jimnoneill/paper-to-field-training huggingface dataset:
Using Energy-Minimization Profiles to Measure Protein Resistance to Drugs

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

A mutation to the amino acid sequence of a protein can cause a biomolecule to be resistant to the intended effects of a drug. Assessing the changes of a drug's efficacy in response to mutations via mutagenesis wet-lab experiments is prohibitively time consuming for even a single point mutation, let alone for all possible mutations. Existing approaches for inferring mutation-induced drug resistance are available, but all of them reason about mutations of residues at or very near the protein-drug interface. However, there are examples of mutations far away from the region where the ligand binds, but which nonetheless render a protein resistant to the effects of the drug. We present a proof-of-concept computational pipeline that generates in silico the set of all possible single point mutations in a protein-ligand complex. We assess drug resistance via energy profiles for short runs of molecular dynamics of the mutants. We assess the impact of mutations far away from the protein-drug interface and provide case studies for exploring how amino acid substitutions both near and far away from where the ligand interacts with a protein target have a stabilizing or destabilizing effect on the protein-drug complex.
Intergenerational Transmission of Posttraumatic Orientation to Bodily Signals Following Child Maltreatment

Field: Psychology (Social Sciences)

Recent studies have indicated that CM (child maltreatment) may influence individuals' perception of their bodies, often resulting in a posttraumatic orientation to bodily signals (OBS). Given the intricate relationship between bodily and interpersonal experiences, it is hypothesized that posttraumatic OBS may be intergenerationally transmitted. However, knowledge regarding this phenomenon, and its underlying mechanisms, remains limited. Two studies tested (a) the link between CM and posttraumatic OBS, mediated by posttraumatic stress (PTS) symptoms and attachment security, and (b) the intergenerational transmission of a posttraumatic OBS following CM among dyads of parents and their young adult offspring. The first study included 445 young adults (mean age = 352, SD = 10.2), and the second study included 393 dyads (parents’ mean age = 58, SD = 5.91; offspring's mean age = 27, SD = 3.91). The participants completed self-reported questionnaires. Study 1 found that posttraumatic OBS was associated with CM, through the mediation of PTS symptoms (indirect effect = 0.15, p = .005), and insecure attachment (indirect effects between 0.132 and 1.44, p < .006). The second study found two pathways of intergenerational transmission. The first pathway showed indirect paths between parents’ CM exposure and offspring’s posttraumatic OBS, through parents’ reaction to CM (PTS symptoms, anxious attachment, and avoidant attachment) and posttraumatic OBS (indirect effects between 0.006 and 0.013, p < .039). The second pathway revealed indirect links between parents’ CM exposure and offspring’s posttraumatic OBS, through parents’ and offspring’s reaction to CM (indirect effects between 0.006 and 0.56, p < .015). The study’s findings add empirical evidence that posttraumatic OBS is a significant implication of CM. The second study illuminates the intergenerational transmission of a posttraumatic OBS following parental CM exposure, uncovering PTS symptoms, and insecure attachment styles as potential underlying mechanisms.
Leontodon longirostris genome draft 418Mb

Field: Agricultural and Biological Sciences (Life Sciences)

1-Leontodon-genome-draft-418Mb.fasta: sequences in FASTA format of the 410,019 scaffolds and contigs that were considered the 418 Mb genome draft for Leontodon longirostris.
2-Maker853GeneModels-in1007LongestFragments.gff: the 853 MAKER-based gene models deduced from the 1007 longest (>10 kb) fragments of the 418 Mb genome draft.
3-FunctionalAnnot-MakerGeneModels-in1007LongestFragments.tsv: Functional annotation of the predicted 853 proteins deduced from MAKER-based gene models.
4-Reconstructed-472ChimaericModels.fasta: sequences in FASTA format of the 472 GeneAssembler-based gene models reconstructed using the short (<10 kb) genome fragments from the 418 Mb genome draft.
5-ShortGenomeFragments-in472ChimaericModels.tsv: list of contigs and scaffolds from the 418 Mb genome draft that were used to reconstruct each chimaeric, GeneAssembler-based gene model.
6-GeneAssemblerChimaericModels-in472ChimaericModels.gff: annotation of the 472 GeneAssember-based, chimaeric gene models by genome location.
7-FunctionalAnnotation472ChimaericModels.xlsx: comprehensive functional annotation of the 472 GeneAssember-based, chimaeric gene models, including the predicted protein length, the number of exons identified in that gene model, a fragmentation index (0-1 range, where 0 means that all exons in the model come from one single sequence contig, and 1 means that each exon comes from a different contig) and the human-readable description of the predicted protein sequence taken from the GFF file.
Claisened Hexafluoro Inhibits Metastatic Spreading of Amoeboid Melanoma Cells

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

Metastatic melanoma is characterized by poor prognosis and a low free-survival rate. Thanks to their high plasticity, melanoma cells are able to migrate exploiting different cell motility strategies, such as the rounded/amoeboid-type motility and the elongated/mesenchymal-type motility. In particular, the amoeboid motility strongly contributes to the dissemination of highly invasive melanoma cells and no treatment targeting this process is currently available for clinical application. Here, we tested Claisened Hexafluoro as a novel inhibitor of the amoeboid motility. Reported data demonstrate that Claisened Hexafluoro specifically inhibits melanoma cells moving through amoeboid motility by deregulating mitochondrial activity and activating the AMPK signaling. Moreover, Claisened Hexafluoro is able to interfere with the adhesion abilities and the stemness features of melanoma cells, thus decreasing the in vivo metastatic process. This evidence may contribute to pave the way for future possible therapeutic applications of Claisened Hexafluoro to counteract metastatic melanoma dissemination.
Concerted Differential Changes of Helical Dynamics\nand Packing upon Ligand Occupancy in a Bacterial Chemoreceptor

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

Transmembrane\nreceptors are central components of the chemosensory\nsystems by which motile bacteria detect and respond to chemical gradients.\nAn attractant bound to the receptor periplasmic domain generates conformational\nsignals that regulate a histidine kinase interacting with its cytoplasmic\ndomain. Ligand-induced signaling through the periplasmic and transmembrane\ndomains of the receptor involves a piston-like helical displacement,\nbut the nature of this signaling through the >200 Å four-helix\ncoiled coil of the cytoplasmic domain had not yet been identified.\nWe performed single-molecule Förster resonance energy transfer\nmeasurements on Escherichia coli aspartate\nreceptor homodimers inserted into native phospholipid bilayers enclosed\nin nanodiscs. The receptors were labeled with fluorophores at diagnostic\npositions near the middle of the cytoplasmic coiled coil. At these\npositions, we found that the two N-helices of the homodimer were more\ndistant, that is, less tightly packed and more dynamic than the companion\nC-helix pair, consistent with previous deductions that the C-helices\nform a stable scaffold and the N-helices are dynamic. Upon ligand\nbinding, the scaffold pair compacted further, while separation and\ndynamics of the dynamic pair increased. Thus, ligand binding had asymmetric\neffects on the two helical pairs, shifting mean distances in opposite\ndirections and increasing the dynamics of one pair. We suggest that\nthis reflects a conformational change in which differential alterations\nto the packing and dynamics of the two helical pairs are coupled.\nThese coupled changes could represent a previously unappreciated mode\nof conformational signaling that may well occur in other coiled-coil\nsignaling proteins.
A termination checker for Isabelle Hoare logic

Field: Computer Science (Physical Sciences)

Abstract. Hoare logic is widely used for software specification and verification. Frequently we need to prove the total correctness of a program: to prove that the program not only satisfies its pre- and post-conditions but also terminates. We have implemented a termination checker for Isabelle’s Hoare logic. The tool can be used as an oracle, where Isabelle accepts its claim of termination. The tool can also be used as an Isabelle method for proving the entire total correctness specification. For many loop structures, verifying the tool’s termination claim within Isabelle is essentially automatic. 1
Blood pressure changes alter tracheobronchial cough: computational model of the respiratory-cough network and in vivo experiments in anesthetized cats

Field: Neuroscience (Life Sciences)

We tested the hypothesis, motivated in part by a coordinated computational cough network model, that alterations of mean systemic arterial blood pressure (BP) influence the excitability and motor pattern of cough. Model simulations predicted suppression of coughing by stimulation of arterial baroreceptors. In vivo experiments were conducted on anesthetized spontaneously breathing cats. Cough was elicited by mechanical stimulation of the intrathoracic airways. Electromyograms (EMG) of inspiratory parasternal, expiratory abdominal, laryngeal posterior cricoarytenoid (PCA), and thyroarytenoid muscles along with esophageal pressure (EP) and BP were recorded. Transiently elevated BP significantly reduced cough number, cough-related inspiratory, and expiratory amplitudes of EP, peak parasternal and abdominal EMG, and maximum of PCA EMG during the expulsive phase of cough, and prolonged the cough inspiratory and expiratory phases as well as cough cycle duration compared with control coughs. Latencies from the beginning of stimulation to the onset of cough-related diaphragm and abdominal activities were increased. Increases in BP also elicited bradycardia and isocapnic bradypnea. Reductions in BP increased cough number; elevated inspiratory EP amplitude and parasternal, abdominal, and inspiratory PCA EMG amplitudes; decreased total cough cycle duration; shortened the durations of the cough expiratory phase and cough-related abdominal discharge; and shortened cough latency compared with control coughs. Reduced BP also produced tachycardia, tachypnea, and hypocapnic hyperventilation. These effects of BP on coughing likely originate from interactions between barosensitive and respiratory brainstem neuronal networks, particularly by modulation of respiratory neurons within multiple respiration/cough-related brainstem areas by baroreceptor input.
Data from Phase I/II Study of Oncolytic HSV<sup>GM-CSF</sup> in Combination with Radiotherapy and Cisplatin in Untreated Stage III/IV Squamous Cell Cancer of the Head and Neck

Field: Medicine (Health Sciences)

<div>Abstract<p><b>Purpose:</b> This study sought to define the recommended dose of JS1/34.5-/47-/GM-CSF, an oncolytic herpes simplex type-1 virus (HSV-1) encoding human granulocyte-macrophage colony-stimulating factor (GM-CSF), for future studies in combination with chemoradiotherapy in patients with squamous cell cancer of the head and neck (SCCHN).</p><p><b>Experimental Design:</b> Patients with stage III/IVA/IVB SCCHN received chemoradiotherapy (70 Gy/35 fractions with concomitant cisplatin 100 mg/m<sup>2</sup> on days 1, 22, and 43) and dose-escalating (10<sup>6</sup>, 10<sup>6</sup>, 10<sup>6</sup>, 10<sup>6</sup> pfu/mL for cohort 1; 10<sup>6</sup>, 10<sup>7</sup>, 10<sup>7</sup>, 10<sup>7</sup> for cohort 2; 10<sup>6</sup>, 10<sup>8</sup>, 10<sup>8</sup>, 10<sup>8</sup> for cohort 3) JS1/34.5-/47-/GM-CSF by intratumoral injection on days 1, 22, 43, and 64. Patients underwent neck dissection 6 to 10 weeks later. Primary end points were safety and recommended dose/schedule for future study. Secondary end points included antitumor activity (radiologic, pathologic). Relapse rates and survival were also monitored.</p><p><b>Results</b>: Seventeen patients were treated without delays to chemoradiotherapy or dose-limiting toxicity. Fourteen patients (82.3%) showed tumor response by Response Evaluation Criteria in Solid Tumors, and pathologic complete remission was confirmed in 93% of patients at neck dissection. HSV was detected in injected and adjacent uninjected tumors at levels higher than the input dose, indicating viral replication. All patients were seropositive at the end of treatment. No patient developed locoregional recurrence, and disease-specific survival was 82.4% at a median follow-up of 29 months (range, 19-40 months).</p><p><b>Conclusions:</b> JS1/34.5-/47-/GM-CSF combined with cisplatin-based chemoradiotherapy is well tolerated in patients with SCCHN. The recommended phase II dose is 10<sup>6</sup>, 10<sup>8</sup>, 10<sup>8</sup>, 10<sup>8</sup>. Locoregional control was achieved in all patients, with a 76.5% relapse-free rate so far. Further study of this approach is warranted in locally advanced SCCHN. Clin Cancer Res; 16(15); 4005–15. ©2010 AACR.</p></div>
Abstract 813: Exercise Attenuates Heart failure in Cardiac Lipoprotein Lipase/CD36 Double Knockout Mice

Field: Medicine (Health Sciences)

The adult heart derives 70% of its ATP from fatty acids (FA), many of which are delivered via lipoprotein lipase (LpL) mediated hydrolysis of lipoproteins, followed by diffusion or uptake through FAT/CD36. In heart failure, metabolism shifts towards increased glucose utilization and less FA oxidation. Mechanisms by which exercise improves heart function in heart failure are not fully understood. We hypothesized that exercise mediated improvements in heart function require improved substrate uptake via induction of LpL and CD36. We created 4 groups of mice ( n=9 –10/group ): control, CD36 Knockout ( Cd36 −/− ), cardiac LpL Knockout (hLpL0), and Double Knockout (DKO, hLpL0/ Cd36 −/− ). Heart lipid uptake, measured using radiolabeled human VLDL and mouse chylomicrons, showed a significant reduction in cardiac VLDL-TG uptake in hLpL0 (49±23%), Cd36 −/− (64±17%) and DKO (76±5%; p Cd36 −/− mice, but was not statistically significant. Reduced uptake of chylomicron TG-derived FA however, was only found in DKO. Interestingly, loss of cardiac LpL reduced cardiac VLDL-cholesteryl ester (CE) uptake in hLpL0 (81%) and DKO (73%) (p CD36 −/− mice. Similarly, vitamin A (RE) uptake was reduced in both hLpL0 and DKO mice but not in CD36 −/− . Mice were assigned to sedentary or exercise (swimming) groups at 14 weeks. Cardiac function, assessed by echocardiography, was reduced in sedentary DKO mice (%fractional shortening (%FS) 26.6 vs 37.6 in controls; p Cd36 −/− mice. Surprisingly, exercise training in DKO mice led to an improvement in %FS (33.6; p=0.09) and normalization of heart failure gene expression (p
The Effectiveness of Acupuncture in Diabetic Peripheral Neuropathy

Field: Medicine (Health Sciences)

This is a preliminary study of acupuncture effectiveness in treatment of peripheral neuropathy in type-2 diabetic patients at Sao Hai Chaloemphrakiat Hospital in Sao Hai district, Saraburi province, Thailand. The study was conducted in 48 patients divided into two groups: one with acupuncture plus medications as an experimental group and the other with only medications as control group. The drugs used included amitriptyline hydrochloride 10mg/day and vitamin B12, while seven main acupuncture points were Quchi (LI 11), Weiwanxianshu (EX-B3), Shenshu (BL 23), Guanyuan (CV 4), Zusanli (ST 36), Hegu (LI 4), and Sanyinjiao (SP 6). Four peripheral neurological examination scores were used to indicate the treatment results, namely Neuropathy Symptom Score (NSS), Score Scale of Clinical Symptom for DPN (SS-DPN), Michigan Diabetes Neuropathy Score (MDNS) and Neuropathy Disability Score (NDS). The results showed that acupuncture combined with medications could markedly reduce numbness in the lower extremities better than medications alone (RR = 0.223, 95% CI = 0.062-0.794). In evaluating reaction by NSS, patients in the control group showed the effective rate of 8.32%, but 91.52% in the experimental group, whereas by SS-DPN, there was improvement in effectiveness in both groups, with the control group at the rate of 45.76%, and 79.04 % in the experimental group. However, it showed no improvement in effectiveness or 0% in the control group while the experimental group revealed the effective rate of 95.68% when evaluating by MDNS. Lastly, in evaluating by NDS, patients with medications alone had the effective rate of 37.45%, but the experimental group 91.52%. Nevertheless, the patient satisfaction with the quality of life was at the same level for both groups.
The influence of homocysteine on the expressions of ABCA1 and ACAT1 in the formation of THP-1 monocyte-derived foam cells

Field: Medicine (Health Sciences)

Objective To investigate the influence of homocysteine(Hcy) on the expressions of ATP-binding cassette transporter A1(ABCA1) and acylcoenzyme A: cholesterol acyltransferase-1(ACAT1) in the formation of THP-1 monocyte-derived foam cells.Methods THP-1 monocytes were cultured with phorbol myristate acetate(PMA) and oxidized low density lipoprotein(ox-LDL) so as to copy foam cell model,and then intervened by 50,100,200 and 500 μmol/L Hcy and 100 μmol/L Hcy+folic acid+vitamin B12(Vit B12) for 72 h.The control group(not intervened by Hcy) was set.The formation of foam cells was analyzed by the oil red O staining.The intracellular total cholesterol(TC),free cholesterol(FC) and cholesterol ester(CE) of foam cells were measured by enzymatic end point determination in order to observe the effects of Hcy on foam cell CE efflux.Fluorescence quantitative reverse transcription polymerase chain reaction(RT-PCR) detected the expressions of ABCA1 mRNA and ACAT1 mRNA.Western blotting tested the expressions of ABCA1 protein and ACAT1 protein.Results After the intervention of Hcy,oil red O staining showed that the formation of foam cells was increased significantly,but not in dose-effect relationship.The positive percentage of experimental group(50,100,200 and 500 μmol/L Hcy and 100 μmol/L Hcy+folic acid+Vit B12) was higher than that of control group(P0.05,P0.01).The 100 μmol/L Hcy group was the most significant one(P0.01).The outflow of foam intracellular TC,FC and CE was reduced significantly compared with control group(P0.05),and the 100 μmol/L Hcy group was the most significant one(P0.01).The 100 μmol/L Hcy+folic acid+Vit B12 group showed that the formation of foam cells was decreased,whereas the cholesterol efflux was increased compared with 100 μmol/L Hcy group.RT-PCR showed that the expression of ABCA1 mRNA was decreased,but ACAT1 mRNA was increased,and the 100 μmol/L Hcy group was the most significant effect one(P0.01).Western blotting showed that the expressions of ABCA1 protein and ACAT1 protein were consistent with mRNA expression.Conclusions Hcy reduces the expression of ABCA1,in the contrast,the expression of ACAT1 is increased.Both of them promote the formation of foam cells.
Learning to Generate Samples from Noise through Infusion Training

Field: Computer Science (Physical Sciences)

In this work, we investigate a novel training procedure to learn a generative model as the transition operator of a Markov chain, such that, when applied repeatedly on an unstructured random noise sample, it will denoise it into a sample that matches the target distribution from the training set. The novel training procedure to learn this progressive denoising operation involves sampling from a slightly different chain than the model chain used for generation in the absence of a denoising target. In the training chain we infuse information from the training target example that we would like the chains to reach with a high probability. The thus learned transition operator is able to produce quality and varied samples in a small number of steps. Experiments show competitive results compared to the samples generated with a basic Generative Adversarial Net
Occupational stress of professional nurses in South Africa

Field: Health Professions (Health Sciences)

The objective of this study was to identify occupational stressors for professional nurses in South Africa. A cross-sectional survey design was used. A stratified random sample of professional nurses (n=818; females = 97%) in hospitals in South Africa was used. The Nursing Stress Indicator (NSI) was administrated together with a biographical questionnaire. Three internally consistent stress factors, namely lack of organisational support, job demands and nursing-specific demands, were extracted. The most severe stressors for professional nurses included staff shortages, inadequate salaries and excessive administrative duties. Work overload, fellow workers not doing their job, health risks posed by contact with patients and demands of patients were also identified as stressors. Stress was associated with specific factors, including age, position (rank), care unit, and work experience.
Correlation Between TIGIT Expression on CD8+ T Cells and Higher Cytotoxic Capacity

Field: Immunology and Microbiology (Life Sciences)

Abstract Persistent exposure to antigen leads to T-cell exhaustion and immunologic dysfunction. We examined the immune exhaustion markers T cell immunoglobulin and ITIM domain (TIGIT) and programmed cell death protein 1 (PD-1) in human immunodeficiency virus (HIV)–infected and healthy individuals and the relationship with cytotoxic CD8+ T-lymphocyte activity. Frequencies of TIGIT but not PD-1 were positively correlated with CD8+ T-lymphocyte activity in HIV-aviremic and healthy individuals; however, there was no correlation in HIV-viremic individuals. Transcriptome analyses revealed up-regulation of genes associated with antiviral immunity in TIGIT+CD8+ versus TIGIT−CD8+ T cells. Our data suggest that TIGIT+CD8+ T cells do not necessarily represent a state of immune exhaustion and maintain an intrinsic cytotoxicity in HIV-infected individuals.