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The present study investigated agentive one-on-one intercultural communication between L2 English-speaking international faculty and their L2 English-speaking host colleagues in relation to identity (re)construction. Two foreign professors and their Chinese faculty colleagues participated in the study. The research instruments consisted of reflective journal writing and in-depth, semi-structured interviews. The results indicated that the occasions of the faculty’s communication at Chinese universities were both influenced by and influenced a number of factors. These factors represented self- and other-positioning, agency, appropriation of native speakerism, face-threatening acts, and alterity. Based on the findings of the study, research implications are provided.

TiS2is a transition metal dichalcogenide with semiconducting transport properties, and is considered a potential thermoelectric material owing to its relatively low lattice thermal conductivity originated from van der Waals stacking. In this study, the evolution of electrical and thermal transport properties of TiS2by solid solution alloying with TiSe2are investigated systematically regarding thermoelectric properties. A series of solid solution compositions of Ti(S1 − xSex)2(x= 0, 0.1, 0.2, 0.3, 0.4, and 0.5) polycrystalline samples was synthesized by a conventional solid-state reaction, wherein no secondary phase was formed. As xincreased, the electrical conductivity and carrier concentration gradually increased, while the Seebeck coefficient decreased. Consequently, the power factor decreased. On the other hand, the lattice thermal conductivity is reduced largely to 0.96 W/mK for x= 0.5 at 300 K, compared to 2.3 W/mK for the pristine TiS2sample. Consequently, the thermoelectric figure of merit zTof TiS2was enhanced by solid solution allying with TiSe2, despite deterioration of the electrical transport properties. The maximum zTof 0.41 was observed for x= 0.4 (Ti(S0.6Se0.4)2) at 500 K.

Water molecules can bind to zwitterionic polymers, such as carboxybetaine and sulfobetaine, forming strong hydration layers along the polymer chains. Such hydration layers act as a barrier to impede the attachment of marine fouling organisms; therefore, zwitterionic polymer coatings have been of considerable interest as marine antifouling coatings. However, recent studies have shown that severe adsorption of marine sediments occurs on zwitterionic-polymer-coated surfaces, resulting in the degradation of their marine antifouling performance. Therefore, a novel approach for forming amphiphilic zwitterionic polymers using zwitterionic and hydrophobic monomers is being investigated to simultaneously inhibit both sediment adsorption and marine fouling. In this study, amphiphilic zwitterionic thin polymer brushes composed of sulfobetaine methacrylate (SBMA) and trifluoroethyl methacrylate (TFEMA) were synthesized on Si/SiO2surfaces via surface-initiated atom transfer radical polymerization. For this, a facile metal-ion-mediated method was developed for immobilizing polymerization initiators on solid substrates to subsequently form poly(SBMA-co-TFEMA) brushes on the initiator-coated substrate surface. Poly(SBMA-co-TFEMA) brushes with various SBMA/TFEMA ratios were prepared to determine the composition at which both marine diatom adhesion and sediment adsorption can be prevented effectively. The results indicate that poly(SBMA-co-TFEMA) brushes prepared with an SBMA/TFEMA ratio of 3:7 effectively inhibit both sediment adsorption and marine diatom adhesion, thereby exhibiting balanced marine antifouling properties. Thus, the findings of this study provide important insights into the design of amphiphilic marine antifouling materials.

Introduction:Recipient site preparation using external volume expansion (EVE) increases graft survival in large-volume fat grafting. To improve patient compliance with using the device, we tested a new cyclic high negative-pressure (CHNP) mode that involves 1 h/day at −55 mm Hg, cycled between 1-second negative-pressure activation, followed by a 2-second deactivation period in an animal model. Material and Method:A miniaturized EVE device was applied to 30 8-week-old male Sprague-Dawley rats. The rats were assigned to 3 groups (no pressure for the control group, conventional −25 mm Hg for 8 h/day for conventional EVE, and CHNP mode for the CHNP group). After 28 days, micro-computed tomography was performed and skin biopsy specimens were obtained. Results:The CHNP group showed a 6.6-fold increase and the conventional EVE group showed a 4.4-fold increase in volume compared to the control group. Hematoxylin and eosin staining showed a similar increase in subcutaneous tissue thickness in both EVE groups, compared to the control group. Masson's trichome and proliferating cell nuclear antigen staining showed significantly higher collagen deposition and subdermal adipocytes in EVE groups. Immunohistochemistry against platelet endothelial cell adhesion molecule 1 showed 2.5- and 2.7-times higher vessel density in the conventional and CHNP EVE groups, respectively. There was no statistically significant difference in subcutaneous tissue thickness, collagen deposition, subdermal adipocyte proliferation, and vessel density between the 2 EVE groups. Conclusion:CHNP produced comparable results in recipient site preparation (subcutaneous tissue thickening and angiogenesis) compared to the conventional protocol, while markedly reducing the daily wear-time from 8 hours to 1 hour. Although further clinical data must be acquired, our new pressure setting seems promising and provides a more patient-friendly pre-expansion environment.

Rare coding variants that substantially affect function provide insights into the biology of a gene1–3. However, ascertaining the frequency of such variants requires large sample sizes4–8. Here we present a catalogue of human protein-coding variation, derived from exome sequencing of 983,578 individuals across diverse populations. In total, 23% of the Regeneron Genetics Center Million Exome (RGC-ME) data come from individuals of African, East Asian, Indigenous American, Middle Eastern and South Asian ancestry. The catalogue includes more than 10.4 million missense and 1.1 million predicted loss-of-function (pLOF) variants. We identify individuals with rare biallelic pLOF variants in 4,848 genes, 1,751 of which have not been previously reported. From precise quantitative estimates of selection against heterozygous loss of function (LOF), we identify 3,988 LOF-intolerant genes, including 86 that were previously assessed as tolerant and 1,153 that lack established disease annotation. We also define regions of missense depletion at high resolution. Notably, 1,482 genes have regions that are depleted of missense variants despite being tolerant of pLOF variants. Finally, we estimate that 3% of individuals have a clinically actionable genetic variant, and that 11,773 variants reported in ClinVar with unknown significance are likely to be deleterious cryptic splice sites. To facilitate variant interpretation and genetics-informed precision medicine, we make this resource of coding variation from the RGC-ME dataset publicly accessible through a variant allele frequency browser.

This article presents a wideband 120-GHz CMOS polarization controllable I/Q transmitter for wireless short-range high-speed 6G Internet of Things (IoT). The transmitter consists of an I/Q modulator with a quadrature injection-locked oscillator (QILT) for 16-quadrature amplitude modulation (QAM) and a polarization controller for mismatch reduction between TX and RX antennas. An I/Q calibration is applied to QILT to reduce the I/Q imbalance, and a 1-bit phase shifter and a variable-gain amplifier (VGA) with 8-dB gain control are used to control the linear polarization (LP) in a step of 22.5°. The transmitter was fabricated using a standard 40-nm CMOS process, and the chip size is 2.4 mm2 including pads with a total power consumption of 378 mW. The measured 3-dB bandwidth was 20 GHz with a peak gain of 13 dB, and the image rejection ratio (IMRR) was improved up to 37.8 dBc by applying the I/Q calibration. From the over-the-air (OTA) test, the measured isolation of the dual-polarized antenna was varied from 9 to 22 dB with the 3-dB baseband (BB) bandwidth of 12 GHz. The proposed work achieved the maximum data rate of 20 Gb/s for both quadrature phase shift keying (QPSK) and 16-QAM, and the corresponding error vector magnitudes (EVMs) were −13.4 and −19.1 dB, respectively.

This study proposes an approach to enhance frequency characteristics for AlGaN/gallium nitride (GaN) high-electron-mobility transistors (HEMTs) by employing an air-bridged source-connected field plate to an asymmetric passivation structure. To overcome simulation limitations, we performed the device simulation by matching simulated results with measured data, applying various simulation models, and performing comparative analysis of frequency characteristics between simulated and calculated values using a small-signal equivalent circuit. Thus, the simulation results were well matched with the measured data, achieving an error rate of 1.4%, confirming the device simulation reliability. Asymmetric passivation HEMT for conventional source-connected field plate structures exhibited reduced parasitic capacitances, with notable increased cutoff and maximum oscillation frequencies by 21.7% and 7.8%, respectively. We applied an additional air-bridged source-connected field plate structure to the asymmetric passivation HEMT to further enhance RF performance, significantly increasing cutoff frequency by 31.6% compared with asymmetric passivation with source-connected field plate structure. These results represent outstanding RF performance without any degradation of dc characteristics.

Superhydrophobic surfaces have gained significant research attention for various applications, such as self-cleaning and microfluidics. To develop superhydrophobic surfaces, diverse materials and structures are used to reduce the surface energy. Specific coatings can control the intrinsic contact angle (CA) by reducing the surface energy of a material. In this study, we fabricated and evaluated polymeric superhydrophobic surfaces. The superhydrophobic surfaces exhibited microstructures consisting of two different polymers. To evaluate the wetting properties, we calculated the theoretical Cassie and Wenzel models of the surfaces and compared them to the experimental CA and roll-off angle (ROA). Furthermore, we measured the wetting properties of the surfaces by coating them with octafluorocyclobutane (C4F8) to confirm the effect of coating on the surfaces. This coated surface can control the wetting properties regardless of the material composition, demonstrating the stability of the superhydrophobic surface.

Polydopamine is extensively researched in multiple disciplines due to its ability to coat various solid substrates and undergo secondary functionalization. However, a drawback of polydopamine is its tendency to degrade under strong alkaline conditions. This study aims to address this limitation. Specifically, it is observed that the stability of polydopamine significantly increases when it forms a complex with zirconium (IV). Furthermore, the polydopamine/zirconium (IV) complex demonstrates efficient incorporation of amine compounds, opening up possibilities for further applications. ZrIVcoordination chemistry was used to enhance the stability of polydopamine coatings. The polydopamine coating with ZrIVremained stable even when subjected to strong alkaline conditions and ethylenediaminetetraacetic acid (EDTA) treatment. The polydopamine/ZrIVcomplex coating also demonstrated efficient incorporation of amine compounds.

The Pharma Proteomics Project is a precompetitive biopharmaceutical consortium characterizing the plasma proteomic profiles of 54,219 UK Biobank participants. Here we provide a detailed summary of this initiative, including technical and biological validations, insights into proteomic disease signatures, and prediction modelling for various demographic and health indicators. We present comprehensive protein quantitative trait locus (pQTL) mapping of 2,923 proteins that identifies 14,287 primary genetic associations, of which 81% are previously undescribed, alongside ancestry-specific pQTL mapping in non-European individuals. The study provides an updated characterization of the genetic architecture of the plasma proteome, contextualized with projected pQTL discovery rates as sample sizes and proteomic assay coverages increase over time. We offer extensive insights into transpQTLs across multiple biological domains, highlight genetic influences on ligand–receptor interactions and pathway perturbations across a diverse collection of cytokines and complement networks, and illustrate long-range epistatic effects of ABOblood group and FUT2secretor status on proteins with gastrointestinal tissue-enriched expression. We demonstrate the utility of these data for drug discovery by extending the genetic proxied effects of protein targets, such as PCSK9, on additional endpoints, and disentangle specific genes and proteins perturbed at loci associated with COVID-19 susceptibility. This public–private partnership provides the scientific community with an open-access proteomics resource of considerable breadth and depth to help to elucidate the biological mechanisms underlying proteo-genomic discoveries and accelerate the development of biomarkers, predictive models and therapeutics1.

This paper presents a novel 3-dimensional hybrid segmented layer model (3D HSLM) for coreless axial-flux permanent magnet synchronous motors (AFPMSMs). In the proposed 3D HSLM, the magnetic field sources are divided into the PM array and current-driven electro-magnets, which are captured by the combination of the magnetic scalar potential and vector potential models. This paper proposes a geometry function and cylindrical harmonic index modulation functions in order to correctly capture the curvature effect by the PMs and coils with arbitrary shapes and also the radial edge effect from the finite lengths of the rotor and the stator. The proposed modeling method also enables accurate estimation of the motor characteristics on the on-load conditions using the magnetic vector potential model. The fidelity of the proposed 3D HSLM is validated against the equivalent FEM models for various cases with different PM and coil shapes, in terms of the airgap magnetic fields, motor torque, and flux linkage. The comparison results show that the proposed 3D HSLM yields a modeling accuracy of more than 98 % while significantly reducing the calculation time by two orders of magnitude as compared to the FEM models.

ABSTRACTThis study longitudinally examined university-level students’ stances, communication of negative emotions, and L2 swearing with regard to English-medium instruction (EMI). Sixteen graduate students enrolled in an English-medium course in a university in Korea participated in the study. The research instruments were classroom observations, reflective journal writing, and in-depth, semi-structured interviews. The results indicated that there were three occasions, during small group discussions, on each of which one student articulated her/his language ideologies against EMI and expressed her/his anger in Korean, and swore in English. These occasions occurred due to a student’s opposition to EMI, a student’s opposition to EMI preceded by her own support for it, and a student’s opposition to EMI faced with another student’s support for it, respectively. What affected the occasions included their teacher’s idiosyncratic focus on general vocabulary in addition to subject-specific vocabulary (a factor common to these students), and challenges intrinsic to EMI, face, and the teacher’s excessive academic push.

With aggressive scaling down in integrated circuit technology, the design of double-node-upset (DNU)-resilient latches have become a major issue regarding radiation hardening by design (RHBD). The conventional DNU-resilient latches are mostly based on the Muller C-element (MCE) and the dual-interlocked storage cell (DICE) element, which exhibit severe limitations: charge sharing during the read operation at a system level and large power consumption. Overcoming these limitations, this brief proposes a DNU-resilient latch based on a novel latch element. The proposed latch fully exploits upset polarity awareness, achieving the maximum number of single-event upset (SEU)-insensitive nodes. We develop a novel double modular redundancy architecture for the DNU-resilient latch design with one SEU-immune module. Based on simulation results, the proposed latch achieves up to 27.6X average power-delay-area-product (PDAP) improvement over state-of-the-art DNU-resilient latches.

In this paper, we modify the slotted ALOHA protocol to quickly identify a swarm of drones in unmanned aerial vehicle (UAV) communication environments. Considering the unreliable UAV channel and the fundamental tradeoff between collision and idle slots in slotted ALOHA, we propose an idle-less slotted ALOHA (ILS-ALOHA) protocol that detects and utilizes idle slots to transmit control messages to drones. In ILS-ALOHA, the ground control station recognizes the idle slot promptly at the beginning of each slot and then transmits acknowledgment (ACK) and beacon messages during the remaining period of the idle slot. Therefore, it can control the access of the drone swarm more adaptively and feed back the ACK to the drones more frequently in an error-prone UAV environment without allocating additional slots. The analysis and simulation results show that the proposed ILS-ALOHA protocol outperforms the conventional slotted ALOHA-based protocols in terms of identification time, channel throughput, and probability of successful identification.

We have developed an InAlAs/InGaAs metamorphic high electron mobility transistor device fabrication process where the gate length can be tuned within the range of 0.13 μm–0.16 μm to suit the intended application. The core processes are a two‐step electron‐beam lithography process using a three‐layer resist and gate recess etching process using citric acid. An electron‐beam lithography process was developed to fabricate a T‐shaped gate electrode with a fine gate foot and a relatively large gate head. This was realized through the use of three‐layered resist and two‐step electron beam exposure and development. Citric acid‐based gate recess etching is a wet etching, so it is very important to secure etching uniformity and process reproducibility. The device layout was designed by considering the electrochemical reaction involved in recess etching, and a reproducible gate recess etching process was developed by finding optimized etching conditions. Using the developed gate electrode process technology, we were able to successfully manufacture various monolithic microwave integrated circuits, including low noise amplifiers that can be used in the 28 GHz to 94 GHz frequency range.

In this study, we exploited the properties of nature-inspired hierarchical structures to propose surfaces capable of on-demand directional droplet manipulation. A microline polydimethylsiloxane structure that simulated a bamboo leaf was fabricated, and silica particles were embedded onto its surface to create hierarchical structures. The as-fabricated multiscale line structures exhibited anisotropic wetting properties along the advancing direction. As the embedded particle size increased, the perpendicular roll-off angle (ROA) decreased and the anisotropic roll-off characteristic disappeared, adopting lotus-leaf characteristics. Consequently, the fabricated surface exhibited characteristics of both bamboo and lotus leaves. The roll off could be controlled through different ROAs by changing the particles size of silica on the same surface.

In the era of the knowledge-intensive economy, talent and knowledge are the main strategic resources to support sustainable development of organisations. Talents develop through knowledge acquisition and knowledge is continuously processed, created and updated to improve the competitiveness of the organisation. Therefore, integration of talent management (TM) and intellectual management (IM) provide the fundamental condition to increase the competitiveness of an organisation and support sustainable development. The main purpose of this paper is to suggest an integration model of TM and IM in enterprises and analyse its effectiveness. We have suggested an integrative model including nature, structure, mode, method, and target. In addition, the effectiveness of integration of the TM and IM is proved through a case study. In this part, survey data is used to analyse effectiveness of integration and provide application problems. Finally, we have statistically proved the competitive advantage of enterprises which integrate TM and IM using several methods of statistics.

Plants have developed adaptive mechanisms to withstand mechanical stress, which can hinder their growth and productivity. Anthocyanins, water-soluble pigments found in plants, have been shown to confer tolerance to abiotic stresses in various plant species, including tomato plants (Solanum lycopersicumL.). Although the biosynthesis and regulatory factors of anthocyanins have been well-characterized in tomato plants, it remains unclear whether mechanical stress influences the expression of these genes. The aim of this study was to examine the effects of rubbing-induced mechanical stress on the activation of genes involved in anthocyanin regulation and subsequent anthocyanin accumulation in tomato plants. Our results showed that rubbing treatment triggered morphological changes such as reduced plant height and altered stem and leaf color because of anthocyanin accumulation in different tomato varieties. Transcriptional analysis revealed significant upregulation of anthocyanin regulatory and biosynthetic genes in the rubbed stems when compared with the control stems. Furthermore, a negative regulator of anthocyanin, SlMYBL2, was down-regulated in the rubbed stems. However, no significant differences in the expression of anthocyanin-related genes were observed in leaves obtained from the rubbed stems, without directly rubbing the leaves themselves, when compared with the control leaves. These findings indicate that rubbing treatment specifically and immediately activated the expression of anthocyanin-related genes in the areas subjected to mechanical stress. Moreover, we suggest that specific regulatory factors influence anthocyanin accumulation throughout the plant, even in areas not directly exposed to mechanical stress.

•We identified risk factors associated with EM and LM in CRAB bacteraemia.•CRAB bacteraemia with high severity will progress to a rapidly fatal course.•The only independent risk factor for EM was the severity of illness.•LM was associated with both severity of illness and specific sites of infection.

•Bacteremia due to 5 kinds of MDRO occurred in 7979 patients and caused 3280 deaths.•Bacteremia due to MDRO caused $294 505 002 in socioeconomic loss.•Tremendous clinical and economic burden occurred with MDRO bacteraemia.

IMPORTANCE: Atrial fibrillation (AF) can develop following thoracic irradiation. However, the critical cardiac substructure responsible for AF has not been properly studied. OBJECTIVE: To describe the incidence of AF in patients with lung cancer and determine predictive cardiac dosimetric parameters. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was performed at a single referral center and included 239 patients diagnosed with limited-stage small cell lung cancer (SCLC) and 321 patients diagnosed with locally advanced non–small cell lung cancer (NSCLC) between August 2008 and December 2019 who were treated with definitive chemoradiotherapy. EXPOSURES: Radiation dose exposure to cardiac substructures, including the chambers, coronary arteries, and cardiac conduction nodes, were calculated for each patient. MAIN OUTCOMES AND MEASURES: Main outcomes were AF and overall survival. RESULTS: Of the 239 and 321 patients with SCLC and NSCLC, the median (IQR) age was 68 (60-73) years and 67 (61-75) years, and 207 (86.6%) and 261 (81.3%) were men, respectively. At a median (IQR) follow-up time of 32.7 (22.1-56.6) months, 9 and 17 patients experienced new-onset AF in the SCLC and NSCLC cohorts, respectively. The maximum dose delivered to the sinoatrial node (SAN Dmax) exhibited the highest predictive value for prediction of AF. A higher SAN Dmax significantly predicted an increased risk of AF in patients with SCLC (adjusted hazard ratio [aHR], 14.91; 95% CI, 4.00-55.56; P < .001) and NSCLC (aHR, 15.67; 95% CI, 2.08-118.20; P = .008). However, SAN Dmax was not associated with non-AF cardiac events. Increased SAN Dmax was significantly associated with poor overall survival in patients with SCLC (aHR, 2.68; 95% CI, 1.53-4.71; P < .001) and NSCLC (aHR, 1.97; 95% CI, 1.45-2.68; P < .001). CONCLUSIONS AND RELEVANCE: In this cohort study, results suggest that incidental irradiation of the SAN during chemoradiotherapy may be associated with the development of AF and increased mortality. This supports the need to minimize radiation dose exposure to the SAN during radiotherapy planning and to consider close follow-up for the early detection of AF in patients receiving thoracic irradiation.

Herein, a soft and flexible polymer composite sensor with a surface structure is manufactured that is sensitive to a wide range of mechanical stimuli, including small actions and large motions. A polymer sensor performing with a piezoresistive mechanism is proposed by synthesizing a new conductive polymer composite to fabricate a microline structure by itself, named Ag-reduced poly(ethylene glycol) diacrylate (PEGDA) composite directional bending sensor (ACBS). A simple but effective process of forming nanoparticles (NPs) and surface structures is a notable characteristic. High sensitivity to a small stimulus was achieved by forming Ag NPs within PEGDA, particularly concentrating on the surface and applying the microline structure. With the structural characteristics of a line structure, the ACBS achieved anisotropic sensitivity to bulk motion along the arranged line direction. The excellent sensitivity of this polymer sensor was experimentally demonstrated via water droplets, blowing, and breathing. Combining the advantages of a simple synthetic and simple fabrication process along with the fabrication ability of the microsurface structure with the material itself and the conductive Ag/PEGDA integrated layer, this ACBS is outstanding as a soft and flexible polymer composite sensor and has potential application in physical devices such as wearable devices and biosensors.

Knowledge regarding the genetic risk loci for gestational diabetes mellitus (GDM) is still limited. In this study, we performed a two-stage genome-wide association analysis in Korean women. In the stage 1 genome scan, 468 women with GDM and 1,242 nondiabetic control women were compared using 2.19 million genotyped or imputed markers. We selected 11 loci for further genotyping in stage 2 samples of 931 case and 783 control subjects. The joint effect of stage 1 plus stage 2 studies was analyzed by meta-analysis. We also investigated the effect of known type 2 diabetes variants in GDM. Two loci known to be associated with type 2 diabetes had a genome-wide significant association with GDM in the joint analysis, rs7754840, a variant in CDKAL1, had the strongest association with GDM (odds ratio 1.518; P = 6.65 x [10.sup.-16]). A variant near MTNR1B, rs10830962, was also significantly associated with the risk of GDM (1.454; P = 2.49 x [10.sup.-13]). We found that there is an excess of association between known type 2 diabetes variants and GDM above what is expected under the null hypothesis. In conclusion, we have confirmed that genetic variants in CDKAL1 and near MTNRIB are strongly associated with GDM in Korean women. There seems to be a shared genetic basis between GDM and type 2 diabetes. Diabetes 61:531-541, 2012, There has been a marked increase in our understanding of the genetic predisposition to type 2 diabetes as a result of the technical advances in array-based genotyping and the knowledge [...]

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3–50, P< 2.14 × 10−6) and 32 genes at a false discovery rate of <5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure and function of the synapse. The associations of the NMDA (N-methyl-d-aspartate) receptor subunit GRIN2Aand AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GRIA3provide support for dysfunction of the glutamatergic system as a mechanistic hypothesis in the pathogenesis of schizophrenia. We observe an overlap of rare variant risk among schizophrenia, autism spectrum disorders1, epilepsy and severe neurodevelopmental disorders2, although different mutation types are implicated in some shared genes. Most genes described here, however, are not implicated in neurodevelopment. We demonstrate that genes prioritized from common variant analyses of schizophrenia are enriched in rare variant risk3, suggesting that common and rare genetic risk factors converge at least partially on the same underlying pathogenic biological processes. Even after excluding significantly associated genes, schizophrenia cases still carry a substantial excess of URVs, which indicates that more risk genes await discovery using this approach.

Background: Although impaired left ventricular (LV) diastolic function is a prominent feature of hypertrophic cardiomyopathy (HCM), diastolic function and its relation to exercise capacity in apical HCM (ApHCM) has not [...]

The enhancement of surface wettability by hydrophilic polymer coatings has been of great interest because it has been used to address several technical challenges such as biofouling and surface fogging. Among the hydrophilic polymers, zwitterionic polymers have been extensively utilized to coat solid surfaces due to their excellent capability to bind water molecules, thereby forming dense hydration layers on the solid surfaces. For these zwitterionic polymers to function appropriately on the solid surfaces, techniques for fixing polymers onto the solid surface with high efficiency are required. Herein, we report a new approach to graft zwitterionic polymers onto solid substrates. The approach is based on the mussel-inspired surface chemistry and metal coordination. It consists of polydopamine coating and the coordination-driven grafting of the zwitterionic polymers. Polydopamine coating enables the versatile surface immobilization of catechols. Zwitterionic polymers are then easily fixed onto the catechol-immobilized surface by metal-mediated crosslinking reactions. Using this approach, nanometer-thick zwitterionic polymer layers that are highly resistant to bacterial adhesion and fog generation could be successfully fabricated on solid substrates in a substrate-independent manner.

AbstractDisasters are often unforeseen events. Hospitals form a critical component of any country’s disaster management medical support system. To ensure optimal operations, minimize chaos, and allow flexibility in response, planning and practice are crucial. Singapore Health Services (SingHealth) collaborated with Hasanuddin University (UnHas) in Makassar, Indonesia, to develop a Hospital Disaster Medical Support (HDMS) program for the province of South Sulawesi, Indonesia. An assessment of the needs of the hospitals in Makassar, Indonesia, for disaster preparedness was carried out. A curriculum for the HDMS program was developed based on the assessment. Discussions with stakeholders of various hospitals were held for the implementation of this program. A total of 310 participants were trained in this program over the two-year period. The feedback from the participants was positive. The exercises provided a more realistic simulation of the concepts of hospital management in a disaster situation. Up to 73 persons were also trained as program instructors during this period. The development of the cadre of instructors in hospital disaster medical support will likely help sustain the program for the next few years.

ABSTRACTRadon (Rn) is a natural and toxic radioactive gas that accumulates indoors, mainly in low-ventilated underground floors and basements. Several factors make prediction of indoor Rn exposure in enclosed spaces challenging. In this study, we investigated the influence of soil, geology, topography, atmospheric variables, radiation, urbanization, community economic well-being, and monthly and yearly variations on indoor Rn concentrations. We analyzed 7,515 monthly indoor Rn measurements in 623 zip codes from two U.S. States (Michigan and Minnesota) during 2005–2018 using a random forest model. Using Shapley Additive exPlanations (SHAP) values we investigated the contribution of each factor using variable importance and partial dependence plots. Factors that predict indoor Rn differed between states, with topographical, geological and soil composition being most influential. Cross-validated Pearson correlation between predictions and measurements was 0.68 (RMSE = 47.8 Bq/m3) in Minnesota, and 0.67 (RMSE = 52.5 Bq/m3) in Michigan. Our results underline the importance of soil structure for radon exposure, presumably due to strapped Rn in soil. The differences across states also suggest that Rn studies performing model development should consider geographical variables, along with other factors. As indoor Rn levels are multifactorial, an understanding of the factors that influence its emanation and build up indoors will help better assess spatial and temporal variations, which will be useful to improve prevention and mitigation control strategies.Implications: Radon exposure has become a year-round problem as people spend most of their time indoors. In North America, radon exposure is increasing over time and awareness related to its health effects remains low in the general population. Several factors make prediction of indoor radon exposure in enclosed spaces challenging. In this study, we used random forest to investigate the influence of factors on indoor radon in the Midwest United States. We found that topography, geology, and soil composition were the most influential factors on indoor radon levels. These results will help better assess spatial and temporal variations, which will further help better prevention and mitigation control strategies.

Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3–2.8, one-sided p= 6.0 × 10−4), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p= 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ.

Advances in microscale 3D cell culture systems have helped to elucidate cellular physiology, understand mechanisms of stem cell differentiation, produce pathophysiological models, and reveal important cell–cell and cell–matrix interactions. An important consideration for such studies is the choice of material for encapsulating cells and associated extracellular matrix (ECM). This Review focuses on the use of alginate hydrogels, which are versatile owing to their simple gelation process following an ionic cross-linking mechanism in situ, with no need for procedures that can be potentially toxic to cells, such as heating, the use of solvents, and UV exposure. This Review aims to give some perspectives, particularly to researchers who typically work more with poly(dimethylsiloxane) (PDMS), on the use of alginate as an alternative material to construct microphysiological cell culture systems. More specifically, this Review describes how physicochemical characteristics of alginate hydrogels can be tuned with regards to their biocompatibility, porosity, mechanical strength, ligand presentation, and biodegradability. A number of cell culture applications are also described, and these are subcategorized according to whether the alginate material is used to homogeneously embed cells, to micropattern multiple cellular microenvironments, or to provide an outer shell that creates a space in the core for cells and other ECM components. The Review ends with perspectives on future challenges and opportunities for 3D cell culture applications.

ABSTRACTDaily fine (PM2.5) and coarse (PM10-2.5) particle matter (PM) samples collected at Parque O’Higgins station in downtown Santiago de Chile have been studied to find the trends in concentration from 1998 to 2018. Elemental concentration was obtained using X-ray fluorescence (XRF). Regression models from previous studies indicate that the PM2.5and PM10-2.5fractions have had a continuous decrease since 1988 mostly due to several policy control measures carried out over several decades. PM2.5has decreased from 68.3 in 1988 to 27.6 μg/m3in 2018 (60.4%). However, if only the last 8 years are considered (2011–2018), a leveling off can be observed in PM10-2.5and PM2.5, which points to a change in the tendency. Cluster analysis of the elements in the fine and coarse fractions were identified to evaluate trends in the contributing sources. In the fine fraction, the mass contribution of crustal elements (Si, Al, Ca, and Fe) has remained stable in the last 8 years, and mass contribution of elements (Pb, Br, and Cl) associated to anthropogenic sources (traffic, wood burning) has also remained stable in the same period. For the coarse fraction, the contribution of one group of elements associated to crustal or anthropogenic sources has remained stable, and another group has decreased in the last 8 years. The leveling off can be ascribed to decreased rainfall during the last 8 years that have promoted soil dryness and resuspension of dust facilitated by wind or vehicular traffic. Mean temperatures have increased in the last 30 years, but have not contributed directly to the leveling of the concentration.Implications: Regression models indicate that the PM2.5(fine) and PM10-2.5(coarse) fractions at Parque O’Higgins station in Santiago de Chile have had a continuous decrease since 1988 mostly due to several policy control measures carried out over several decades. However, in the last 8 years (2011–2018), a leveling off can be observed in PM10-2.5and PM2.5. X-ray fluorescence (XRF) analysis was performed in the fine fractions indicating that the mass contribution of crustal elements (Ca, Al, Si, Fe) to the fine fraction has remained stable. This phenomenon can be ascribed to decreased rainfall during the last 8 years that have promoted soil dryness and resuspension of dust facilitated by wind or vehicular traffic. The crustal elements in the coarse fraction have also remained stable.

Inhaling radon and its progeny is associated with adverse health outcomes. However, previous studies of the health effects of residential exposure to radon in the United States were commonly based on a county-level temporally invariant radon model that was developed using measurements collected in the mid- to late 1980s. We developed a machine learning model to predict monthly radon concentrations for each ZIP Code Tabulation Area (ZCTA) in the Greater Boston area based on 363,783 short-term measurements by Spruce Environmental Technologies, Inc., during the period 2005–2018. A two-stage ensemble-based model was developed to predict radon concentrations for all ZCTAs and months. Stage one included 12 base statistical models that independently predicted ZCTA-level radon concentrations based on geological, architectural, socioeconomic, and meteorological factors for each ZCTA. Stage two aggregated the predictions of these 12 base models using an ensemble learning method. The results of a 10-fold cross-validation showed that the stage-two model has a good prediction accuracy with a weighted R2of 0.63 and root mean square error of 22.6 Bq/m3. The community-level time-varying predictions from our model have good predictive precision and accuracy and can be used in future prospective epidemiological studies in the Greater Boston area.

Coronary artery calcium (CAC) score is a clinically validated marker of cardiovascular disease risk. We developed and validated a novel cardiovascular risk stratification system based on deep-learning-predicted CAC from retinal photographs.

Dystrophinopathy is an X-linked recessive muscular dystrophy caused by mutations in the DMDgene. Herein we describe the prenatal detection of DMDgene mutations in a patient with no family history, by multiplex ligation-dependent probe amplification (MLPA) after noninvasive prenatal screening (NIPS).

Subvariants of the Omicron lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficiently escape neutralizing antibody responses induced by both vaccination and infection with antigenically distinct variants. Here, we describe the potency and breadth of neutralizing and binding antibody responses against a large panel of variants following an Omicron BA.1 or BA.2 breakthrough infection in a heterogeneous cohort of individuals with diverse exposure histories. Both BA.1 and BA.2 breakthrough infections significantly boost antibody levels and broaden antibody reactivity. However, this broader immunity induced by BA.1 and BA.2 breakthrough infections does not neutralize Omicron BQ and XBB subvariants efficiently. While these subvariants are not neutralized well by post-breakthrough sera, suggesting escape, binding non-neutralizing antibody responses are sustained. In summary, our data suggest that while BA.1 and BA.2 breakthrough infections broaden the immune response to SARS-CoV-2 spike, the induced neutralizing antibody response is still outpaced by viral evolution.

The antifouling efficacy of hydrophilic polymer coatings is closely related to their surface charge. Many biological foulants such as mammalian cells and marine microalgae possess a negative surface charge, discouraging the use of positively charged polymer coatings for antifouling purposes. Instead, electrically neutral yet hydrophilic polymers have been widely employed, leveraging hydration layers to create a barrier against fouling. However, challenges arise in marine environments where both living marine organisms and sediments can adhere to solid surfaces, rendering previous findings less directly applicable. This study investigates the impact of a polymer coating surface charge on marine antifouling properties. Polymer brushes with various charges are applied to solid substrates, and the adhesion behavior of marine diatoms is assessed under both marine sediment-free and marine sediment conditions. The results underscore the effectiveness of negatively charged polymer brush coatings in marine antifouling, regardless of sediment presence.

In this work, we prepared 90 nm thick Ti3C2Tx–graphene oxide (GO) membranes laminated on a porous support by mixing GO with Ti3C2Tx. This process was chosen to prevent the penetration of target molecules through inter-edge defects or voids with poor packing. The lattice period of the prepared membrane was 14.28 Å, as being swelled with water, resulting in an effective interlayer spacing of around 5 Å, which corresponds to two layers of water molecules. The composite membranes effectively rejected dye molecules with hydrated radii above 5 Å, as well as positively charged dye molecules, during pressure-driven filtration at 5 bar. Rejection rates were 68% for methyl red, 99.5% for methylene blue, 93.5% for rose Bengal, and 100% for brilliant blue (hydrated radii of 4.87, 5.04, 5.88, and 7.98 Å, respectively). Additionally, the rejections of composite membrane were compared with GO membrane and Ti3C2Txmembrane.

This study proposes a novel technique for soil characterization, utilizing laser transmission to observe the sedimentation process. This method significantly diminishes specimen disturbances, human errors, and the required sample size, making it a more time and cost-effective alternative to traditional methods. Detailed models capturing the intricacies of the sedimentation process, including influential factors such as particle diameter and mass concentration, are delineated. Moreover, we suggest a method to extrapolate the cumulative grain size distribution from the laser transmission profile of a soil sample. Collectively, this research presents an efficient and promising approach to soil characterization, leveraging laser light for sedimentation monitoring.

Concomitant iatrogenic proximal venous stenosis increases venous pressure and can be a risk factor for unfavorable outcomes of lymphaticovenular anastomosis (LVA) in extremities with secondary lymphedema. This study investigated the frequency and relevant factors of venous stenosis in patients diagnosed with secondary lymphedema who underwent LVA.

•We identified 7 new genetic regions for factor VIII levels, 1 for von Willebrand factor levels, and 3 in a combined analysis.•Silencing B3GNT2and CD36reduced factor VIII release in vitro.Silencing B3GNT2, CD36, and PDIA3reduced von Willebrand factor release.

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes)1. In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%.

ObjectiveAn understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.DesignTo identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.ResultsWe identified 13 loci that reached genome-wide significance (p<5×10−8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.ConclusionGenetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.

Methylated bis-triethylene glycolic crown-5-calix[4]arene (M-BTC5A) as a phase-transfer catalyst showed the best performance among other analogues and even conventional Kryptofix 222 in the nucleophilic aromatic 18F-fluorination of diaryliodonium tosylate precursors owing to (i) the efficient release of reactive “naked” [18F]fluoride, (ii) the high stabilization of the precursor in the reaction, and, presumably, (iii) the ease of access between the precursor and the K18F/M-BTC5A complex facilitated by π–π interactions. [18F]Flumazenil was produced in high radiochemical yield using M-BTC5A.

AbstractPreparation is key to dealing with the rising number of disasters occurring globally. Teams may be inexperienced, but they cannot be inadequately prepared. Rescue providers must be equipped with knowledge, skills, equipment, and supplies to manage the complex demands of a disaster. To bridge the gaps in disaster management training, the Singapore Health Services, in collaboration with the University of Hasanuddin, developed a tailored training program for the teaching of medical support at the disaster site in Indonesia. This project was conducted in Makassar for participants in the province of South Sulawesi. Over the 2-year period, the project benefitted 301 participants, with 73 identified to become Master Trainers to take over local ownership and leadership of the program. The Master Trainers would continue the training of new participants, as well as work within their agencies and with each other to bring about changes to significantly improve disaster management in Indonesia.

We report a facile approach for the fabrication of a marine antifouling coating using the red algae-derived polysaccharide, carrageenan (CAR). Because CAR is hydrophilic and negatively charged, we hypothesized that it would form strong hydration layers upon adsorption onto solid surfaces, thereby exhibiting marine antifouling properties. Although various types of CAR can be used for marine antifouling, a universally applicable coating method has not yet been developed; thus, a systematic study on the marine antifouling property of CAR coating is lacking. Here, we fabricated a versatile CAR coating via ZrIV-mediated multiple cross-linking reactions between the sulfate groups of CAR and metal ions and successfully deposited κ-, ι-, and λ-CAR onto solid surfaces. Specifically, λ-CAR showed superior marine antifouling performance, as evidenced by the results of the marine diatom adhesion assays.

γ-MnO2nanorod-assembled hierarchical micro-spheres with abundant oxygen defects are synthesized by a simple thermal treatment approach as oxygen reduction electrocatalysts for Al (aluminum) - air batteries. The rich oxygen vacancies on the surface of γ-MnO2are verified by morphology, structure, electron paramagnetic resonance (EPR) and X-ray photoelectron spectroscopy (XPS) results. The oxygen reduction reaction (ORR) electrocatalytic activity of γ-MnO2is significantly improved by the incoming oxygen vacancies. The γ-MnO2nanorod-assembled hierarchical micro-spheres calcined under 300 °C in Ar atmosphere show the best ORR performance. The primary Al-air batteries using γ-MnO2catalysts as the cathode, which demonstrates excellent peal power density of 318 mW cm−2when applying the γ-MnO2catalysts with optimal amount of oxygen vacancies.