

Musa, Wahab, Ku Mahamud, Ku Ruhana, Salim, Sardi, Sediyono, Agung, Musa, Wahab, Ku Mahamud, Ku Ruhana, Salim, Sardi, and Sediyono, Agung

Abstract

Energy consumption planning of an area is very important. It is essential to accurately predict the amount of short-term power required by an area using a highly effective prediction technique. The real-value-genetics-algorithm (RVGA) is the most effective technique that is currently used. However, the RVGA has some drawbacks, including the fact that it gets caught in premature convergence even when the search is performed over long iterations. This study proposes a hybrid prediction algorithm which comprises the RVGA and the extended-Nelder-Mead (ENM) algorithm. The ENM was implemented to speed up the search for the best among all solutions produced by the RVGA. The RVGA was configured to run under small iterations, and the ENM was used to achieve convergence. Experiments were performed on historical datasets containing the monthly electricity demand of the Gorontalo area, a region in Indonesia. The performance of the hybrid algorithm was compared to the hybrid Genetic Algorithm-Particle Swarm Optimisation (GA-PSO) and Real Coded-Genetic Algorithm (RC-GA) energy demand models based on the mean-absolute-percentage-error (MAPE), mean-square-error (MSE), root-mean-square-error (RMSE), and mean-absolute-deviation (MAD) error rates. The results showed that the proposed hybrid algorithm’s MAPE, MSE, RMSE, and MAD errors were 2.95 percent, 0.13 percent, 0.36 percent and 1.29 percent, respectively. Based on the accuracy measure obtained from this study, it implies that the RVGAENM hybrid is the best model for forecasting monthly electricity demand.

Published
2024

5. Investigation of a complex conjugate matching circuit for a piezoelectric energy harvester

Author

Ku Ahamad, Ku Nurul Edhura, Shuttleworth, Roger, and Durovic, Sinisa

Subjects
621.31, piezoelectric cantilever energy harvesting circuit, Energy Harvesting, Amplified Inductor circuit, Complex conjugate matching, Piezoelectric energy harvester
Abstract

The work described in this thesis is aimed at developing a novel piezoelectric cantilever energy harvesting circuit, so that more energy can be obtained from a particular piezoelectric harvester than is possible using conventional circuits. The main focus of the work was to design, build and test a proof of principle system, and not a commercial version, so as to determine any limitations to the circuit. The circuit functions by cancelling the capacitive output reactance of the piezoelectric harvester with a simulated inductance, and is based on an idea proposed by Qi in 2011. Although Qi's approach demonstrated that the circuit could function, the system proved too lossy, and so a less lossy version is attempted here. Experimental and software simulations are provided to verify the theoretical predictions. A prototype amplified inductor circuit was simulated and tested. From the simulation results, although harmonic current losses were found in the circuit, it was found that the circuit should produce an amplified effective inductance and a maximum output power of 165mW. The effective inductance is derived from the voltage across the 2H inductor, and this voltage is amplified and applied to the circuit via an inverter, to provide an extra simulated inductance, so that the overall inductance can be resonated with the piezoelectric harvester output capacitance. Hence the capacitive impedance of the harvester is nearly cancelled. The study and analysis of the amplified inductor circuit was carried out for a single cantilever harvester. Both open loop and closed loop testing of the system were carried out. The open loop test showed that the concept should function as predicted. The purpose of the closed loop test was to make the system automatically adjust for different resonance frequencies. The circuit was tested at 52Vpp inverter output voltage, and demonstrated a harvested power of 145.5mW. Experimental results show that the harvester output power is boosted from 8.8mW as per the manufacturer data sheet to 145.5mW (16.5 times). This is approximately double the power available using circuits described in the literature.

Published
2018

6. Healthcare seeking behaviour as a link between tuberculosis and socioeconomic factors

Author

Ku, Chu-Chang, Dodd, Peter, and Dixon, Simon

Subjects
610
Abstract

Socioeconomic barriers to tuberculosis care-seeking and costs due to care-seeking lead to unfavourable treatment, epidemiological and economic outcomes. Especially in the post-2015 era, socioeconomic interventions for tuberculosis control are receiving increasing attention. In Taiwan, the National Health Insurance programme minimises out-of-pocket expenses for patients, but important delays to tuberculosis treatment still exist. Based on the population and tuberculosis epidemiology in Taiwan, I develop an analysis for profiling the efficacy of tuberculosis care provision and patients' care-seeking pathways. The results highlight that the interrupted tuberculosis evaluation processes and low diagnostic capacity in small local hospitals stands as key causes of extended delays to treatment, unfavourable outcomes, and costs. I analyse socioeconomic status (SES) of employment, vulnerability, and residential contexts, to identify risk factors for different aspects of care-seeking. To link the care-seeking pathways to the nationwide tuberculosis epidemiology, I develop a data-driven hybrid simulation model. The model integrates the advantages of agent-based approaches in representing detail, and equation-based approaches in simplicity and low computational cost. This approach makes feasible Monte-Carlo experiments for robust inferences without over-simplifying the care-seeking details of interest. By comparing the hybrid model simulations with a corresponding equation-based comparator, I confirm its validity. I considered interventions to improve universal health coverage by decentralising tuberculosis diagnostic capacity. I modelled specific interventions increasing the coverage of tuberculosis diagnostic capacity using various SES-targeted scale-up strategies. These show potential benefits in terms of reducing dropouts and reducing the tuberculosis burden, without significant increases in the inequality of care-seeking costs. I suggest considering additional SES variables such as education, health illiteracy, and social segregation to find other care-seeking barriers. Further investigations of SES-related interventions against tuberculosis, including formal impact and health economic evaluation, should be pursued in collaboration with policymakers able to advise on feasibility and patients able to advise on acceptability.

Published
2019

7. Disruption of the light/dark cycle and outcome after experimental stroke

Author

Ku Mohd Noor, Ku Mastura

Subjects
616.8, R Medicine (General)
Abstract

Circadian rhythms optimise health by ensuring that the internal rhythms of metabolism and cardiovascular physiology are synchronised to daily variations in the light/dark cycle and other recurrent environmental challenges. Disruption in in the light/dark cycle (photoperiod disruption; PD) which occurs during shift work has been associated with changes in metabolism or physiology, (e.g. hypertension, hyperglycaemia) that may influence outcome after stroke. Evidence from pre-clinical studies indicates that hyperglycaemia and hypertension are associated with increased lesion growth and final infarct after focal cerebral ischaemia. Therefore, it was hypothesised that PD would impact on physiological parameters and increase sensitivity to focal cerebral ischaemia. Investigating the effect of chronic photoperiod disruption on outcome following permanent focal cerebral ischaemia For this purpose, a PD protocol was employed to simulate shift work patterns of light/dark (LD) exposure. Male Wistar rats were exposed to either a 12:12 LD cycle or a 6-hour phase advance protocol for 9 weeks. This was done by switching the lights on 6 hours earlier than the previous photoperiod every 3 days. T2-weighted MRI was performed at 48 hours after permanent middle cerebral artery occlusion. Chronic PD for 9 weeks did not significantly affect food intake, body weight and key physiological parameters such as blood glucose and blood pressure and did not increase sensitivity to ischaemic damage in young, normotensive rats. This suggests that light alone is not a single factor to induce circadian disruption. The potentially adverse impact of shift work on stroke outcome may require additional factors such as high fat/high sugar diet or pre-existing co-morbidities. Characterisation and optimisation of animal model for transient focal cerebral ischaemia Results from the previous study of permanent ischaemia raised the question as to on how PD impacts on stroke outcome in the presence of reperfusion. In addition, since the majority of stroke patients present with co-morbid factors, subsequent studies aimed to determine the impact of PD in the presence of pre-existing hypertension following transient focal ischaemia. Prior to this a pilot study was conducted to optimise the time of middle cerebral artery (MCA) occlusion and to characterise the associated neurological and functional outcomes. The following information was used to inform the subsequent studies; 1) the optimal MCA occlusion time in spontaneously hypertensive rats (SHR) was 30 min and 2) transient MCA occlusion resulted in reproducible functional impairments in both neurological score and the adhesive label test assessed at 7-days. Impact of photoperiod disruption on sensitivity to focal cerebral ischaemia and microglia activation in spontaneously hypertensive rats Adult male SHR underwent 30 min transient MCAO following the 9-week PD protocol. Reperfusion resulted in significant tissue salvage. However, PD in the presence of pre-existing hypertension did not exacerbate ischaemic lesion evolution assessed by diffusion-weighted MRI, and by measuring the final infarct volume. Furthermore, PD alone did not induce significant changes in microglia activation in the brains of SHR that were not subjected to ischaemia. Poor collaterals and pre-existing hypertension in SHR may explained to lesser effect of PD on lesion evolution, as there may have been less penumbral tissue available for PD to exert its detrimental effect. Conclusion The studies presented in this thesis demonstrated that PD did not increase sensitivity to focal cerebral ischaemia in normotensive rats. Similarly, PD in the context of major stroke co-morbidity/risk factor did not exacerbate ischaemic damage. This suggest that the primary mechanism of cardiometabolic disturbances among shift workers may not primarily mediated by shifting in the light/dark cycle.

Published
2017

8. Generalised hybrid fuzzy multi criteria decision making based on intuitive multiple centroid defuzzification

Author

Ku Khalif, Ku Muhammad Naim and Gegov, Alexander Emilov

Subjects
006.3
Abstract

The concept of fuzzy multi criteria decision making process has received significant attention from research community due to its successful applications for human based decision making problems under fuzzy environment. It complements the decision makers to evaluate their subjective judgements under situations that are vague, imprecise, random and uncertain in nature. Inspired by such real applications, in this research study, the theoretical foundation of a hybrid fuzzy multi criteria decision making model based on new centroid defuzzification method is proposed. The proposed model tackles some issues that may be associated with the selection problems of the multi criteria decision making such as deriving decision criteria important weights, ranking various alternatives, suitable combination of fuzzy multi criteria decision making techniques and proper defuzzification method used. In developing the hybrid model, two multi criteria decision making techniques are integrated which are; 1) consistent fuzzy preference relations and; 2) fuzzy technique for order of preference by similarity to ideal solution. It is also incorporated together with new defuzzification method namely intuitive multiple centroid. In the view of evidence outlined in this study, the proposed model serves as a generic multi criteria decision making procedure, particularly when fuzzy sets are involved in the decision process. The two major contributions from this study are that: 1) The intuitive multiple centroid defuzzification capable to cater all possible representations of fuzzy sets reasonably and consistent with human intuition or judgment. 2) The generalised hybrid fuzzy multiple decision making model using intuitive multiple centroid gives better computation to evaluate criteria and alternatives in decision making problems under different uncertain environment. Furthermore, an empirical validation of the proposed model is investigated through conducting a case study of staff recruitment in MESSRS SAPRUDIN, IDRIS & CO, Malaysia. In this case study, a group of three decision makers, and four finalist of candidates are selected to take part of this case study. Their involvement achieved the first objective of the case study. At the end of the case study, a sensitivity analysis is conducted to indicate the robustness and the consistency of the results obtained. It is concluded that the proposed model is indeed beneficial under different environment.

Published
2016

9. Empagliflozin Induces Vascular Relaxation in Rat Coronary Artery Due to Activation of BK Channels

Author

Kong,Qi, Qian,Ling-ling, Zhang,Lei, Liu,Huan-huan, Yang,Fan, Zhang,Xiao-lu, Wang,Chao, Zhao,Xiao-xi, Li,Ku-lin, Wang,Ru-xing, Kong,Qi, Qian,Ling-ling, Zhang,Lei, Liu,Huan-huan, Yang,Fan, Zhang,Xiao-lu, Wang,Chao, Zhao,Xiao-xi, Li,Ku-lin, and Wang,Ru-xing

Abstract

Qi Kong,1 Ling-ling Qian,1 Lei Zhang,1 Huan-huan Liu,1,2 Fan Yang,1 Xiao-lu Zhang,1 Chao Wang,1 Xiao-xi Zhao,1 Ku-lin Li,1 Ru-xing Wang1,2 1Department of Cardiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China; 2Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, People’s Republic of ChinaCorrespondence: Ru-xing Wang; Ku-lin Li, Department of Cardiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China, Email ruxingw@aliyun.com; liyantong2002@126.comPurpose: The aim of this study was to investigate the effects and mechanisms of SGLT2 inhibitor empagliflozin on diabetic coronary function.Methods: A rat diabetic model was established by injection of streptozotocin. Rats in the treated group were administered empagliflozin by gavage and rat coronary vascular tensions were measured after eight weeks. Large conductance calcium activated K+ channel currents were recorded using a patch clamp technique, while human coronary artery smooth muscle cells were used to explore the underlying mechanisms.Results: After incubation with empagliflozin (10, 30, 100, 300, 1000 μmol/L), the Δ relaxation % of rat coronary arteries were 2.459 ± 1.304, 3.251 ± 1.119, 6.946 ± 3.407, 28.36 ± 11.47, 86.90 ± 3.868, respectively. Without and with empagliflozin in the bath solution, BK channel opening probabilities at a membrane potential of +60 mV were 0.0458 ± 0.0517 and 0.3413 ± 0.2047, respectively (p < 0.05, n = 4 cells). After incubation with iberiotoxin, the Δ tensions of rat coronary arteries in the control (Ctrl), untreated (DM), low empagliflozin (10 mg/kg/d)-treated (DM+L-EMPA) and high empagliflozin (30mg/kg/d)-treated (DM+H-EMPA) group were 103.20 ± 5.85, 40.37 ± 22.12, 99.47 ±

Published
2024

10. Whole-genome bisulfite sequencing identifies stage- and subtype-specific DNA methylation signatures in pancreatic cancer

Author

Wang, Sarah S, Wang, Sarah S, Hall, Madison L, Lee, EunJung, Kim, Soon-Chan, Ramesh, Neha, Lee, Sang Hyub, Jang, Jin-Young, Bold, Richard J, Ku, Ja-Lok, Hwang, Chang-Il, Wang, Sarah S, Wang, Sarah S, Hall, Madison L, Lee, EunJung, Kim, Soon-Chan, Ramesh, Neha, Lee, Sang Hyub, Jang, Jin-Young, Bold, Richard J, Ku, Ja-Lok, and Hwang, Chang-Il

Abstract

In pancreatic ductal adenocarcinoma (PDAC), no recurrent metastasis-specific mutation has been found, suggesting that epigenetic mechanisms, such as DNA methylation, are the major contributors of late-stage disease progression. Here, we performed the first whole-genome bisulfite sequencing (WGBS) on mouse and human PDAC organoid models to identify stage-specific and molecular subtype-specific DNA methylation signatures. With this approach, we identified thousands of differentially methylated regions (DMRs) that can distinguish between the stages and molecular subtypes of PDAC. Stage-specific DMRs are associated with genes related to nervous system development and cell-cell adhesions, and are enriched in promoters and bivalent enhancers. Subtype-specific DMRs showed hypermethylation of GATA6 foregut endoderm transcriptional networks in the squamous subtype and hypermethylation of EMT transcriptional networks in the progenitor subtype. These results indicate that aberrant DNA methylation contributes to both PDAC progression and subtype differentiation, resulting in significant and reoccurring DNA methylation patterns with diagnostic and prognostic potential.

Published
2024

11. PED in 2024: improving the community deposition of structural ensembles for intrinsically disordered proteins

Author

European Commission, National Center for High Performance Computing (Turkey), Ghafouri, Hamidreza, Lazar, Tamas, Del Conte, Alessio, Tenorio Ku, Luiggi G., Tompa, Peter, Tosatto, Silvio C. E., Monzon, Alexander Miguel, European Commission, National Center for High Performance Computing (Turkey), Ghafouri, Hamidreza, Lazar, Tamas, Del Conte, Alessio, Tenorio Ku, Luiggi G., Tompa, Peter, Tosatto, Silvio C. E., and Monzon, Alexander Miguel

Abstract

The Protein Ensemble Database (PED) (URL: https://proteinensemble.org) is the primary resource for depositing structural ensembles of intrinsically disordered proteins. This updated version of PED reflects advancements in the field, denoting a continual expansion with a total of 461 entries and 538 ensembles, including those generated without explicit experimental data through novel machine learning (ML) techniques. With this significant increment in the number of ensembles, a few yet-unprecedented new entries entered the database, including those also determined or refined by electron paramagnetic resonance or circular dichroism data. In addition, PED was enriched with several new features, including a novel deposition service, improved user interface, new database cross-referencing options and integration with the 3D-Beacons network-all representing efforts to improve the FAIRness of the database. Foreseeably, PED will keep growing in size and expanding with new types of ensembles generated by accurate and fast ML-based generative models and coarse-grained simulations. Therefore, among future efforts, priority will be given to further develop the database to be compatible with ensembles modeled at a coarse-grained level.

Published
2024

12. Series of (([1,1′-Biphenyl]-2-yl)methyl)sulfinylalkyl Alicyclic Amines as Novel and High Affinity Atypical Dopamine Transporter Inhibitors with Reduced hERG Activity

Author

Ku, Therese C., Cao, Jianjing, Won, Sung Joon, Guo, Jiqing, Camacho-Hernandez, Gisela A., Okorom, Amarachi V., Salomon, Kristine Walloe, Lee, Kuo Hao, Loland, Claus J., Duff, Henry J., Shi, Lei, Newman, Amy Hauck, Ku, Therese C., Cao, Jianjing, Won, Sung Joon, Guo, Jiqing, Camacho-Hernandez, Gisela A., Okorom, Amarachi V., Salomon, Kristine Walloe, Lee, Kuo Hao, Loland, Claus J., Duff, Henry J., Shi, Lei, and Newman, Amy Hauck

Abstract

Currently, there are no FDA-approved medications for the treatment of psychostimulant use disorders (PSUD). We have previously discovered “atypical” dopamine transporter (DAT) inhibitors that do not display psychostimulant-like behaviors and may be useful as medications to treat PSUD. Lead candidates (e.g., JJC8-091, 1) have shown promising in vivo profiles in rodents; however, reducing hERG (human ether-à-go-go-related gene) activity, a predictor of cardiotoxicity, has remained a challenge. Herein, a series of 30 (([1,1′-biphenyl]-2-yl)methyl)sulfinylalkyl alicyclic amines was synthesized and evaluated for DAT and serotonin transporter (SERT) binding affinities. A subset of analogues was tested for hERG activity, and the IC50 values were compared to those predicted by our hERG QSAR models, which showed robust predictive power. Multiparameter optimization scores (MPO > 3) indicated central nervous system (CNS) penetrability. Finally, comparison of affinities in human DAT and its Y156F and Y335A mutants suggested that several compounds prefer an inward facing conformation indicating an atypical DAT inhibitor profile., Currently, there are no FDA-approved medications for the treatment of psychostimulant use disorders (PSUD). We have previously discovered “atypical” dopamine transporter (DAT) inhibitors that do not display psychostimulant-like behaviors and may be useful as medications to treat PSUD. Lead candidates (e.g., JJC8-091, 1) have shown promising in vivo profiles in rodents; however, reducing hERG (human ether-à-go-go-related gene) activity, a predictor of cardiotoxicity, has remained a challenge. Herein, a series of 30 (([1,1′-biphenyl]-2-yl)methyl)sulfinylalkyl alicyclic amines was synthesized and evaluated for DAT and serotonin transporter (SERT) binding affinities. A subset of analogues was tested for hERG activity, and the IC50 values were compared to those predicted by our hERG QSAR models, which showed robust predictive power. Multiparameter optimization scores (MPO > 3) indicated central nervous system (CNS) penetrability. Finally, comparison of affinities in human DAT and its Y156F and Y335A mutants suggested that several compounds prefer an inward facing conformation indicating an atypical DAT inhibitor profile.

Published
2024

13. Modifications to 1-(4-(2-Bis(4-fluorophenyl)methyl)sulfinyl)alkyl Alicyclic Amines That Improve Metabolic Stability and Retain an Atypical DAT Inhibitor Profile

Author

Okorom, Amarachi V., Camacho-Hernandez, Gisela Andrea, Salomon, Kristine, Lee, Kuo Hao, Ku, Therese C., Cao, Jianjing, Won, Sung Joon, Friedman, Jacob, Lam, Jenny, Paule, James, Rais, Rana, Klein, Benjamin, Xi, Zheng Xiong, Shi, Lei, Loland, Claus J., Newman, Amy Hauck, Okorom, Amarachi V., Camacho-Hernandez, Gisela Andrea, Salomon, Kristine, Lee, Kuo Hao, Ku, Therese C., Cao, Jianjing, Won, Sung Joon, Friedman, Jacob, Lam, Jenny, Paule, James, Rais, Rana, Klein, Benjamin, Xi, Zheng Xiong, Shi, Lei, Loland, Claus J., and Newman, Amy Hauck

Abstract

Atypical dopamine transporter (DAT) inhibitors have shown therapeutic potential in the preclinical models of psychostimulant use disorders (PSUD). In rats, 1-(4-(2-((bis(4-fluorophenyl)methyl)sulfinyl)ethyl)-piperazin-1-yl)-propan-2-ol (JJC8–091, 3b) was effective in reducing the reinforcing effects of both cocaine and methamphetamine but did not exhibit psychostimulant behaviors itself. Improvements in DAT affinity and metabolic stability were desirable for discovering pipeline drug candidates. Thus, a series of 1-(4-(2-bis(4-fluorophenyl)methyl)sulfinyl)alkyl alicyclic amines were synthesized and evaluated for binding affinities at DAT and the serotonin transporter (SERT). Replacement of the piperazine with either a homopiperazine or a piperidine ring system was well tolerated at DAT (Ki range = 3–382 nM). However, only the piperidine analogues (20a–d) showed improved metabolic stability in rat liver microsomes as compared to the previously reported analogues. Compounds 12b and 20a appeared to retain an atypical DAT inhibitor profile, based on negligible locomotor activity in mice and molecular modeling that predicts binding to an inward-facing conformation of DAT., Atypical dopamine transporter (DAT) inhibitors have shown therapeutic potential in the preclinical models of psychostimulant use disorders (PSUD). In rats, 1-(4-(2-((bis(4-fluorophenyl)methyl)sulfinyl)ethyl)-piperazin-1-yl)-propan-2-ol (JJC8-091, 3b) was effective in reducing the reinforcing effects of both cocaine and methamphetamine but did not exhibit psychostimulant behaviors itself. Improvements in DAT affinity and metabolic stability were desirable for discovering pipeline drug candidates. Thus, a series of 1-(4-(2-bis(4-fluorophenyl)methyl)sulfinyl)alkyl alicyclic amines were synthesized and evaluated for binding affinities at DAT and the serotonin transporter (SERT). Replacement of the piperazine with either a homopiperazine or a piperidine ring system was well tolerated at DAT (Ki range = 3-382 nM). However, only the piperidine analogues (20a-d) showed improved metabolic stability in rat liver microsomes as compared to the previously reported analogues. Compounds 12b and 20a appeared to retain an atypical DAT inhibitor profile, based on negligible locomotor activity in mice and molecular modeling that predicts binding to an inward-facing conformation of DAT.

Published
2024

14. AnyV2V: A Plug-and-Play Framework For Any Video-to-Video Editing Tasks

Author

Ku, Max, Wei, Cong, Ren, Weiming, Yang, Harry, Chen, Wenhu, Ku, Max, Wei, Cong, Ren, Weiming, Yang, Harry, and Chen, Wenhu

Abstract

Video-to-video editing involves editing a source video along with additional control (such as text prompts, subjects, or styles) to generate a new video that aligns with the source video and the provided control. Traditional methods have been constrained to certain editing types, limiting their ability to meet the wide range of user demands. In this paper, we introduce AnyV2V, a novel training-free framework designed to simplify video editing into two primary steps: (1) employing an off-the-shelf image editing model (e.g. InstructPix2Pix, InstantID, etc) to modify the first frame, (2) utilizing an existing image-to-video generation model (e.g. I2VGen-XL) for DDIM inversion and feature injection. In the first stage, AnyV2V can plug in any existing image editing tools to support an extensive array of video editing tasks. Beyond the traditional prompt-based editing methods, AnyV2V also can support novel video editing tasks, including reference-based style transfer, subject-driven editing, and identity manipulation, which were unattainable by previous methods. In the second stage, AnyV2V can plug in any existing image-to-video models to perform DDIM inversion and intermediate feature injection to maintain the appearance and motion consistency with the source video. On the prompt-based editing, we show that AnyV2V can outperform the previous best approach by 35\% on prompt alignment, and 25\% on human preference. On the three novel tasks, we show that AnyV2V also achieves a high success rate. We believe AnyV2V will continue to thrive due to its ability to seamlessly integrate the fast-evolving image editing methods. Such compatibility can help AnyV2V to increase its versatility to cater to diverse user demands., Comment: preprint

Published
2024

15. Sim2Real in Reconstructive Spectroscopy: Deep Learning with Augmented Device-Informed Data Simulation

Author

Chen, Jiyi, Li, Pengyu, Wang, Yutong, Ku, Pei-Cheng, Qu, Qing, Chen, Jiyi, Li, Pengyu, Wang, Yutong, Ku, Pei-Cheng, and Qu, Qing

Abstract

This work proposes a deep learning (DL)-based framework, namely Sim2Real, for spectral signal reconstruction in reconstructive spectroscopy, focusing on efficient data sampling and fast inference time. The work focuses on the challenge of reconstructing real-world spectral signals under the extreme setting where only device-informed simulated data are available for training. Such device-informed simulated data are much easier to collect than real-world data but exhibit large distribution shifts from their real-world counterparts. To leverage such simulated data effectively, a hierarchical data augmentation strategy is introduced to mitigate the adverse effects of this domain shift, and a corresponding neural network for the spectral signal reconstruction with our augmented data is designed. Experiments using a real dataset measured from our spectrometer device demonstrate that Sim2Real achieves significant speed-up during the inference while attaining on-par performance with the state-of-the-art optimization-based methods.

Published
2024

16. VideoBadminton: A Video Dataset for Badminton Action Recognition

Author

Li, Qi, Chiu, Tzu-Chen, Huang, Hsiang-Wei, Sun, Min-Te, Ku, Wei-Shinn, Li, Qi, Chiu, Tzu-Chen, Huang, Hsiang-Wei, Sun, Min-Te, and Ku, Wei-Shinn

Abstract

In the dynamic and evolving field of computer vision, action recognition has become a key focus, especially with the advent of sophisticated methodologies like Convolutional Neural Networks (CNNs), Convolutional 3D, Transformer, and spatial-temporal feature fusion. These technologies have shown promising results on well-established benchmarks but face unique challenges in real-world applications, particularly in sports analysis, where the precise decomposition of activities and the distinction of subtly different actions are crucial. Existing datasets like UCF101, HMDB51, and Kinetics have offered a diverse range of video data for various scenarios. However, there's an increasing need for fine-grained video datasets that capture detailed categorizations and nuances within broader action categories. In this paper, we introduce the VideoBadminton dataset derived from high-quality badminton footage. Through an exhaustive evaluation of leading methodologies on this dataset, this study aims to advance the field of action recognition, particularly in badminton sports. The introduction of VideoBadminton could not only serve for badminton action recognition but also provide a dataset for recognizing fine-grained actions. The insights gained from these evaluations are expected to catalyze further research in action comprehension, especially within sports contexts.

Published
2024

17. FlyKD: Graph Knowledge Distillation on the Fly with Curriculum Learning

Author

Ku, Eugene and Ku, Eugene

Abstract

Knowledge Distillation (KD) aims to transfer a more capable teacher model's knowledge to a lighter student model in order to improve the efficiency of the model, making it faster and more deployable. However, the student model's optimization process over the noisy pseudo labels (generated by the teacher model) is tricky and the amount of pseudo labels one can generate is limited due to Out of Memory (OOM) error. In this paper, we propose FlyKD (Knowledge Distillation on the Fly) which enables the generation of virtually unlimited number of pseudo labels, coupled with Curriculum Learning that greatly alleviates the optimization process over the noisy pseudo labels. Empirically, we observe that FlyKD outperforms vanilla KD and the renown Local Structure Preserving Graph Convolutional Network (LSPGCN). Lastly, with the success of Curriculum Learning, we shed light on a new research direction of improving optimization over noisy pseudo labels.

Published
2024

18. A Survey of Lottery Ticket Hypothesis

Author

Liu, Bohan, Zhang, Zijie, He, Peixiong, Wang, Zhensen, Xiao, Yang, Ye, Ruimeng, Zhou, Yang, Ku, Wei-Shinn, Hui, Bo, Liu, Bohan, Zhang, Zijie, He, Peixiong, Wang, Zhensen, Xiao, Yang, Ye, Ruimeng, Zhou, Yang, Ku, Wei-Shinn, and Hui, Bo

Abstract

The Lottery Ticket Hypothesis (LTH) states that a dense neural network model contains a highly sparse subnetwork (i.e., winning tickets) that can achieve even better performance than the original model when trained in isolation. While LTH has been proved both empirically and theoretically in many works, there still are some open issues, such as efficiency and scalability, to be addressed. Also, the lack of open-source frameworks and consensual experimental setting poses a challenge to future research on LTH. We, for the first time, examine previous research and studies on LTH from different perspectives. We also discuss issues in existing works and list potential directions for further exploration. This survey aims to provide an in-depth look at the state of LTH and develop a duly maintained platform to conduct experiments and compare with the most updated baselines.

Published
2024

19. VLM-PL: Advanced Pseudo Labeling Approach for Class Incremental Object Detection via Vision-Language Model

Author

Kim, Junsu, Ku, Yunhoe, Kim, Jihyeon, Cha, Junuk, Baek, Seungryul, Kim, Junsu, Ku, Yunhoe, Kim, Jihyeon, Cha, Junuk, and Baek, Seungryul

Abstract

In the field of Class Incremental Object Detection (CIOD), creating models that can continuously learn like humans is a major challenge. Pseudo-labeling methods, although initially powerful, struggle with multi-scenario incremental learning due to their tendency to forget past knowledge. To overcome this, we introduce a new approach called Vision-Language Model assisted Pseudo-Labeling (VLM-PL). This technique uses Vision-Language Model (VLM) to verify the correctness of pseudo ground-truths (GTs) without requiring additional model training. VLM-PL starts by deriving pseudo GTs from a pre-trained detector. Then, we generate custom queries for each pseudo GT using carefully designed prompt templates that combine image and text features. This allows the VLM to classify the correctness through its responses. Furthermore, VLM-PL integrates refined pseudo and real GTs from upcoming training, effectively combining new and old knowledge. Extensive experiments conducted on the Pascal VOC and MS COCO datasets not only highlight VLM-PL's exceptional performance in multi-scenario but also illuminate its effectiveness in dual-scenario by achieving state-of-the-art results in both., Comment: Accept to CVPRW2024 (CLvision). The camera-ready version of the manuscript

Published
2024

20. ModSRAM: Algorithm-Hardware Co-Design for Large Number Modular Multiplication in SRAM

Author

Ku, Jonathan, Zhang, Junyao, Shan, Haoxuan, Samudrala, Saichand, Wu, Jiawen, Zheng, Qilin, Li, Ziru, Rajendran, JV, Chen, Yiran, Ku, Jonathan, Zhang, Junyao, Shan, Haoxuan, Samudrala, Saichand, Wu, Jiawen, Zheng, Qilin, Li, Ziru, Rajendran, JV, and Chen, Yiran

Abstract

Elliptic curve cryptography (ECC) is widely used in security applications such as public key cryptography (PKC) and zero-knowledge proofs (ZKP). ECC is composed of modular arithmetic, where modular multiplication takes most of the processing time. Computational complexity and memory constraints of ECC limit the performance. Therefore, hardware acceleration on ECC is an active field of research. Processing-in-memory (PIM) is a promising approach to tackle this problem. In this work, we design ModSRAM, the first 8T SRAM PIM architecture to compute large-number modular multiplication efficiently. In addition, we propose R4CSA-LUT, a new algorithm that reduces the cycles for an interleaved algorithm and eliminates carry propagation for addition based on look-up tables (LUT). ModSRAM is co-designed with R4CSA-LUT to support modular multiplication and data reuse in memory with 52% cycle reduction compared to prior works with only 32% area overhead., Comment: DAC 2024

Published
2024

21. Exponential Cluster Synchronization in Fast Switching Network Topologies: A Pinning Control Approach with Necessary and Sufficient Conditions

Author

Du, Ku, Kang, Yu, Du, Ku, and Kang, Yu

Abstract

This research investigates the intricate domain of synchronization problem among multiple agents operating within a dynamic fast switching network topology. We concentrate on cluster synchronization within coupled linear system under pinning control, providing both necessary and sufficient conditions. As a pivotal aspect, this paper aim to president the weakest possible conditions to make the coupled linear system realize cluster synchronization exponentially. Within the context of fast switching framework, we initially examine the necessary conditions, commencing with the transformation of the consensus problem into a stability problem, introducing a new variable to make the coupled system achieve cluster synchronization if the system is controllable; communication topology switching fast enough and the coupling strength should be sufficiently robust. Then, by using the Lyapunov theorem, we also present that the state matrix controllable is necessary for cluster synchronization. Furthermore, this paper culminating in the incorporation of contraction theory and an invariant manifold, demonstrating that the switching topology has an average is imperative for achieving cluster synchronization. Finally, we introduce three simulations to validate the efficacy of the proposed approach.

Published
2024

22. Towards Multi-domain Face Landmark Detection with Synthetic Data from Diffusion model

Author

Li, Yuanming, Kim, Gwantae, Kwak, Jeong-gi, Ku, Bon-hwa, Ko, Hanseok, Li, Yuanming, Kim, Gwantae, Kwak, Jeong-gi, Ku, Bon-hwa, and Ko, Hanseok

Abstract

Recently, deep learning-based facial landmark detection for in-the-wild faces has achieved significant improvement. However, there are still challenges in face landmark detection in other domains (e.g. cartoon, caricature, etc). This is due to the scarcity of extensively annotated training data. To tackle this concern, we design a two-stage training approach that effectively leverages limited datasets and the pre-trained diffusion model to obtain aligned pairs of landmarks and face in multiple domains. In the first stage, we train a landmark-conditioned face generation model on a large dataset of real faces. In the second stage, we fine-tune the above model on a small dataset of image-landmark pairs with text prompts for controlling the domain. Our new designs enable our method to generate high-quality synthetic paired datasets from multiple domains while preserving the alignment between landmarks and facial features. Finally, we fine-tuned a pre-trained face landmark detection model on the synthetic dataset to achieve multi-domain face landmark detection. Our qualitative and quantitative results demonstrate that our method outperforms existing methods on multi-domain face landmark detection., Comment: 6 pages, ICASSP 2024 accepted

Published
2024

23. BlenDA: Domain Adaptive Object Detection through diffusion-based blending

Author

Huang, Tzuhsuan, Huang, Chen-Che, Ku, Chung-Hao, Chen, Jun-Cheng, Huang, Tzuhsuan, Huang, Chen-Che, Ku, Chung-Hao, and Chen, Jun-Cheng

Abstract

Unsupervised domain adaptation (UDA) aims to transfer a model learned using labeled data from the source domain to unlabeled data in the target domain. To address the large domain gap issue between the source and target domains, we propose a novel regularization method for domain adaptive object detection, BlenDA, by generating the pseudo samples of the intermediate domains and their corresponding soft domain labels for adaptation training. The intermediate samples are generated by dynamically blending the source images with their corresponding translated images using an off-the-shelf pre-trained text-to-image diffusion model which takes the text label of the target domain as input and has demonstrated superior image-to-image translation quality. Based on experimental results from two adaptation benchmarks, our proposed approach can significantly enhance the performance of the state-of-the-art domain adaptive object detector, Adversarial Query Transformer (AQT). Particularly, in the Cityscapes to Foggy Cityscapes adaptation, we achieve an impressive 53.4% mAP on the Foggy Cityscapes dataset, surpassing the previous state-of-the-art by 1.5%. It is worth noting that our proposed method is also applicable to various paradigms of domain adaptive object detection. The code is available at:https://github.com/aiiu-lab/BlenDA, Comment: ICASSP(2024):2024 IEEE International Conference on Acoustics, Speech and Signal Processing

Published
2024

24. Language-Universal Speech Attributes Modeling for Zero-Shot Multilingual Spoken Keyword Recognition

Author

Yen, Hao, Ku, Pin-Jui, Siniscalchi, Sabato Marco, Lee, Chin-Hui, Yen, Hao, Ku, Pin-Jui, Siniscalchi, Sabato Marco, and Lee, Chin-Hui

Abstract

We propose a novel language-universal approach to end-to-end automatic spoken keyword recognition (SKR) leveraging upon (i) a self-supervised pre-trained model, and (ii) a set of universal speech attributes (manner and place of articulation). Specifically, Wav2Vec2.0 is used to generate robust speech representations, followed by a linear output layer to produce attribute sequences. A non-trainable pronunciation model then maps sequences of attributes into spoken keywords in a multilingual setting. Experiments on the Multilingual Spoken Words Corpus show comparable performances to character- and phoneme-based SKR in seen languages. The inclusion of domain adversarial training (DAT) improves the proposed framework, outperforming both character- and phoneme-based SKR approaches with 13.73% and 17.22% relative word error rate (WER) reduction in seen languages, and achieves 32.14% and 19.92% WER reduction for unseen languages in zero-shot settings.

Published
2024

25. MMLU-Pro: A More Robust and Challenging Multi-Task Language Understanding Benchmark

Author

Wang, Yubo, Ma, Xueguang, Zhang, Ge, Ni, Yuansheng, Chandra, Abhranil, Guo, Shiguang, Ren, Weiming, Arulraj, Aaran, He, Xuan, Jiang, Ziyan, Li, Tianle, Ku, Max, Wang, Kai, Zhuang, Alex, Fan, Rongqi, Yue, Xiang, Chen, Wenhu, Wang, Yubo, Ma, Xueguang, Zhang, Ge, Ni, Yuansheng, Chandra, Abhranil, Guo, Shiguang, Ren, Weiming, Arulraj, Aaran, He, Xuan, Jiang, Ziyan, Li, Tianle, Ku, Max, Wang, Kai, Zhuang, Alex, Fan, Rongqi, Yue, Xiang, and Chen, Wenhu

Abstract

In the age of large-scale language models, benchmarks like the Massive Multitask Language Understanding (MMLU) have been pivotal in pushing the boundaries of what AI can achieve in language comprehension and reasoning across diverse domains. However, as models continue to improve, their performance on these benchmarks has begun to plateau, making it increasingly difficult to discern differences in model capabilities. This paper introduces MMLU-Pro, an enhanced dataset designed to extend the mostly knowledge-driven MMLU benchmark by integrating more challenging, reasoning-focused questions and expanding the choice set from four to ten options. Additionally, MMLU-Pro eliminates the trivial and noisy questions in MMLU. Our experimental results show that MMLU-Pro not only raises the challenge, causing a significant drop in accuracy by 16% to 33% compared to MMLU but also demonstrates greater stability under varying prompts. With 24 different prompt styles tested, the sensitivity of model scores to prompt variations decreased from 4-5% in MMLU to just 2% in MMLU-Pro. Additionally, we found that models utilizing Chain of Thought (CoT) reasoning achieved better performance on MMLU-Pro compared to direct answering, which is in stark contrast to the findings on the original MMLU, indicating that MMLU-Pro includes more complex reasoning questions. Our assessments confirm that MMLU-Pro is a more discriminative benchmark to better track progress in the field.

Published
2024

26. Time-Varying Constraint-Aware Reinforcement Learning for Energy Storage Control

Author

Jeong, Jaeik, Ku, Tai-Yeon, Park, Wan-Ki, Jeong, Jaeik, Ku, Tai-Yeon, and Park, Wan-Ki

Abstract

Energy storage devices, such as batteries, thermal energy storages, and hydrogen systems, can help mitigate climate change by ensuring a more stable and sustainable power supply. To maximize the effectiveness of such energy storage, determining the appropriate charging and discharging amounts for each time period is crucial. Reinforcement learning is preferred over traditional optimization for the control of energy storage due to its ability to adapt to dynamic and complex environments. However, the continuous nature of charging and discharging levels in energy storage poses limitations for discrete reinforcement learning, and time-varying feasible charge-discharge range based on state of charge (SoC) variability also limits the conventional continuous reinforcement learning. In this paper, we propose a continuous reinforcement learning approach that takes into account the time-varying feasible charge-discharge range. An additional objective function was introduced for learning the feasible action range for each time period, supplementing the objectives of training the actor for policy learning and the critic for value learning. This actively promotes the utilization of energy storage by preventing them from getting stuck in suboptimal states, such as continuous full charging or discharging. This is achieved through the enforcement of the charging and discharging levels into the feasible action range. The experimental results demonstrated that the proposed method further maximized the effectiveness of energy storage by actively enhancing its utilization., Comment: ICLR 2024 Workshop: Tackling Climate Change with Machine Learning

Published
2024

27. Salient Object-Aware Background Generation using Text-Guided Diffusion Models

Author

Eshratifar, Amir Erfan, Soares, Joao V. B., Thadani, Kapil, Mishra, Shaunak, Kuznetsov, Mikhail, Ku, Yueh-Ning, de Juan, Paloma, Eshratifar, Amir Erfan, Soares, Joao V. B., Thadani, Kapil, Mishra, Shaunak, Kuznetsov, Mikhail, Ku, Yueh-Ning, and de Juan, Paloma

Abstract

Generating background scenes for salient objects plays a crucial role across various domains including creative design and e-commerce, as it enhances the presentation and context of subjects by integrating them into tailored environments. Background generation can be framed as a task of text-conditioned outpainting, where the goal is to extend image content beyond a salient object's boundaries on a blank background. Although popular diffusion models for text-guided inpainting can also be used for outpainting by mask inversion, they are trained to fill in missing parts of an image rather than to place an object into a scene. Consequently, when used for background creation, inpainting models frequently extend the salient object's boundaries and thereby change the object's identity, which is a phenomenon we call "object expansion." This paper introduces a model for adapting inpainting diffusion models to the salient object outpainting task using Stable Diffusion and ControlNet architectures. We present a series of qualitative and quantitative results across models and datasets, including a newly proposed metric to measure object expansion that does not require any human labeling. Compared to Stable Diffusion 2.0 Inpainting, our proposed approach reduces object expansion by 3.6x on average with no degradation in standard visual metrics across multiple datasets., Comment: Accepted for publication at CVPR 2024's Generative Models for Computer Vision workshop

Published
2024

28. MANTIS: Interleaved Multi-Image Instruction Tuning

Author

Jiang, Dongfu, He, Xuan, Zeng, Huaye, Wei, Cong, Ku, Max, Liu, Qian, Chen, Wenhu, Jiang, Dongfu, He, Xuan, Zeng, Huaye, Wei, Cong, Ku, Max, Liu, Qian, and Chen, Wenhu

Abstract

Large multimodal models (LMMs) have shown great results in single-image vision language tasks. However, their abilities to solve multi-image visual language tasks is yet to be improved. The existing LMMs like OpenFlamingo, Emu2, Idefics gain their multi-image ability through pre-training on hundreds of millions of noisy interleaved image-text data from the web, which is neither efficient nor effective. In this paper, we aim to build strong multi-image LMMs via instruction tuning with academic-level resources. Therefore, we meticulously construct Mantis-Instruct containing 721K multi-image instruction data to train a family of models Mantis. The instruction tuning empowers Mantis with different multi-image skills like co-reference, comparison, reasoning, and temporal understanding. We evaluate Mantis on five multi-image benchmarks and seven single-image benchmarks. Mantis-SigLIP can achieve SoTA results on all the multi-image benchmarks and beat the strongest multi-image baseline, Idefics2-8B by an average of 11 absolute points. Notably, Idefics2-8B was pre-trained on 140M interleaved multi-image data, which is 200x larger than Mantis-Instruct. We observe that Mantis performs equivalently well on the held-in and held-out benchmarks, which shows its generalization ability. Notably, we found that Mantis can even match the performance of GPT-4V on multi-image benchmarks. We further evaluate Mantis on single-image benchmarks and demonstrate that Mantis also maintains a strong single-image performance on par with CogVLM and Emu2. Our results show that multi-image abilities are not necessarily gained through massive pre-training, instead, it can be gained by the low-cost instruction tuning. Our work provides new perspectives on how to improve LMMs' multi-image abilities., Comment: 9 pages, 3 figures, 8 tables

Published
2024

29. DOCCI: Descriptions of Connected and Contrasting Images

Author

Onoe, Yasumasa, Rane, Sunayana, Berger, Zachary, Bitton, Yonatan, Cho, Jaemin, Garg, Roopal, Ku, Alexander, Parekh, Zarana, Pont-Tuset, Jordi, Tanzer, Garrett, Wang, Su, Baldridge, Jason, Onoe, Yasumasa, Rane, Sunayana, Berger, Zachary, Bitton, Yonatan, Cho, Jaemin, Garg, Roopal, Ku, Alexander, Parekh, Zarana, Pont-Tuset, Jordi, Tanzer, Garrett, Wang, Su, and Baldridge, Jason

Abstract

Vision-language datasets are vital for both text-to-image (T2I) and image-to-text (I2T) research. However, current datasets lack descriptions with fine-grained detail that would allow for richer associations to be learned by models. To fill the gap, we introduce Descriptions of Connected and Contrasting Images (DOCCI), a dataset with long, human-annotated English descriptions for 15k images that were taken, curated and donated by a single researcher intent on capturing key challenges such as spatial relations, counting, text rendering, world knowledge, and more. We instruct human annotators to create comprehensive descriptions for each image; these average 136 words in length and are crafted to clearly distinguish each image from those that are related or similar. Each description is highly compositional and typically encompasses multiple challenges. Through both quantitative and qualitative analyses, we demonstrate that DOCCI serves as an effective training resource for image-to-text generation -- a PaLI 5B model finetuned on DOCCI shows equal or superior results compared to highly-performant larger models like LLaVA-1.5 7B and InstructBLIP 7B. Furthermore, we show that DOCCI is a useful testbed for text-to-image generation, highlighting the limitations of current text-to-image models in capturing long descriptions and fine details.

Published
2024

30. Human factors of ubiquitous computing : ambient cueing in the digital kitchen?

Author

Ku Azir, Ku Nurul Fazira

Subjects
004.01, QA75 Electronic computers. Computer science, TX Home economics
Abstract

This thesis is concerned with the uses of Ubiquitous Computing (UbiComp) in everyday domestic environments. The concept of UbiComp promises to shift computing away from the desktop into everyday objects and settings. It has the twin goals of providing ‘transparent’ technologies where the information has been thoroughly embedded into everyday activities and objects (thus making the computer invisible to the user) and also (and more importantly) of seamless integration of these technologies into the activities of their users. However, this raises the challenge of how best to support interaction with a ‘transparent’ or ‘invisible’ technology; if the technology is made visible, it will attract the user's attention to it and away from the task at hand, but if it is hidden, then how can the user cope with malfunctions or other problems in the technology? We approach the design of Human-Computer Interaction in the ubiquitous environment through the use of ambient displays, i.e. the use of subtle cueing, embedded in the environment which is intended to guide human activity. This thesis draws on the concept of stimulus-response compatibility and applies this to the design ambient display. This thesis emphasizes the need to understand the users’ perspectives and responses in any particular approach that has been proposed. Therefore, the main contributions of this thesis focus on approaches to improve human performance in the ubiquitous environment through ambient display.

Published
2014

32. Rape myth acceptance : a non-western perspective

Author

Sham Ku, Deniece Kimberly

Subjects
364.15, BF Psychology, HV Social pathology. Social and public welfare
Abstract

The majority of research on rape myth acceptance (RMA) has been reported from a largely North American and European perspective. While this has certainly advanced our understanding of the area, generalising the experiences of western populations fails to take into account the sociocultural factors that are embedded in the realities of sexual violence across non-western societies. This thesis aims to examine RMA in non-western countries. Following the Introduction, a systematic review of the existing literature on the demographic and attitudinal factors associated with RMA in adults in non-western societies (Asia, Africa, Latin America, and the Middle East) is presented. The results are consistent with western findings, however, the paucity of available research in non-western societies indicates a need for further research. In the next chapter, an empirical study contributes to this limited evidence base by exploring the relationship between RMA and a number of demographic and attitudinal factors, using a sample population of men and women from Jamaica. Participants’ RMA was measured using the Acceptance of Modern Myths about Sexual Aggression (AMMSA; Gerger et al., 2007). The AMMSA was appraised in terms of its psychometric properties in the penultimate chapter and was considered to be an appropriate choice of psychometric instrument for the study. The final chapter draws the thesis together by discussing the main findings and implications for future research and practice.

Published
2015

34. The trajectory of industrialisation of cultural policy in Taiwan (1994-2012)

Author

Ku, Shu-Shiun, Upchurch, Anna, and Taylor, Calvin

Subjects
338.0951249
Abstract

This thesis aims to investigate the trajectory of industrialisation in Taiwan’s cultural policy from 1994 to 2012. In order to identify significant discursive and structural factors that have shaped and underpinned the transformation of industrialisation of cultural policy, this research takes the Cultural Political Economy (CPE) as the theoretical perspective and adopts Jim McGuigan’s three discourses of cultural policy to explain the dialectic process between discursive formation and structuration. This thesis reveals that the projects of cultural industries, as well as the cultural and creative industries, emerged as a strategic response to changing political, economic and social structuration over the past two decades. In this context, the meaning of industrialisation has been entangled in multiple state projects and multiple articulations with local practice and diverse imaginaries. From the analysis, there are three core research findings and implications. Firstly, the hegemonic discourse ‘Industrialisation of Culture; Culturalisation of Industries’ has been mobilised by the state as a strategic fix, in three respective phases, to manage the issues of democratisation, the formation of national identity, the challenges of economic transformation, rural regeneration and cultural citizenship. Secondly, this research highlights policy implications for the industrialisation of cultural policy in Taiwan and other newly democratised countries. Taiwan’s case indicates that the cultural industries do not naturally contain economic discourse; they can bear democratic meanings, such as empowerment, participation and cultural citizenship, by state projects and local practice to engage people in public affairs and cultural events. Thirdly, this research has theoretical implications for cultural policy and CPE. In the field of cultural policy, this research, which adopts the theoretical perspective of CPE with three discourses of cultural policy, uncovers the dialectic between discourse formation and structuration; furthermore, it provides an empirical approach with the supplement of three discourses of cultural policy for applying CPE in cultural policy studies to investigate the evolution of hegemonic discourse and structuration.

Published
2015

35. Multi-targeted therapy resistance via drug-induced secretome fucosylation.

Author

Aldonza, Mark Borris D, Aldonza, Mark Borris D, Cha, Junghwa, Yong, Insung, Ku, Jayoung, Sinitcyn, Pavel, Lee, Dabin, Cho, Ryeong-Eun, Delos Reyes, Roben D, Kim, Dongwook, Kim, Soyeon, Kang, Minjeong, Ku, Yongsuk, Park, Geonho, Sung, Hye-Jin, Ryu, Han Suk, Cho, Sukki, Kim, Tae Min, Kim, Pilnam, Cho, Je-Yoel, Kim, Yoosik, Aldonza, Mark Borris D, Aldonza, Mark Borris D, Cha, Junghwa, Yong, Insung, Ku, Jayoung, Sinitcyn, Pavel, Lee, Dabin, Cho, Ryeong-Eun, Delos Reyes, Roben D, Kim, Dongwook, Kim, Soyeon, Kang, Minjeong, Ku, Yongsuk, Park, Geonho, Sung, Hye-Jin, Ryu, Han Suk, Cho, Sukki, Kim, Tae Min, Kim, Pilnam, Cho, Je-Yoel, and Kim, Yoosik

Abstract

Cancer secretome is a reservoir for aberrant glycosylation. How therapies alter this post- translational cancer hallmark and the consequences thereof remain elusive. Here, we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. Large-scale pharmacogenomics revealed that fucosylation genes display widespread association with resistance to these therapies. In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. Label-free proteomics of N-glycoproteomes identified fucosylation of the antioxidant PON1 as a critical component of the therapy-induced secretome (TIS). N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. Core fucosylation in the Golgi impacts PON1 stability and folding prior to secretion, promoting a more degradation-resistant PON1. Global and PON1-specific secretome de-N-glycosylation both limited the expansion of resistant clones in a tumor regression model. We defined the resistance-associated transcription factors (TFs) and genes modulated by the N-glycosylated TIS via a focused and transcriptome-wide analyses. These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. Our findings demonstrate that core fucosylation is a common modification indirectly induced by targeted therapies that paradoxically promotes resistance.

Published
2023

36. Enabling Delay-Sensitive Modern Vehicular Applications by Using Resource Limited Vehicular Edge Computing Systems

Author

Ku, Yu-Jen, Dey, Sujit1, Ku, Yu-Jen, Ku, Yu-Jen, Dey, Sujit1, and Ku, Yu-Jen

Abstract

This study aims at using Road-side Unit (RSU)-assisted Vehicular Edge Computing (VEC) systems to support nowadays compute-intensive and delay-sensitive vehicular applications. Vehicles can offload these applications to the VEC server at the RSU to ease the burden on their limited onboard computing resources. Although VEC servers usually have higher computing capacity than vehicles, their computing resource, as well as the RSU's communication and energy resources, are not unlimited due to deployment constraints and operating costs. Our goal is to find the optimal resource allocation strategies for the RSU-assisted VEC systems to enable low-latency compute-intensive vehicular applications for vehicles.In the first part of the study, we consider Solar-powered RSU-assisted VEC systems, where the RSUs are solely powered by solar energy. Firstly, we aim to minimize service disruption of the offloaded vehicular applications under the intermittent solar power supply. We propose a two-phase approach that jointly optimizes solar energy usage and storage, user association, and RSU’s computing and communication resource allocation for the involved RSUs and vehicles in the VEC system. Secondly, we further reduce the application’s execution delay by a framework that uses computing resources from both the VEC server and the vehicle's local computing (VLC) unit for application execution through task partitioning and offloading. Furthermore, the framework is able to adjust the VEC server’s platform configuration and balance between the vehicular application’s execution delay and its application-level performance, according to the available computing, communication, and solar energy resources of the Solar-powered RSU.In the second part of the study, we focus on using the RSU-assisted VEC system to support an emerging advanced vehicular application, the multi-vehicle perception fusion. It is challenging to effectively allocate RSU’s computing and communication resources to support the

Published
2023

37. Point-of-care diagnostic platforms for loop-mediated isothermal amplification

Author

Atçeken, Nazente; Dabbagh, Sajjad Rahmani; Taşoğlu, Savaş (ORCID 0000-0003-4604-217X & YÖK ID 291971), Alseed, Muhammad Munzer; Yetisen, Ali K., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); KU Arçelik Research Center for Creative Industries (KUAR) / KU Arçelik Yaratıcı Endüstriler Uygulama ve Araştırma Merkezi (KUAR), Graduate School of Sciences and Engineering; College of Engineering, Department of Design Technology and Society; Department of Mechanical Engineering, Atçeken, Nazente; Dabbagh, Sajjad Rahmani; Taşoğlu, Savaş (ORCID 0000-0003-4604-217X & YÖK ID 291971), Alseed, Muhammad Munzer; Yetisen, Ali K., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); KU Arçelik Research Center for Creative Industries (KUAR) / KU Arçelik Yaratıcı Endüstriler Uygulama ve Araştırma Merkezi (KUAR), Graduate School of Sciences and Engineering; College of Engineering, and Department of Design Technology and Society; Department of Mechanical Engineering

Abstract

The loop-mediated isothermal amplification (LAMP) method is one of the Nucleic acid amplification tests (NAATs) that allows for the amplification of target regions without using a thermal cycle. With its unique primer design, LAMP ensures the rapid replication of the targeted DNA region with high specificity and high efficiency. LAMP technology is used for diagnostic purposes in pathogen detection due to its ease of use, low cost, and simplicity without requiring complex equipment. A wide range of LAMP diagnostic platforms have been developed for applications in bacteria, virus, and parasitic pathogen detection. Herein, the methodology of LAMP technology and its applications in pathogen detection and SNP genotyping and mutation detection are discussed. Point-of-care (PoC) LAMP platforms designed with the principles of microfluidic chip technology, including LAMP-on-a-chip, paper-based LAMP, and smartphone-based LAMP applications have been elaborated. LAMP technology represents a fast, robust, and reliable diagnostic platform for point-of-care testing., Scientific and Technological Research Council of Turkey (TÜBİTAK) 2232 International Fellowship for Outstanding Researchers Award; European Union (EU); Horizon 2020; Marie Sklodowska-Curie Individual Fellowship; Alexander von Humboldt Research Fellowship for Experienced Researchers, and Royal Academy Newton-Katip Celebi Transforming Systems Through Partnership award (120N019) for financial support of this research. This work was partially supported by Science Academy's Young Scientist Awards Program (BAGEP), Outstanding Young Scientists Awards (GEBIP), and Bilim Kahramanlari Dernegi The Young Scientist Award.

Published
2023

38. Observations of the Crab Nebula and Pulsar with the Large-Sized Telescope Prototype of the Cherenkov Telescope Array

Author

Project, CTA-LST, Abe, H., Abe, K., Abe, S., Aguasca-Cabot, A., Agudo, I., Crespo, N. Alvarez, Antonelli, L. A., Aramo, C., Arbet-Engels, A., Arcaro, C., Artero, M., Asano, K., Aubert, P., Baktash, A., Bamba, A., Larriva, A. Baquero, Baroncelli, L., de Almeida, U. Barres, Barrio, J. A., Batkovic, I., Baxter, J., González, J. Becerra, Bernardini, E., Bernardos, M. I., Medrano, J. Bernete, Berti, A., Bhattacharjee, P., Biederbeck, N., Bigongiari, C., Bissaldi, E., Blanch, O., Bonnoli, G., Bordas, P., Borghese, A., Bulgarelli, A., Burelli, I., Buscemi, M., Cardillo, M., Caroff, S., Carosi, A., Cassol, F., Cauz, D., Ceribella, G., Chai, Y., Cheng, K., Chiavassa, A., Chikawa, M., Chytka, L., Cifuentes, A., Contreras, J. L., Cortina, J., Costantini, H., D'Amico, G., Dalchenko, M., De Angelis, A., de Lavergne, M. de Bony, De Lotto, B., de Menezes, R., Deleglise, G., Delgado, C., Mengual, J. Delgado, della Volpe, D., Dellaiera, M., Depaoli, D., Di Piano, A., Di Pierro, F., Di Tria, R., Di Venere, L., Díaz, C., Dominik, R. M., Prester, D. Dominis, Donini, A., Dorner, D., Doro, M., Elsässer, D., Emery, G., Escudero, J., Ramazani, V. Fallah, Ferrara, G., Ferrarotto, F., Fiasson, A., Coromina, L. Freixas, Fröse, S., Fukami, S., Fukazawa, Y., Garcia, E., López, R. Garcia, Gasbarra, C., Gasparrini, D., Geyer, F., Paiva, J. Giesbrecht, Giglietto, N., Giordano, F., Giro, E., Gliwny, P., Godinovic, N., Grau, R., Green, D., Green, J., Gunji, S., Hackfeld, J., Hadasch, D., Hahn, A., Hashiyama, K., Hassan, T., Hayashi, K., Heckmann, L., Heller, M., Llorente, J. Herrera, Hirotani, K., Hoffmann, D., Horns, D., Houles, J., Hrabovsky, M., Hrupec, D., Hui, D., Hütten, M., Iarlori, M., Imazawa, R., Inada, T., Inome, Y., Ioka, K., Iori, M., Ishio, K., Iwamura, Y., Jacquemont, M., Martinez, I. Jimenez, Jurysek, J., Kagaya, M., Karas, V., Katagiri, H., Kataoka, J., Kerszberg, D., Kobayashi, Y., Kong, A., Kubo, H., Kushida, J., Lainez, M., Lamanna, G., Lamastra, A., Flour, T. Le, Linhoff, M., Longo, F., López-Coto, R., López-Moya, M., López-Oramas, A., Loporchio, S., Lorini, A., Luque-Escamilla, P. L., Majumdar, P., Makariev, M., Mandat, D., Manganaro, M., Manicò, G., Mannheim, K., Mariotti, M., Marquez, P., Marsella, G., Martí, J., Martinez, O., Martínez, G., Martínez, M., Marusevec, P., Mas-Aguilar, A., Maurin, G., Mazin, D., Guillen, E. Mestre, Micanovic, S., Miceli, D., Miener, T., Miranda, J. M., Mirzoyan, R., Mizuno, T., Gonzalez, M. Molero, Molina, E., Montaruli, T., Monteiro, I., Moralejo, A., Morcuende, D., Morselli, A., Mrakovcic, K., Murase, K., Nagai, A., Nagataki, S., Nakamori, T., Nickel, L., Nievas, M., Nishijima, K., Noda, K., Nosek, D., Nozaki, S., Ohishi, M., Ohtani, Y., Oka, T., Okazaki, N., Okumura, A., Orito, R., Otero-Santos, J., Palatiello, M., Paneque, D., Pantaleo, F. R., Paoletti, R., Paredes, J. M., Pech, M., Pecimotika, M., Peresano, M., Pérez, A., Pietropaolo, E., Pirola, G., Plard, C., Podobnik, F., Poireau, V., Polo, M., Pons, E., Prandini, E., Prast, J., Principe, G., Priyadarshi, C., Prouza, M., Rando, R., Rhode, W., Ribó, M., Rizi, V., Fernandez, G. Rodriguez, Ruiz, J. E., Saito, T., Sakurai, S., Sanchez, D. A., Šarić, T., Sato, Y., Saturni, F. G., Schleicher, B., Schmuckermaier, F., Schubert, J. L., Schussler, F., Schweizer, T., Arroyo, M. Seglar, Silvia, R., Sitarek, J., Sliusar, V., Spolon, A., Strišković, J., Strzys, M., Suda, Y., Sunada, Y., Tajima, H., Takahashi, H., Takahashi, M., Takata, J., Takeishi, R., Tam, P. H. T., Tanaka, S. J., Tateishi, D., Tejedor, L. A., Temnikov, P., Terada, Y., Terauchi, K., Terzic, T., Teshima, M., Tluczykont, M., Tokanai, F., Torres, D. F., Travnicek, P., Truzzi, S., Tutone, A., Uhlrich, G., Vacula, M., Vallania, P., van Scherpenberg, J., Acosta, M. Vázquez, Verguilov, V., Viale, I., Vigliano, A., Vigorito, C. F., Vitale, V., Voutsinas, G., Vovk, I., Vuillaume, T., Walter, R., Will, M., Yamamoto, T., Yamazaki, R., Yoshida, T., Yoshikoshi, T., Zywucka, N., Bernloehr, K., Gueta, O., Kosack, K., Maier, G., Watson, J., Rijeka, University of, Physics, Department of, Rijeka, Croatia, Physics, Institute for Theoretical, Astrophysics, Würzburg, Universität, Nord, Campus Hubland, Würzburg, Germany, Physik, Institut für Theoretische, IV, Lehrstuhl, Plasma-Astroteilchenphysik, Bochum, Ruhr-Universität, Bochum, La Sapienza, INFN Sezione di Roma, Rome, Italy, ILANCE, Laboratory, CNRS - University of Tokyo International Research, Kashiwa, Chiba, Japan, Program, Physics, Science, Graduate School of Advanced, Engineering, University, Hiroshima, Hiroshima, Vergata, INFN Sezione di Roma Tor, Physics, Faculty of, Informatics, Applied, Lodz, University of, Lodz, Poland, Split, University of, FESB, Split, University, Yamagata, Yamagata, University, Tohoku, Institute, Astronomical, Aobaku, Sendai, Osijek, Josip Juraj Strossmayer University of, Osijek, dell'Aquila, INFN Dipartimento di Scienze Fisiche e Chimiche - Università degli Studi, Institute, Gran Sasso Science, L'Aquila, Oiwakecho, Kitashirakawa, Kyoto, Astronomy, Department of, Geneva, University of, Versoix, Switzerland, Sciences, Astronomical Institute of the Czech Academy of, Prague, Republic, Czech, Science, Faculty of, University, Ibaraki, Mito, Ibaraki, University, Waseda, Shinjuku, Tokyo, di Trieste, INFN Sezione, di Trieste, Università degli Studi, Trieste, INFN, di Siena, Università degli Studi, Fisiche, Dipartimento di Scienze, dell'Ambiente, della Terra e, di Fisica, Sezione, Siena, de Jaén, Escuela Politécnica Superior, de Jaén, Universidad, Lagunillas, Campus Las, Jaén, Spain, Physics, Saha Institute of Nuclear, Bidhannagar, Kolkata, India, Research, Institute for Nuclear, Energy, Nuclear, Sciences, Bulgarian Academy of, Sofia, Bulgaria, Sciences, FZU - Institute of Physics of the Czech Academy of, Praha, di Palermo, Dipartimento di Fisica e Chimica 'E. Segrè' Università degli Studi, Scienze, via delle, Palermo, de Electronica, Grupo, de Madrid, Universidad Complutense, Complutense, Av., Madrid, Physics, Department of Applied, Zagreb, University of, Zagreb, Center, Hiroshima Astrophysical Science, Higashi-Hiroshima, RIKEN, Physical, Institute of, Research, Chemical, Wako, Saitama, University, Charles, Particle, Institute of, Physics, Nuclear, Physics, Division of, Astronomy, Science, Graduate School of, University, Kyoto, Sakyo-ku, Research, Institute for Space-Earth Environmental, University, Nagoya, Chikusa-ku, Nagoya, Institute, Kobayashi-Maskawa, Particles, for the Origin of, Universe, the, Technology, Graduate School of, Industrial, Sciences, Social, University, Tokushima, Tokushima, Sciences, Department of Physical, University, Aoyama Gakuin, Fuchinobe, Sagamihara, Kanagawa, IRFU, CEA, Paris-Saclay, Université, Gif-sur-Yvette, France, University, Saitama, Sakura-ku, city, Saitama, di Torino, Dipartimento di Fisica - Universitá degli Studi, Torino, University, Konan, Kobe, Hyogo, Japan), Heidelberg, Zeuthen, Saclay, CEA, Merisiers, Orme des, France), Project, CTA-LST, Abe, H., Abe, K., Abe, S., Aguasca-Cabot, A., Agudo, I., Crespo, N. Alvarez, Antonelli, L. A., Aramo, C., Arbet-Engels, A., Arcaro, C., Artero, M., Asano, K., Aubert, P., Baktash, A., Bamba, A., Larriva, A. Baquero, Baroncelli, L., de Almeida, U. Barres, Barrio, J. A., Batkovic, I., Baxter, J., González, J. Becerra, Bernardini, E., Bernardos, M. I., Medrano, J. Bernete, Berti, A., Bhattacharjee, P., Biederbeck, N., Bigongiari, C., Bissaldi, E., Blanch, O., Bonnoli, G., Bordas, P., Borghese, A., Bulgarelli, A., Burelli, I., Buscemi, M., Cardillo, M., Caroff, S., Carosi, A., Cassol, F., Cauz, D., Ceribella, G., Chai, Y., Cheng, K., Chiavassa, A., Chikawa, M., Chytka, L., Cifuentes, A., Contreras, J. L., Cortina, J., Costantini, H., D'Amico, G., Dalchenko, M., De Angelis, A., de Lavergne, M. de Bony, De Lotto, B., de Menezes, R., Deleglise, G., Delgado, C., Mengual, J. Delgado, della Volpe, D., Dellaiera, M., Depaoli, D., Di Piano, A., Di Pierro, F., Di Tria, R., Di Venere, L., Díaz, C., Dominik, R. M., Prester, D. Dominis, Donini, A., Dorner, D., Doro, M., Elsässer, D., Emery, G., Escudero, J., Ramazani, V. Fallah, Ferrara, G., Ferrarotto, F., Fiasson, A., Coromina, L. Freixas, Fröse, S., Fukami, S., Fukazawa, Y., Garcia, E., López, R. Garcia, Gasbarra, C., Gasparrini, D., Geyer, F., Paiva, J. Giesbrecht, Giglietto, N., Giordano, F., Giro, E., Gliwny, P., Godinovic, N., Grau, R., Green, D., Green, J., Gunji, S., Hackfeld, J., Hadasch, D., Hahn, A., Hashiyama, K., Hassan, T., Hayashi, K., Heckmann, L., Heller, M., Llorente, J. Herrera, Hirotani, K., Hoffmann, D., Horns, D., Houles, J., Hrabovsky, M., Hrupec, D., Hui, D., Hütten, M., Iarlori, M., Imazawa, R., Inada, T., Inome, Y., Ioka, K., Iori, M., Ishio, K., Iwamura, Y., Jacquemont, M., Martinez, I. Jimenez, Jurysek, J., Kagaya, M., Karas, V., Katagiri, H., Kataoka, J., Kerszberg, D., Kobayashi, Y., Kong, A., Kubo, H., Kushida, J., Lainez, M., Lamanna, G., Lamastra, A., Flour, T. Le, Linhoff, M., Longo, F., López-Coto, R., López-Moya, M., López-Oramas, A., Loporchio, S., Lorini, A., Luque-Escamilla, P. L., Majumdar, P., Makariev, M., Mandat, D., Manganaro, M., Manicò, G., Mannheim, K., Mariotti, M., Marquez, P., Marsella, G., Martí, J., Martinez, O., Martínez, G., Martínez, M., Marusevec, P., Mas-Aguilar, A., Maurin, G., Mazin, D., Guillen, E. Mestre, Micanovic, S., Miceli, D., Miener, T., Miranda, J. M., Mirzoyan, R., Mizuno, T., Gonzalez, M. Molero, Molina, E., Montaruli, T., Monteiro, I., Moralejo, A., Morcuende, D., Morselli, A., Mrakovcic, K., Murase, K., Nagai, A., Nagataki, S., Nakamori, T., Nickel, L., Nievas, M., Nishijima, K., Noda, K., Nosek, D., Nozaki, S., Ohishi, M., Ohtani, Y., Oka, T., Okazaki, N., Okumura, A., Orito, R., Otero-Santos, J., Palatiello, M., Paneque, D., Pantaleo, F. R., Paoletti, R., Paredes, J. M., Pech, M., Pecimotika, M., Peresano, M., Pérez, A., Pietropaolo, E., Pirola, G., Plard, C., Podobnik, F., Poireau, V., Polo, M., Pons, E., Prandini, E., Prast, J., Principe, G., Priyadarshi, C., Prouza, M., Rando, R., Rhode, W., Ribó, M., Rizi, V., Fernandez, G. Rodriguez, Ruiz, J. E., Saito, T., Sakurai, S., Sanchez, D. A., Šarić, T., Sato, Y., Saturni, F. G., Schleicher, B., Schmuckermaier, F., Schubert, J. L., Schussler, F., Schweizer, T., Arroyo, M. Seglar, Silvia, R., Sitarek, J., Sliusar, V., Spolon, A., Strišković, J., Strzys, M., Suda, Y., Sunada, Y., Tajima, H., Takahashi, H., Takahashi, M., Takata, J., Takeishi, R., Tam, P. H. T., Tanaka, S. J., Tateishi, D., Tejedor, L. A., Temnikov, P., Terada, Y., Terauchi, K., Terzic, T., Teshima, M., Tluczykont, M., Tokanai, F., Torres, D. F., Travnicek, P., Truzzi, S., Tutone, A., Uhlrich, G., Vacula, M., Vallania, P., van Scherpenberg, J., Acosta, M. Vázquez, Verguilov, V., Viale, I., Vigliano, A., Vigorito, C. F., Vitale, V., Voutsinas, G., Vovk, I., Vuillaume, T., Walter, R., Will, M., Yamamoto, T., Yamazaki, R., Yoshida, T., Yoshikoshi, T., Zywucka, N., Bernloehr, K., Gueta, O., Kosack, K., Maier, G., Watson, J., Rijeka, University of, Physics, Department of, Rijeka, Croatia, Physics, Institute for Theoretical, Astrophysics, Würzburg, Universität, Nord, Campus Hubland, Würzburg, Germany, Physik, Institut für Theoretische, IV, Lehrstuhl, Plasma-Astroteilchenphysik, Bochum, Ruhr-Universität, Bochum, La Sapienza, INFN Sezione di Roma, Rome, Italy, ILANCE, Laboratory, CNRS - University of Tokyo International Research, Kashiwa, Chiba, Japan, Program, Physics, Science, Graduate School of Advanced, Engineering, University, Hiroshima, Hiroshima, Vergata, INFN Sezione di Roma Tor, Physics, Faculty of, Informatics, Applied, Lodz, University of, Lodz, Poland, Split, University of, FESB, Split, University, Yamagata, Yamagata, University, Tohoku, Institute, Astronomical, Aobaku, Sendai, Osijek, Josip Juraj Strossmayer University of, Osijek, dell'Aquila, INFN Dipartimento di Scienze Fisiche e Chimiche - Università degli Studi, Institute, Gran Sasso Science, L'Aquila, Oiwakecho, Kitashirakawa, Kyoto, Astronomy, Department of, Geneva, University of, Versoix, Switzerland, Sciences, Astronomical Institute of the Czech Academy of, Prague, Republic, Czech, Science, Faculty of, University, Ibaraki, Mito, Ibaraki, University, Waseda, Shinjuku, Tokyo, di Trieste, INFN Sezione, di Trieste, Università degli Studi, Trieste, INFN, di Siena, Università degli Studi, Fisiche, Dipartimento di Scienze, dell'Ambiente, della Terra e, di Fisica, Sezione, Siena, de Jaén, Escuela Politécnica Superior, de Jaén, Universidad, Lagunillas, Campus Las, Jaén, Spain, Physics, Saha Institute of Nuclear, Bidhannagar, Kolkata, India, Research, Institute for Nuclear, Energy, Nuclear, Sciences, Bulgarian Academy of, Sofia, Bulgaria, Sciences, FZU - Institute of Physics of the Czech Academy of, Praha, di Palermo, Dipartimento di Fisica e Chimica 'E. Segrè' Università degli Studi, Scienze, via delle, Palermo, de Electronica, Grupo, de Madrid, Universidad Complutense, Complutense, Av., Madrid, Physics, Department of Applied, Zagreb, University of, Zagreb, Center, Hiroshima Astrophysical Science, Higashi-Hiroshima, RIKEN, Physical, Institute of, Research, Chemical, Wako, Saitama, University, Charles, Particle, Institute of, Physics, Nuclear, Physics, Division of, Astronomy, Science, Graduate School of, University, Kyoto, Sakyo-ku, Research, Institute for Space-Earth Environmental, University, Nagoya, Chikusa-ku, Nagoya, Institute, Kobayashi-Maskawa, Particles, for the Origin of, Universe, the, Technology, Graduate School of, Industrial, Sciences, Social, University, Tokushima, Tokushima, Sciences, Department of Physical, University, Aoyama Gakuin, Fuchinobe, Sagamihara, Kanagawa, IRFU, CEA, Paris-Saclay, Université, Gif-sur-Yvette, France, University, Saitama, Sakura-ku, city, Saitama, di Torino, Dipartimento di Fisica - Universitá degli Studi, Torino, University, Konan, Kobe, Hyogo, Japan), Heidelberg, Zeuthen, Saclay, CEA, Merisiers, Orme des, and France)

Abstract

CTA (Cherenkov Telescope Array) is the next generation ground-based observatory for gamma-ray astronomy at very-high energies. The Large-Sized Telescope prototype (LST-1) is located at the Northern site of CTA, on the Canary Island of La Palma. LSTs are designed to provide optimal performance in the lowest part of the energy range covered by CTA, down to $\simeq 20$ GeV. LST-1 started performing astronomical observations in November 2019, during its commissioning phase, and it has been taking data since then. We present the first LST-1 observations of the Crab Nebula, the standard candle of very-high energy gamma-ray astronomy, and use them, together with simulations, to assess the basic performance parameters of the telescope. The data sample consists of around 36 hours of observations at low zenith angles collected between November 2020 and March 2022. LST-1 has reached the expected performance during its commissioning period - only a minor adjustment of the preexisting simulations was needed to match the telescope behavior. The energy threshold at trigger level is estimated to be around 20 GeV, rising to $\simeq 30$ GeV after data analysis. Performance parameters depend strongly on energy, and on the strength of the gamma-ray selection cuts in the analysis: angular resolution ranges from 0.12 to 0.40 degrees, and energy resolution from 15 to 50%. Flux sensitivity is around 1.1% of the Crab Nebula flux above 250 GeV for a 50-h observation (12% for 30 minutes). The spectral energy distribution (in the 0.03 - 30 TeV range) and the light curve obtained for the Crab Nebula agree with previous measurements, considering statistical and systematic uncertainties. A clear periodic signal is also detected from the pulsar at the center of the Nebula., Comment: Accepted in ApJ. v3: updated author list and acknowledgements, fixed typos and other minor issues

Published
2023

39. Taguchi-Grey Relational Analysis Method for Parameter Tuning of Multi-objective Pareto Ant Colony System Algorithm

Author

Muthana, Shatha Abdulhadi, Ku Mahamud, Ku Ruhana, Muthana, Shatha Abdulhadi, and Ku Mahamud, Ku Ruhana

Abstract

In any metaheuristic, the parameter values strongly affect the efficiency of an algorithm’s search. This research aims to find the optimal parameter values for the Pareto Ant Colony System (PACS) algorithm, which is used to obtain solutions for the generator maintenance scheduling problem. For optimal maintenance scheduling with low cost, high reliability, and low violation, the parameter values of the PACS algorithm were tuned using the Taguchi and Gray Relational Analysis (Taguchi-GRA) method through search-based approach. The new parameter values were tested on two systems. i.e., 26- and 36-unit systems for window with operational hours [3000-5000]. The gray relational grade (GRG) performance metric and the Friedman test were used to evaluate the algorithm’s performance. The Taguchi-GRA method that produced the new values for the algorithm’s parameters was shown to be able to provide a better multi-objective generator maintenance scheduling (GMS) solution. These values can be benchmarked in solving multi-objective GMS problems using the multi-objective PACS algorithm and its variants.

Published
2023

40. Enhanced feature clustering method based on ant colony optimization for feature selection

Author

Almazini, Hassan, Ku-Mahamud, Ku Ruhana, Almazini, Hussein Fouad, Almazini, Hassan, Ku-Mahamud, Ku Ruhana, and Almazini, Hussein Fouad

Abstract

The popular modified graph clustering ant colony optimization (ACO) algorithm (MGCACO) performs feature selection (FS) by grouping highly correlated features. However, the MGCACO has problems in local search, thus limiting the search for optimal feature subset. Hence, an enhanced feature clustering with ant colony optimization (ECACO) algorithm is proposed. The improvement constructs an ACO feature clustering method to obtain clusters of highly correlated features. The ACO feature clustering method utilizes the ability of various mechanisms, such as local and global search to provide highly correlated features. The performance of ECACO was evaluated on six benchmark datasets from the University California Irvine (UCI) repository and two deoxyribonucleic acid microarray datasets, and its performance was compared against that of five benchmark metaheuristic algorithms. The classifiers used are random forest, k-nearest neighbors, decision tree, and support vector machine. Experimental results on the UCI dataset show the superior performance of ECACO compared with other algorithms in all classifiers in terms of classification accuracy. Experiments on the microarray datasets, in general, showed that the ECACO algorithm outperforms other algorithms in terms of average classification accuracy. ECACO can be utilized for FS in classification tasks for high-dimensionality datasets in various application domains such as medical diagnosis, biological classification, and health care systems.

Published
2023

41. Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Author

Matuozzo, D, Talouarn, E, Marchal, A, Zhang, P, Manry, J, Seeleuthner, Y, Zhang, Y, Bolze, A, Chaldebas, M, Milisavljevic, B, Gervais, A, Bastard, P, Asano, T, Bizien, L, Barzaghi, F, Abolhassani, H, Abou Tayoun, A, Aiuti, A, Alavi Darazam, I, Allende, L, Alonso-Arias, R, Arias, A, Aytekin, G, Bergman, P, Bondesan, S, Bryceson, Y, Bustos, I, Cabrera-Marante, O, Carcel, S, Carrera, P, Casari, G, Chaibi, K, Colobran, R, Condino-Neto, A, Covill, L, Delmonte, O, El Zein, L, Flores, C, Gregersen, P, Gut, M, Haerynck, F, Halwani, R, Hancerli, S, Hammarstrom, L, Hatipoglu, N, Karbuz, A, Keles, S, Kyheng, C, Leon-Lopez, R, Franco, J, Mansouri, D, Martinez-Picado, J, Metin Akcan, O, Migeotte, I, Morange, P, Morelle, G, Martin-Nalda, A, Novelli, G, Novelli, A, Palabiyik, F, Pan-Hammarstrom, Q, de Diego, R, Planas-Serra, L, Pleguezuelo, D, Prando, C, Pujol, A, Reyes, L, Riviere, J, Rodriguez-Gallego, C, Rojas, J, Rovere-Querini, P, Schluter, A, Shahrooei, M, Sobh, A, Soler-Palacin, P, Tandjaoui-Lambiotte, Y, Tipu, I, Tresoldi, C, Troya, J, van de Beek, D, Zatz, M, Zawadzki, P, Al-Muhsen, S, Alosaimi, M, Alsohime, F, Baris-Feldman, H, Butte, M, Constantinescu, S, Cooper, M, Dalgard, C, Fellay, J, Heath, J, Lau, Y, Lifton, R, Maniatis, T, Mogensen, T, von Bernuth, H, Lermine, A, Vidaud, M, Boland, A, Deleuze, J, Nussbaum, R, Kahn-Kirby, A, Mentre, F, Tubiana, S, Gorochov, G, Tubach, F, Hausfater, P, Al-Mulla, F, Anderson, M, Andreakos, E, Feldman, H, Belot, A, Biggs, C, Bogunovic, D, Bondarenko, A, Bousfiha, A, Brodin, P, Bustamante, C, Chakravorty, S, Christodoulou, J, Desai, M, Drolet, B, Baghdadi, J, Espinosa-Padilla, S, Froidure, A, Hagin, D, Henrickson, S, Hsieh, E, Husebye, E, Imai, K, Itan, Y, Jarvis, E, Karamitros, T, Kisand, K, Ku, C, Ling, Y, Lucas, C, Marodi, L, Milner, J, Mironska, K, Morio, T, Ng, L, O'Farrelly, C, Okada, S, Planas, A, Quintana-Murci, L, Renia, L, Resnick, I, Sancho-Shimizu, V, Sediva, A, Seppanen, M, Shcherbina, A, Slaby, O, Snow, A, Spaan, A, Tancevski, I, Tangye, S, Ramaswamy, S, Turvey, S, Uddin, F, Uddin, M, Vinh, D, Casanova, J, Vacher, Y, Gysembergh-Houal, A, Demerville, L, Chachoua, A, Abad, S, Abassi, R, Abdellaoui, A, Abdelmalek, A, Abdoul, H, Abergel, H, Abeud, F, Abgrall, S, Abisror, N, Adechian, M, Aderdour, N, Admane, H, Adnet, F, Afritt, S, Agostini, H, Aguilar, C, Agut, S, Aiello, T, Kaci, M, Oufella, H, Ajeenthiravasan, G, Alauzy, V, Alby-Laurent, F, Allard, L, Alyanakian, M, Borrero, B, Amam, S, Amrouche, L, Andronikof, M, Anglicheau, D, Anguel, N, Annane, D, Aounzou, M, Aparicio, C, Aratus, G, Arlet, J, Arzoine, J, Aslangul, E, Assefi, M, Aubry, A, Audiffred, L, Audureau, E, Auger, C, Auregan, J, Awotar, C, Milla, S, Azan, D, Azemar, L, Azzouguen, B, Elrufaai, M, Badsi, A, Bakouboula, P, Balcerowiak, C, Balde, F, Baldivia, E, Bangamingo, E, Baptiste, A, Baran-Marszak, F, Barau, C, Barget, N, Baronnet, F, Barthelemy, R, Baudel, J, Baudry, C, Baudry, E, Beaugerie, L, Belamri, A, Belaube, N, Belilita, R, Bellassen, P, Belmokhtar, R, Beltran, I, Benainous, R, Benallaoua, M, Benamouzig, R, Benbara, A, Benhida, J, Benkhelouf, A, Benlagha, J, Benmostafa, C, Benothmane, S, Bentifraouine, M, Berard, L, Bernier, Q, Berti, E, Bertier, A, Berton, L, Bessis, S, Beurton, A, Bianco, C, Bianquis, C, Bidar, F, Blanche, P, Blayau, C, Bleibtreu, A, Blin, E, Bloch-Queyrat, C, Boissier, M, Bollens, D, Bolzoni, M, Bompard, R, Bonnet, N, Bonnouvrier, J, Botha, S, Boucenna, W, Bouchama, F, Bouchaud, O, Bouchghoul, H, Boudjebla, T, Boudjema, N, Bouffard, C, Bougle, A, Bouguerra, M, Bouras, L, Bourcier, A, Durand, A, Bourrier, A, Bouscarat, F, Bouvry, D, Bouziri, N, Bouzrara, O, Bribier, S, Brugier, D, Brunel, M, Bui, E, Buisson, A, Bukreyeva, I, Bureau, C, Cadranel, J, Cailhol, J, Calin, R, Vega, C, Canavaggio, P, Cancella, M, Cantin, D, Cao, A, Carbillon, L, Carlier, N, Cassard, C, Castor, G, Cauchy, M, Cha, O, Chaigne, B, Challal, S, Champion, K, Chariot, P, Chas, J, Chauveau, S, Chauvin, A, Chauvin, C, Chavarot, N, Chebbout, K, Cherai, M, Cherubini, I, Chevalier, A, Chiarabini, T, Chinet, T, Chocron, R, Choinier, P, Chommeloux, J, Choquet, C, Choupeaux, L, Chousterman, B, Ciocan, D, Clarke, A, Clavere, G, Clavier, F, Clement, K, Clerc, S, Cohen, Y, Cohen, F, Cohen, A, Coilly, A, Colboc, H, Colin, P, Collet, M, Comarmond, C, Combacon, E, Combes, A, Comparon, C, Constantin, J, Cordel, H, Cordier, A, Costantini, A, Chalumeau, N, Couffignal, C, Coupeau, D, Creange, A, Lamarre, Y, Da Silveira, C, Kayani, S, De Castro, N, De Rycke, Y, Del Pozo, L, Delannoy, Q, Delay, M, Deleris, R, Delforge, J, Delphine, L, Demare, N, Demeret, S, Demoule, A, Deniau, A, Depret, F, Derolez, S, Derradji, O, Derridj, N, Descamps, V, Deschamps, L, Desconclois, C, Desnos, C, Desongins, K, Dhote, R, Diallo, B, Didier, M, Diemer, M, Diez, S, Djadi-Prat, J, Monnory, F, Djebara, S, Djebra, N, Djietcheu, M, Djillali, H, Djouadi, N, Donneger, S, Dos Santos, C, Dournon, N, Dres, M, Droctove, L, Drogrey, M, Dropy, M, Drouet, E, Dubosq, V, Dubreucq, E, Dubus, E, Duchemann, B, Duchenoy, T, Dudoignon, E, Dufau, R, Dumas, F, Duran, C, Duron, E, Durrbach, A, Duvivier, C, Ebstein, N, Khalifa, J, Elabbadi, A, Elie, C, Ernotte, G, Esling, A, Etienne, M, Eyer, X, Fartoukh, M, Fayali, T, Fermaut, M, Fiorentino, A, Fliss, S, Fournier, M, Fournier, B, Francois, H, Freynet, O, Frigout, Y, Fromont, I, Fuentes, A, Furet, T, Galand, J, Garnier, M, Gaubert, A, Gaudry, S, Gaugain, S, Gauthier, D, Gautier, M, Georgin-Lavialle, S, Geromin, D, Ghalayini, M, Ghaleh, B, Ghezal, M, Gibelin, A, Gimeno, L, Girard, B, Leprieur, B, Gomes, D, Gomes-Pires, E, Gouge, A, Gouja, A, Goulet, H, Goupil, S, De Bouille, J, Gras, J, Greffe, S, Grimaldi, L, Guedeney, P, Guidet, B, Guillo, M, Gulczynski, M, Hadjam, T, Haguenauer, D, Hammal, S, Hammoudi, N, Hanon, O, Harrois, A, Hautem, C, Hekimian, G, Heming, N, Hermine, O, Ho, S, Houllier, M, Huot, B, Huscenot, T, Saied, W, Ikherbane, G, Imarazene, M, Ingiliz, P, Iratni, L, Jaureguiberry, S, Jean-Marc, J, Jeyarajasingham, D, Jouany, P, Jouis, V, Jourdaine, C, Kafif, O, Kallala, R, Katsahian, S, Kelesyan, L, Keo, V, Ketz, F, Khamis, W, Khelili, E, Khellaf, M, Youkou, C, Kounis, I, Kpalma, G, Krause, J, Labbe, V, Lacombe, K, Lacorte, J, Lafont, A, Lafont, E, Lagha, L, Lamhaut, L, Lancelot, A, Landman, C, Lanternier, F, Larcheveque, C, Combe, C, Lassel, L, Laverdant, B, Lavergne, C, Lavillegrand, J, Lazureanu, P, Le Guennec, L, Leberre, L, Leblanc, C, Leboyer, M, Lecomte, F, Lecorre, M, Leenhardt, R, Lefebvre, M, Lefebvre, B, Legendre, P, Leger, A, Legros, L, Legrosse, J, Lehuunghia, S, Lemarec, J, Leporrier-Ext, J, Lesein, M, Lesur, H, Levy, V, Levy, A, Lopes, E, Lopes, A, Lopez, V, Lopinto, J, Lortholary, O, Louadah, B, Loze, B, Lucas, M, Lucasamichi, A, Luong, L, Magazimama-Ext, A, Maingret, D, Mameri, L, Manivet, P, Mansouri, C, Marcault, E, Marey, J, Marin, N, Marois, C, Martin, O, Martineau, L, Martinez-Lopez, C, Martyniuck, P, De Farcy, P, Marzouk, N, Masmoudi, R, Mebazaa, A, Mechai, F, Mecozzi, F, Mediouni, C, Megarbane, B, Meghadecha, M, Mejean, E, Mekinian, A, Abdelhadi, N, Mekni, R, Meliti, T, Lima, B, Meng, P, Merbah, S, Messani, F, Messaoudi, Y, Mewasing, B, Meziane, L, Michelot-Burger, C, Mignot, F, Minka, F, Miyara, M, Moine, P, Molina, J, Montegnies-Boulet, A, Monti, A, Montlahuc, C, Montout, A, Moores, A, Morbieu, C, Mortelette, H, Mouly, S, Muzaffar, R, Nacerddine, C, Nadal, M, Nadif, H, Nassarmadji, K, Natella, P, Ndingamondze, S, Neraal, S, Nguyen, C, N'Guyen, B, Larmurier, I, Nlomenyengue, L, Noel, N, Nunes, H, Omar, E, Ouazene, Z, Ouedraogo, E, Ouelaa, W, Oukhedouma, A, Amara, Y, Oya, H, Oziel, J, Padilla, T, Paillaud, E, Paiva, S, Parfait, B, Parize, P, Parizot, C, Parrot, A, Pavot, A, Peaudecerf, L, Pene, F, Pepin, M, Pernet, J, Pernin, C, Petit, M, Peyrony, O, Pietri, M, Pietri, O, De Chambrun, M, Pinson, M, Pintado, C, Pires, C, Planquette, B, Poirier, S, Pomel, A, Pons, S, Ponscarme, D, Pourcelot, A, Pourcher, V, Pouvaret, A, Prever, F, Previlon, M, Prevost, M, Provoost, M, Quemeneur, C, Rafat, C, Rami, A, Ranque, B, Raphael, M, Raphalen, J, Rastoin, A, Raux, M, Rebai, A, Reby, M, Regent, A, Regrag, A, Resche-Rigon, M, Ressaire, Q, Richard, C, Richard, M, Robert, M, Rohaut, B, Rolland-Debord, C, Ropers, J, Roque-Afonso, A, Rosso, C, Rousseaux, M, Rousseaux, N, Roux, S, Roux, L, Rouzaud, C, Rozes, A, Rubenstein, E, Sabate, J, Sabet, S, Sacleux, S, Kermanach, N, Saliba, F, Salmon, D, Savale, L, Savary, G, Sberro, R, Scemla, A, Schlemmer, F, Schwartz, M, Sedfi, S, Sefir-Kribel, S, Seksik, P, Sellier, P, Selves, A, Sembach, N, Semerano, L, Senat, M, Sene, D, Serris, A, Sese, L, Sghiouar, N, Sigaux, J, Siguier, M, Silvain, J, Simon, N, Simon, T, Skandri, L, Slimani, M, Snauwaert, A, Sokol, H, Soliman, H, Soltani, N, Soyer, B, Steg, G, Suarez, L, Szwebel, T, Taffame, K, Tantet, C, Tateo, M, Theodose, I, Thiebaud, P, Thomas, C, Tiercelet, K, Tisserand, J, Tomczak, C, Torelino, K, Touam-Ext, F, Toumi, L, Toury, G, Toy-Miou, M, Lien, O, Trandinh, A, Treluyer, J, Trinque, B, Truchot, J, Tunesi, S, Turpin, M, Turpin, A, Urbina, T, Narvaez, R, Uzunhan, Y, Vaittinadaayar, P, Valent, A, Valentian, M, Valin, N, Vallet, H, Vaz, M, Vazquezibarra, M, Vedie, B, Velly, L, Verstuyft, C, Viallette, C, Vicaut, E, Vignes, D, Vimpere, D, Virlouvet, M, Voiriot, G, Voisot, L, Weiss, E, Weiss, N, Winchenne, A, Yordanov, Y, Zafrani, L, Zaidan, M, Zaidi, W, Zak, C, Zarhrate-Ghoul, A, Zatout, O, Zeino, S, Zeitouni, M, Zemirli, N, Zerah, L, Zia, O, Ziol, M, Zolario, O, Zuber, J, Andrejak, C, Angoulvant, F, Bachelet, D, Bartoli, M, Basmaci, R, Behilill, S, Beluze, M, Benkerrou, D, Bhavsar, K, Bouadma, L, Bouchez, S, Bouscambert, M, Cervantes-Gonzalez, M, Chair, A, Coelho, A, D'Ortenzio, E, Debray, M, Deconinck, L, Deplanque, D, Descamps, D, Desvallee, M, Diallo, A, Diouf, A, Dorival, C, Dubos, F, Duval, X, Elharrar, B, Eloy, P, Enouf, V, Esperou, H, Esposito-Farese, M, Devouge, E, Gault, N, Gaymard, A, Ghosn, J, Gigante, T, Gilg, M, Guedj, J, Hoctin, A, Hoffmann, I, Houas, I, Hulot, J, Jaafoura, S, Kaguelidou, F, Kali, S, Khalil, A, Khan, C, Laouenan, C, Laribi, S, Le, M, Le Hingrat, Q, Le Mestre, S, Le Nagard, H, Lescure, F, Levy, Y, Lingas, G, Lucet, J, Malvy, D, Mambert, M, Meziane, A, Mouquet, H, Mullaert, J, Neant, N, Nguyen, D, Noret, M, Nseir, S, Papadopoulos, A, Paul, C, Peiffer-Smadja, N, Perpoint, T, Petrov-Sanchez, V, Peytavin, G, Pham, H, Picone, O, Puechal, O, Rabaud, C, Rosa-Calatrava, M, Rossignol, B, Rossignol, P, Roy, C, Schneider, M, Su, R, Tardivon, C, Tellier, M, Teoule, F, Terrier, O, Timsit, J, Tual, C, Van Der Werf, S, Vanel, N, Veislinger, A, Visseaux, B, Wiedemann, A, Yazdanpanah, Y, Alavoine, L, Behillil, S, Burdet, C, Charpentier, C, Dechanet, A, Ecobichon, J, Frezouls, W, Houhou, N, Lehacaut, J, Letrou, S, Lina, B, Manchon, P, Nouroudine, M, Piquard, V, Quintin, C, Thy, M, Vignali, V, Chahine, A, Waucquier, N, Migaud, M, Djossou, F, Mergeay-Fabre, M, Lucarelli, A, Demar, M, Bruneau, L, Gerardin, P, Maillot, A, Payet, C, Laviolle, B, Laine, F, Paris, C, Desille-Dugast, M, Fouchard, J, Pistone, T, Perreau, P, Gissot, V, Goas, C, Montagne, S, Richard, L, Chirouze, C, Bouiller, K, Desmarets, M, Meunier, A, Bourgeon, M, Lefevre, B, Jeulin, H, Legrand, K, Lomazzi, S, Tardy, B, Gagneux-Brunon, A, Bertholon, F, Botelho-Nevers, E, Christelle, K, Nicolas, L, Roufai, L, Amat, K, Couffin-Cadiergues, S, Hendou, S, Foti, G, Bellani, G, Citerio, G, Contro, E, Pesci, A, Valsecchi, M, Cazzaniga, M, Abad, J, Accordino, G, Achille, C, Aguilera-Albesa, S, Aguilo-Cucurull, A, Ozkan, E, Albisures, J, Aldave, J, Ramos, M, Khan, T, Aliberti, A, Nadji, S, Alkan, G, Alkhater, S, Allardet-Servent, J, Alshahrani, M, Alsina, L, Amoura, Z, Antoli, A, Arrestier, R, Aubart, M, Auguet, T, Avramenko, I, Azot, A, Bahram, S, Bajolle, F, Baldanti, F, Baldolli, A, Ballester, M, Barrou, B, Basso, S, Bayhan, G, Bezrodnik, L, Bilbao, A, Blanchard-Rohner, G, Blanco, I, Blandinieres, A, Blazquez-Gamero, D, Bloomfield, M, Bolivar-Prados, M, Borghesi, A, Borie, R, Botdhlo-Nevers, E, Bousquet, A, Boutolleau, D, Bouvattier, C, Boyarchuk, O, Bravais, J, Briones, M, Brunner, M, Bruno, R, Bueno, M, Bukhari, H, Bustamante, J, Agra, J, Capra, R, Carapito, R, Carrabba, M, Casasnovas, C, Caseris, M, Cassaniti, I, Castelle, M, Castelli, F, de Vera, M, Castro, M, Catherinot, E, Celik, J, Ceschi, A, Chalumeau, M, Charbit, B, Cheng, M, Clave, P, Clotet, B, Codina, A, Comoli, P, Corsico, A, Sozeri, B, Coskuner, T, Cvetkovski, A, Cyrus, C, Dalmau, D, Danion, F, Darley, D, Das, V, Dauby, N, Dauger, S, De Munter, P, de Pontual, L, Dehban, A, Delplancq, G, Desguerre, I, Di Sabatino, A, Diehl, J, Dobbelaere, S, Dominguez-Garrido, E, Dubost, C, Ekwall, O, Bozdemir, S, Elnagdy, M, Emiroglu, M, Endo, A, Erdeniz, E, Aytekin, S, Lasa, M, Euvrard, R, Fabio, G, Faivre, L, Falck, A, Faure, M, Arquero, M, Ferrer, R, Ferreres, J, Francois, B, Fumado, V, Fung, K, Fusco, F, Gagro, A, Solis, B, Garcon, P, Gaussem, P, Gayretli, Z, Gil-Herrera, J, Gilardin, L, Gatineau, A, Girona-Alarcon, M, Godinez, K, Goffard, J, Gonzales, N, Gonzalez-Granado, L, Gonzalez-Montelongo, R, Guerder, A, Gulhan, B, Gumucio, V, Hanitsch, L, Gunst, J, Hadjadj, J, Hariyan, T, Heppekcan, D, Hernandez-Brito, E, Ho, P, Holanda-Pena, M, Horcajada, J, Hraiech, S, Humbert, L, Hung, I, Iglesias, A, Inigo-Campos, A, Jamme, M, Arranz, M, Jimeno, M, Jordan, I, Yuksek, S, Kara, Y, Karahan, A, Yasar, K, Kasapcopur, O, Kashimada, K, Demirkol, Y, Kido, Y, Kizil, C, Kilic, A, Klocperk, A, Koutsoukou, A, Krol, Z, Ksouri, H, Kuentz, P, Kwan, A, Kwan, Y, Kwok, J, Lagier, J, Lam, D, Lampropoulou, V, Le Bourgeois, F, Leo, Y, Leung, D, Levin, M, Levy, M, Levy, R, Li, Z, Lilleri, D, Lima, E, Linglart, A, Lopez-Collazo, E, Lorenzo-Salazar, J, Louapre, C, Lubetzki, C, Lung, K, Luyt, C, Lye, D, Magnone, C, Marchioni, E, Marioli, C, Marjani, M, Marques, L, Pereira, J, Pueyo, D, Marzana, I, Mata-Martinez, C, Mathian, A, Matos, L, Matthews, G, Mayaux, J, McLaughlin-Garcia, R, Meersseman, P, Mege, J, Mekontso-Dessap, A, Melki, I, Meloni, F, Meritet, J, Merlani, P, Akcan, O, Mezidi, M, Millereux, M, Million, M, Mirault, T, Mircher, C, Mirsaeidi, M, Mizoguchi, Y, Modi, B, Mojoli, F, Moncomble, E, Melian, A, Martinez, A, Morandeira, F, Mordacq, C, Munoz-Barrera, A, Nafati, C, Nagashima, S, Nakagama, Y, Neven, B, Neves, J, Ng, Y, Nielly, H, Medina, Y, Cuadros, E, Ocejo-Vinyals, J, Okamoto, K, Oualha, M, Ouedrani, A, Ozcelik, T, Ozkaya-Parlakay, A, Pagani, M, Papadaki, M, Parola, P, Pascreau, T, Paul, S, Paz-Artal, E, Pedraza, S, Pellecer, N, Pellegrini, S, Perez-Fernandez, X, Philippe, A, Philippot, Q, Picod, A, Piralla, A, Ploin, D, Poissy, J, Poncelet, G, Poulakou, G, Pouletty, M, Pourshahnazari, P, Qiu-Chen, J, Quentric, P, Rambaud, T, Raoult, D, Raoult, V, Rebillat, A, Redin, C, Resmini, L, Ricart, P, Richard, J, Rigo-Bonnin, R, Rivet, N, Rocamora-Blanch, G, Rodero, M, Rodrigo, C, Rodriguez, L, 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F., Gault N., Gaymard A., Ghosn J., Gigante T., Gilg M., Guedj J., Hoctin A., Hoffmann I., Houas I., Hulot J. -S., Jaafoura S., Kaguelidou F., Kali S., Khalil A., Khan C., Laouenan C., Laribi S., Le M., Le Hingrat Q., Le Mestre S., Le Nagard H., Lescure F. -X., Levy Y., Lingas G., Lucet J. C., Malvy D., Mambert M., Meziane A., Mouquet H., Mullaert J., Neant N., Nguyen D., Noret M., Nseir S., Papadopoulos A., Paul C., Peiffer-Smadja N., Perpoint T., Petrov-Sanchez V., Peytavin G., Pham H., Picone O., Puechal O., Rabaud C., Rosa-Calatrava M., Rossignol B., Rossignol P., Roy C., Schneider M., Su R., Tardivon C., Tellier M. -C., Teoule F., Terrier O., Timsit J. -F., Tual C., Van Der Werf S., Vanel N., Veislinger A., Visseaux B., Wiedemann A., Yazdanpanah Y., Alavoine L., Behillil S., Burdet C., Charpentier C., Dechanet A., Ecobichon J. -L., Frezouls W., Houhou N., Lehacaut J., Letrou S., Lina B., Manchon P., Nouroudine M., Piquard V., Quintin C., Thy M., Vignali V., Chahine A., Waucquier N., Migaud M. -C., Djossou F., Mergeay-Fabre M., Lucarelli A., Demar M., Bruneau L., Gerardin P., Maillot A., Payet C., Laviolle B., Laine F., Paris C., Desille-Dugast M., Fouchard J., Pistone T., Perreau P., Gissot V., Goas C. L. E., Montagne S., Richard L., Chirouze C., Bouiller K., Desmarets M., Meunier A., Bourgeon M., Lefevre B., Jeulin H., Legrand K., Lomazzi S., Tardy B., Gagneux-Brunon A., Bertholon F., Botelho-Nevers E., Christelle K., Nicolas L., Roufai L., Amat K., Couffin-Cadiergues S., Hendou S., Foti G., Bellani G., Citerio G., Contro E., Pesci A., Valsecchi M. G., Cazzaniga M., Abad J., Accordino G., Achille C., Aguilera-Albesa S., Aguilo-Cucurull A., Ozkan E. A., Albisures J. A. R., Aldave J. C., Ramos M. A., Khan T. A., Aliberti A., Nadji S. A., Alkan G., AlKhater S. A., Allardet-Servent J., Alshahrani M. S., Alsina L., Amoura Z., Antoli A., Arrestier R., Aubart M., Auguet T., Avramenko I., Azot A., Bahram S., Bajolle F., Baldanti F., Baldolli A., Ballester M., Barrou B., Basso S., Bayhan G. I., Bezrodnik L., Bilbao A., Blanchard-Rohner G., Blanco I., Blandinieres A., Blazquez-Gamero D., Bloomfield M., Bolivar-Prados M., Borghesi A., Borie R., Botdhlo-Nevers E., Bousquet A., Boutolleau D., Bouvattier C., Boyarchuk O., Bravais J., Briones M. L., Brunner M. -E., Bruno R., Bueno M. R. P., Bukhari H., Bustamante J., Agra J. J. C., Capra R., Carapito R., Carrabba M., Casasnovas C., Caseris M., Cassaniti I., Castelle M., Castelli F., de Vera M. C., Castro M. V., Catherinot E., Celik J. B., Ceschi A., Chalumeau M., Charbit B., Cheng M. P., Clave P., Clotet B., Codina A., Comoli P., Corsico A. G., Sozeri B., Coskuner T., Cvetkovski A., Cyrus C., Dalmau D., Danion F., Darley D. R., Das V., Dauby N., Dauger S., De Munter P., de Pontual L., Dehban A., Delplancq G., Desguerre I., Di Sabatino A., Diehl J. -L., Dobbelaere S., Dominguez-Garrido E., Dubost C., Ekwall O., Bozdemir S. E., Elnagdy M. H., Emiroglu M., Endo A., Erdeniz E. H., Aytekin S. E., Lasa M. P. E., Euvrard R., Fabio G., Faivre L., Falck A., Faure M., Arquero M. F., Ferrer R., Ferreres J., Francois B., Fumado V., Fung K. S. C., Fusco F., Gagro A., Solis B. G., Garcon P., Gaussem P., Gayretli Z., Gil-Herrera J., Gilardin L., Gatineau A. G., Girona-Alarcon M., Godinez K. A. C., Goffard J. -C., Gonzales N., Gonzalez-Granado L. I., Gonzalez-Montelongo R., Guerder A., Gulhan B., Gumucio V. D., Hanitsch L. G., Gunst J., Hadjadj J., Hariyan T., Heppekcan D., Hernandez-Brito E., Ho P. -K., Holanda-Pena M. S., Horcajada J. P., Hraiech S., Humbert L., Hung I. F. N., Iglesias A. D., Inigo-Campos A., Jamme M., Arranz M. J., Jimeno M. -T., Jordan I., Yuksek S. K., Kara Y. B., Karahan A., Yasar K. K., Kasapcopur O., Kashimada K., Demirkol Y. K., Kido Y., Kizil C., Kilic A. O., Klocperk A., Koutsoukou A., Krol Z. J., Ksouri H., Kuentz P., Kwan A. M. C., Kwan Y. W. M., Kwok J. S. Y., Lagier J. -C., Lam D. S. Y., Lampropoulou V., Le Bourgeois F., Leo Y. -S., Leung D., Levin M., Levy M., Levy R., Li Z., Lilleri D., Lima E. J. A. B., Linglart A., Lopez-Collazo E., Lorenzo-Salazar J. M., Louapre C., Lubetzki C., Lung K. -C., Luyt C. -E., Lye D. C., Magnone C., Marchioni E., Marioli C., Marjani M., Marques L., Pereira J. M., Pueyo D. M., Marzana I., Mata-Martinez C., Mathian A., Matos L. R. B., Matthews G. V., Mayaux J., McLaughlin-Garcia R., Meersseman P., Mege J. -L., Mekontso-Dessap A., Melki I., Meloni F., Meritet J. -F., Merlani P., Akcan O. M., Mezidi M., Millereux M., Million M., Mirault T., Mircher C., Mirsaeidi M., Mizoguchi Y., Modi B. P., Mojoli F., Moncomble E., Melian A. M., Martinez A. M., Morandeira F., Mordacq C., Mouly S. J., Munoz-Barrera A., Nafati C., Nagashima S., Nakagama Y., Neven B., Neves J. F., Ng Y. -Y., Nielly H., Medina Y. N., Cuadros E. N., Ocejo-Vinyals J. G., Okamoto K., Oualha M., Ouedrani A., Ozcelik T., Ozkaya-Parlakay A., Pagani M., Papadaki M., Parola P., Pascreau T., Paul S., Paz-Artal E., Pedraza S., Pellecer N. C. G., Pellegrini S., Perez-Fernandez X. L., Philippe A., Philippot Q., Picod A., Piralla A., Ploin D., Poissy J., Poncelet G., Poulakou G., Pouletty M. S., Pourshahnazari P., Qiu-Chen J. L., Quentric P., Rambaud T., Raoult D., Raoult V., Rebillat A. -S., Redin C., Resmini L., Ricart P., Richard J. -C., Rigo-Bonnin R., rivet N., Rocamora-Blanch G., Rodero M. P., Rodrigo C., Rodriguez L. A., Rodriguez-Palmero A., Romero C. S., Rothenbuhler A., Roux D., Rovina N., Rozenberg F., Ruch Y., Ruiz M., del Prado M. Y. R., Ruiz-Rodriguez J. C., Sabater-Riera J., Saks K., Salagianni M., Sanchez O., Sanchez-Montalva A., Sanchez-Ramon S., Schidlowski L., Schmidt J., Schmidt M., Schuetz C., Schweitzer C. E., Scolari F., Seijo L., Seminario A. G., Seng P., Senoglu S., Seppanen M., Llovich A. S., Siguret V., Siouti E., Smadja D. M., Smith N., Solanich X., Sole-Violan J., Soler C., Stella G. M., Stepanovskiy Y., Stoclin A., Taccone F., Taupin J. -L., Tavernier S. J., Tello L. V., Terrier B., Thiery G., Thorball C., Thorn K., Thumerelle C., Tolstrup M., Tomasoni G., Toubiana J., Alvarez J. T., Triantafyllia V., Trouillet-Assant S., Tsang O. T. Y., Tserel L., Tso E. Y. K., Tucci A., Oz S. K. T., Ursini M. V., Utsumi T., Vabres P., Valencia-Ramos J., Van Den Rym A. M., Vandernoot I., Velez-Santamaria V., Veliz S. P. Z., Vidigal M. C., Viel S., Villain C., Vilaire-Meunier M. E., Villar-Garcia J., Vincent A., Volokha A., Vuotto F., Wauters E., Wauters J., Wu A. K. L., Wu T. -C., Yahsi A., Yesilbas O., Yildiz M., Young B. E., Yukselmis U., Zecca M., Zuccaro V., Van Praet J., Lambrecht B. N., Van Braeckel E., Bosteels C., Hoste L., Hoste E., Bauters F., De Clercq J., Heijmans C., Slabbynck H., Naesens L., Florkin B., Boulanger C., Vanderlinden D., Berkell M., Carelli V., Malhotra S., Mattiaccio A., Pippucci T., Seri M., Tacconelli E., van Agtmael M., Algera A. G., Appelman B., van Baarle F., Bax D., Beudel M., Bogaard H. J., Bomers M., Bonta P., Bos L., Botta M., de Brabander J., de Bree G., de Bruin S., Buis D. T. P., Bugiani M., Bulle E., Cloherty O. C. A., Dijkstra M., Dongelmans D. A., Dujardin R. W. G., Elbers P., Fleuren L., Geijtenbeek S. G. T., Girbes A., Goorhuis B., Grobusch M. P., Hafkamp F., Hagens L., Hamann J., Harris V., Hemke R., Heunks S. M. H. L., Hollmann M., Horn J., Hovius J. W., de Jong M. D., Koning R., Lim E. H. T., van Mourik N., Nellen J., Nossent E. J., Paulus F., Peters E., Pina-Fuentes D. A. I., van der Poll T., Preckel B., Prins J. M., Raasveld J., Reijnders T., de Rotte M. C. F. J., Schinkel M., Schultz M. J., Schrauwen F. A. P., Schuurmans A., Schuurmans J., Sigaloff K., Slim M. A., Smeele P., Smit M., Stijnis C. S., Stilma W., Teunissen C., Thoral P., Tsonas A. M., Tuinman P. R., van der Valk M., Veelo D., Volleman C., de Vries H., Vught L. A., van Vugt M., Wouters D., Zwinderman A. H., Brouwer M. C., Wiersinga W. J., Vlaar A. P. J., Tompkins M. F., Alba C., Hupalo D. N., Rosenberger J., Sukumar G., Wilkerson M. D., Zhang X., Lack J., Oler A. J., Dobbs K., Danielson J. J., Biondi A., Bettini L. R., D'Angio' M., Beretta I., Imberti L., Sottini A., Quaresima V., Quiros-Roldan E., Rossi C., Meyts I., Zhang S. -Y., Puel A., Notarangelo L. D., Boisson-Dupuis S., Su H. C., Boisson B., Jouanguy E., Zhang Q., Abel L., and Cobat A.

Abstract

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

Published
2023

42. TCP6, a regulator in Arabidopsis gametophyte development and DNA damage response

Author

Ku, Chuan-Chih, Doerner, Peter, and Goodrich, Justin

Subjects
572, TCP, gametophyte, pollen, embryo sac, cell cycle, DNA double-stranded breaks, DSB
Abstract

Plants have developed intricate mechanisms to control growth in response to a variety of environmental cues, to compensate its immobility and to survive in both normal and adverse conditions. The TCP proteins are a family of plant-specific, basic helix-loop-helix (bHLH) transcription factors that involve in different aspects in plant growth and developmental control. The Arabidopsis TCP20 has been shown to involve in coordinating cell growth and proliferation, and in growth arrest in response to DNA double-stranded breaks (DSB). In this thesis, the main interest is to examine the function of Arabidopsis TCP6, which shares the highest homology with TCP20, and like TCP20, contains a putative ATM phosphorylation motif that suggests potential involvement in the ATM/ATR-mediated DSB responses. Expressional analysis including transcript measurement and reporter gene tagging demonstrated that TCP6 is expressed in flowers, in particular in the first mitotic event of pollen and ovule/embryo sac development, indicating that TCP6 potentially involves in regulating the mitotic cell cycle during gametophyte development. Yet no gametophytic or fertility-affecting mutant phenotype was observed in the tcp6 single and tcp6/tcp20 double mutants, which may be due to high functional redundancy. The tcp6/tcp20 double mutant seedlings exhibited significantly higher growth performances in true leaf growth compared to wild type when treated with gamma radiation, implying that both functional TCP6 and TCP20 are involved in response to gamma radiation-generated DSBs. The work of this thesis provides the first expressional and functional characterizations of TCP6, with the results suggesting that TCP6 and other class I TCPs play a role in regulating growth under both normal and stress conditions.

Published
2014

43. Quotidian micro-spectacles : Ulysses and fashion

Author

Ku, P., Sayeau, M., and Mitchell, C.

Subjects
823
Abstract

Quotidian Micro-Spectacles: Ulysses and Fashion wishes to make a contribution to Joycean studies in the research area that has been known as cultural studies. Over nearly three decades, there have been seminal works in this research area, such as Cheryl Herr’s Joyce’s Anatomy of Culture, R. Brandon Kershner’s The Culture of Joyce’s Ulysses, Garry Leonard’s Advertising and Commodity Culture in Joyce, and articles featured in James Joyce Quarterly Volume 30 (Fall 1992-Summer/Fall 1993); this thesis focuses on one specific aspect of commodity culture––that is, fashion items––in Ulysses, believing that a microscopic scrutiny at the details of these fashion items would reveal how Joyce’s innovative language and narrative in Ulysses are rooted in and interlaced with technologies that have inconspicuously yet greatly changed people’s daily life during the period of time when Joyce was writing Ulysses. Through the microscopic gaze, this thesis identifies a colonial phenomenon that is ubiquitous amongst Ulysses’s mist of language-game, that is, the omnipresence of English fashion: Stephen Dedalus’s adherence to mourning dress, Leopold Bloom’s meticulousness about dress codes, Gerty MacDowell’s obsession with dame fashion, the Circean mise-en-scène of millinery spectacles, and Molly Bloom’s desire for Edwardian lingerie. Whereas many of Joyce’s Dubliners demonstrate a non-serviam stance against the British Empire, they seem pretty much unconscious of the fact that they are hopelessly colonised by miscellaneous English commodities. Therefore, the ultimate aim of this thesis is to read Ulysses into a testimony to the modern life trapped in the global capitalism: once subaltern Dubliners become assimilated into this Anglicising spectacle, there is no way out. They cannot help but exploit themselves to be fashionable.

Published
2014

44. 'Aptlie framed for the dittie' : a study of setting sacred Latin texts to music in sixteenth-century England

Author

Ku, Christopher Jun-Sheng and Rees, Owen L.

Subjects
780, 16th Century music, Tudor Music, underlay, scribal transmission, text-music relationships
Abstract

Although considerable attention has been paid to the texting practices of specific composers and certain repertoires, a comprehensive study of the practice of texting in the sacred Latin‐texted vocal works of sixteenth‐century England remains to be undertaken. How did English composers, scribes, and singers of the sixteenth century set words to music? Today, the general impression that emerges from critical apparatuses of modern performing editions, where manuscripts of vocal music copied by sixteenth-century English copyists are concerned, is negative: they are regarded as casual, often‐contradictory transmissions, replete with idiosyncrasies and arbitrary placement of text. But the detail in five hundred‐year‐old primary sources cannot and should not be so easily dismissed. Through a series of case studies drawn from the largest and most complete music manuscripts of English provenance that date from approximately 1500–90 — the Eton Choirbook, the Lambeth Choirbook, the Caius Choirbook, the ‘Forrest‐Heather’ Partbooks, the Peterhouse Partbooks (Henrician Set), the Sadler Partbooks, the Baldwin Partbooks, and the Dow Partbooks — this dissertation offers a fresh perspective on the many texting variants present in the sources, subjecting them to critical analysis to ascertain what prompted a scribe to copy a passage of music and its text in a particular way. Occasionally, a variant was indeed no more than a result of scribal error or inattention. More often than not, however, a scribe was either resolving an ambiguity that he perceived in his exemplar or deliberately infusing the copy with his own concepts of ideal texting. Three specific areas of interest are traced in the dissertation: the texting of long‐note cantus firmi, the treatment of melismata, and the relationship between music, prosody, and textual syntax. At the outset of the century, cantus firmus lines, as scribes copied them, required a certain amount of interpretation before they could be realised; melismata were an integral part of the compositional style that functioned as punctuation for the music; and textual coherence was unnecessary if it could not be achieved within the constraints of the music. By the close of the century, cantus firmus lines were copied literally with no additional interpretation required on the part of the performer; melismata were reduced to a purely decorative function; and textual integrity and correct prosody had become defining factors in how a piece of music was composed and formally organised. The specifics of what carried musicians from one extreme to the other in the interim is at the heart of this study. This dissertation is part of the growing body of research on the music of sixteenth‐century England. In enquiring into the minutiae of setting Latin text to music during this period, an area that heretofore has been relatively unexplored, it is hoped that this project will contribute to the total knowledge in the wider field of studies in text‐music relations.

Published
2014

45. Interacting Markov branching processes

Author

Ku, Ho Ming

Subjects
510
Abstract

In engineering, biology and physics, in many systems, the particles or members give birth and die through time. These systems can be modeled by continuoustime Markov Chains and Markov Processes. Applications of Markov Processes are investigated by many scientists, Jagers [1975] for example . In ordinary Markov branching processes, each particles or members are assumed to be identical and independent. However, in some cases, each two members of the species may interact/collide together to give new birth. In considering these cases, we need to have some more general processes. We may use collision branching processes to model such systems. Then, in order to consider an even more general model, i.e. each particles can have branching and collision effect. In this case the branching component and collision component will have an interaction effect. We consider this model as interacting branching collision processes. In this thesis, in Chapter 1, we firstly look at some background, basic concepts of continuous-time Markov Chains and ordinary Markov branching processes. After revising some basic concepts and models, we look into more complicated models, collision branching processes and interacting branching collision processes. In Chapter 2, for collision branching processes, we investigate the basic properties, criteria of uniqueness, and explicit expressions for the extinction probability and the expected/mean extinction time and expected/mean explosion time. In Chapter 3, for interacting branching collision processes, similar to the structure in last chapter, we investigate the basic properties, criteria of uniqueness. Because of the more complicated model settings, a lot more details are required in considering the extinction probability. We will divide this section into several parts and consider the extinction probability under different cases and assumptions. After considering the extinction probability for the interacting branching processes, we notice that the explicit form of the extinction probability may be too complicated. In the last part of Chapter 3, we discuss the asymptotic behavior for the extinction probability of the interacting branching collision processes. In Chapter 4, we look at a related but still important branching model, Markov branching processes with immigration, emigration and resurrection. We investigate the basic properties, criteria of uniqueness. The most interesting part is that we investigate the extinction probability with our technique/methods using in Chapter 4. This can also be served as a good example of the methods introducing in Chapter 3. In Chapter 5, we look at two interacting branching models, One is interacting collision process with immigration, emigration and resurrection. The other one is interacting branching collision processes with immigration, emigration and resurrection. we investigate the basic properties, criteria of uniqueness and extinction probability. My original material starts from Chapter 4. The model used in chapter 4 were introduced by Li and Liu [2011]. In Li and Liu [2011], some calculation in cases of extinction probability evaluation were not strictly defined. My contribution focuses on the extinction probability evaluation and discussing the asymptotic behavior for the extinction probability in Chapter 4. A paper for this model will be submitted in this year. While two interacting branching models are discussed in Chapter 5. Some important properties for the two models are studied in detail.

Published
2014
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46. Spectral-energy efficiency trade-off of relay-aided cellular networks

Author

Ku, Ivan Chui Choon, Wang, Cheng-Xiang, and Thompson, John

Subjects
621.382
Abstract

Wireless communication networks are traditionally designed to operate at high spectral e ciency with less emphasis on power consumption as it is assumed that endless power supply is available through the power grid where the cells are connected to. As new generations of mobile networks exhibit decreasing gains in spectral e ciency, the mobile industry is forced to consider energy reform policies in order to sustain the economic growth of itself and other industries relying on it. Consequently, the energy e ciency of conventional direct transmission cellular networks is being examined while alternative green network architectures are also explored. The relay-aided cellular network is being considered as one of the potential network architecture for energy e cient transmission. However, relaying transmission incurs multiplexing loss due to its multi-hop protocol. This, in turn, reduces network spectral e ciency. Furthermore, interference is also expected to increase with the deployment of Relay Stations (RSs) in the network. This thesis examines the power consumption of the conventional direct transmission cellular network and contributes to the development of the relay-aided cellular network. Firstly, the power consumption of the direct transmission cellular network is investigated. While most work considered transmitter side strategies, the impact of the receiver on the Base Station (BS) total power consumption is investigated here. Both the zero-forcing and minimum mean square error weight optimisation approaches are considered for both the conventional linear and successive interference cancellation receivers. The power consumption model which includes both the radio frequency transmit power and circuit power is described. The in uence of the receiver interference cancellation techniques, the number of transceiver antennas, circuit power consumption and inter-cell interference on the BS total power consumption is investigated. Secondly, the spectral-energy e ciency trade-o in the relay-aided cellular network is investigated. The signal forwarding and interference forwarding relaying paradigms are considered with the direct transmission cellular network taken as the baseline. This investigation serves to understand the dynamics in the performance trade-o . To select a suitable balance point in the trade-o , the economic e ciency metric is proposed whereby the spectral-energy e ciency pair which maximises the economic pro tability is found. Thus, the economic e ciency metric can be utilised as an alternative means to optimise the relay-aided cellular network while taking into account the inherent spectral-energy e ciency trade-o . Finally, the method of mitigating interference in the relay-aided cellular network is demonstrated by means of the proposed relay cooperation scheme. In the proposed scheme, both joint RS decoding and independent RS decoding approaches are considered during the broadcast phase while joint relay transmission is employed in the relay phase. Two user selection schemes requiring global Channel State Information (CSI) are considered. The partial semi-orthogonal user selection method with reduced CSI requirement is then proposed. As the cooperative cost limits the practicality of cooperative schemes, the cost incurred at the cooperative links between the RSs is investigated for varying degrees of RS cooperation. The performance of the relay cooperation scheme with di erent relay frequency reuse patterns is considered as well. In a nutshell, the research presented in this thesis reveals the impact of the receiver on the BS total power consumption in direct transmission cellular networks. The relayaided cellular network is then presented as an alternative architecture for energy e cient transmission. The economic e ciency metric is proposed to maximise the economic pro tability of the relay network while taking into account the existing spectral-energy e ciency trade-o . To mitigate the interference from the RSs, the relay cooperation scheme for advanced relay-aided cellular networks is proposed.

Published
2013

48. Workplace learning and interaction between individual identity, social relations and organizational environment : a comparative study between micro and small companies

Author

Ku, Mui Sing Alice, Bishop, Daniel, and Beck, Vanessa

Subjects
658.3124
Abstract

This study aims to investigate how individual identities, social relations and organizational strategies interact in the workplace learning of SMEs. The practices within the micro and small financial consulting companies in Hong Kong are compared. The influence of the owner-manager, learning culture, power and emotion on learning will also be investigated. A qualitative approach was adopted and semi-structured interviews accompanied with observation and document analysis were used. A total of thirty respondents from 2 small and 3 micro companies were involved in this study. All companies were subsidiary of two mother companies. Data from interviews, observation and documents was analyzed. An inclination towards formal learning at organization level was found. However, both formal and informal learning were seen as central to professional development. Multi- dimensional Identity evolved as career and life span change and this impacted on the learning behavior of respondents. Learning helped to build a better professional image. Learning also occurred when respondents participated within a community. The influence of the owner on learning within the firm changes with the formation process and company size. Small firms, with greater formalization and specialization use formal training more frequently than the micro firms. In particular, externally-provided formal training is used to supplement in-house training. Power distribution is affected by size and formation process. Also emotion affects learning from individual to company levels. Ultimately, the findings support the conclusion that the factors influencing the small firm's approach to learning are highly complex. Specifically, social relations at group level in combination with subjective individual dispositions and the structural organizational environment are implicated in orientating the small firm towards particular types of learning. Workplace learning cannot be properly understood without an appreciation of these multi-level influences and the interaction between them. Furthermore, the findings indicate that preferred modes of learning in some types of small firm may be of a more formal kind than the literature on learning in small firms has sometimes assumed.

Published
2012

49. Education for liberal democracy : Fred Clarke and educational reconstruction in England 1936-1952

Author

Ku, Hsiao-Yuh

Subjects
353.80941
Abstract

This thesis explores the connection between the democratic ideas of Fred Clarke (1880-1952), an English educationist, and his contribution to educational reconstruction in England in the 1940s. By drawing on biographical method and documentary research, this thesis demonstrates that Clarke's democratic ideas reflected the ideals of liberal democracy and ways in which his ideas informed his positions on various issues of the educational reform and his actions or activities towards them, which constituted his substantial contribution to the reform. Three general themes in this thesis support the main argument. First, Clarke's ideas about the distinction between community and the State, his conception of equality, and his emphasis on free personality and moral qualities of all citizens found their roots in the ideals of liberal democracy, especially those of developmental democracy. Second, Clarke's ideas of democracy underlay his positions on educational issues such as the reorganization of the central authority; the public schools; the administrative system, selection and organization of secondary education; further education; teacher education and the teaching profession; and adult education. Third, Clarke contributed himself to the reform primarily through arousing and guiding public opinion by means of his speeches, writings, cooperative actions, engagement in professional organizations, and the publication of the first report of the Central Advisory Council, School and Life (1947), which were also in accordance with his ideas of democracy. Clarke also exerted his influence on cultural elites through discussion groups and on policy-makers and key figures through memoranda, private meetings and correspondence. Given these findings, this thesis helps fill a significant gap in the current knowledge as to Clarke's democratic ideas, his contribution to educational reconstruction in the 1940s, and above all, the intimate link between them. Moreover, it sheds some light on the nature and tensions of the major educational reform of this period.

Published
2012

50. Lubrication of high sliding silicon micromachines

Author

Ku, Ingrid Siu Ying, Spikes, Hugh, and Holmes, Andrew

Subjects
621.89
Abstract

A major challenge in silicon devices based on micro-electro-mechanical systems (MEMS) is the provision of effective lubrication for sliding parts. This greatly limits the development and exploitation of MEMS devices, with current designs avoiding sliding contacts where possible. This thesis describes research aimed at lubricating high sliding MEMS devices. A micro-scaled tribometer has been constructed to obtain measurements of friction between two sliding silicon surfaces. This work focuses on lubricating MEMS with liquids, a self-replenishing lubrication method which had been dismissed previously as they were assumed to carry too much viscous drag. The major finding is that ferromagnetic fluids make excellent lubricants for sliding MEMS surfaces. These fluids provide low friction at high speeds, and reduce the boundary friction at low speeds when the hydrodynamic film is absent. The properties of such fluids allow the liquid to be contained in the presence of a magnetic field, meaning that only a small, localised amount is required. Low viscosity liquids were also shown to provide acceptably low friction at high speeds. These results agreed reasonably well with theory. Friction modifier (FM) additives were added to low viscosity liquids in order to reduce boundary friction by forming boundary films, when no hydrodynamic film is generated at low speeds. Drag has also been shown to be insignificant. A study of the wear of silicon surfaces under prolonged sliding was conducted. Previous studies have focussed on dry coatings and apparently untreated surfaces. In this thesis, the effects of different surface preparations, the use of low viscosity liquids and vapour phase lubrication on wear have been studied. This thesis concludes that it is feasible to use liquids to lubricate sliding MEMS. High sliding MEMS is possible and practicable in future if self-replenishing methods, such as those studied in this work, are employed in real devices.

Published
2011
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