Miracle-dz/UniFAR-FTUs huggingface dataset:
Classification of Complete Proteomes of Different Organisms and Protein Sets Based on Their Protein Distributions in Terms of Some Key Attributes of Proteins

The existence of complete genome sequences makes it important to develop different approaches for classification of large-scale data sets and to make extraction of biological insights easier. Here, we propose an approach for classification of complete proteomes/protein sets based on protein distributions on some basic attributes. We demonstrate the usefulness of this approach by determining protein distributions in terms of two attributes: protein lengths and protein intrinsic disorder contents (ID). The protein distributions based on L and ID are surveyed for representative proteome organisms and protein sets from the three domains of life. The two-dimensional maps (designated as fingerprints here) from the protein distribution densities in the LD space defined by ln(L) and ID are then constructed. The fingerprints for different organisms and protein sets are found to be distinct with each other, and they can therefore be used for comparative studies. As a test case, phylogenetic trees have been constructed based on the protein distribution densities in the fingerprints of proteomes of organisms without performing any protein sequence comparison and alignments. The phylogenetic trees generated are biologically meaningful, demonstrating that the protein distributions in the LD space may serve as unique phylogenetic signals of the organisms at the proteome level.
Acid-sensing ion channels interact with and inhibit BK K+ channels

Acid-sensing ion channels (ASICs) are neuronal non-voltage-gated cation channels that are activated when extracellular pH falls. They contribute to sensory function and nociception in the peripheral nervous system, and in the brain they contribute to synaptic plasticity and fear responses. Some of the physiologic consequences of disrupting ASIC genes in mice suggested that ASIC channels might modulate neuronal function by mechanisms in addition to their H+-evoked opening. Within ASIC channel's large extracellular domain, we identified sequence resembling that in scorpion toxins that inhibit K+ channels. Therefore, we tested the hypothesis that ASIC channels might inhibit K+ channel function by coexpressing ASIC1a and the high-conductance Ca2+- and voltage-activated K+ (BK) channel. We found that ASIC1a associated with BK channels and inhibited their current. Reducing extracellular pH disrupted the association and relieved the inhibition. BK channels, in turn, altered the kinetics of ASIC1a current. In addition to BK, ASIC1a inhibited voltage-gated Kv1.3 channels. Other ASIC channels also inhibited BK, although acidosis-dependent relief of inhibition varied. These results reveal a mechanism of ion channel interaction and reciprocal regulation. Finding that a reduced pH activated ASIC1a and relieved BK inhibition suggests that extracellular protons may enhance the activity of channels with opposing effects on membrane voltage. The wide and varied expression patterns of ASICs, BK, and related K+ channels suggest broad opportunities for this signaling system to alter neuronal function.
Antibiotic overprescribing : Still a major concern Antibiotic overuse

Despite universal agreement that antibiotic overprescribing is a problem, the practice continues to vex us. Antibiotic use—whether appropriate or not—has been linked to rising rates of antimicrobial resistance, disruption of the gut microbiome leading to Clostridium difficile infections, allergic reactions, and increased health care costs (TABLE 1). And yet, physicians continue to overprescribe this class of medication. A 2016 Centers for Disease Control and Prevention (CDC) report estimates that at least 30% of antibiotics prescribed in US outpatient settings are unnecessary. Another report cites a slightly higher figure across a variety of health care settings. Pair these findings with the fact that there are currently few new drugs in development to target resistant bacteria, and you have the potential for a post-antibiotic era in which common infections could become lethal. In 2003, the CDC launched its “Get Smart: Know When Antibiotics Work” program, focused on decreasing inappropriate antibiotic use in the outpatient setting. In 2014, the White House released the National Action Plan for Combating Antibiotic-Resistant Bacteria with a goal of decreasing inappropriate outpatient antibiotic use by 50% and inappropriate inpatient use by 20% by 2020. And, on an international level, the World Health Organization (WHO) developed a 5-year strategic framework in 2015 for implementing its Global Action Plan on Antimicrobial Resistance. Family practitioners are on the front lines of this battle. Here’s what we can do now.
Effect of oral versus intramuscular Vitamin D replacement in apparently healthy adults with Vitamin D deficiency

Context: A number of controversies exist regarding appropriate treatment strategy for Vitamin D deficiency. Aims: The aim of this study was to investigate the efficacy of equivalent doses of oral cholecalciferol (60,000 IU weekly for 5 weeks) versus intramuscular (IM) cholecalciferol (300,000 IU) in correcting Vitamin D deficiency in apparently healthy volunteers working in a hospital. Settings and Design: Prospective randomized open-label single institution study. Subjects and Methods: This study enrolled 40 apparently healthy adults with Vitamin D deficiency into 2 arms. The oral cholecalciferol group (n = 20) received oral cholecalciferol 60,000 IU weekly for 5 weeks while the IM cholecalciferol group (n = 20) received a single injection of cholecalciferol 300,000 IU. The main outcome measure was serum 25-hydroxyvitamin D (25OHD) levels at baseline, 6 and 12 weeks after the intervention. Statistical Analysis Used: Differences in serum 25OHD and other biochemical parameters at baseline and follow-up were analyzed using general linear model. Results: Mean 25OHD level at baseline was 5.99 ± 1.07 ng/mL and 7.40 ± 1.13 ng/mL (P = 0.332) in the oral cholecalciferol and IM cholecalciferol group, respectively. In the oral cholecalciferol group, serum 25OHD level was 20.20 ± 1.65 ng/mL at 6 weeks and 16.66 ± 1.36 ng/mL at 12 weeks. The corresponding serum 25OHD levels in the IM cholecalciferol group were 20.74 ± 1.81 ng/mL and 25.46 ± 1.37 ng/mL at 6 and 12 weeks, respectively. At 12 weeks, the mean 25OHD levels in IM cholecalciferol group was higher as compared to the oral cholecalciferol group (25.46 ± 1.37 vs. 16.66 ± 1.36 ng/mL; P< 0.001). Conclusions: Both oral and IM routes are effective for the treatment of Vitamin D deficiency. 25-hydroxyvitamin D levels in the IM cholecalciferol group showed a sustained increase from baseline.
Short fused? associations between white matter connections, sex steroids, and aggression across adolescence

Functional neuroimaging studies in adults show that aggression involves reduced brain communication between subcortical and cortical areas dedicated to motivation and control, respectively. Prior research indicates that sex steroid hormone production during adolescence negatively influences the rapid development of white matter connectivity between subcortical and cortical areas during adolescence and may potentiate aggression. Here, we tested this hypothesis in 258 participants between 8 and 25 years of age by using Diffusion Weighted Imaging to examine the microstructure of white matter connections within the fronto‐temporal‐subcortical network. Trait aggression was measured using the Buss Perry Aggression Questionnaire and testosterone and estradiol levels were measured in saliva. Results indicated that higher levels of testosterone were associated with less white matter integrity within the fronto‐temporal‐subcortical network (i.e., higher mean diffusivity [MD] longitudinal [LD], and radial diffusivity [RD]). Furthermore, lower fractional anisotropy and higher MD, LD, and RD values within this network increased expressive forms of aggression and reduced inhibited forms of aggression (hostility). Our study indicates higher levels of testosterone relating to lower quality of structural cortical‐subcortical connectivity, arguably resulting in a shift from inhibited towards expressive forms of aggression. Our data adds evidence to the idea that aggressive tendencies are subcortically driven, but individuals with relatively high testosterone might have lower structural connectivity within cortical control areas, resulting in a stronger tendency to act on these aggressive tendencies. Hum Brain Mapp 36:1043–1052, 2015. © 2014 Wiley Periodicals, Inc.
Immunolocalization of G Protein‐Coupled Estrogen Receptor in the Pig Epididymis

The presence of estrogen in the genital ducts of different mammalian species has been extensively studied and the estrogen influence on the functional activity of the male genital tract has been hypothesized. Conversely, very few data have been reported on pig excurrent ducts: the localization of classical estrogen receptors (ERα and ERβ) is scarcely known, while the expression of the G protein‐coupled receptor (GPER1), a membrane estrogen receptor, is still unknown in pig. The aim of the present study was to evaluate GPER1 expression in the different regions of the mature pig epididymis, using immunohistochemistry, western blot and RT‐PCR analyses. The results showed that GPER1 is mainly expressed in the epithelial cells of the corpus epididymis compared to the caput and the cauda, while muscle cells are moderately immunostained and stromal cells are unstained. The presence of GPER1 was confirmed by Western blot and RT‐PCR analyses. In our study, we have demonstrated for the first time the GPER1 expression in male porcine epididymis, revealing a new mediator of estrogen signaling at this site. In conclusion, these new data suggest that estrogen action via GPER1 may contribute to sperm maturation in the corpus and sperm protection/storage in the cauda. Interestingly, the presence of GPER1 in the muscle layer may be indicative of a possible GPER1 involvement in the estrogen regulation of duct contractility. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.
Outlet: Outsourcing Wearable Computing to the Ambient Mobile Computing Edge

Wearable devices, <italic>e.g.,</italic> smart glass and watch, could achieve fine-grained human-centric sensing nowadays, but still lack sufficient capacities to execute sophisticated data processing algorithms. This paper presents <italic>Outlet</italic> to explore the feasibility to leverage the available computing resources from user’s ambience, <italic>e.g.,</italic> from nearby smart phones, tablets, computers, Wi-Fi APs, and so on, to form a mobile computing edge. We can then outsource wearable computing tasks to this ambient edge to locally digest the sensory data for prompt user feedback and reaction, as it is perfectly located in user’s vicinity. The <italic>Outlet</italic> design avoids the traditional offloading to the remote clouds, whose performance may highly depend on the high-speed Internet connectivity and availability. To enable the <italic>Outlet</italic> design, we identify three major challenges: context dependence, scattered resources, and resource dynamics, and propose a series of key techniques to address each of them. To examine <italic>Outlet</italic> ’s performance, we conduct extensive trace-driven evaluations and the results indicate promising performance achieved by <italic>Outlet</italic>, <italic>e.g.,</italic> mostly within 97.6% to 99.5% closeness of the optimal performance and always outperforming the baseline approach under various system settings.
An RNAi Screen Identifies New Genes Required for Normal Morphogenesis of Larval Chordotonal Organs

The proprioceptive chordotonal organs (ChO) of a fly larva respond to mechanical stimuli generated by muscle contractions and consequent deformations of the cuticle. The ability of the ChO to sense the relative displacement of its epidermal attachment sites likely depends on the correct mechanical properties of the accessory (cap and ligament) and attachment cells that connect the sensory unit (neuron and scolopale cell) to the cuticle. The genetic programs dictating the development of ChO cells with unique morphologies and mechanical properties are largely unknown. Here we describe an RNAi screen that focused on the ChO’s accessory and attachment cells and was performed in 2nd instar larvae to allow for phenotypic analysis of ChOs that had already experienced mechanical stresses during larval growth. Nearly one thousand strains carrying RNAi constructs targeting more than 500 candidate genes were screened for their effects on ChO morphogenesis. The screen identified 31 candidate genes whose knockdown within the ChO lineage disrupted various aspects of cell fate determination, cell differentiation, cellular morphogenesis and cell-cell attachment. Most interestingly, one phenotypic group consisted of genes that affected the response of specific ChO cell types to developmental organ stretching, leading to abnormal pattern of cell elongation. The ‘cell elongation’ group included the transcription factors Delilah and Stripe, implicating them for the first time in regulating the response of ChO cells to developmental stretching forces. Other genes found to affect the pattern of ChO cell elongation, such as αTub85E, β1Tub56D, Tbce, CCT8, mys, Rac1 and shot, represent putative effectors that link between cell-fate determinants and the realization of cell-specific mechanical properties.
Atrophy patterns in cerebral amyloid angiopathy with and without cortical superficial siderosis

Objective To investigate differential atrophy patterns based on the presence of cortical superficial siderosis (cSS) and the role of cSS in predicting amyloid positivity in memory clinic patients fulfilling the diagnostic criteria for probable cerebral amyloid angiopathy (CAA). Methods We retrospectively collected data from 44 cognitively impaired patients with probable CAA who underwent 3-dimensional, T1-weighted MRIs (cSS+, n = 27; cSS−, n = 17). Amyloid-positive patients with Alzheimer disease (AD) (n = 56) and amyloid-negative cognitively normal participants (n = 34) were recruited as controls. Among the patients with CAA who underwent amyloid-PET scans (75.0%), we investigated whether amyloid-negative cases were unevenly distributed based on cSS presentation. APOE genotypes, Mini-Mental State Examination scores, and cortical atrophy pattern along with hippocampal volume were compared across groups. Results Ten patients with probable CAA presented amyloid negativity and all of them belonged to the cSS− group (58.8%). Compared to the cSS− group, the cSS+ group presented higher APOE ε4 frequency, worse memory dysfunction, and lower hippocampal volume. Compared with cognitively normal participants, the cSS+ group exhibited atrophy in the precuneus, posterior cingulate, parietotemporal, superior frontal, and medial temporal areas, a pattern similar to AD-specific atrophy. The cSS− group exhibited atrophy in the parietotemporal, superior frontal, and precentral regions. Conclusion Our findings imply that the current version of the Boston criteria may not be sufficient enough to remove non-CAA cases from a cognitively impaired population, especially in the absence of cSS. Patients with probable CAA presenting cSS appear to reflect a CAA phenotype that shares pathologic hallmarks with AD, providing insight into the CAA-to-AD continuum.
Exploring the Feasibility of Adsorptive Removal of ZnO Nanoparticles from Wastewater

This study tested the feasibility of adsorptive removal of ZnO nanoparticles using activated carbon from wastewater. The effects of pH (5, 6, 7, 8, and 9) and nanoparticle/activated carbon concentration ratios (10, 1, 0.1, 0.01, and 0.001) on the removal were studied in batch kinetic studies in both deionized water and wastewater. The adsorption capacity of activated carbon for ZnO nanoparticles were found to be 9.3 ± 0.8 mg/g (93% removal) and 8.2 ± 3.7 mg/g (85% removal) at 640 and 780 min in deionized and wastewater respectively at optimum conditions (pH 8; 10g/L activated carbon concentration, 100mg/L ZnO nanoparticle concentration). The rate constant was lowest at ratio 0.01 and pH 8, and highest at ratio 10 and 1 and pH 5 and 6. Pseudo‐second‐order and the Weber‐Morris model best described the adsorption process. Characterization analysis also confirmed the deposition of ZnO nanoparticles onto activated carbon. Overall activated carbon successfully removed ZnO nanoparticles using the adsorptive process.
CYP1A1 Relieves Lipopolysaccharide-Induced Inflammatory Responses in Bovine Mammary Epithelial Cells

The expression of cytochrome P4501A1 (CYP1A1) enzyme is changed in various organs during the host response to inflammation or infection, leading to alterations in the metabolism of endogenous and exogenous compounds. Results of this study showed that CYP1A1 expression was significantly downregulated in the mammary tissue of bovine with mastitis, in inflammatory epithelial cells (INEs) extracted from the tissue, and in lipopolysaccharide- (LPS-) induced INEs compared with their corresponding counterparts. Overexpression of CYP1A1 in bovine mammary epithelial cells alleviated the LPS-induced inhibition of epithelial proliferation, abated the LPS-induced increase of gene expression and protein secretion of inflammatory cytokine tumor necrosis factor-α and interleukin-6, and attenuated the LPS-induced activation of NF-κB signaling. These findings suggest that CYP1A1 has immense potential in the regulation of inflammatory responses in bovine mammary epithelial cells during mastitis and may serve as a useful therapeutic target in mitigating injuries caused by inflammatory overreaction.
Modeling and stability analysis for multiple parallel grid-connected inverters system

The Phase-Locked Loop (PLL) plays an important role in stability of three-phase grid-connected inverter system. However, the existing literature all neglect the influence of PLL when analyzing the stability of multiple parallel grid-connected inverters system. So this paper builds the model of the system and analyzes the system stability with considering the influence of PLL. Besides, this paper demonstrates that there exist admittance coupling among multiple parallel inverters. Thus, owing to the coupling effect, it can not obtain the multiple parallel grid-connected inverters admittance by accumulating each inverter admittance in parallel directly. Modeling the inverter mutual coupling is presented in this paper. The correctness of the modeling approach and stability analysis are verified by experimental results with RT-LAB.
A hydromechanical and biochemical model of stomatal conductance

A mathematical model of stomatal conductance is presented. It is based on whole-plant and epidermal hydromechanics, and on two hypotheses: (1) the osmotic gradient across guard cell membranes is proportional to the concentration of ATP in the guard cells; and (2) the osmotic gradient that can be sustained per unit of ATP is proportional to the turgor pressure of adjacent epidermal cells. In the present study, guard cell [ATP] is calculated using a previously published model that is based on a widely used biochemical model of C 3 mesophyll photosynthesis. The conductance model for Vicia faba L. is parameterized and tested As with most other stomatal models, the present model correctly predicts the stomatal responses to variations in transpiration rate, irradiance and intercellular CO 2 . Unlike most other models, however, this model can predict the transient stomatal opening often observed before conductance declines in response to decreases in humidity, soil water potential, or xylem conductance. The model also explicitly accommodates the mechanical advantage of the epidermis and correctly predicts that stomata are relatively insensitive to the ambient partial pressure of oxygen, as a result of the assumed dependence on ATP concentration.
The Dorsolateral Prefrontal Cortex Plays a Role in Self-Initiated Elaborative Cognitive Processing during Episodic Memory Encoding: rTMS Evidence

During episodic memory encoding, elaborative cognitive processing can improve later recall or recognition. While multiple studies examined the neural correlates of encoding strategies, few studies have explicitly focused on the self-initiation of elaborative encoding. Repetitive transcranial magnetic stimulation (rTMS), a method which can transiently disrupt neural activity, was administered during an associative encoding task. rTMS was either applied to the left dorsolateral prefrontal cortex (DLPFC) or to the vertex (a control region not involved in memory encoding) during presentation of pairs of words. Pairs could be semantically related or not related. Two encoding instructions were given, either cueing participants to analyze semantic relationships (cued condition), or to memorize the pair without any specific strategy cues (the self-initiated condition). Participants filled out a questionnaire regarding their use of memory strategies and performed a cued-recall task. We hypothesized that if the DLPFC plays a role in the self-initiation of elaborative encoding we would observe a reduction in memory performance in the self-initiated condition, particularly for related. We found a significant correlation between the effects of rTMS and strategy use, only in the self-initiated condition with related pairs. High strategy users showed reduced performance following DLPFC stimulation, while low strategy users tended to show increased recall following DLPFC stimulation during encoding. These results suggest the left DLPFC may be involved in the self-initiation of memory strategy use, and individuals may utilize different neural networks depending on their use of encoding strategies.
Analyses of selected safety endpoints in phase 1 and late-phase clinical trials of anti-PD-1 and PD-L1 inhibitors: prediction of immune-related toxicities

Purpose Anti-PD1 and PD-L1 antibodies are associated with immune-related adverse effects (irAEs). This analysis aims to assess the discrepancies between frequencies of irAEs observed in phase 1 trials with those seen in late-phase trials and to evolve the field of drug development. Methods PubMed search was conducted for articles published until December of 2016. Trials needed to have at least one of the study arms consisting of nivolumab, pembrolizumab or atezolizumab monotherapy. Trials were matched based on compound used and similarity of populations. All toxicities were reported as frequencies and percentages. P-values to assess differences between matches and non-matches of phase 1 and late-phase trials and between early and late-phase trials themselves were obtained via Fisher's exact test. Odds ratios were obtained via logistic regression. Results Our search yielded 15 late-phase and 10 matching phase 1 trials; n = 4823 and n = 1650, respectively. The most common AEs seen in phase 1 trials were also observed in late-phase trials except for phase 1 trials (median n = 118) with < 118 patients (P = 0.048). Rash, pruritus, and diarrhea were the most frequently irAEs reported. Only colitis was more frequent in late-phase studies (P = 0.045). Conclusion Toxicities of anti-PD-1 and PD-L1 observed in phase 1 trials and late-phase trials are similar. There is positive correlation between phase 1 trial sample size and concordance of toxicity frequencies seen in late-phase studies. In conclusion, current immunotherapy phase 1 trials are appropriate in assessing safety profile of anti-PD-1 and PD-L1 antibodies.