Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutation screen of the GAD2 gene and association study of alcoholism in three populations

Synaptic actions of γ‐amino butyric acid (GABA) have been implicated in many facets of ethanol's effects and risk for alcoholism. We examined whether variation in glutamate decarboxylase‐2 (GAD2), a gene encoding for a major enzyme in the synthesis of GABA, contributes to risk of alcohol dependence (AD). We screened GAD2 for sequence variants using dHPLC in a population of 96 individuals. Several single nucleotide polymorphisms (SNPs), including four rare non‐synonymous polymorphisms, were identified. Thirteen SNPs located in the GAD2 gene were genotyped in a sample of 113 Russian males with AD and 100 Russian male controls. These analyses revealed a modest association between the functional GAD2 −243 A > G SNP (rs2236418) and AD (allele P = 0.038, genotype P = 0.008). An additional sample of 138 Russian males with AD were genotyped for the GAD2 −243 A > G. These analyses supported an association of this polymorphism with AD (combined sample allele P = 0.038, genotype P = 0.0009). We extended these findings to additional populations: a sample of 538 college students assessed using the AUDIT and a sample of European–American (EA) AD subjects (n = 235) and controls (n = 310). Analyses in these populations did not support a role for GAD2 in alcoholism. In summary, the results of an extensive search for an association of GAD2 with AD suggest that variation in GAD2 is not a major risk factor for AD in EAs. The functional promoter GAD2 −243 A > G variant may influence risk for AD in some populations, or its role may be limited to susceptibility to severe AD. © 2006 Wiley‐Liss, Inc.
Measuring the true height of water films on surfaces

Measuring the level of hydrophilicity of heterogeneous surfaces and the true height of water layers that form on them in hydrated conditions has a myriad of applications in a wide range of scientific and technological fields. Here, we describe a true non-contact mode of operation of atomic force microscopy in ambient conditions and a method to establish the source of apparent height. A dependency of the measured water height on operational parameters is identified with water perturbations due to uncontrolled modes of imaging where intermittent contact with the water layer, or even the surface, might occur. In this paper we show how to (1) determine when the water is being perturbed and (2) distinguish between four different interaction regimes. Each of the four types of interaction produces measurements ranging from fractions of the true height in one extreme to values which are as large as four times the real height in the other. We show the dependence of apparent height on the interaction regime both theoretically and empirically. The agreement between theory and experiment on a BaF2(111) sample displaying wet and un-wet regions validates our results.
Evaluation of the effects of aerobic training during hemodialysis on autonomic heart rate modulation in patients with chronic renal disease

Abstract Introduction: Chronic renal disease (CRD) affects a large portion of the population and is directly related to cardiovascular problems and hypertension, among others. Studies show that heart rate variability is directly affected by these problems. Physical-oriented exercises have been shown to be of fundamental importance in improving the adverse effects to dialysis treatment. Objective: To analyze the effects of aerobic training during hemodialysis on autonomic heart rate modulation in patients with CRD. Method: Experimental study of an open, single group clinical trial. In this clinical trial, patients with CRD will initially undergo international physical activity questionnaire and kidney disease quality of life short form protocols, as well as monitoring of heart rate systolic, and diastolic blood pressure. After evaluation of the initial parameters, patients will undergo an aerobic exercise program for 12 weeks, in 3 weekly sessions, lasting 30 minutes a session. These evaluations will allow for a greater control of the disease, and monitoring of any improvements in the quality of life and self-esteem of these patients. Ethics and dissemination: This study was approved following the guidelines and norms that regulate research involving human subjects, in Resolution No. 466/12 of the National Health Council. It was approved by the Research Ethics Committee of the Faculty of Juazeiro do Norte, with the number 1962 092. All patients who agree to participate in the research will sign the informed consent form. The results will be disseminated through peer-reviewed journal articles and conferences.
Volumetric imaging parameters are significant for predicting the pathological complete response of preoperative concurrent chemoradiotherapy in local advanced rectal cancer

Abstract Preoperative concurrent chemoradiotherapy (CCRT) as the standard treatment for locally advanced rectal cancer (LARC) has been widely used in clinic. Its efficiency influences the prognosis and the selection of subsequent treatment. The current criteria for evaluating the prognosis of patients with extremely sensitive preoperative CCRT include the clinical complete remission response (cCR) and pathological complete response (pCR), but those with cCR may not necessarily achieve pCR, and the pCR can be confirmed only after surgery. Some scholars believe that patients with pCR after CCRT can be categorized as ‘watch and wait’. Therefore, it is extremely important to find a way to predict the pCR status of patients before therapy. In this study, we examined the expression of stem cell markers and obtained direct and derivative volumetric imaging parameters before treatment. Subsequently, these factors and the general clinical data were adopted into a regression model, and the correlation between them and the pCR was analyzed. We found that the pCR of LARC was positively correlated with tumor compactness (TC), whereas it was negatively correlated with approximate tumor volume (ATV), real tumor volume (RTV), total surface area of the tumor (TSA) and tumor maximum longitudinal length (TML). In these meaningful predictors, the positive predictive values and the negative predictive values of TC were 74.73% and 94.61%, respectively. Compared with other possible predictors, TC is the most encouraging predictor of pCR. Our findings provide a way for clinicians to predict the sensitivity of preoperative CCRT and will help to select individualized treatment options for LARC patients.
An NLRP3 inflammasome-triggered cytokine storm contributes to Streptococcal toxic shock-like syndrome (STSLS)

Infection with the Streptococcus suis (S. suis) epidemic strain can cause Streptococcal toxic shock-like syndrome (STSLS), which is characterized by a cytokine storm, dysfunction of multiple organs and a high incidence of mortality despite adequate treatment. Despite some progress concerning the contribution of the inflammatory response to STSLS, the precise mechanism underlying STSLS development remains elusive. Here, we use a murine model to demonstrate that caspase-1 activity is critical for STSLS development. Furthermore, we show that inflammasome activation by S. suis is mainly dependent on NLRP3 but not on NLRP1, AIM2 or NLRC4. The important role of NLRP3 activation in STSLS is further confirmed in vivo with the NLRP3 inhibitor MCC950 and nlrp3-knockout mice. By comparison of WT strain with isogenic strains with mutation of various virulence genes for inflammasome activation, Suilysin is essential for inflammasome activation, which is dependent on the membrane perforation activity to cause cytosolic K+ efflux. Moreover, the mutant strain msly (P353L) expressing mutagenic SLY without hemolytic activity was unable to activate the inflammasome and does not cause STSLS. In summary, we demonstrate that the high membrane perforation activity of the epidemic strain induces a high level of NLRP3 inflammasome activation, which is essential for the development of the cytokine storm and multi-organ dysfunction in STSLS and suggests NLRP3 inflammasome as an attractive target for the treatment of STSLS.
Training data ... ... 0 1 1 0 1 0 0 1 Convolution and pooling layers fc layers Hashing layer Regularized center loss Bike Car Bird Dicycle Semantic embedding loss

Hashing has been widely utilized for fast image retrieval recently. With semantic information as supervision, hashing approaches perform much better, especially when combined with deep convolution neural network(CNN). However, in practice, new concepts emerge every day, making collecting supervised information for re-training hashing model infeasible. In this paper, we propose a novel zero-shot hashing approach, called Discrete Similarity Transfer Network (SitNet), to preserve the semantic similarity between images from both “seen” concepts and new “unseen” concepts. Motivated by zero-shot learning, the semantic vectors of concepts are adopted to capture the similarity structures among classes, making the model trained with seen concepts generalize well for unseen ones. We adopt a multi-task architecture to exploit the supervised information for seen concepts and the semantic vectors simultaneously. Moreover, a discrete hashing layer is integrated into the network for hashcode generating to avoid the information loss caused by real-value relaxation in training phase, which is a critical problem in existing works. Experiments on three benchmarks validate the superiority of SitNet to the state-of-the-arts.
Non-rigid dense bijective maps

We present a novel approach to the computation of dense correspondence maps between shapes in a non-rigid setting. The problem is defined in terms of functional correspondences. We deal with the non-injectivity of the solution of the functional map framework due to the under-determinedness of the original problem. Key to our approach is the injectivity constraint plugged directly into the problem to optimize, achieved casting it as an assignment problem. This leads to an iterative process which yields a high quality bijective map between the shapes. In the experimental section we present both quantitative and qualitative results, showing that the proposed approach is competitive with the current state-of-the-art on quasi-isometric shape matching benchmarks.
THE EFFECT OF DIETARY INTERVENTION ON CHANGES IN TOTAL CHOLESTEROL, BLOOD PRESSURE AND WEIGHT IN A CAMBRIDGE STUDY

The study examined the impact of dietary advice on cholesterol reduction, to see whether diet was more effective when preceded by a cholesterol estimation. A total of 635 healthy individuals aged between 40 and 60 years attended a general practice cardiovascular risk screening in 1990. All subjects had their blood pressure, body mass index and smoking history recorded, and 50% were randomised to cholesterol measurement. Two years later, all individuals were invited to participate in a follow‐up screening and 356 individuals took part (158 men, 198 women). All the above estimations were undertaken in 100% of attendees. The mean total cholesterol levels and weight declined in the subjects who were given dietary advice and had their cholesterol measured, while the mean cholesterol level increased slightly in subjects who did not receive dietary advice but had their cholesterol measured. There was a significant increase in diastolic blood pressure in all patients. The figures for reported smokers decreased from 22.4% to 19.4% in men and 19.4% to 8.4% in women. The results suggest that dietary advice can achieve a sustained reduction in cholesterol levels, but may require the stimulus of a prior cholesterol estimation.
Network perspective of science and technology policy research community in Taiwan

This study proposes a way of mapping Sci-Tech policy research community by quantitatively analyzing Sci-Tech policy research projects funded by Taiwan government in recent thirty years. Taiwans Sci-Tech policy rsearch networks composed by research community and knowledge distribution are quantitatively investigated by the use of network theory and Taiwans Sci-Tech policy research map is created to obtain the purpose of two-dimensional visualization. The 3-dimensional networks and two-dimensional knowledge maps on the basis of the Taiwans Sci-Tech policy research projects can be depicted differently by choosing different information as network actor, e.g. institute, project investigator or keyword, to reflect Sci-Tech policy research structures in micro, meso, and macro-levels, respectively. Sci-Tech policy research projects are retrieved from GRB (Government Research Bulletin) database which archives research projects sponsored by Taiwan government. A total of 143 projects are retrieved in this study, most of research projects (59%) belong to the field of management, economics, and other (social). It can be observed that more Sci-Tech policy research projects in the field of technology management have been funded, and also the coverage of fields has been increased since 2000. This indicates not only the emergence but also the interdisciplinary phenomenon of Sci-Tech policy research in Taiwan.
Evaluation of methods for estimating distribution grid stress due to future installations of photovoltaic units

The rising number of photovoltaic (PV) units in distribution grids will necessitate significant investments in grid reinforcement. In research and practice, various methods are employed to estimate grid stress due to future installations of PV units. In this paper, the most common methods are presented and their accuracy is evaluated in a comparative case study. We find that methods assuming homogeneous plant sizes significantly underestimate grid stress. A probabilistic approach that assumes heterogeneous PV plant sizes provides considerably more accurate estimates.
Implementing an integrated community based health systems strengthening approach to improve HIV survival in Northern Togo

ABSTRACT To disseminate lessons learned from the implementation experience of a public-private sector partnership, we describe a comprehensive HIV/AIDS program including 5-year survival outcomes for individuals who initiated antiretroviral therapy (ART) treatment in Togo from 2010 to 2015. A retrospective case study analysis was conducted from a cohort of patients receiving ART at an HIV/AIDS care clinic in Kara Region, Togo. Kaplan-Meier curves with Log rank tests were used to compare estimated survival curves by demographic and clinical characteristics. Associations were described between survival probability and age, gender, World Health Organization (WHO) disease stage, and timing of ART initiation. Cox proportional hazard model was used to determine predictors of mortality. After approximately five-years since ART initiation (1780 days), there were 114 deaths, with a survival probability of 75.3% (95% CI: 70.3–80.6%). Participants with advanced WHO disease stage were more likely at risk of death relative to patients categorized as WHO Stage 1, with Stage 4 approximately 9 times more likely (aHR 9.22, 95% CI 4.29–19.84). Our study suggests that delivering comprehensive HIV care through a private-public partnership may serve as a model to expand and improve HIV/AIDS care as well as high quality primary care.
Analysis of nonnucleoside drug-resistant variants of human immunodeficiency virus type 1 reverse transcriptase

A number of chemically distinct nonnucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) have been reported. Several lines of evidence, including the isolation of RT mutants that show cross resistance, suggest that, despite their structural diversity, many of these inhibitors bind to a common site on HIV-1 RT. We have recently reported that, on the basis of analyses of HIV-1/HIV-2 chimeras, the natural product calanolide A may interact with a different site or sites in HIV-1 RT. We have used BspMI cassette mutagenesis to prepare a collection of HIV-1 RT mutants that show resistance to the known members of the general class of nonnucleoside inhibitors. This collection of mutants can be used to determine whether a new drug will show cross resistance with known inhibitors and to define amino acid positions critical for the action of the drugs. The mutants were used to analyze calanolide A, 1H,3H-thiazolo[3,4-a]benzimidazole(4i), and the acyclic nucleoside analog 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine. These analyses suggest that all three drugs interact with HIV-1 RT within the previously defined common binding site for nonnucleoside inhibitors. However, the drugs respond differently to the panel of drug-resistant HIV-1 RTs, indicating that while the binding sites of the drugs overlap they are not identical.
Zinc ions increase GH signaling ability through regulation of available plasma membrane‐localized GHR

It is well known that zinc ion (Zn2+) can regulate the biological activity of growth hormone (GH). However, until now, the mechanism by which Zn2+ regulates GH biological activity remains unclear. In the current study, we first performed molecular docking between Zn2+ and porcine GH (pGH) using computational biology. We then explored the effect of Zn2+ on the GH signaling ability in the cell model expressing porcine growth hormone receptor (GHR). It was found that the phosphorylation levels of Janus kinase 2, signal transducers and activators of transcription 5/3/1, and GHR increased significantly under Zn2+ treatment, indicating that Zn2+ can enhance the signaling ability of GH/GHR. On this basis, we further explored how Zn2+ regulates the biological activity of GH/GHR. The results showed that downregulation and turnover of GHR changed under Zn2+/pGH treatment. Zn2+ enhanced the membrane residence time of pGH/GHR and delayed GHR downregulation. Further investigation showed that the internalization dynamic of pGH/GHR was changed by Zn2+, which prolonged the residence time of pGH/GHR in the cell membrane. These factors acted together to upregulate the signaling of GH/GHR. This study lays a foundation for further exploration of the biological effects of Zn2+ on GH.
Toward a best practice framework in business model innovation

While business model innovation as driver of success is well established, limited research has been conducted on how companies can systematically innovate their business models. Against this background this paper consolidates the state of both academic and practitioner-oriented literature on business model innovation. Based on a systematic review of literature published over the past 19 years, we synthesize our findings into a multi-dimensional framework of business model innovation.
Reward Expectation Modulates Local Field Potentials, Spiking Activity and Spike-Field Coherence in the Primary Motor Cortex

Abstract Reward modulation (M1) could be exploited in developing an autonomously updating brain-computer interface (BCI) based on a reinforcement learning (RL) architecture. For an autonomously updating RL-based BCI system, we would need a reward prediction error, or a state-value representation from the user’s neural activity, which the RL-BCI agent could use to update its BCI decoder. In order to understand the multifaceted effects of reward on M1 activity, we investigated how neural spiking, oscillatory activities and their functional interactions are modulated by conditioned stimuli related reward expectation. To do so, local field potentials (LFPs) and single/multi-unit activities were recorded simultaneously and bilaterally from M1 cortices while four non-human primates (NHPs) performed cued center-out reaching or grip force tasks either manually using their right arm/hand or observed passively. We found that reward expectation influenced the strength of α (8–14 Hz) power, α-γ comodulation, α spike-field coherence (SFC), and firing rates (FRs) in general in M1. Furthermore, we found that an increase in α-band power was correlated with a decrease in neural spiking activity, that FRs were highest at the trough of the α-band cycle and lowest at the peak of its cycle. These findings imply that α oscillations modulated by reward expectation have an influence on spike FR and spike timing during both reaching and grasping tasks in M1. These LFP, spike, and spike-field interactions could be used to follow the M1 neural state in order to enhance BCI decoding (An et al., 2018; Zhao et al., 2018).
The Detection of the Pipe Crack Utilizing the Operational Modal Strain Identified from Fiber Bragg Grating

The small and light-weight pipeline is widely used in hydraulic system for aerospace engineering. The crack is one of the most common failures in the pipelines so that its incipient detection can further avoid the catastrophic damage of the piping system. The electrical and piezoelectric sensors are conventionally used for the structural health monitoring (SHM), while these are not suitable for the cascaded pipelines in harsh environment because the added mass will change the modal characteristics of the cascaded pipelines. The Fiber Bragg Grating (FBG) sensor with light-weight, multiplexed, and anti-electromagnetic interference properties, are employed to obtain the modal strain transmissibility with a novel diagram of the operational modal analysis (OMA). Based on the OMA an enhanced damage indicator is proposed to detect the crack. After going through analytical modeling, finite element modeling (FEM) and its corresponding experiments, it is concluded that the presented method is effective and accurate to detect and locate the crack.
An Effective, Economical and Ultra-Fast Method for Hydrophobic Modification of NCC Using Poly(Methylhydrogen)Siloxane

Poor compatibility between nanocellulose crystals (NCCs) and major polymers has limited the application of NCC as bio-reinforcements. In this work, an effective and ultra-fast method was investigated to significantly improve the hydrophobicity of NCC by using poly(methylhydrogen)siloxane (PMHS) as modifier. PMHS possessed amounts of reactive –Si–H groups and hydrophobic –CH3 groups. The former groups were reactive with the hydroxyl groups of NCC, while the latter groups afforded NCC very low surface energy. As the weight ratio of PMHS to NCC was only 0.0005%, the hydrophobicity of NCC was significantly improved by increasing the water contact angle of NCC from 0° to 134°. The effect of weight ratio of PMHS to NCC and the hydrogen content of –Si–H in PMHS on the hydrophobicity and thermal stability was investigated in detail by Fourier transform infrared spectroscopy (FTIR), (X-ray Diffraction) XRD and (thermogravimetric analysis) TGA. The results indicated that PMHS chains were covalently grafted onto NCC and PMHS modification improved the thermal stability of NCC.
Proteasome-dependent degradation of intracellular carbamylated proteins

Carbamylation, which corresponds to the binding of isocyanic acid to the amino groups of proteins, is a nonenzymatic post-translational modification responsible for alterations of protein structural and functional properties. Tissue accumulation of carbamylation-derived products and their role in pathological processes such as atherosclerosis or chronic renal failure have been previously documented. However, few studies have focused on the carbamylation of intracellular proteins and their subsequent role in cellular aging. This study aimed to determine the extent of intracellular protein carbamylation, its impact on cell functions and the ability of cells to degrade these modified proteins. Fibroblasts were incubated with cyanate or urea and the carbamylation level was evaluated by immunostaining and homocitrulline quantification. The results showed that carbamylated proteins accumulated intracellularly and that all proteins were susceptible. The presence of intracellular carbamylated proteins did not modify cell proliferation or type I collagen synthesis nor did it induce cell senescence, but it significantly decreased cell motility. Fibroblasts were able to degrade carbamylated proteins through the ubiquitin-proteasome system. In conclusion, intracellular proteins are susceptible to carbamylation but their accumulation does not seem to deeply affect cell function, owing largely to their elimination by the ubiquitin-proteasome system.