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α-Fetoprotein (AFP) is expressed by stem-like and poor outcome hepatocellular cancer tumors and is a clinical tumor biomarker. AFP has been demonstrated to inhibit dendritic cell (DC) differentiation and maturation and to block oxidative phosphorylation. To identify the critical metabolic pathways leading to human DC functional suppression, here, we used two recently described single-cell profiling methods, scMEP (single-cell metabolic profiling) and SCENITH (single-cell energetic metabolism by profiling translation inhibition). Glycolytic capacity and glucose dependence of DCs were significantly increased by tumor-derived, but not normal cord blood–derived, AFP, leading to increased glucose uptake and lactate secretion. Key molecules in the electron transport chain in particular were regulated by tumor-derived AFP. These metabolic changes occurred at mRNA and protein levels, with negative impact on DC stimulatory capacity. Tumor-derived AFP bound significantly more polyunsaturated fatty acids (PUFA) than cord blood–derived AFP. PUFAs bound to AFP increased metabolic skewing and promoted DC functional suppression. PUFAs inhibited DC differentiation in vitro, and ω-6 PUFAs conferred potent immunoregulation when bound to tumor-derived AFP. Together, these findings provide mechanistic insights into how AFP antagonizes the innate immune response to limit antitumor immunity.Significance:α-Fetoprotein (AFP) is a secreted tumor protein and biomarker with impact on immunity. Fatty acid–bound AFP promotes immune suppression by skewing human dendritic cell metabolism toward glycolysis and reduced immune stimulation.

α-Fetoprotein (AFP) is expressed by stem-like and poor outcome hepatocellular cancer tumors and is a clinical tumor biomarker. AFP has been demonstrated to inhibit dendritic cell (DC) differentiation and maturation and to block oxidative phosphorylation. To identify the critical metabolic pathways leading to human DC functional suppression, here, we used two recently described single-cell profiling methods, scMEP (single-cell metabolic profiling) and SCENITH (single-cell energetic metabolism by profiling translation inhibition). Glycolytic capacity and glucose dependence of DCs were significantly increased by tumor-derived, but not normal cord blood–derived, AFP, leading to increased glucose uptake and lactate secretion. Key molecules in the electron transport chain in particular were regulated by tumor-derived AFP. These metabolic changes occurred at mRNA and protein levels, with negative impact on DC stimulatory capacity. Tumor-derived AFP bound significantly more polyunsaturated fatty acids (PUFA) than cord blood–derived AFP. PUFAs bound to AFP increased metabolic skewing and promoted DC functional suppression. PUFAs inhibited DC differentiation in vitro, and ω-6 PUFAs conferred potent immunoregulation when bound to tumor-derived AFP. Together, these findings provide mechanistic insights into how AFP antagonizes the innate immune response to limit antitumor immunity. Significance: α-Fetoprotein (AFP) is a secreted tumor protein and biomarker with impact on immunity. Fatty acid–bound AFP promotes immune suppression by skewing human dendritic cell metabolism toward glycolysis and reduced immune stimulation.

In this paper, we consider a distributed constrained optimization problem with delayed subgradient information over the time-varying communication network, where each agent can only communicate with its neighbors and the communication channel has a limited data rate. We propose an adaptive quantization method to address this problem. A mirror descent algorithm with delayed subgradient information is established based on the theory of Bregman divergence. With non-Euclidean Bregman projection-based scheme, the proposed method essentially generalizes many previous classical Euclidean projection-based distributed algorithms. Through the proposed adaptive quantization method, the optimal value without any quantization error can be obtained. Furthermore, comprehensive analysis on convergence of the algorithm is carried out and our results show that the optimal convergence rate $O(1/\sqrt{T})$ can be obtained under appropriate conditions. Finally, numerical examples are presented to demonstrate the effectiveness of our algorithm and theoretical results.

Liver disease causes relative compromise of the host immune system through multiple overlapping mechanisms and is an established risk factor for invasive fungal diseases including candidiasis and cryptococcosis. This immunologic derangement also leads to rapid progression of disease with resultant increases in morbidity and mortality. We describe severe coccidioidomycosis cases in the setting of liver dysfunction. Collaborative multi-center epidemiologic studies should be performed to determine the incidence of severe coccidioidomycosis in patients with concurrent liver disease.

Objective Toxoplasma gondii is a ubiquitous parasite of medical and veterinary importance; however, there exists no cure for chronic toxoplasmosis. Metabolic enzymes required for the production and maintenance of tissue cysts represent promising targets for novel therapies. Here, we use reverse genetics to investigate the role of Toxoplasma phosphoglucomutase 1, PGM1, in Toxoplasma growth and cystogenesis. Results We found that disruption of pgm1 did not significantly affect Toxoplasma intracellular growth and the lytic cycle. pgm1-defective parasites could differentiate into bradyzoites and produced cysts containing amylopectin in vitro. However, cysts produced in the absence of pgm1 were significantly smaller than wildtype. Together, our findings suggest that PGM1 is dispensable for in vitro growth but contributes to optimal Toxoplasma cyst development in vitro, thereby necessitating further investigation into the function of this enzyme in Toxoplasma persistence in its host.

Purpose The purpose of this paper is to fit a logit model for dry bulkers transporting grains through the Panama Canal versus alternative routes destined to East Asia, originating on the US Gulf and East Coast. This is with the purpose of better understanding the attributes. Design/methodology/approach In this paper, grain transits both through the Panama Canal and alternative routes, which are examined, and a logit model is developed to explain the route decision from a carrier/vessel operator point of view. Findings Transit draft is the most important attribute in the route decision process for grains according to this study. Also, Panamax bulkers are the preferred vessel size into China, especially through the Cape of Good Hope route, impacting Panama Canal’s market share for grains. Research limitations/implications This research used only a full year of grain traffic data approximating fiscal year 2018 (October 1, 2017 to September 30, 2018). Data will come mostly from the Panama Canal transit data and observations using IHS’s Market Intelligence Network (MINT). Originality/value This paper is highly dependent on visual observations of grains vessels through alternative routes using AIS data from MINT software.

Alternative splicing is critical for human gene expression regulation and plays an important role in multiple human diseases. In this context, RNA sequencing has emerged as powerful approach to detect alternative splicing events.In parallel, fast alignment-free methods have emerged as a viable alternative to quantify gene and transcript level abundance from RNAseq data. However, the ability to detect differential splicing events is dependent on the annotation of the transcript reference provided by the user.Here, we introduce a new reference transcriptome aware of splicing events, TRAWLING, which simplifies the detection of aberrant splicing events in a fast and simple way. In addition, we evaluate the performances and the benefits of aligning transcriptome data to TRAWLING using three different RNA sequencing datasets: whole transcriptome sequencing, single cell RNA sequencing and Digital RNA with pertUrbation of Genes.Collectively, our comprehensive evaluation underlines the value of using TRAWLING in transcriptomic data analysis.Availability and implementationOur code is available athttps://github.com/Novartis/TRAWLING

Context: Despite increasing promising reports regarding composite titanium (Ti)/PolyEtherEtherKetone (PEEK) cages, further longer-term, quality research is required. Synthetic bone graft substitutes are another rapidly developing area of spinal surgical research. Aims: The purpose of this study is to evaluate the outcomes of an integral fixation composite Ti/PEEK cage for anterior cervical discectomy and fusion (ACDF) and compare a synthetic bone graft substitute (β-tricalcium phosphate; [βTCP]) with allograft processed using supercritical fluid technology. Methods and Design: Data from 195 consecutive patients were prospectively collected from a single centre. Indications were largely degenerative. Allograft and βTCP were used in a 3:1 randomization protocol. Patients were followed up for a minimum of 6 months and up to 48 months. Clinical outcomes included visual analogue scale and neck oswestry disability index. Radiographic outcomes included fusion rates, subsidence rates and implant complications. Results: Graft sub-cohorts were largely comparable and included 133 and 52 patients in the allograft and βTCP sub-cohorts, respectively. Clinical outcomes overall significantly improved (P < 0.001), with no significant inter-cohort differences. There were no implant-related complications. Overall fusion rate was 94.1% (175/186). The allograft cohort produced a significantly greater fusion rate of 97.7% (126/129) compared to 77.6% (38/49) for the βTCP cohort (P = 0.001). Conclusions: This study demonstrates the viability of an integral fixation composite Ti/PEEK ACDF device in effectively and safely improving patient outcomes and achieving fusion. Allograft is more effective in achieving fusion compared to βTCP, though both were similarly efficacious in improving clinical outcomes.

Parkinson’s disease (PD) is a complex neurodegenerative disease with a range of causes and clinical presentations. Over 76 genetic loci (comprising 90 SNPs) have been associated with PD by the most recent GWAS meta-analysis. Most of these PD-associated variants are located in non-coding regions of the genome and it is difficult to understand what they are doing and how they contribute to the aetiology of PD. We hypothesised that PD-associated genetic variants modulate disease risk through tissue-specific expression quantitative trait loci (eQTL) effects. We developed and validated a machine learning approach that integrated tissue-specific eQTL data on known PD-associated genetic variants with PD case and control genotypes from the Wellcome Trust Case Control Consortium. In so doing, our analysis ranked the tissue-specific transcription effects for PD-associated genetic variants and estimated their relative contributions to PD risk. We identified roles for SNPs that are connected with INPP5P, CNTN1, GBA and SNCA in PD. Ranking the variants and tissue-specific eQTL effects contributing most to the machine learning model suggested a key role in the risk of developing PD for two variants (rs7617877 and rs6808178) and eQTL associated transcriptional changes of EAF1-AS1 within the heart atrial appendage. Similarly, effects associated with eQTLs located within the Brain Cerebellum were also recognized to confer major PD risk. These findings were replicated in two additional, independent cohorts (the UK Biobank, and NeuroX) and thus warrant further mechanistic investigations to determine if these transcriptional changes could act as early contributors to PD risk and disease development.

Background Musculoskeletal disorders can contribute to injurious falls and incur significant societal and healthcare burdens. Identification of fallers from non-fallers through wearable-based gait analysis can facilitate timely intervention to assist mobility and prevent falls whilst improving care and attention for high fall-risk patients. In this study, we use wearable sensor-based gait analysis to introduce a novel variable to assess walking stability in fallers and non-fallers – the Walking Orientation Randomness Metric. The WORM score quantifies the stability, or ‘figure-of-eight’ motion of a subject’s trunk during walking as an indicator of a falls-predictive (pathological) gait. Methods WORM is calculated as the ‘figure-of-eight’ oscillation mapped out in the transverse-plane by the upper body’s centre-point during a walking bout. A sample of patients presenting to the Prince of Wales Hospital (Sydney, Australia) with a primary diagnosis of “falls for investigation” and age-matched healthy controls (non-fallers) from the community were recruited. Participants were fitted at the sternal angle with the wearable accelerometer, MetaMotionC (Mbientlab Inc., USA) and walked unobserved (at self-selected pace) for 5-50 m along an obstacle-free, carpeted hospital corridor. Results Participants comprised of 16 fallers (mean age: 70 + 17) and 16 non-fallers (mean age: 70 + 9) based on a recent fall(s) history. The (median) WORM score was 17-fold higher (p 0.51 cm) show high sensitivity (88%) and specificity (94%). Conclusion In this pilot study we have introduced the WORM score, demonstrating its discriminative performance in a preliminary sample size of 16 fallers. WORM is a novel gait metric assessing walking stability as measured by truncal way during ambulation and shows promise for objective and clinical evaluation of fallers.

This study attempts to fit a global demand model for soybean traffic through the Panama Canal using Ordinary Least Square. Most of the soybean cargo through the interoceanic waterway is loaded on the U.S. Gulf and East Coast ports -mainly destined to East Asia, especially China-, and represented about 34% of total Panama Canal grain traffic between fiscal years 2010–19. To estimate the global demand model for soybean traffic, we are considering explanatory variables such as effective toll rates through the Panama Canal, U.S. Gulf- Asia and U.S. Pacific Northwest- Asia freight rates, Baltic Dry Index, bunker costs, soybean export inspections from the U.S. Gulf and Pacific Northwest, U.S. Gulf soybean basis levels, Brazil’s soybean exports and average U.S. dollar index. As part of the research, we are pursuing the estimation of the toll rate elasticity of vessels transporting soybeans via the Panama Canal. Data come mostly from several U.S. Department of Agriculture sources, Brazil’s Secretariat of Foreign Trade (SECEX) and from Panama Canal transit information. Finally, after estimation of the global demand model for soybean traffic, we will discuss the implications for future soybean traffic through the waterway, evaluating alternative routes and sources for this trade.

Background/purpose Although much has been written about the medical learning environment, the patient, who is the focus of care, is rarely the focus in this literature. The purpose of this study was to explore the role of the patient as an active participant with agency in the medical learning environment from the standpoint of the learner, the attending physician, and most importantly, the patient. We hoped to gain insights into the mechanisms that can reinforce professional values such as patient-centred and respectful behaviours in a patient-present learning environment. Methods We conducted this study in an ambulatory internal medicine clinic using "patient-present" clinic visits. All case presentations occurred in examination rooms with the patient. We invited participants (attending physicians, undergraduate and postgraduate learners, patients and family members) to participate in semi-structured interviews after each clinic visit to explore the impact of the patient-present learning environment. We recruited 34 participants in the study; 10 attending physicians, 12 learners, 10 patients and 2 family members. We analyzed the data deductively using a conceptual framework of agency. Summary/results We identified three major insights: 1. Patients felt engaged and valued opportunities to be heard; 2. Attending physicians and learners reported a more respectful learning environment and a positive though challenging teaching and learning experience; and 3. A hidden curriculum emerged in a performance-based view of professional behaviour. Conclusions Patient-present teaching engaged patients and enhanced their agency by recasting the patient as the central focus within the healthcare encounter. We identified a tension between performing and learning. This study adds new insights to the concept of patient centredness and professionalism from the perspectives of all participants in the medical teaching and learning environment.

Background Walking is a fundamental part of living, and its importance is not limited by age or medical status. Reduced walking speed (WS), or gait velocity, is a sign of advancing age, various disease states, cognitive impairment, mental illness and early mortality. Activity levels, as defined in the literature as “daily step count” (DSC), is also a relevant measure of health status. A deterioration in our walking metrics, such as reduced WS and DSC, is associated with poor health outcomes. These objective measures are of such importance, that walking speed has been dubbed “the 6th vital sign”. We report a new objective measure that scores walking using the relevant metrics of walking speed and daily step count, into an easy-to-understand score from 0 (nil mobility) to 100 (excellent mobility), termed the Simplified Mobility Score (SMoS™). We have provided equal weighting to walking speed and daily step count, using a simple algorithm to score each metric out of 50. Methods Gait data was collected from 182 patients presenting to a tertiary hospital spinal unit with complaints of pain and reduced mobility. Walking speed was measured from a timed walk along an unobstructed pathway. Daily step count information was obtained from patients who had enabled step count tracking on their devices. The SMoS of the sample group were compared to expected population values calculated from the literature using 2-tailed Z tests. Results There were significantly reduced SMoS in patients who presented to the spinal unit than those expected at each age group for both genders, except for the 50–59 age bracket where no statistically significant reduction was observed. Even lower scores were present in those that went on to have surgical management. There was a significant correlation of SMoS scores with subjective disability scores such as the Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) in this cohort. Conclusions The SMoS is a simple and effective scoring tool which is demonstrably altered in spinal patients across age and gender brackets and correlates well with subjective disability scores. The SMoS has the potential to be used as a screening tool in primary and specialised care settings.

The authors have requested that this preprint be removed from Research Square.

IntroductionA novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was recently identified as the pathogen responsible for the COVID-19 outbreak. SARS-CoV-2 triggers severe pneumonia, which leads to acute respiratory distress syndrome and death in severe cases. As reported, SARS-CoV-2 is 80% genetically identical to the 2003 SARS-CoV virus. Angiotensin-converting enzyme 2 (ACE2) has been identified as the main receptor for entry of both SARS-CoV and SARS-CoV-2 into human cells. ACE2 is normally expressed in cardiovascular and lung type II alveolar epithelial cells, where it positively modulates the RAS system that regulates blood flow, pressure, and fluid homeostasis. Thus, virus-induced reduction of ACE2 gene expression is considered to make a significant contribution to severe acute respiratory failure. Chromatin remodeling plays a significant role in the regulation of ACE2 gene expression and the activity of regulatory elements within the genome.MethodsHere, we integrated data on physical chromatin interactions within the genome organization (captured by Hi-C) with tissue-specific gene expression data to identify spatial expression quantitative trait loci (eQTLs) and thus regulatory elements located within the ACE2 gene.ResultsWe identified regulatory elements withinACE2that control the expression of PIR, CA5B, and VPS13C in the lung. The gene products of these genes are involved in inflammatory responses,de novopyrimidine and polyamine synthesis, and the endoplasmic reticulum, respectively.ConclusionOur study, although limited by the fact that the identification of the regulatory interactions is putative until proven by targeted experiments, supports the hypothesis that viral silencing ofACE2alters the activity of gene regulatory regions and promotes an intra-cellular environment suitable for viral replication.

We present a novel neural-network-based pipeline for segmentation of 3D muscle and bone structures from localized 2D ultrasound data of the human arm. Building from the U-Net [1] neural network framework, we examine various data augmentation techniques and training data sets to both optimize the network’s performance on our data set and hypothesize strategies to better select training data, minimizing manual annotation time while maximizing performance. We then employ this pipeline to generate the OpenArm 2.0 data set, the first factorial set of multi-subject, multi-angle, multi-force scans of the arm with full volumetric annotation of the biceps and humerus. This data set has been made available on SimTK (https://simtk.org/projects/openarm) to enable future exploration of muscle force modeling, improved musculoskeletal graphics, and assistive device control.

Pre-trained language models (PTLMs) have achieved impressive performance on commonsense inference benchmarks, but their ability to employ commonsense to make robust inferences, which is crucial for effective communications with humans, is debated. In the pursuit of advancing fluid human-AI communication, we propose a new challenge, RICA: Robust Inference capability based on Commonsense Axioms, that evaluates robust commonsense inference despite textual perturbations. To generate data for this challenge, we develop a systematic and scalable procedure using commonsense knowledge bases and probe PTLMs across two different evaluation settings. Extensive experiments on our generated probe sets with more than 10k statements show that PTLMs perform no better than random guessing on the zero-shot setting, are heavily impacted by statistical biases, and are not robust to perturbation attacks. We also find that fine-tuning on similar statements offer limited gains, as PTLMs still fail to generalize to unseen inferences. Our new large-scale benchmark exposes a significant gap between PTLMs and human-level language understanding and offers a new challenge for PTLMs to demonstrate commonsense., Comment: Accepted in EMNLP 2021 main conference. 20 pages, 8 figures

Informed by the ‘quality of life’ model with specific reference to Chinese culture, this article uses reliable and publicly available information seldom used in historical or heritage study to identify the designs of flats and builders of the “Kowloon Walled City” (hereafter the City) and reliable oral testimonies to refute some myths about the quality of life within it. This settlement has been notoriously misrepresented by some as a city of darkness that was razed from the face of the Earth before 1997 to fulfill a pre-war dream of the colonial government. This article confirms the view that this extremely short-lived concrete jungle, mystified as a horrifying, disorderly-built, and unplanned territory, was a product of un-organised small builders that had been hitherto unreported. The layout and designs of the housing units were different from that prescribed by the Buildings Ordinance, but were, in fact, developed within a consciously planned boundary that was a result of international politics. Although the City’s overall built environment was poor due to a lack of natural light penetration, the designs of its individual flats were comparable, if not better than, typical units in contemporary public rental housing blocks, many of which had to be demolished less than 20 years after their construction due to structural defects. This article uses the ‘quality of life’ model, which has hitherto been limited to medical and social, rather than historical or anthropological, studies, to evaluate how design and housing satisfaction affected City residents’ quality of life.

Objectives The present narrative review aims to collate the literature regarding the current use of wearable gait measurement devices for falls-risk assessment in neurological and non-neurological populations. Thereby, this review seeks to determine the extent to which the aforementioned barriers inhibit clinical use. Background Falls contribute a significant disease burden in most western countries, resulting in increased morbidity and mortality with substantial therapeutic costs. The recent development of gait analysis sensor technologies has enabled quantitative measurement of several gait features related to falls risk. However, three main barriers to implementation exist: accurately measuring gait-features associated with falls, differentiating between fallers and non-fallers using these gait features, and the accuracy of falls predictive algorithms developed using these gait measurements. Methods Searches of Medline, PubMed, Embase and Scopus were screened to identify 46 articles relevant to the present study. Studies performing gait assessment using any wearable gait assessment device and analysing correlation with the occurrence of falls during a retrospective or prospective study period were included. Risk of Bias was assessed using the Centre for Evidence Based Medicine (CEBM) Criteria. Conclusions Falls prediction algorithms based entirely, or in-part, on gait data have shown comparable or greater success of predicting falls than existing stratification scoring systems such as the 10-meter walk test or timed-up-and-go. However, data is lacking regarding their accuracy in neurological patient populations. Inertial measurement units (IMU) have displayed competency in obtaining and interpreting gait metrics relevant to falls risk. They have the potential to enhance the accuracy and efficiency of falls risk assessment in inpatient and outpatient setting.

Compulsive eating is a common symptom of different conditions, including obesity, binge eating disorder and bulimia. One hypothesis is that contemporary food products promote compulsive eating via addiction-like mechanisms. However, what is the addictive substance in food, and what is the phenotypic overlap between obesity / eating disorders and addictions are questions that remain unresolved. In this review, we applied a multilevel framework of addiction, which encompasses the ‘drug’ (certain foods), the person's mindset, and the context, to improve understanding of compulsive eating. Specifically, we reviewed evidence on the addictive properties of specific foods, the neurocognitive systems that control dietary choices, and their interaction with physical, emotional and social contexts. We focused on different target groups to illustrate distinct aspects of the proposed framework: the impact of food and contextual factors were examined across a continuum, with most studies conducted on healthy participants and subclinical populations, whereas the review of neurocognitive aspects focused on clinical groups in which the alterations linked to addictive and compulsive eating are particularly visible. The reviewed evidence suggest that macronutrient composition and level of processing are associated with the addictive properties of food; there are overlapping neuroadaptations in reward and decision-making circuits across compulsive eating conditions; and there are physical and social contexts that fuel compulsive eating by exploiting reward mechanisms and their interaction with emotions. We conclude that a biopsychosocial model that integrates food, neurobiology and context can provide a better understanding of compulsive eating manifestations in a transdiagnostic framework.

Introduction The aim of this study was to assess if the complex anatomy of aortic aneurysm and aortic dissection can be accurately reproduced from a contrast-enhanced computed tomography (CT) scan into a three-dimensional (3D) printed model. Methods Contrast-enhanced cardiac CT scans from two patients were post-processed and produced as 3D printed thoracic aorta models of aortic aneurysm and aortic dissection. The transverse diameter was measured at five anatomical landmarks for both models, compared across three stages: the original contrast-enhanced CT images, the stereolithography (STL) format computerised model prepared for 3D printing and the contrast-enhanced CT of the 3D printed model. For the model with aortic dissection, measurements of the true and false lumen were taken and compared at two points on the descending aorta. Results Three-dimensional printed models were generated with strong and flexible plastic material with successful replication of anatomical details of aortic structures and pathologies. The mean difference in transverse vessel diameter between the contrast-enhanced CT images before and after 3D printing was 1.0 and 1.2 mm, for the first and second models respectively (standard deviation: 1.0 mm and 0.9 mm). Additionally, for the second model, the mean luminal diameter difference between the 3D printed model and CT images was 0.5 mm. Conclusion Encouraging results were achieved with regards to reproducing 3D models depicting aortic aneurysm and aortic dissection. Variances in vessel diameter measurement outside a standard deviation of 1 mm tolerance indicate further work is required into the assessment and accuracy of 3D model reproduction.

In this paper, event-triggered control scheme for partial synchronization of k-valued logical control networks(KVLCNs) is studied. By using semi-tensor product(STP) method, necessary and sufficient conditions for the partial state/output synchronization of KVLCNs are obtained. Furthermore, an algorithm is proposed to design state feedback event-mggered controllers for partial synchronization of KVLCNs. Finally, a numerical example is given to illustrate the effectiveness of the theoretical results.

Contains fulltext : 167696.pdf (Publisher’s version ) (Open Access) Genomic imprinting is a mechanism in which gene expression varies depending on parental origin. Imprinting occurs through differential epigenetic marks on the two parental alleles, with most imprinted loci marked by the presence of differentially methylated regions (DMRs). To identify sites of parental epigenetic bias, here we have profiled DNA methylation patterns in a cohort of 57 individuals with uniparental disomy (UPD) for 19 different chromosomes, defining imprinted DMRs as sites where the maternal and paternal methylation levels diverge significantly from the biparental mean. Using this approach we identified 77 DMRs, including nearly all those described in previous studies, in addition to 34 DMRs not previously reported. These include a DMR at TUBGCP5 within the recurrent 15q11.2 microdeletion region, suggesting potential parent-of-origin effects associated with this genomic disorder. We also observed a modest parental bias in DNA methylation levels at every CpG analyzed across approximately 1.9 Mb of the 15q11-q13 Prader-Willi/Angelman syndrome region, demonstrating that the influence of imprinting is not limited to individual regulatory elements such as CpG islands, but can extend across entire chromosomal domains. Using RNA-seq data, we detected signatures consistent with imprinted expression associated with nine novel DMRs. Finally, using a population sample of 4,004 blood methylomes, we define patterns of epigenetic variation at DMRs, identifying rare individuals with global gain or loss of methylation across multiple imprinted loci. Our data provide a detailed map of parental epigenetic bias in the human genome, providing insights into potential parent-of-origin effects.

A brief intervention using Zero-time Exercise (ZTEx), a foot-in-the-door approach, was developed to reduce sedentary behaviour and increase physical activity. ZTEx refers to the integration of simple strength- and stamina-enhancing physical activity into daily life, which can be done anytime, anywhere and by anyone. This paper presents the development, feasibility, and preliminary evidence for the effectiveness of this intervention under the Hong Kong Jockey Club FAMILY Project. Needs assessments were conducted with social workers from the Christian Family Services Center(CFSC) and the Social Welfare Department (SWD). This single group prospective ZTEx intervention trial, guided by the Health Action Process Approach, included a 3-hr core session at baseline and a 1-hr booster session at 1-month follow-up. Fifty-six participants (social and service-related workers) from CFSC (n = 28) and SWD (n = 28) received the intervention and completed the self-administered questionnaires at baseline. Forty-nine and 43 participants completed the 1-month and 3-month self-administered questionnaires, respectively. Fifteen participants attended the focus group interviews to share their feedback on ZTEx intervention after implementing their community-based ZTEx activities. Intention-to-treat analysis was conducted with missing data replaced by baseline values. Participants reported significant decreases in sitting time by 27 (2, 52) minutes (mean [95% confidence interval]) and 36 (0.2, 71) minutes on a weekday, increases in physical activity while seated by 0.7 (0.2, 1.4) days and 1.1 (0.6, 1.7) days in a week, and improvements in perceived knowledge, outcome expectancies and plan on doing ZTEx at the 1-month and 3-month follow-up, respectively. Balance and muscle strength significantly improved at the 1-month follow-up. The effect ranged from small to large (Cohen's d: 0.27-1.05, all p < 0.05). The qualitative feedbacks support the quantitative findings. Our findings show early evidence that ZTEx effectively reduced sedentary behaviour and enhanced physical activity and fitness. Further trials on this simple and low-cost intervention as the first step to promote higher intensity exercise are warranted.

The construction industry is one of the riskiest industries with a large number of deaths and injuries every year. Large amounts of money are spent annually on workers’ compensation. Thus, it is important to investigate the factors which affect accident compensation in the eyes of judges. In this research paper, we utilized the court case reports available in HKLII from 2000 to 2015. Most of the victims have studied in secondary schools, are aged between 30 and 49 and have a monthly salary of less than HK$20,000. All the data were then analyzed and summarized by the content analysis method. After that, we used the Markov Chain Monte Carlo simulation and System-GMM dynamic panel econometrics method to study the dynamic relationship between these factors and the compensation for accidents. Academically, analysis of accident compensation in the past usually depended on analysis by the labour department. There is a limited number of quantitative court case reports analysis based on economic modelling. Furthermore, none of the previous research utilized the dynamic panel technique to study the relationships. It also fills the gap of the research in identifying whether non-Cantonese speakers are in disadvantage positions when they seek for compensation, longer hearings favour the contractors and whether mental disorder after accident shall lead to larger amount of compensation. Practically, the research offer important information for contractors and employers who may need to pay compensation due to workers’ accidents. The results show that non-Cantonese speakers receive less compensation as compared to locals and court cases with longer hearings are usually associated with larger amount of compensation. There is, however, no significant difference between victims with and without mental disorder in terms of compensation.

We develop a set of methods to improve on the results of self-supervised learning using context. We start with a baseline of patch based arrangement context learning and go from there. Our methods address some overt problems such as chromatic aberration as well as other potential problems such as spatial skew and mid-level feature neglect. We prevent problems with testing generalization on common self-supervised benchmark tests by using different datasets during our development. The results of our methods combined yield top scores on all standard self-supervised benchmarks, including classification and detection on PASCAL VOC 2007, segmentation on PASCAL VOC 2012, and "linear tests" on the ImageNet and CSAIL Places datasets. We obtain an improvement over our baseline method of between 4.0 to 7.1 percentage points on transfer learning classification tests. We also show results on different standard network architectures to demonstrate generalization as well as portability. All data, models and programs are available at: https://gdo-datasci.llnl.gov/selfsupervised/., Comment: Accepted paper at CVPR 2018

Ferromagnetic materials have been utilized as recording media in data storage devices for many decades. The confinement of a material to a two-dimensional plane is a significant bottleneck in achieving ultra-high recording densities, and this has led to the proposition of three-dimensional (3D) racetrack memories that utilize domain wall propagation along the nanowires. However, the fabrication of 3D magnetic nanostructures of complex geometries is highly challenging and is not easily achieved with standard lithography techniques. Here, we demonstrate a new approach to construct 3D magnetic nanostructures of complex geometries using a combination of two-photon lithography and electrochemical deposition. The magnetic properties are found to be intimately related to the 3D geometry of the structure, and magnetic imaging experiments provide evidence of domain wall pinning at the 3D nanostructured junction.

This paper investigates how culture affects people’s attitudes towards directors’ duties in the People’s Republic of China by surveying a sample of Chinese business executives. If cultural practices lead people to behave differently from what the law prescribes, it is a serious regulatory oversight. Our results suggest that Chinese cultural values do matter when it comes to the perception of breaches of directors’ duties. Specifically, we find that respondents who identify with moral-discipline related traditional Chinese values are more lenient to the chairman breaching his director's duties, whereas respondents who subscribe to modern Chinese values are less receptive to the director failing to report the chairman’s contravention of his director’s duties. These results suggest that it is imperative for China’s law-makers to rethink their approach to regulating directors’ duties instead of the wholesale transplantation of laws from Western countries.

Diamond color centers show promise in quantum photonics applications. However practical implementation is limited by low photon collection efficiency. We report precise fabrication of structures which substantially increase collection efficiency from color centers. © 2011 OSA.

MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs) and other functional non-coding RNAs (ncRNAs) have emerged as pivotal regulators involved in multiple biological processes. Recently, ncRNA control of gene expression has been identified as a critical regulatory mechanism in the immune system. Despite the great efforts made to discover and characterize ncRNAs, the functional role for most remains unknown. To facilitate discoveries in ncRNA regulation of immune system related processes we developed the database of immunologically relevant ncRNAs (IRNdb), a database of ncRNAs, their immunologically relevant targets, associated biological pathways and experiments. We integrated mouse data on predicted and experimentally verified ncRNA-target interactions, ncRNA and gene annotations, biological pathways and processes, and experimental data in a uniform format with a user-friendly web interface. The current version of IRNdb documents 3,799 experimentally confirmed miRNA-target interactions between 265 miRNAs and 1,633 murine and human-derived immune-related targets. In addition, we recorded 22,453 lncRNA - immune target and 377 PIWI-interacting RNA - immune target interactions. IRNdb is a comprehensive searchable data repository which will be of help in uncovering the role of ncRNAs in immune system related processes.

Inefficient state-owned enterprises in China were compelled to restructure to remain competitive, which resulted in phenomenal economic growth. While economically successful, China did not initially have any indigenous laws to regulate companies or control this growth, so Chinese lawmakers had to transplant corporate laws from developed Western countries. However, this transplantation process did not occur without problems, and certain domestic attributes had to be supplemented in corporate legislation to correspond with Chinese socialistic objectives and cultural values. This article analyzes the key attributes of Chinese corporate governance and regulations concerning shareholders’ rights and, in the process, highlights provisions that are peculiar and characterized as uniquely Chinese, ultimately raising more questions than answers for shareholders.

PurposeThe purpose of this paper is to forecast the performance and adoption of residential energy management technology (REMT).Design/methodology/approachThe paper integrates scenarios, analogy and Bass diffusion model.FindingsFour different scenarios were identified. Bass curve parameters were extracted through many different existing devices, and then fit into each scenario subjectively to produce four different kinds of diffusion curves.Originality/valueThe approach and the model provide decision and policy makers to evaluate how they should position new energy management innovations based on the desired type of diffusion.

PurposeTo better understand the issues on compliance and ethics in taxation, this paper reviews and discusses the extant literature with a focus on individual taxpayers. As prior studies mainly provide tax compliance and ethics information in the USA, this paper attempts to explore similar issues in a non‐US economy by articulating real‐life perspectives of tax compliance behavior in Hong Kong.Design/methodology/approachThe first part of this study undertakes an extensive review of literature on compliance and ethics in taxation. The second part of this study provides real‐life perspectives of tax compliance behavior for individual taxpayers by examining three informal tax cases in Hong Kong.FindingsThe first major finding from literature review is that ethical beliefs could be an effective means to improve tax compliance, particularly for taxpayers with lower levels of moral development. Secondly, as tax compliance rate is higher when taxpayer has a stronger moral belief that tax evasion is not ethical, a stronger enforcement effort might have a positive overall effect on tax compliance.Research limitations/implicationsIn Hong Kong, there is a lack of general ethics education for the public. The authors therefore suggest the introduction of general ethics education for all citizens in Hong Kong to enhance level of moral development in order to improve tax compliance at large.Originality/valueThe examination of the actions of taxpayers provides insightful information on tax compliance and ethics issues as prior research suggests that ethics ultimately lies in actions and hence actions should be used to study the ethical development.

We design a new device which can directly emit ans OAM-carrying light beams. The innovative OAM emitter opens a new horizon in the field of OAM-based optical and quantum communications.

Hepatocellular carcinoma (HCC) is a common cancer and ranks the third lethal cancer worldwide. However, the detail molecular mechanisms underlying the initiation and progression of HCC remain poorly understood. Liver carcinogenesis is a multistep process that is driven by the accumulation of genetic and epigenetic alterations. Mutational landscape and driver mutations have recently been delineated by high-throughput sequencing studies. On the other hand, our current knowledge about epigenetic deregulation in human HCC is limited. Histone modification is a major component of epigenetic regulation, and deregulation of histone medication could alter local chromatin structure and gene expression. We hypothesized that deregulation of histone methyltransferases might contribute to HCC development. In this study, we showed that trithorax-group protein ASH1L was frequently up-regulated in human HCC. Overexpression of ASH1L was detected in 40% of primary HCCs and significantly associated with larger tumor size, present of venous invasion and tumor microsatellite formation. Up-regulation of ASH1L also correlated with increased Ki67 expression. ASH1L is a histone methyltransferase specific for catalyzing transcriptional-active H3K4 and H3K36 methylation. We showed that stable knockdown of ASH1L significantly suppressed HCC cell proliferation and colony formation. We further demonstrated that knockdown of ASH1L inhibited HCC cell migration. In addition, we investigated the underlying mechanisms contribute to ASH1L up-regulation. We showed that up-regulation of ASH1L in human HCC was contributed by chromosome amplification at chromosome 1q22. Furthermore, we showed that ASH1L was negatively regulated by miR-142. Therefore, down-regulation of miR-142 contributed to ASH1L up-regulation in HCC. In summary, our findings suggested that ASH1L was frequently up-regulated in human HCC due to chromosome amplification and miRNA deregulation. Citation Format: Lai Wei, Felice H. Tsang, Daniel Ho, Cheuk-Ting Law, Mengnuo Chen, Long-Hin Tsang, Carmen Cl Wong, Irene Ol Ng, Chun-Ming Wong. Expression and functions of ASH1L in liver cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1380. doi:10.1158/1538-7445.AM2017-1380

In this paper, a wavelet-based neural network (WNN) is introduced for continuous nonlinear system identification. The adaptive weight learning laws are derived based on Lyapunov stability theory for static and dynamical system identification respectively. It is proved that the identification error will converge to zero and the weight will be bounded in the case of no modeling error. Simulation results demonstrate the effectiveness of the proposed identification methodology.