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Yeast cultures (YCs) are defined as promising feed additives that maintain the health of birds and improve growth performance by modulating gut microbiota. YCs contain effective metabolites such as glycine, fructose, inositol, galactose, and sucrose. This study investigated the effects of YCs and their effective metabolites on carcass traits and cecal microflora in broilers. A total of 280 one-day-old mixed-sex Arbor Acres broilers were randomly allocated to seven groups. The basal diet (control DZ) was supplemented with various proportions of glycine, fructose, inositol, galactose, and sucrose (Groups A, B, and C), 24-hour grown Saccharomyces cerevisiae cultures (Group D) (YC), and a commercial yeast culture product (SZ) at concentrations of 0.1% and 1% (Groups E and F). Bodyweight of broilers was correlated positively with proportions of Proteobacteria in Group C and Lactobacillus and Roseburia in Group B (P

The effect of hydrostatic pressure up to 27 GPa on the Raman scattering (RS) in bulk HfS$_2$ is investigated. There are two transformations of RS spectra, which take place during compression at pressure between 5.7 GPa and 9.8 GPa as well as between 12.8 GPa and 15.2 GPa. Seven vibrational modes can be observed after the transformation, as compared to four modes before the transformation. The observed change suggests structural change in the material of yet unknown nature. The frequencies of the RS modes observed above the transformation change linearly with pressure and corresponding pressure coefficients have been determined. The other transition manifests itself as a change in the RS lineshape. While a series of well-defined RS modes are observed under pressure below the transition, broad spectral bands can be seen at higher pressure. The overall lineshape of the spectra resembles that of disordered materials. The lineshape does not change during decompression, which suggests permanent nature of the high-pressure transition., 4 pages, 4 figures

Contains fulltext : 287159.pdf (Publisher’s version ) (Closed access) Pharmacometric modelling plays a key role in both the design and analysis of regulatory trials in paediatric drug development. Studies in adults provide a rich source of data to inform the paediatric investigation plans, including knowledge on drug pharmacokinetics (PK), safety and efficacy. In children, drug disposition differs widely from birth to adolescence but extrapolating adult to paediatric PK, safety and efficacy either with pharmacometric or physiologically based approaches can help design or in some cases reduce the need for clinical studies. Aspects to consider when extrapolating PK include the maturation of drug metabolizing enzyme expression, glomerular filtration, drug excretory systems, and the expression and activity of specific transporters in conjunction with other drug properties such as fraction unbound. Knowledge of these can be used to develop extrapolation tools such as allometric scaling plus maturation functions or physiologically based PK. PK/pharmacodynamic approaches and well-designed clinical trials in children are of key importance in paediatric drug development. In this white paper, state-of-the-art of current methods used for paediatric extrapolation will be discussed. This paper is part of a conect4children implementation of innovative methodologies including pharmacometric and physiologically based PK modelling in clinical trial design/paediatric drug development through dissemination of expertise and expert advice. The suggestions arising from this white paper should define a minimum set of standards in paediatric modelling and contribute to the regulatory science.

Shower development dynamics for a jet traveling through the quark-gluon plasma (QGP) is a multiscale process, where the heavy flavor mass is an important scale. During the high virtuality portion of the jet evolution in the QGP, emission of gluons from a heavy flavor is modified owing to heavy quark mass. Medium-induced radiation of heavy flavor is sensitive to microscopic processes (e.g. diffusion), whose virtuality dependence is phenomenologically explored in this study. In the lower virtuality part of shower evolution, i.e. when the mass is comparable to the virtuality of the parton, scattering and radiation processes of heavy quarks differ from light quarks. The effects of these mechanisms on shower development in heavy flavor tagged showers in the QGP is explored here. Furthermore, this multiscale study examines dynamical pair production of heavy flavor (via virtual gluon splittings) and their subsequent evolution in the QGP, which is not possible otherwise. A realistic event-by-event simulation is performed using the JETSCAPE framework. Energy-momentum exchange with the medium proceeds using a weak coupling recoil approach. Using leading hadron and open heavy flavor observables, differences in heavy versus light quark energy-loss mechanisms are explored, while the importance of heavy flavor pair production is highlighted along with future directions to study., Comment: 6 pages, 3 figures, contribution to the Hard Probes 2023 proceedings

The Leaf Area Index (LAI) is vital for predicting winter wheat yield. Acquisition of crop conditions via Sentinel-2 remote sensing images can be hindered by persistent clouds, affecting yield predictions. Synthetic Aperture Radar (SAR) provides all-weather imagery, and the ratio between its cross- and co-polarized channels (C-band) shows a high correlation with time series LAI over winter wheat regions. This study evaluates the use of time series Sentinel-1 VH/VV for LAI imputation, aiming to increase spatial-temporal density. We utilize a bidirectional LSTM (BiLSTM) network to impute time series LAI and use half mean squared error for each time step as the loss function. We trained models on data from southern Germany and the North China Plain using only LAI data generated by Sentinel-1 VH/VV and Sentinel-2. Experimental results show BiLSTM outperforms traditional regression methods, capturing nonlinear dynamics between multiple time series. It proves robust in various growing conditions and is effective even with limited Sentinel-2 images. BiLSTM's performance surpasses that of LSTM, particularly over the senescence period. Therefore, BiLSTM can be used to impute LAI with time-series Sentinel-1 VH/VV and Sentinel-2 data, and this method could be applied to other time-series imputation issues.

Multi-antenna global navigation satellite systems (GNSS) can provide attitude measurement information for GNSS/INS integrated system. However, once the wrong attitude measurement is used in the tight coupled model, it is easy to lead to filtering divergence. Therefore, fault detection and exclusion (FDE) is very important for multi-antenna attitude determination. Because the baseline length information is often used as prior information in attitude determination, it cannot be used as the statistic of FDE again. In this paper, we propose a new statistic for attitude FDE, differential inter-system biases (DISB), and jointly use DISB, baseline length, standard deviation, and ratio to perform FDE for multi-antenna GNSS attitudes. The obtained attitudes with high reliability is added to the GNSS/INS tight coupled positioning model for measurement update. A set of urban vehicular data is used to verify the method. The results show that the DISB has FDE capabilities comparable to the baseline length information, which will be a powerful supplement when the baseline length information cannot be used. Compared to the single-antenna GNSS/INS tight coupled model, The accuracy of yaw,pitch and roll of the RTK/INS tightly coupled model with multi-antenna attitude measurement is improved by 57-64%,26-29% and 26-32% respectively, and the accuracy of the PPP/INS tightly coupled model with multi-antenna attitude measurement is improved by 60-61%,51-53% and 41-44% respectively., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Memristors have been widely studied as artificial synapses in neuromorphic circuits, due to their functional similarity with biological synapse, low operating power, and high integration density. In this work, a memristor bridge synapse for SNN with excellent linearity and soft-bound synaptic plasticity is designed and utilized for a neuron circuit implementing the robust spike-timing dependent plasticity (STDP) learning. This is the first of its kind demonstrating successful pulse width encoded multiple-step quantized STDP, with mixed-signal neuron possessing linear weight update. Physical models are employed to study the performance of proposed synapse and circuit, and simulations are carried out based on the MATLAB Simulink and Simscape. An improved memristor model which exhibits balanced flexibility, efficiency, convergence, and emulation performance, is developed though including the nonlinear Joule effect and weak signal effect. By using the improved memristor model in pattern learning, the influence of weak signal induced weight variation on circuit performance can be rigorously assessed. Moreover, the robustness and compatibility of the neuron circuit are greatly enhanced by employing the clock-based square-wave pulsed to process and program the synaptic weight. This proposed circuit could give an inspiration for combining the analog memristive synapse and leaky integrate-and-fire neuron with digital control units, prompting their development as edge computing devices., Comment: 10 pages, 25 figures

Recently, many pre-trained language models for source code have been proposed to model the context of code and serve as a basis for downstream code intelligence tasks such as code completion, code search, and code summarization. These models leverage masked pre-training and Transformer and have achieved promising results. However, currently there is still little progress regarding interpretability of existing pre-trained code models. It is not clear why these models work and what feature correlations they can capture. In this paper, we conduct a thorough structural analysis aiming to provide an interpretation of pre-trained language models for source code (e.g., CodeBERT, and GraphCodeBERT) from three distinctive perspectives: (1) attention analysis, (2) probing on the word embedding, and (3) syntax tree induction. Through comprehensive analysis, this paper reveals several insightful findings that may inspire future studies: (1) Attention aligns strongly with the syntax structure of code. (2) Pre-training language models of code can preserve the syntax structure of code in the intermediate representations of each Transformer layer. (3) The pre-trained models of code have the ability of inducing syntax trees of code. Theses findings suggest that it may be helpful to incorporate the syntax structure of code into the process of pre-training for better code representations., Accepted by ICSE 2022 (The 44th International Conference on Software Engineering)

Deep learning methods based on Fully convolution networks (FCNs) have shown an impressive progress in building outline delineation from very high resolution (VHR) remote sensing (RS) imagery. Common issues still exist in extracting precise building shapes and outlines, often resulting in irregular edges and over smoothed corners. In this paper, we use PolyMapper, a recently introduced deep-learning framework that is able to predict object outlines in a vector representation directly. We have introduced two main modifications to this baseline method. First, we introduce EffcientNet as backbone feature encoder to our network, which uses compound coefficient to scale up all dimensions of depth/width/resolution uniformly, to improve the processing speed with fewer parameters. Second, we integrate a boundary refinement block (BRB) to strengthen the boundary feature learning and to further improve the accuracy of corner prediction. The results demonstrate that the end-to-end learnable model is capable of delineating polygons of building outlines that closely approximate the structure of reference labels. Experiments on the crowdAI building instance segmentation datasets show that our model outperforms PolyMapper in all COCO metrics, for instance showing a 0.13 higher mean Average Precision (AP) value and a 0.60 higher mean Average Recall value. Also qualitative results show that our method segments building instances of various shapes more accurately.

Overload instability is a self-excited phenomenon that occurs in Francis turbines working over the Best Efficiency Point. It provokes huge power swings and pressure fluctuations in the hydraulic circuit. One particular issue is that this phenomenon appears suddenly and just before its onset the machine can operate in a very stable manner. In this study, we show that artificial intelligence techniques such as Neural Networks can be used to evaluate the risk of overload instability several seconds before its appearance. Experimental data, acquired during several overload instability tests in a huge prototype, has been used. The techniques proposed in this paper could be used in advanced condition monitoring systems and could permit a safer operation of the turbine working at high loads.

Symmetries play a crucial role in the classification of topological phases of matter. Although recent studies have established a powerful framework to search for and classify topological phases based on symmetry indicators, there exists a large class of fragile topology beyond the description. The Euler class characterizing the topology of two-dimensional real wave functions is an archetypal fragile topology underlying some important properties, such as non-Abelian braiding of crossing nodes and higher-order topology. However, as a minimum model of fragile topology, the two-dimensional topological Euler insulator consisting of three bands remains a significant challenge to be implemented in experiments. Here, we experimentally realize a three-band Hamiltonian to simulate a topological Euler insulator with a trapped-ion quantum simulator. Through quantum state tomography, we successfully evaluate the Euler class, Wilson loop flow and entanglement spectra to show the topological properties of the Hamiltonian. We also measure the Berry phases of the lowest energy band, illustrating the existence of four crossing points protected by the Euler class. The flexibility of the trapped-ion quantum simulator further allows us to probe dynamical topological features including skyrmion-antiskyrmion pairs and Hopf links in momentum-time space from quench dynamics. Our results show the advantage of quantum simulation technologies for studying exotic topological phases and open a new avenue for investigating fragile topological phases in experiments., Comment: 19 pages including appendixes, 12 figures

Although the concept of Luttinger liquid (LL) that describes a one-dimensional (1D) interacting fermion system collapses in higher dimensions, it has been proposed to be closely related to many mysteries including the normal state of cuprate superconductor, unconventional metal, and quantum criticality. Therefore, the generalization of LL model to higher dimensions has attracted substantial research attention. Here we systematically investigate the electronic structure of a quasi-2D compound η-Mo4O11 using high-resolution angle-resolved photoemission spectroscopy and ab-initio calculation. Remarkably, we reveal a prototypical LL behavior originating from the crossing quasi-1D chain arrays hidden in the quasi-2D crystal structure. Our results suggest that η-Mo4O11 materializes the long sought-after crossed LL phase, where the orthogonal orbital components significantly reduce the coupling between intersecting quasi-1D chains and therefore maintain the essential properties of LL. Our finding not only presents a realization of 2D LL, but also provides a new angle to understand non-Fermi liquid behaviors in other 2D and 3D quantum materials.

Dissipation is often considered as a detrimental effect in quantum systems for unitary quantum operations. However, it has been shown that suitable dissipation can be useful resources in both quantum information and quantum simulation. Here, we propose and experimentally simulate a dissipative phase transition (DPT) model using a single trapped ion with an engineered reservoir. We show that the ion’s spatial oscillation mode reaches a steady state after the alternating application of unitary evolution under a quantum Rabi model Hamiltonian and sideband cooling of the oscillator. The average phonon number of the oscillation mode is used as the order parameter to provide evidence for the DPT. Our work highlights the suitability of trapped ions for simulating open quantum systems and shall facilitate further investigations of DPT with various dissipation terms.

Smartwatches are increasingly popular in our daily lives. Motion gestures are a common way of interacting with smartwatches, e.g., users can make a movement in the air with their arm wearing the watch to trigger a specific command of the smartwatch. Motion gesture interaction can compensate for the small screen size of the smartwatch to some extent and enrich smartwatch-based interactions. An important aspect of motion gesture interaction lies in how to determine the start and end of a motion gesture. This paper is aimed at selecting gestures as suitable delimiters for motion gesture interaction with the smartwatch. We designed six gestures ("shaking wrist left and right,""shaking wrist up and down,""holding fist and opening,""turning wrist clockwise,""turning wrist anticlockwise,"and "shaking wrist up") and conducted two experiments to compare the performance of these six gestures. Firstly, we used dynamic time warping (DTW) and feature extraction with KNN (K-nearest neighbors) to recognize these six gestures. The average recognition rate of the latter algorithm for the six gestures was higher than that of the former. And with the latter algorithm, the recognition rate for the first three of the six gestures was greater than 98%. According to experiment one, gesture 1 (shaking wrist left and right), gesture 2 (shaking wrist up and down), and gesture 3 (holding fist and opening) were selected as the candidate delimiters. In addition, we conducted a questionnaire data analysis and obtained the same conclusion. Then, we conducted the second experiment to investigate the performance of these three candidate gestures in daily scenes to obtain their misoperation rates. The misoperation rates of two candidate gestures ("shaking wrist left and right"and "shaking wrist up and down") were approximately 0, which were significantly lower than that of the third candidate gesture. Based on the above experimental results, gestures "shaking wrist left and right"and "shaking wrist up and down"are suitable as motion gesture delimiters for smartwatch interaction.

Objective: Explore the risk factors related to the recurrence of MDD and provide a basis for the prevention and control of MDD. Methods: Patients with MDD were extracted from two large, multi-center clinical datasets. The inpatients and outpatients between January 2000 and December 2015 were collected. Eligible patients were 18-90 years-old and had a diagnosis of MDD. The MDD were identified based on the MDD-related ICD-9- CM diagnosis codes; and MDD-related ICD-10-CM diagnosis codes. Eventually, 140,497 patients were qualified for further analysis, including 69.2% female patients. Among of 140,497, 20, 078 patients (14.3%) had no comorbidities. Logistic regression, SVM, and LSTM were employed to predict the key risk factors associated with MDD recurrence. Results: The MDD patients with married /life partners had a lower prevalence rate (9.2%) of MDD recurrence than the patients with single marital status (11.8%). The primary MDD patients had a higher MDD recurrent rate (11.7%) than secondary MDD patients (10.5%). Primary MDD was associated with MDD recurrence (OR 2.49, 95% CI 1.53-3.96) via logistic regression analysis. Insomnia, anxiety and single marital status were also top-ranked risk factors for the MDD recurrence. The prediction accuracy of logistic regression, SVM and LSTM were 0.736, 0.791 and 0.834, respectively. Conclusions: Building statistical models by mining existing EHR data can explore the risk factors associated with MDD recurrence. Our results indicated that primary MDD, never married, anxiety symptoms, and insomnia were risk factors for MDD recurrence. The prediction accuracy of the LSTM model was higher than the other two approaches.

Educational inequalities in mortality have been observed for decades, however the underlying biological mechanisms are not well known. We assessed the mediating role of altered aging of immune cells functioning captured by DNA methylation changes in blood (known as epigenetic clocks) in educational associated all-cause mortality. Data were from eight prospective population-based cohort studies, representing 13,021 participants. We found educational inequalities in mortality were larger for men than for women, estimated by hazard differences and ratios. Epigenetic clocks explained approximately 50% of educational inequalities in mortality for men, while the proportion was small for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the WHO risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors.

Most covalent organic frameworks (COFs) are synthesized using solvothermal conditions (>120 °C, >72 h) in harmful organic solvents. We report a strategy for rapidly synthesizing imine-linked COFs (< 60 min) in aqueous acetic acid using sonochemistry, avoiding most of the downsides of solvothermal methods. We first synthesized seven known COFs using this method and obtained crystallinity and porosity comparable to or better than materials from previously reported solvothermal routes. This sonochemical method even works in highly sustainable solvents, such as food-grade vinegar. The generality of the method was demonstrated by preparing two unreported COFs. Finally, we showed that one sonochemical COF is an excellent photocatalyst for sacrificial hydrogen evolution from water with a more sustained catalytic performance than its solvothermal analog. The speed, ease and generality of this sonochemical method with no sacrifice in material quality makes it an enabling methodology for rapid discovery of new functional COF materials.

Some fungi may promote plant growth by production of siderophores, Indole Acetic Acid (IAA) and phosphorus dissolving capability. In this study, eight fungi were isolated from the mushroom substrate, and their siderophores production, IAA production and phosphorus dissolving traits were determined. Although there was no significant difference in IAA production among the eight fungi, but the strain M13026-2 was a fungus with strong growth promoting traits compared with other seven fungi. In order to study the correlation between the growth promoting effect of cucumber pot culture and the above three traits, five fungi with different strength of traits were tested in pot. As a result, M13026- 2 which was identified as Talaromyces purpureogenus could significantly improve the growth parameters of cucumber seedlings, and could colonize in the rhizosphere soil and the tissue of cucumber stably. All the results suggested that the most relevant to their ability to promote plant growth is the trait of phosphorus dissolving, followed by siderophores production. The results of this study will provide scientific basis for the efficient selection and identification of a large number of fungi resources with the function of promoting plant growth, and reveal the good application potential of T. purpureogenus in agriculture fields.

The process of CO2-SAG flooding involves conventional miscible CO2 flooding until breakthrough (BT), followed by a period of CO2 soaking or shut-in, and then a continuation of the miscible CO2 flooding. The SAG process provides different improvements in the oil recovery for different positions of each layer in multilayer reservoirs, and has different effects on the distribution of pore throat blocking and adsorption of asphaltene to mineral surfaces. In this paper, both miscible CO2-SAG and conventional CO2 flooding experiments have been carried out at reservoir conditions and on multi-layer systems composed of 3 long cores each with increasing porosities and permeabilities, which were connected in parallel. After CO2-SAG flooding oil recovery factors (RF) of the low, medium and high permeability cores were 7.7%, 8.3%, and 7.6% higher compared to the RFs after CO2 flooding, respectively. The respective fractional oil production (FOP) of each long core was 10.6%, 27.7%, and 61.6% after CO2-SAG flooding, with less difference between each long core than for CO2 flooding. After CO2 flooding, the permeability of the high permeability core at the injection end dropped by 24.5–25.8%, which is 5.5–14.3% higher than the value at the outlet. The permeability decrease due to CO2-SAG flooding was 0.7–9.7% higher than that due to CO2 flooding, and the distribution of permeability decline was more homogeneous. The contribution of the total permeability decrease attributable to asphaltene particle blockage due to CO2 flooding was 84.7–62.7%, 5.2–10.1% higher than that due to CO2-SAG flooding, gradually decreasing along the flow direction. Complex two-phase flow of oil and gas is more likely to cause pore throat blockage instead of causing the adsorption of asphaltene precipitation.

Lung cancer continues to be the leading cause of cancer deaths and more than one million lung cancer patients will die every year worldwide. Radiotherapy (RT) plays an important role in lung cancer treatment, but the side effects of RT are pneumonitis and pulmonary fibrosis. RT-induced lung injury causes damage to alveolar-epithelial cells and vascular endothelial cells. Macrophages play an important role in the development of pulmonary fibrosis despite its role in immune response. These injury activated macrophages develop into classically activated M1 macrophage or alternative activated M2 macrophage. It secretes cytokines, interleukins, interferons, and nitric oxide. Several pro-inflammatory lipids and pro-apoptotic proteins cause lipotoxicity such as LDL, FC, DAG, and FFA. The overall findings in this review conclude the importance of macrophages in inducing toxic/inflammatory effects during RT of lung cancer, which is clinically vital to treat the radiation-induced fibrosis.

The ulnar nerve compressed in the cubital tunnel is called Cubital tunnel syndrome in the clinic.we also found that there are cysts compress the ulnar nerve in cubital tunnel through preoperative ultrasonograhy. This case report is the description of heterotopic cysts that compress the ulnar nerve in our clinical practice.

Mulberry is admired for its landscaping and possesses high development prospects and scientific research value. Mitochondria are the plants' powerhouse that produces energy to carry out life processes. In this study, the mt genome of Morus L(M. atropurpurea and M. multicaulis)were annotated and assembled. The circular mt genome of M. multicaulis has a length of 361,546bp, contains 54 genes, including 31 protein-coding genes, 20 tRNA genes, and 3 rRNA genes and composition of A(27.38%), T (27.20%), C (22.63%) and G (22.79%). The sequence repeats, RNA editing gene and migration from cp to mt and was observed in M. multicaulis mt genome. Phylogenetic analysis based on the complete mt genomes of Morus and other 28 species reflects an exact evolutionary and taxonomic status. Furthermore, we investigation on mt genome size, organization, and plastomes at the global level and pi analysis of Morus genome was investigated and compared to other land plants. The results indicate that the exist mt genome's variation in plants. We reported the mt genome assembly and annotation of a halophytic model plant, M. multicaulis, and subsequent analysis, which provided us with a comprehensive understanding of the Morus mt genome.

Novel hollow flower-like SnO structures have been successfully synthesized by using a facile solvothermal method approach, which injecting LiN(SiMe3)2 to the solution of SnCl2 and oleamine. The as-synthesized hollow flower-like SnO structures were aggregated by ultrathin SnO nanosheets with large surface area and exhibit narrow size distribution of ~2.0 µm. The electrochemical performance of hollow flower-like SnO structures were examined as an anode material in coin cells for lithium-ion batteries. It demonstrates excellent lithium ion batteries performance as characterized by the cycling stability, specific capacity, cyclic voltammetry and rate performance. The measured discharge capacity is 361.4 mAh g-1 after 50 charge/discharge cycles with 46% capacity retention, which indicated a improving in cyclic stability. This result demonstrated that the specific hollow structure has great potential as the electrodes for lithium ion batteries. This work may provide an attractive road to synthesize other hollow-flower structures of transition metal oxides.

Smoking remains one of the leading preventable causes of death. Smoking leaves a strong signature on the blood methylome as shown in multiple studies using the Infinium HumanMethylation450 BeadChip. Here, we explore novel blood methylation smoking signals on the Illumina MethylationEPIC BeadChip (EPIC) array, which also targets novel CpG-sites in enhancers. A smoking-methylation meta-analysis was carried out using EPIC DNA methylation profiles in 1407 blood samples from four UK population-based cohorts, including the MRC National Survey for Health and Development (NSHD) or 1946 British birth cohort, the National Child Development Study (NCDS) or 1958 birth cohort, the 1970 British Cohort Study (BCS70), and the TwinsUK cohort (TwinsUK). The overall discovery sample included 269 current, 497 former, and 643 never smokers. Replication was pursued in 3425 trans-ethnic samples, including 2325 American Indian individuals participating in the Strong Heart Study (SHS) in 1989-1991 and 1100 African-American participants in the Genetic Epidemiology Network of Arteriopathy Study (GENOA). Altogether 952 CpG-sites in 500 genes were differentially methylated between smokers and never smokers after Bonferroni correction. There were 526 novel smoking-associated CpG-sites only profiled by the EPIC array, of which 486 (92%) replicated in a meta-analysis of the American Indian and African-American samples. Novel CpG sites mapped both to genes containing previously identified smoking-methylation signals and to 80 novel genes not previously linked to smoking, with the strongest novel signal in SLAMF7. Comparison of former versus never smokers identified that 37 of these sites were persistently differentially methylated after cessation, where 16 represented novel signals only profiled by the EPIC array. We observed a depletion of smoking-associated signals in CpG islands and an enrichment in enhancer regions, consistent with previous results. This study identified novel smoking-associated signals as possible biomarkers of exposure to smoking and may help improve our understanding of smoking-related disease risk. This study was supported by the Economic and Social Research Council (ESRC, Grant Number ES/N000404/1 to J.T.B). Data governance for access to UK birth cohort data was provided by the METADAC data access committee, funded by ESRC, Wellcome and MRC (2015–2018: Grant Number MR/N01104X/1 2018–2020: Grant Number ES/S008349/1). This work made use of data and samples generated by the 1958 Birth Cohort (NCDS), which is managed by the Centre for Longitudinal Studies at the UCL Institute of Education, funded by the ESRC (Grant Number ES/M001660/1); blood sample collection was funded by MRC (Grant G0000934). Access to these resources was enabled via the Wellcome Trust and MRC: 58FORWARDS Grant (108439/Z/15/Z). Before 2015 biomedical resources were maintained under the Wellcome Trust and Medical Research Council 58READIE Project (Grant Numbers WT095219MA and G1001799). Work undertaken at Great Ormond Street Hospital/University College London, Institute of Child Health, is in part supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. The UK Medical Research Council also provided core funding for the MRC National Survey of Health and Development (Grant MC_UU_00019/1). The TwinsUK study is supported by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007–2013); the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London and/or the NIHR Clinical Research Facility. The SHS study received support from the National Heart, Lung, and Blood Institute (NHLBI) of the USA (under contract numbers 75N92019D00027, 75N92019D00028, 75N92019D00029 and 75N92019D00030) and previous Grants (R01HL090863, R01HL109315, R01HL109301, R01HL109284, R01HL109282 and R01HL109319 and Cooperative Agreements: U01HL41642, U01HL41652, U01HL41654, U01HL65520 and U01HL65521), from the National Institutes of Health Sciences of the USA (R01ES021367, R01ES025216, P42ES010349, P30ES009089) and from “la Caixa” Foundation (ID 100010434) (fellowship code “LCF/BQ/DR19/11740016”). The GENOA study received funding from U01HL054457, RC1HL100185, R01HL119443, R01HL133221, R01HL141292. Sí

In strong contrast to the limited repair within the mammalian central nervous system, the spinal cord of adult zebrafish is capable of regeneration following injury. Understanding the mechanism underlying neural regeneration and functional recovery in spinal cord-injured zebrafish may lead to effective therapies for human spinal cord injury (SCI). Since neuropeptide Y (NPY) plays a protective role in the pathogenesis of several neurological diseases, in the present study, the effects of NPY on neuronal repair and subsequent recovery of motor function in adult zebrafish post-SCI were evaluated. Real-time quantitative PCR (qRT-PCR), in situ hybridization (ISH) and immunostaining of NPY revealed decreased NPY expression at 12 hours (h), 6 days (d) and 21 d after SCI. Double-immunostaining for NPY and Islet-1, a motoneuron marker, showed that NPY was expressed in spinal cord motoneurons. NPY morpholino (MO) treatment resulted in suppressed locomotor recovery and axon regrowth. PCNA and Islet-1 double-staining showed suppressed motoneuron proliferation in NPY-MO zebrafish. Similar to NYP, the mRNA level for NPY1R was also expressed within motoneurons and downregulated at 12 h and 21 d after SCI. Collectively, these data suggest that NPY expression in motoneurons promotes locomotor recovery and axon regrowth in adult zebrafish, possibly by regulating motoneuron proliferation through the activation of NPY1R.

Utilizing an interdigitated microelectrode chip modified with an antibody probe, and integrating dielectrophoresis enrichment with interfacial capacitance sensing, a real-time immunosensor is presented for detection of trace level biomarkers from virus.

Protein lysine acetylation (Kac) is an important post-translational modification present in both animal and plant cells. Here, we reported the results from a proteomic investigation of Kac in soybean leaves. We totally identified 3148 acetylation sites in 1538 proteins from three biological replicates, among 59 lysine acetylation sites in core histones, represents the largest acetylome dataset in plants to date. Gene Ontology (GO) functional analysis illustrated that most of the acetylated proteins involved in metabolic processes (include carboxylic acid metabolic process, oxoacid metabolic process, nucleoside metabolic process, nucleoside phosphate metabolic process, and ribose phosphate metabolic process). KEGG pathway enrichment showed Kac plays an important role in Photosynthesis, Carbon fixation in photosynthetic organisms and Citrate cycle (TCA cycle). Meanwhile we also find a total of 17 conserved Kac motifs. All together, our study not only provides the first global and most extensive lysine acetylation analysis in soybean leaves, but also suggest that lysine acetylation is play an important and unique role in plants.

Background and AimsQueries of electronic health record (EHR) data repositories allow for automated data collection. These techniques have not been utilized in hepatology due to previous inability to capture hepatic encephalopathy (HE) grades, which are inputs for acute-on-chronic liver failure (ACLF) models. Here, we describe a methodology to utilizing EHR data to calculate rolling ACLF scores.MethodsWe examined 239 patient-admissions with end-stage liver disease 7/2014-6/2019. We mapped EHR flowsheet data to determine HE grades and calculated two longitudinally updated ACLF scores. We validated HE grades and ACLF diagnoses via chart review; and calculated sensitivity, specificity, and Cohen’s kappa.ResultsOf 239 patient-admissions analyzed, 37% women, 46% non-Hispanic White, median age 60 years, median MELD-Na at admission. Of the 239, 7% were diagnosed with NACSELD-ACLF at admission, 27% during the hospitalization, and 9% at discharge. Forty percent diagnosed with CLIF-C-ACLF at admission, 51% during the hospitalization, and 34% at discharge.From chart review of 51 admissions, we found sensitivities and specificities for any HE (grades 1-4) were 92-97% and 76-95%, respectively; for severe HE (grades 3-4) were 100% and 78-98%, respectively. Cohen’s kappa between flowsheet and chart review HE grades ranged 0.55-0.72. Sensitivities and specificities for NACSELD-ACLF diagnoses were 75-100% and 96-100%, respectively; for CLIF-C-ACLF diagnoses were 91-100% and 96-100%, respectively. We generated approximately 28 unique ACLF scores per patient per admission-day.ConclusionIn this study, we developed an informatics-based methodology for to calculate longitudinally updated ACLF scores. This opens new analytic potentials, such big data methods to develop electronic phenotypes for ACLF patients.

Background Diabetic patients are prone to osteoporosis. Both zoledronic acid and metformin have certain anti-osteoporotic effects.Here we explore the anti-osteoporotic effect of the combination of two drugs. Methods 12-week-old DB/DB mice were divided into DB/DB group, zoledronic acid group,metformin group and zoledronic acid combined with metformin group, WT mice were treated as WT group alone. The mice were killed after ten weeks. Then using Micro-ct to scan the tibia and stain the contralateral lower limbs with HE. Results First, we find that the body weight of DB/DB mice treated with metforminre stable and their blood glucose reduce.Second, after HE staining,it is observed under light microscope that there are a large number of adipocytes, few bone trabeculae, few osteoblasts and osteoclasts in the bone marrow cavity in the DB/DB group compared with the WT group, while the number of bone trabeculae in the combined treatment group is higher than that in the zoledronic acid group or metformin group, and a large number of blood cells, blood vessels and adipocytes are found in the bone marrow cavity of the combined drug group compared with the zoledronic acid group. Last, the results of Micro-ct present that, comparing with the DB/DB group and the metformin group,SMI is significantly different(P

Utilizing an interdigitated microelectrode chip modified with an antibody probe, and integrating dielectrophoresis enrichment with interfacial capacitance sensing, a strategy is presented for detection of trace level spike-protein from SARS-CoV-2 on food.

SUMMARYProtein isoforms generated by alternative splicing contribute to proteome diversity. Due to the lack of effective techniques, isoform-specific functions, expression, localization, and signaling mechanisms of endogenous proteinsin vivoare unknown for most genes. Here we report a genetic method, termedisoTarget, for blocking the expression of a targeted isoform without affecting the other isoforms and for conditional tagging the targeted isoform for multi-level analyses in select cells. ApplyingisoTargetto two mutually exclusive isoforms ofDrosophilaDscam, Dscam[TM1] and [TM2], we found that endogenous Dscam[TM1] is localized in dendrites while Dscam[TM2] is in both dendrites and axons. We demonstrate that the difference in subcellular localization between Dscam[TM1] and [TM2], rather than any difference in biochemical properties, leads to the two isoforms’ differential contributions to dendrite and axon development. Moreover, withisoTarget, we discovered that the subcellular enrichment of functional partners results in a DLK/Wallenda-Dscam[TM2]-Dock signaling cascade specifically in axons.isoTargetis an effective technique for studying how alternative splicing enhances proteome complexity.

Cryogenic cutting is becoming an attractive machining method for difficult-to-cut materials. However, it’s very difficult to analyze directly their cutting mechanism at low temperature. In order to better understand the various physical phenomena in the cryogenic cutting of titanium alloy, the Charpy impact test of Ti-6Al-4V titanium alloy at low temperatures (as low as -196 °C) was undertaken in this work. The Charpy absorbed energy of Ti-6Al-4V titanium alloy at low temperatures was investigated firstly. Then, by observing the microscopic and macroscopic morphology of the fracture, the impact properties and fracture modes of Ti-6Al-4V titanium alloy at low temperatures were analyzed. It was found that the impact toughness of Ti-6Al-4V titanium alloy reduces when the temperature decreases from 20 °C to -196 °C, and the fracture appears a tendency to become brittle. Meanwhile, three kinds of areas, i.e. shear lip area, fiber area, and radiation area, were found on the fracture morphology at each temperature. Those areas correspond to the shear fracture zone, crack initiation zone, and crack extension zone, respectively. With the decrease in temperature, the proportion of fiber area decreases, and the radiation area appears and increases gradually. However, fiber areas were still observed on the macroscopic morphology of the fracture under − 196 °C, which suggests that Ti-6Al-4V titanium alloy still has the ability to deform plastically at such low temperatures. The research result in this work provide a fundamental support for analyzing the cutting mechanism of Ti-6Al-4V titanium alloy at low temperatures.

Cardiac injury and dysfunction occur in COVID-19 patients and increase the risk of mortality. Causes are ill defined, but could be direct cardiac infection and/or ‘cytokine-storm’ induced dysfunction. To identify mechanisms and discover cardio-protective drugs, we use a state-of-the-art pipeline combining human cardiac organoids with high throughput phosphoproteomics and single nuclei RNA sequencing. We identify that ‘cytokine-storm’ induced diastolic dysfunction can be caused by a cocktail of interferon gamma, interleukin 1β and poly(I:C) and also human COVID-19 serum. Bromodomain protein 4 (BRD4) is activated along with pathology driving fibrotic and induced nitric oxide synthase genes. BRD inhibitors fully recover function in hCO and totally prevent death in a cytokine-storm mouse model. BRD inhibition decreases transcription of multiple genes, including fibrotic, induced nitric oxide synthase and ACE2, and prevention of cardiac infection with SARS-CoV2. Thus, BRD inhibitors are promising candidates to prevent COVID-19 mediated cardiac damage. Funding: We acknowledge grant and fellowship support from the National Health and Medical Research Council of Australia (J.E.H., M.J.S., C.R.E., T.B.), Heart Foundation of Australia (J.E.H.), QIMR Berghofer Medical Research Institute (J.E.H.), The Stafford Fox Foundation (E.R.P.), the Royal Children’s Hospital Foundation (E.R.P.), Australian Research Council Strategic Initiative in Stem Cell Science (Stem Cells Australia) (E.R.P. and J.E.H.) and the Medical Research Future Fund (MRFF9200008) (J.E.H., T.B., M.J.S., K.P.A.MD., C.R.E., E.R.P.). M.J.S. is supported by Health and Medical Research Council of Australia Program (APP1132519) and Investigator (APP1173958) grants. A.S. is also supported by Investigator grant (APP1173880). The Murdoch Children’s Research Institute is supported by the Victorian Government’s Operational Infrastructure Support Program. This project received support from Dynomics Inc. J.E.H. is supported by a Snow Medical Fellowship. Conflict of Interest: R.J.M., J.E.H., G.A.Q.-R., D.M.T. and E.R.P. are listed as co-inventors on pending patents held by The University of Queensland and QIMR Berghofer Medical Research Institute that relate to cardiac organoid maturation and putative cardiac regeneration therapeutics. J.E.H. is a coinventor on licensed patents held by the University of Goettingen. R.J.M, E.R.P., D.M.T., B.G. and J.E.H. are co-founders, scientific advisors and stockholders in Dynomics Inc. D.M.T. and B.G. are employees of Dynomics Inc. /Dynomics Pty Ltd. QIMR Berghofer Medical Research Institute has filed a patent on the use of BRD inhibitors. Ethical Approval: Animal work was approved by the QIMR Berghofer Medical Research Institute Animal Ethics Committee. Ethical approval for the use of human embryonic stem cells (hESCs) was obtained from QIMR Berghofer’s Ethics Committee and was carried out in accordance with the National Health and Medical Research Council of Australia (NHMRC) regulations. Procedures complied with standards set under Australian guidelines for animal welfare and experiments were subject to Monash University animal welfare ethics review (Approval #MARP/2019/13606).

Ion trap is one of the most promising candidates for quantum computing. Current schemes mainly focus on a linear chain of up to about one hundred ions in a Paul trap. To further scale up the qubit number, one possible direction is to use 2D or 3D ion crystals (Wigner crystals). In these systems, ions are generally subjected to large micromotion due to the strong fast-oscillating electric field, which can significantly influence the performance of entangling gates. In this work, we develop an efficient numerical method to design high-fidelity entangling gates in a general 3D ion crystal. We present numerical algorithms to solve the equilibrium configuration of the ions and their collective normal modes. We then give a mathematical description of the micromotion and use it to generalize the gate scheme for linear ion chains into a general 3D crystal. The involved time integral of highly oscillatory functions is expanded into a fast-converging series for accurate and efficient evaluation and optimization. As a numerical example, we show a high-fidelity entangling gate design between two ions in a 100-ion crystal, with a theoretical fidelity of 99.9\%.

Topological superconductors have long been predicted to host Majorana zero modes which obey non-Abelian statistics and have potential for realizing non-decoherence topological quantum computation. However, material realization of topological superconductors is still a challenge in condensed matter physics. Utilizing high-resolution angle-resolved photoemission spectroscopy and first-principles calculations, we predict and then unveil the coexistence of topological Dirac semimetal and topological insulator states in the vicinity of Fermi energy ($E_F$) in the titanium-based oxypnictide superconductor BaTi$_2$Sb$_2$O. Further spin-resolved measurements confirm its spin-helical surface states around $E_F$, which are topologically protected and give an opportunity for realization of Majorana zero modes and Majorana flat bands in one material. Hosting dual topological superconducting states, the intrinsic superconductor BaTi$_2$Sb$_2$O is expected to be a promising platform for further investigation of topological superconductivity., Comment: 6 pages, 4 figures

In this paper, based on the classic Chua's circuit, a charge-controlled memristor is introduced to design a novel four-dimensional chaotic system. The complex dynamics of the novel chaotic system such as equilibrium points, stability, dissipation, bifurcation diagrams, Lyapunov exponent spectra and phase portraits are investigated. By varying the initial conditions of the system, it is found from numerical simulations that the system shows some dynamics of great interests including double-wings chaotic attractors, coexisting periodic-chaotic bubbles, asymmetric and symmetric coexisting attrators. The results show that the novel circuit system has extreme multistablity., Comment: 7 pages, 9 figures

The signatures of topological superconductivity (TSC) in the superconducting materials with topological nontrivial states prompt intensive researches recently. Utilizing high-resolution angle-resolved photoemission spectroscopy and first-principles calculations, we demonstrate multiple Dirac fermions and surface states in superconductor BaSn$_3$ with a critical transition temperature of about 4.4 K. We predict and then unveil the existence of two pairs of type-\uppercase\expandafter{\romannumeral1} topological Dirac fermions residing on the rotational axis. Type-\uppercase\expandafter{\romannumeral2} Dirac fermions protected by screw axis are confirmed in the same compound. Further calculation for the spin helical texture of the observed surface states originating from the Dirac fermions give an opportunity for realization of TSC in one single material. Hosting multiple Dirac fermions and topological surface states, the intrinsic superconductor BaSn$_3$ is expected to be a new platform for further investigation of the topological quantum materials as well as TSC., 6 pages, 4 figures

Acting as a proto-oncogene, long noncoding RNAs (lncRNAs) urothelial carcinoembryonic antigen 1 (UCA1) plays a key role in the occurrence and development of several human tumors. However, the expression and biological functions of UCA1 in glioma are less known. This study discussed the expression of UCA1 in glioma and its effect on the proliferation and cell cycle of glioma cells.LncRNA UCA1 expressions in 64 glioma samples (Grade I-II in 22 cases and Grade III-IV in 42 cases, according to WHO criteria) and 10 normal brain samples were detected using real-time fluorescence quantitative PCR. On this basis, the correlations of UCA1 to clinicopathological characteristics and prognosis of glioma were assessed. Then, using qPCR, the lncRNA UCA1 expressions in glioma cell lines and astrocytes were detected. UCA1-overexpressing glioma cell lines U87 and U251 were further detected after siRNA transfection of these two cell lines, and the impact on cell proliferation and cell cycle was assessed with CCK-8 (cell counting kit-8) assay and flow cytometry method (FCM), respectively. The expression of cyclin D1, a cell cycle-related protein, was detected using Western Blot.LncRNA UCA1 expression in the glioma samples was obviously higher as compared with the normal brain samples (P 0.001), and the expression was correlated significantly with grading of the tumors (P 0.05). However, lncRNA UCA1 expression was not correlated with age, gender, tumor size and KPS score (P 0.05). After interference of UCA1 expression by siRNA transfection, the proliferation of both U251 and SHG-44 cells was inhibited (P 0.05), with more cells arrested in G0/G1 (P 0.05). Moreover, cyclin D1 expression was also downregulated considerably.LncRNA UCA1 can promote the proliferation and cell cycle progression of glioma cells by upregulating cyclin D1 transcription. So UCA1 may serve as an independent prognostic indicator and a novel therapeutic target for glioma.

Topological nodal-line semimetals (TNLSMs) are materials whose conduction and valence bands cross each other, meeting a topologically-protected closed loop rather than discrete points in the Brillouin zone (BZ). The anticipated properties for TNLSMs include drumhead-like nearly flat surface states, unique Landau energy levels, special collective modes, long-range Coulomb interactions, or the possibility of realizing high-temperature superconductivity. Recently, SrAs3 has been theoretically proposed and then experimentally confirmed to be a TNLSM. Here, we report high-pressure experiments on SrAs3, identifying a Lifshitz transition below 1 GPa and a superconducting transition accompanied by a structural phase transition above 20 GPa. A topological crystalline insulator (TCI) state is revealed by means of density functional theory (DFT) calculations on the emergent high-pressure phase. As the counterpart of topological insulators, TCIs possess metallic boundary states protected by crystal symmetry, rather than time reversal. In consideration of topological surface states (TSSs) and helical spin texture observed in the high-pressure state of SrAs3, the superconducting state may be induced in the surface states, and is most likely topologically nontrivial, making pressurized SrAs3 a strong candidate for topological superconductor., Comment: 22 pages, 5 figures

BACKGROUND: For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH [SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). OBJECTIVE: To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). METHODS: Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/ kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). RESULTS: A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. CONCLUSIONS: In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.

Flat-spectrum radio quasar PKS~1229$-$02 with a knotty and asymmetric radio morphology was identified as the optical and radio counterpart of a $��$-ray source. In this paper, we study the properties, e.g. morphology, opacity, polarization and kinematics of the jet in PKS~1229$-$02 using radio interferometry. With our results, we find that the knotty and asymmetric morphology of this source may probably shaped by the interaction between its anterograde jet and the nonuniform dense ambient medium. By reproducing a Spectral Energy Distribution of PKS~1229$-$02 with the obtained kinematic parameters, we find that the relativistic beaming effect in PKS~1229$-$02 is not strong enough to produce the reported $��$-ray emission, i.e. PKS~1229$-$02 may not be a $��$-ray AGN. The misidentification may probably due to the poor spatial resolution of the $��$-ray detector of the previous generation., Accepted by Research in Astronomy and Astrophysics

SUMMARY Protein isoforms generated by alternative splicing contribute to proteome diversity. Because of the lack of effective techniques, the isoform-specific function, expression, localization, and signaling of endogenous proteins are unknown for most genes. Here, we report a genetic method, isoTarget, for multi-purpose studies of targeted isoforms in select cells. Applying isoTarget to two isoforms of Drosophila Dscam, Dscam[TM1] and [TM2], we found that, in neurons, endogenous Dscam[TM1] is in dendrites, whereas Dscam[TM2] is in both dendrites and axons. We demonstrate that the difference in subcellular localization, rather than biochemical properties, leads to the two isoforms’ functional differences. Moreover, we show that the subcellular enrichment of functional partners results in a DLK/Wallenda-Dscam[TM2]-Dock signaling cascade in axons. We further apply isoTarget to study two isoforms of a GABA receptor to demonstrate its general applicability. isoTarget is an effective technique for studying how alternative splicing enhances proteome complexity., Graphical Abstract, In Brief Liu et al. develop a genetic method that enables the investigation of isoform-specific function, expression, localization, and signaling of endogenous proteins in select cells. Using this method, they demonstrate that the difference in subcellular localization of two isoforms of Down syndrome cell adhesion molecule leads to functional differences between them.

© 2018 Author(s). Recently, an irreversible polymorphic transition from face-centered cubic to hexagonal close-packing was surprisingly observed under high pressure in the prototype CoCrFeMnNi high-entropy alloys (HEAs) by various research groups. This unexpected phase transition brings new insights into the stability of HEAs, and its irreversibility stimulates exploration for new HEAs via high-pressure compression synthesis. However, the onset pressure for the phase transition was reported to fluctuate over a vast range from ∼7 to above 49 GPa in the reported experiments. The reason for this inconsistency remains unclear and puzzles the HEA community. To address this problem, this work systematically investigates the effects of non-hydrostaticity and grain size. Our results demonstrate that larger deviatoric stress induced by the non-hydrostaticity of the pressure medium and larger grain size of the initial sample can both promote a phase transition and, therefore, considerably depress the onset pressure.

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Learning from categorical data is a critical yet challenging task. Current research focuses on either leveraging the complex interaction between and within categorical values to generate a numerical representation, or designing a model that can tackle this types of data directly. However, both of these paradigms overlook the relation between the data characteristics and learning model hypothesis. In this paper, we propose a model-aware categorical data embedding framework that jointly reveals the intrinsic categorical data characteristics and optimizes the fitness of the representation for the follow-up learning model. An ELM-aware and a SVM-aware representation methods have been instantiated under this framework. Extensive experiments of classification with the embedded representation on 17 data sets demonstrate that the proposed framework can significantly improve the categorical data representation performance compared with state-of-the-art competitors.

Background and purpose Polymorphisms in coagulation genes have been associated with early-onset ischemic stroke. Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin−protein C system (THBD and PROCR) may similarly be associated with early-onset ischemic stroke. We explored this hypothesis utilizing a multi-stage design of discovery and replication. Methods Discovery was performed in the Genetics-of-Early-Onset Stroke (GEOS) Study, a biracial population-based case-control study of ischemic stroke among men and women aged 15–49 including 829 cases of first ischemic stroke (42.2% African-American) and 850 age-comparable stroke-free controls (38.1% African-American). Twenty-four single-nucleotide-polymorphisms (SNPs) in THBD and 22 SNPs in PROCR were evaluated. Following LD pruning (r2≥0.8), we advanced uncorrelated SNPs forward for association analyses. Associated SNPs were evaluated for replication in an early-onset ischemic stroke population (onset-age Results Among GEOS Caucasians, PROCR rs9574, which was in strong LD with 8 other SNPs, and one additional independent SNP rs2069951, were significantly associated with ischemic stroke (rs9574, OR = 1.33, p = 0.003; rs2069951, OR = 1.80, p = 0.006) using an additive-model adjusting for age, gender and population-structure. Adjusting for risk factors did not change the associations; however, associations were strengthened among those without risk factors. PROCR rs9574 also associated with early-onset ischemic stroke in the replication sample (OR = 1.08, p = 0.015), but not older-onset stroke. There were no PROCR associations in African-Americans, nor were there any THBD associations in either ethnicity. Conclusion PROCR polymorphisms are associated with early-onset ischemic stroke in Caucasians.