Miracle-dz/UniFAR-FTUs huggingface dataset:
Peptide-Major Histocompatibility Complex Class I Binding Prediction Based on Deep Learning With Novel Feature

Peptide-based vaccine development needs accurate prediction of the binding affinity between major histocompatibility complex I (MHC I) proteins and their peptide ligands. Nowadays more and more machine learning methods have been developed to predict binding affinity and some of them have become the popular tools. However most of them are designed by the shallow neural networks. Bengio said that deep neural networks can learn better fits with less data than shallow neural networks. In our case, some of the alleles only have dozens of peptide data. In addition, we transform each peptide into a characteristic matrix and input it into the model. As we know when dealing with the problem that the input is a matrix, convolutional neural network (CNN) can find the most critical features by itself. Obviously, compared with the traditional neural network model, CNN is more suitable for predicting binding affinity. Different from the previous studies which are based on blocks substitution matrix (BLOSUM), we used novel feature to do the prediction. Since we consider that the order of the sequence, hydropathy index, polarity and the length of the peptide could affect the binding affinity and the properties of these amino acids are key factors for their binding to MHC, we extracted these information from each peptide. In order to make full use of the data we have obtained, we have integrated different lengths of peptides into 15mer based on the binding mode of peptide to MHC I. In order to demonstrate that our method is reliable to predict peptide-MHC binding, we compared our method with several popular methods. The experiments show the superiority of our method.
Involvement of the eIF2α Kinase GCN2 in UV-B Responses

GCN2 (general control nonrepressed 2) is a serine/threonine-protein kinase that regulates translation in response to stressors such as amino acid and purin deprivation, cold shock, wounding, cadmium, and UV-C exposure. Activated GCN2 phosphorylates the α-subunit of the eukaryotic initiation factor 2 (eIF2) leading to a drastic inhibition of protein synthesis and shifting translation to specific mRNAs. To investigate the role of GCN2 in responses to UV-B radiation its activity was analyzed through eIF2α phosphorylation assays in mutants of the specific UV-B and stress signaling pathways of Arabidopsis thaliana. EIF2α phosphorylation was detectable 30 min after UV-B exposure, independent of the UV-B photoreceptor UV RESISTANCE LOCUS8 and its downstream signaling components. GCN2 dependent phosphorylation of eIF2α was also detectable in mutants of the stress related MAP kinases, MPK3 and MPK6 and their negative regulator map kinase phosphatase1 (MKP1). Transcription of downstream components of the UV-B signaling pathway, the Chalcone synthase (CHS) was constitutively higher in gcn2-1 compared to wildtype and further increased upon UV-B while GLUTATHIONE PEROXIDASE7 (GPX7) behaved similarly to wildtype. The UVR8 independent FAD-LINKED OXIDOREDUCTASE (FADox) had a lower basal expression in gcn2-1 which was increased upon UV-B. Since high fluence rates of UV-B induce DNA damage the expression of the RAS ASSOCIATED WITH DIABETES PROTEIN51 (RAD51) was quantified before and after UV-B. While the basal expression was similar to wildtype it was significantly less induced upon UV-B in the gcn2-1 mutant. This expression pattern correlates with the finding that gcn2 mutants develop less cyclobutane pyrimidine dimers after UV-B exposure. Quantification of translation with the puromycination assay revealed that gcn2 mutants have an increased rate of translation which was also higher upon UV-B. Growth of gcn2 mutants to chronic UV-B exposure supports GCN2’s role as a negative regulator of UV-B responses. The elevated resistance of gcn2 mutants towards repeated UV-B exposure points to a critical role of GCN2 in the regulation of translation upon UV-B.
Ice-Binding Proteins in a Chrysophycean Snow Alga: Acquisition of an Essential Gene by Horizontal Gene Transfer

All ice-associated algae examined so far have genes for ice-binding proteins (IBPs), which suggest that these proteins are essential for survival in icy habitats. The most common type of IBP, type 1 IBPs (also referred to as DUF3494 IBPs), is also found in ice-associated bacteria and fungi. Previous studies have suggested that algal IBP genes were acquired by horizontal transfer from other microorganisms (probably bacteria). However, it remains unclear whether this is also the case for algae distantly related to the ones examined so far and whether microorganisms other than bacteria could be the donors. Furthermore, there is only limited evidence that these proteins are expressed at low temperature. Here, we show that Kremastochrysopsis austriaca (Chrysophyceae), an Austrian snow alga that is not closely related to any of the ice-associated algae examined so far, also produces IBPs, although their activity was weak. Sequencing the algal genome and the transcriptomes of cells grown at 1 and 15°C revealed three isoforms of a type 1 IBP. In agreement with their putative function, the three isoforms were strongly upregulated by one to two orders of magnitude at 1°C compared to 15°C. In a phylogenetic tree, the K. austriaca IBPs were distant from other algal IBPs, with the closest matches being bacterial proteins. These results suggest that the K. austriaca IBPs were derived from a gene that was acquired from a bacterium unrelated to other IBP donor bacteria and confirm by their presence in yet another alga the essential role of algal IBPs.
Bacterial Biofilm Eradication Agents: A Current Review

Most free-living bacteria can attach to surfaces and aggregate to grow into multicellular communities encased in extracellular polymeric substances called biofilms. Biofilms are recalcitrant to antibiotic therapy and a major cause of persistent and recurrent infections by clinically important pathogens worldwide (e.g., Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus). Currently, most biofilm remediation strategies involve the development of biofilm-inhibition agents, aimed at preventing the early stages of biofilm formation, or biofilm-dispersal agents, aimed at disrupting the biofilm cell community. While both strategies offer some clinical promise, neither represents a direct treatment and eradication strategy for established biofilms. Consequently, the discovery and development of biofilm eradication agents as comprehensive, stand-alone biofilm treatment options has become a fundamental area of research. Here we review our current understanding of biofilm antibiotic tolerance mechanisms and provide an overview of biofilm remediation strategies, focusing primarily on the most promising biofilm eradication agents and approaches. Many of these offer exciting prospects for the future of biofilm therapeutics for a large number of infections that are currently refractory to conventional antibiotics.
Expression Level of HIV-1 Vif Can Be Fluctuated by Natural Nucleotide Variations in the vif-Coding and Regulatory SA1D2prox Sequences of the Proviral Genome

Vif is required for HIV-1 replication in natural target cells by counteracting host restriction factors, APOBEC3 (A3) proteins. We recently demonstrated that Vif expression level can be changed by naturally occurring single-nucleotide variations within SA1D2prox of the HIV-1 genome. We also found that levels for vif/vpr mRNAs are inversely correlated. While amino acid sequence per se is critical for functionality, Vif expression level modulated by signal sequences in its coding region is likely to be important as well. There are two splicing sites in the region involved in vpr expression. To reveal possible fluctuations of Vif-expression level, we examined SA1D2prox and vif gene by chimeric approaches using HIV-1 subtypes B and C with distinct anti-A3 activity. In this report, recombinant clones in subtype B backbone carrying chimeric sequences with respect to SA1D2prox/vif and those within the vif-coding region were generated. Of these, clones containing vif-coding sequence of subtype C, especially its 3′ region, expressed vif/Vif at a decreased level but did at an increased level for vpr/Vpr. Clones with reduced vif/Vif level grew similarly or slightly better than a parental clone in weakly A3G-positive cells but more poorly in highly A3G-expressing cells. Three clones with this property were also tested for their A3-degrading activity. One of the clones appeared to have some defect in addition to the poor ability to express vif/Vif. Taken all together, our results show that natural variations in the SA1D2prox and vif-coding region can change the Vif-expression level and affect the HIV-1 replication potential.
Assessing changes in competency of fourth-year veterinary medical students following a defined clinical experience

Assessing Changes in Competency of Fourth-Year Veterinary Medical Students Following a Defined Clinical Experience. (May 2008) Noberto Francisco Espitia, B. S. , Texas A&M University; M. S. , Texas A&M University Chair of Advisory Committee: Dr. Kim E. Dooley The purpose of this study was to measure the competency of problem solving skills of fourth-year veterinary students. The study identified two primary objectives, (a) define clinical competency for fourth-year veterinary medical students, and (b) construct an instrument to assess the student’s level of clinical competency. A faculty advisory panel identified three themes in the development of a definition of clinical competency, (a) competency was situational, (b) competency was described by ability, and (c) the definition of fourth-year student competence was descriptive within the context of primary patient care. The description of competency contributed to the establishment of parameters applied to the rubric. Student self-assessments were taken twice; initially at the beginning of the clinical rotation, and again at the end of the rotation as a post-clinical assessment. The faculty instructor provided a comparison post-clinical assessment to serve as an authentication of the reliability of the instrument.
Philadelphia Arab-American and Arab Immigrant Health NeedsAssessment

A health needs assessment was conducted on behalf of the Arab American Development Corporation to determine the health needs and behaviors that influence the health of Arab and Arab-Americans in Philadelphia, Pennsylvania. Data were collected with purposeful sampling using two methods: a health assessment survey and focus groups with key informants from the Arab and Arab-American community to contextualize the survey data. Seventy-six adult respondents completed the survey. The major problems identified were: limited access to health care due to uninsured or underinsured; potential language barriers within the health care system as many respondents spoke only Arabic in the home; overweight and obesity: cardiovascular disease and diabetes; risk of residential lead exposure; and symptoms of stress and depression. Iraqi refugees were at additional risk of mental health problems related to experiencing or observing torture in Iraq.
Power Characterization of RAMs. An Experimental Approach

In this paper, we present a flexible methodology for characterizing the power consumption of RAM architectures. The proposed approach overcomes previous limitations by attending to second order effects of internal circuit capacitances and does not rely on technological parameters. The experimental results have been used to provide a set of design guidelines to lead the system designer in the early implementation of RAM hierarchies with low-power constraints. This paper presents the description of the experimental methodology as well as the analysis of some of the collected results. Finally, a typical design case is described.
Association between metabolic body composition status and risk for impaired renal function: A cross-sectional study

Background The risk for obesity-related disorders is proportional to the visceral region and had been observed to be highly related with impaired renal function. In the current study, we aimed to evaluate renal function impairment, according to sex, age, and different status of metabolic body composition. Methods We retrospectively collected from the medical records the basic information and metabolic titers of Chinese adults (13,373 men and 10,175 women) who underwent health checkup from 2013 to 2016. The population was divided into four groups, according to metabolic body composition, including metabolic healthy norms-weight (MHNW), metabolic healthy obesity (MHO), metabolic unhealthy norms-weight (MUNW), and metabolic unhealthy obesity (MUO). The categorical data were compared among the groups and logistic regression analyses were conducted to investigate the association between metabolic body composition status and risk for renal function impairment. Results Across all ages in both sexes, the odds ratios (OR) for renal function impairment were higher in the MHO, MUNW, and MUO groups than in the MHNW group, except for women <45 years old in the MUNW group. However, after adjustment, the trend was no longer significant in all groups under 45 years old. For individuals >45 years old, the relatively high risk for renal function impairment remained significantly associated with the MUNW group (OR 2.95, 95% CI 2.02–4.30 in men and OR 1.95, 95% CI 1.35–2.82 in women) and MUO group (OR 2.33, 95% CI 1.82–3.00 in men and OR 2.67, 95% CI 2.04–3.48 in women). Conclusion Impaired renal function was independently associated with the status of metabolic obesity. However, the trend was only observed in individuals >45 years old, with significant sex difference.
Liposomal Cytarabine as Cancer Therapy: From Chemistry to Medicine

Cancer is the second leading cause of death worldwide. The main modality to fight against cancer is surgery, radiotherapy, and chemotherapy, and more recently targeted therapy, gene therapy and immunotherapy, which play important roles in treating cancer patients. In the last decades, chemotherapy has been well developed. Nonetheless, administration of the drug is not always successful, as limited drug dosage can reach the tumor cells. In this context, the possibility to use an encapsulated anti-cancer drug may potentially solve the problem. Liposomal cytarabine is a formulation with pronounced effectiveness in lymphomatous meningitis and reduced cardiotoxicity if compared to liposomal anthracyclines. Thus, the future liposomal cytarabine use could be extended to other diseases given its reduction in cytotoxic side effects compared to the free formulation. This review summarizes the chemistry and biology of liposomal cytarabine, with exploration of its clinical implications.
Multimodal, Multilingual Grapheme-to-Phoneme Conversion for Low-Resource Languages

Grapheme-to-phoneme conversion (g2p) is the task of predicting the pronunciation of words from their orthographic representation. His- torically, g2p systems were transition- or rule- based, making generalization beyond a mono- lingual (high resource) domain impractical. Recently, neural architectures have enabled multilingual systems to generalize widely; however, all systems to date have been trained only on spelling-pronunciation pairs. We hy- pothesize that the sequences of IPA characters used to represent pronunciation do not capture its full nuance, especially when cleaned to fa- cilitate machine learning. We leverage audio data as an auxiliary modality in a multi-task training process to learn a more optimal inter- mediate representation of source graphemes; this is the first multimodal model proposed for multilingual g2p. Our approach is highly ef- fective: on our in-domain test set, our mul- timodal model reduces phoneme error rate to 2.46%, a more than 65% decrease compared to our implementation of a unimodal spelling- pronunciation model—which itself achieves state-of-the-art results on the Wiktionary test set. The advantages of the multimodal model generalize to wholly unseen languages, reduc- ing phoneme error rate on our out-of-domain test set to 6.39% from the unimodal 8.21%, a more than 20% relative decrease. Further- more, our training and test sets are composed primarily of low-resource languages, demon- strating that our multimodal approach remains useful when training data are constrained.
Measles Virus Ribonucleoprotein Complexes Rapidly Spread across Well-Differentiated Primary Human Airway Epithelial Cells along F-Actin Rings

The ability of viral particles to directly spread cell to cell within the airways without particle release is considered to be highly advantageous to many respiratory viruses. Our previous studies in well-differentiated, primary human airway epithelial cells suggest that measles virus (MeV) spreads cell to cell by eliciting the formation of intercellular membrane pores. Based on a newly generated ribonucleoprotein complex (RNP) “tracker” virus, we document by live-cell microscopy that MeV RNPs move along F-actin rings before entering a new cell. Thus, rather than diffusing through the cytoplasm of a newly infected columnar cell, RNPs take advantage of the cytoskeletal infrastructure to rapidly spread laterally across the human airway epithelium. This results in rapid horizontal spread through the epithelium that does not require particle release. ABSTRACT Measles virus (MeV) is a highly contagious human pathogen that continues to be a worldwide health burden. One of the challenges for the study of MeV spread is the identification of model systems that accurately reflect how MeV behaves in humans. For our studies, we use unpassaged, well-differentiated primary cultures of airway epithelial cells from human donor lungs to examine MeV infection and spread. Here, we show that the main components of the MeV ribonucleoprotein complex (RNP), the nucleocapsid and phosphoprotein, colocalize with the apical and circumapical F-actin networks. To better understand how MeV infections spread across the airway epithelium, we generated a recombinant virus incorporating chimeric fluorescent proteins in its RNP complex. By live cell imaging, we observed rapid movement of RNPs along the circumapical F-actin rings of newly infected cells. This strikingly rapid mechanism of horizontal trafficking across epithelia is consistent with the opening of pores between columnar cells by the viral membrane fusion apparatus. Our work provides mechanistic insights into how MeV rapidly spreads through airway epithelial cells, contributing to its extremely contagious nature. IMPORTANCE The ability of viral particles to directly spread cell to cell within the airways without particle release is considered to be highly advantageous to many respiratory viruses. Our previous studies in well-differentiated, primary human airway epithelial cells suggest that measles virus (MeV) spreads cell to cell by eliciting the formation of intercellular membrane pores. Based on a newly generated ribonucleoprotein complex (RNP) “tracker” virus, we document by live-cell microscopy that MeV RNPs move along F-actin rings before entering a new cell. Thus, rather than diffusing through the cytoplasm of a newly infected columnar cell, RNPs take advantage of the cytoskeletal infrastructure to rapidly spread laterally across the human airway epithelium. This results in rapid horizontal spread through the epithelium that does not require particle release.
Characterization of a Na+–Ca2+ exchanger in podocytes

BACKGROUND Knowledge about Ca(2+) extrusion mechanisms in podocytes is limited. The aim of the study was to test whether a Na(+)-Ca(2+) exchanger (NCX) is present in differentiated podocytes and if so to examine its regulatory properties. METHODS Intracellular Ca(2+) concentration ([Ca(2+)](i)) and intracellular pH were measured microspectrofluorometrically in single podocytes. Expression of NCX mRNA was studied by reverse transcription-polymerase chain reaction. NCX protein expression was investigated by immunocytochemistry. RESULTS Substitution of extracellular Na(+) (from 145 to 0, 5, 10, 20, and 30 mM) with N-methyl-D-glucamine resulted in a Na(+) concentration-dependent, reversible increase of [Ca(2+)](i). Complete extracellular Na(+) substitution (0 Na(+)) increased [Ca(2+)](i) reversibly from 95+/-5 to 275+/-16 and back to 66+/-5 nM (n=205). Raising the intracellular Na(+) concentration by application of 50 micro M monensin increased [Ca(2+)](i) from 105+/-22 to 192+/-45 nM (n=12). The [Ca(2+)](i) response induced by a low Na(+) concentration required extracellular Ca(2+) and did not correlate with changes of intracellular pH. The effect was blocked by the NCX inhibitor benzamil (IC(50) approximately 100 nM). Neither flufenamate (100 micro M, n=6), a blocker of non-selective cation channels, nor Hoe 694 (1 micro M, n=6), an inhibitor of the Na(+)-H(+) exchanger, did significantly influence the [Ca(2+)](i) response induced by extracellular Na(+) depletion. Activation of protein kinase C (PKC) by short-term application (5 min) of phorbol 12-myristate-13-acetate (PMA; 10 nM, n=4; 100 nM, n=7) inhibited Na(+)-Ca(2+) exchange, whereas PKC inhibition by long-term incubation (24 h) with PMA (100 nM, n=9) or bisindolylmaleimide I (100 nM, n=11) both increased Na(+)-Ca(2+) exchange, respectively. Expression of NCX mRNA was detected both in cultured differentiated podocytes and in podocytes directly pulled off from glomeruli ex vivo. NCX protein expression was detected by immunocytochemistry. In a different series of experiments, we studied the potential involvement of the exchanger in podocyte injury induced by the aminonucleoside puromycin. Pre-treatment of podocytes with 0.3 mM puromycin for 24 h significantly reduced the [Ca(2+)](i) response induced by extracellular Na(+) depletion (n=56). Compared with mRNA expression of the housekeeping gene GAPDH, NCX mRNA expression was significantly reduced by puromycin. CONCLUSION Our results demonstrate the presence of a Na(+)-Ca(2+) exchanger in podocytes and its regulation by PKC. Inhibition of Na(+)-Ca(2+) exchange by puromycin may contribute to podocyte injury in PAN nephrosis.
Development of an app for lung cancer survivors (iEXHALE) to increase exercise activity and improve symptoms of fatigue, breathlessness and depression

Exercise‐based self‐management interventions are recommended for lung cancer survivors and can provide physical, psychosocial and emotional relief. Mobile health technologies can encourage self‐management; however, currently, no cancer‐related app addresses exercise‐specific needs of lung cancer survivors. This paper details the design, development and testing of an exercise app for lung cancer survivors (iEXHALE), which aims to increase exercise activity and improve symptoms.
Synthesis of PdM (M=Zn, Cd, ZnCd) Nanosheets with Unconventional Face-Centered Tetragonal Phase as Highly Efficient Electrocatalysts for Ethanol Oxidation.

Recently, crystal-phase engineering has been emerging as a promising strategy to tune the physicochemical properties of noble metal catalysts and further improve their catalytic performance. However, the synthesis of noble metal catalysts with unconventional crystal phase as well as desired composition and morphology still remains a great challenge. Herein, a series of PdM (M=Zn, Cd, ZnCd) nanosheets (NSs) with thickness less than 5 nm has been synthesized via a facile one-pot wet-chemical method. In particular, different from the conventional face-centered cubic (fcc) phase, PdM NSs possess unconventional face-centered tetragonal (fct) phase. As a proof-of-concept application, the fct PdZn NSs exhibit significantly enhanced mass activity and stability in ethanol oxidation reaction, compared to the pure Pd NSs and commercial Pd black catalyst.