gebhart/patrepeval huggingface dataset:
Drug‐resistant lymphocytes in man as indicators of somatic cell mutation (1981)

Direct in vivo tests of somatic mutation in man may provide realism in assessing the genetic risks of potential environmental mutagens. The autoradiographic determination of purine analogue (8-azaguanine; 6-thioguanine) resistant (AGr; TGr) peripheral blood lymphocytes (PBLs) arising in vivo in man is proposed as a candidate test. PBLs bearing the naturally occurring Lesch-Nyhan (LN) mutation are prototype mutant cells. LN PBLs are AGr and TGr, whereas normal PBLs are AG and TG sensitive. When judged by the inhibition of phytohemagglutinin (PHA) stimulated 3H-thymidine incorporation in vitro, analogue-resistant LN PBLs may be distinguished from analogue-sensitive normal PBLs by several methods. Early studies quantitating PHA stimulation by scintillation spectrometry detected down to 1% of LN PBLs in artificial mixtures with normal PBLs. Although LN heterozygous females could be identified on the basis of lymphocyte mosaicism, scintillation spectrometry was too insensitive to detect rare "LN-like" PBLs in non-LN individuals. Autoradiography, however, detected rare TGr PBLs in normal non-LN individuals. Their frequencies did not increase with age. With this method, TGr PBL frequencies in LN heterozygous females were found to range from 1 x 10(-3) to 5 x 10(-2), whereas blood samples from LN males showed from 23% to 100% TGr cells. Rare LN PBLs could be detected in artificial mixtures with normal cells. Studies in human patients undergoing various potential mutagenic therapies assessed the effects of these therapies on the TGr PBL variant frequencies (Vf) of non-LN individuals. Group TGr PBL Vf values were higher in treated patient groups than in controls. However, some untreated patient groups (cancer and psoriasis) also had elevated values, suggesting that disease itself may affect TGr PBL frequencies. Nonetheless, one patient group (vitiligo) showed elevated Vf values in treated (8-methoxypsoralen and long-range UV light = PUVA) but not in untreated patients, suggesting that treatment was responsible for the TGr PBL elevations. Longitudinal studies over time in cancer patients receiving X-irradiation therapy demonstrated that such exposures also are associated with TGr PBL frequency rises and suggested that longitudinal studies may be necessary to relate TGr PBL Vf elevations to specific environmental influences. Variant TGr PBLs were found at frequencies comparable to those in man in the peripheral blood of rats. They increased in a single study following treatment of the animals with a clinical alkylating agent. Characterization of the TGr PBLs suggests that some of these cells are mutants. Presumably the mutant cells arise in vivo by somatic cell mutation.
A Novel Rearrangement of the Taxane Skeleton (1993)

International audience
Excessive daytime sleepiness in a patient with coexisting myotonic dystrophy type 1, myasthenia gravis and Graves’ disease (2017)

A 41-year-old female with history of Graves' disease, bilateral cataract, paroxysmal atrial fibrillation was admitted because of muscle weakness, daytime sleepiness, fatigability, drowsiness, bilateral eyelid ptosis, descending of head and lower jaw. On neurological examination the patient was presented with muscle weakness, muscle atrophy (in face and sternocleidomastoid muscles), features of myotonia and apocamnosis (orbicular muscles). Electromyography revealed myopathic changes, myotonic and pseudomyotonic discharges, positive repetitive nerve stimulation test in proximal muscles. Myotonic dystrophy (MD) diagnosis was confirmed by genetic testing and myasthenia gravis (MG) by a positive titer of cholinergic receptor autoantibodies. In the CSF concentration of hypocretin was significantly decreased.
Application of a dynamic retraining for each patient using case-specific training cohorts to predict survival in breast cancer patients. (2014)

1065 Background: To exceed prediction accuracy of previous multigene prognostic classifiers, we propose a new dynamic predictor. Our classifier does not use a single universal training cohort and an identical list of informative genes to predict the prognosis of new cases but a case-specific predictor is developed for each test case. Methods: Gene expression data from 3,534 breast cancers with clinical annotation including survival was analyzed. For each test case we select a case-specific training subset including only molecularly similar cases and a case-specific predictor is generated. This method yields different training sets and different predictors for each new patient but preserves the independence of model building and validation. The model performance was assessed in leave-one-out validation and also in 325 independent cases. Results: Prognostic discrimination was high for all cases (n=3,534, HR=3.68, p=1.67E-56). The dynamic predictor showed higher overall accuracy (0.68) than the 21-gene predictor (0.64), the 97-gene genomic grade index (0.55) or the 70-gene prognostic signature (0.41). The dynamic predictor was also effective in triple-negative cancers (n=427, HR=3.08, p=0.0093) where the above classifiers all failed. Validation in independent patients yielded similar classification power (HR=3.57). The dynamic classifier is available online at http://www.recurrenceonline.com/?q=Re_training. Conclusions: In summary, we developed a new method to make personalized prognostic prediction using case-specific training cohorts. The dynamic predictors outperform static models developed from single historical training cohorts and they also predict well in triple-negative cancers.
Molecular Dynamics Simulations of the Cytolytic Toxin Cyt1A in Solution (2005)

Cytolytic toxin Cyt1A from Bacillus thuringiensis var. israelensis is used as an environmentally friendly insecticide, but its mode of action has not been clearly established. One main obstacle seems to be the lack of the experimentally determined structure of the toxin. As a first step in computer simulations of Cyt1A, in this paper, a three-dimensional molecular structure of Cyt1A in solution was generated by homology modeling, potential energy minimization and molecular dynamics. Regions of the toxin molecule that manifest increased conformational flexibility--and thus are likely to participate in the initial membrane binding and conformational changes--were then identified. Finally, the simulated structure was used to study the effect of a single amino-acid mutation that is known to abrogate the toxicity of Cyt1A in vivo.
Using empirical and mechanistic models to assess global warming threats to leatherback sea turtles (2013)

MEPS Marine Ecology Progress Series Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsTheme Sections MEPS 501:265-278 (2014) - DOI: https://doi.org/10.3354/meps10665 Using empirical and mechanistic models to assess global warming threats to leatherback sea turtles Peter N. Dudley*, Warren P. Porter Department of Zoology, University of Wisconsin, 250 North Mills Street, Madison 53706, USA *Corresponding author: pdudley@wisc.edu ABSTRACT: Global warming may pose a greater risk to species with unique thermal requirements during each life stage than species with a similar thermal requirement throughout all life stages. The risk to the former is higher because their unique thermal ranges may become geographically or temporally discontiguous. Additionally, modeling global warming's effects on these species is challenging due to their multiple thermal requirements. We explore these issues using leatherback sea turtles Dermochelys coriacea as a study species. The gigantothermy of adult leatherbacks and their subterranean egg incubation means global warming will differentially affect adults and eggs. To assess the unique thermal requirements in each life stage we used 2 distinct modeling approaches: (1) a mechanistic biophysical/physiological model to assess threats to adult leatherbacks, and (2) Bayesian regression with a mechanistic microclimate model to assess threats to leatherback eggs. We combined these models with a comprehensive literature search and a global climate model to establish the future thermal threats to the egg and adult leatherback life stages at 3 major rookeries (Gabon, French Guiana, and West Papua). We found that adult internesting and nesting core temperatures will not rise above the critical thermal maximum; however, at 2 of the 3 sites, adult core body temperatures will rise above the point where hatchlings experience uncoordinated movement. We also found that increased temperatures will greatly reduce success rates of egg clutches in West Papua and Gabon by the end of the 21st century. KEY WORDS: Bayesian · Global warming · Hatchling success · Leatherback · Marine turtles · Modeling · Physiology · Thermal tolerance Full text in pdf format PreviousNextCite this article as: Dudley PN, Porter WP (2014) Using empirical and mechanistic models to assess global warming threats to leatherback sea turtles. Mar Ecol Prog Ser 501:265-278. https://doi.org/10.3354/meps10665 Export citation RSS - Facebook - Tweet - linkedIn Cited by Published in MEPS Vol. 501. Online publication date: March 31, 2014 Print ISSN: 0171-8630; Online ISSN: 1616-1599 Copyright © 2014 Inter-Research.
Supplementary Figure 4 from VTX-2337 Is a Novel TLR8 Agonist That Activates NK Cells and Augments ADCC (2023)

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A computer architecture for highly parallel signal processing (1974)

A computer of unusual architecture is described that achieves highly parallel operation through use of a data-flow program representation. The machine is especially suited for signal processing computations such as waveform generation, modulation, and filtering, in which a group of operations must be performed once for each sample of the signals being processed. The difficulties of processor switching and memory/processor interconnection arising in attempts to adapt Von Neuman type computers for parallel operation are avoided by an organization in which sections of the machine communicate through transmission of information packets, and delays in packet transmission do not compromise effective utilization of the hardware. The design concept is especially suited to implementation using asynchronous logic and large-scale integrated circuits. Application of the concepts to generalized data-flow program languages is under study.
FAM210A is a novel determinant of bone and muscle structure and strength (2018)

Osteoporosis and sarcopenia are common comorbid diseases, yet their shared mechanisms are largely unknown. We found that genetic variation near <i>FAM210A</i> was associated, through large genome-wide association studies, with fracture, bone mineral density (BMD), and appendicular and whole body lean mass, in humans. In mice, <i>Fam210a</i> was expressed in muscle mitochondria and cytoplasm, as well as in heart and brain, but not in bone. Grip strength and limb lean mass were reduced in tamoxifen-inducible <i>Fam210a</i> homozygous global knockout mice (<i>TFam210a</i><sup><i>-/-</i></sup> ), and in tamoxifen-inducible <i>Fam210</i> skeletal muscle cell-specific knockout mice (<i>TFam210aMus</i><sup><i>-/-</i></sup> ). Decreased BMD, bone biomechanical strength, and bone formation, and elevated osteoclast activity with microarchitectural deterioration of trabecular and cortical bones, were observed in <i>TFam210a</i><sup><i>-/-</i></sup> mice. BMD of male <i>TFam210aMus</i><sup><i>-/-</i></sup> mice was also reduced, and osteoclast numbers and surface in <i>TFam210aMus</i><sup><i>-/-</i></sup> mice increased. Microarray analysis of muscle cells from <i>TFam210aMus</i><sup><i>-/-</i></sup> mice identified candidate musculoskeletal modulators. <i>FAM210A</i>, a novel gene, therefore has a crucial role in regulating bone structure and function, and may impact osteoporosis through a biological pathway involving muscle as well as through other mechanisms.
Crystal and Molecular Structures of Trifluoroacrylonitrile, F2CCF−CN, and Trifluorovinyl Isocyanide, F2CCF−NC, by Low-Temperature X-ray Crystallography and ab Initio Calculations (2000)

The structures of trifluoroacrylonitrile, F2C=CF-CN, monoclinic, P2(1/n) (no. 14), a = 8.595(4), b = 8.748(1), c = 5.421(1) A, beta = 102.83(2) degrees, Z = 4, and its thermally unstable isomer trifluorovinyl isocyanide, F2C=CF-NC, monoclinic, P2(1/n), a = 8.501(2), b = 8.828(2), c = 5.599(2) A, beta = 101.11(2) degrees, Z = 4 were determined by X-ray crystal structure analysis at 113 and 128 K, respectively, from single crystals grown by partial melting and gradient cooling in small glass capillaries. Selected experimental bond lengths of F2C=CF-CN/F2C=CF-NC are as follows: C=C 1.326(1)/1.304(2), C...N 1.158(1)/1.167(2) A. The C-F bond lengths of the CF2 group are significantly shorter than those of the CF(NC) and CF(CN) units, respectively. The vibrational frequencies and molecular geometries of this cyanide/isocyanide pair were also calculated by ab initio methods for comparison with the experimental results, which were found to be in general agreement.
Human enteric Caliciviridae: a new prevalent small round-structured virus group defined by RNA-dependent RNA polymerase and capsid diversity (1994)

Sequence comparison of the RNA-dependent RNA polymerases of small round-structured viruses (SRSVs) from 10 recent U.K. outbreaks of gastroenteritis revealed significant genetic variation. Computer analyses indicated that these viruses can be divided into two discrete groups. SRSV group I contains the previously characterized antigenic type 1 Norwalk and type 3 Southampton viruses. The amino acid sequences of the RNA polymerase, capsid and ORF3 of these two viruses are relatively similar (about 92%, 69% and 72% amino acid identity, respectively). A representative member of group II SRSVs, Bristol virus, was subjected to a detailed genetic analysis. Bristol virus is a recent antigenic type 2 isolate from a U.K. hospital outbreak of gastroenteritis. Using a single clinical sample the 3'-terminal 3881 nucleotide cDNA sequence [excluding the poly(A) tail] of this virus was determined. Analysis of the sequence revealed significant differences from those of group I viruses with the RNA polymerase region, capsid and ORF3 showing only about 62%, 43% and 30% amino acid identity respectively with the equivalent proteins of the Norwalk and Southampton viruses. These data suggest that the morphologically identical SRSVs belong to at least two genetically distinct groups.
WASP is activated by phosphatidylinositol-4,5-bisphosphate to restrict synapse growth in a pathway parallel to bone morphogenetic protein signaling (2010)

Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P(2)] is a membrane lipid involved in several signaling pathways. However, the role of this lipid in the regulation of synapse growth is ill-defined. Here we identify PI(4,5)P(2) as a gatekeeper of neuromuscular junction (NMJ) size. We show that PI(4,5)P(2) levels in neurons are critical in restricting synaptic growth by localizing and activating presynaptic Wiscott-Aldrich syndrome protein/WASP (WSP). This function of WSP is independent of bone morphogenetic protein (BMP) signaling but is dependent on Tweek, a neuronally expressed protein. Loss of PI(4,5)P(2)-mediated WSP activation results in increased formation of membrane-organizing extension spike protein (Moesin)-GFP patches that concentrate at sites of bouton growth. Based on pharmacological and genetic studies, Moesin patches mark polymerized actin accumulations and correlate well with NMJ size. We propose a model in which PI(4,5)P(2)- and WSP-mediated signaling at presynaptic termini controls actin-dependent synapse growth in a pathway at least in part in parallel to synaptic BMP signaling.
Inhibitors of Renin: Present and Future (1983)

Four classes of compounds have been demonstrated to be renin inhibitors of high potency: specific antibody, general peptide inhibitors of acid proteases, analogs of angiotensinogen and peptides that are related to the amino-terminal sequence of renin's precursor (Pro-renin). With the purification of renin, specific polyclonal or monoclonal antibodies have become available. The former have already been used extensively in physiologic studies in intact animals. Pepstatin is an inhibitor of many acid proteases. Its in vivo application has been retarded by its relative insolubility, but recent chemical modifications, particularly the addition of charged amino acids at the carboxy-terminus have rendered it more useful. The minimal substrate for renin is an octapeptide segment of the protein substrate: His-Pro-Phe-His-Leu-Leu-Val-Tyr. Variants of this sequence have resulted in competitive inhibitors that are useful in vivo. Recently, remarkably active inhibitors have been synthesized by reducing the peptide bond that is cleaved by renin, producing what may be a transition state inhibitor. Several of these peptides have been shown to be effective as in vivo inhibitors of the hypertensive effect of the enzyme. The development of inhibitors based on Pro-renin sequences are awaited with interest.
Ink Solvent Dependence of the Ionomer Distribution in the Catalyst Layer of a PEMFC (2018)

This study examines the effect of ink composition on the ionomer distribution in the catalyst layer of membrane electrode assemblies (MEA) prepared by decal transfer. We combine both structural and electrochemical characterization techniques to investigate the influence of the ionomer distribution on MEA performance determined by 50 cm 2 active area single-cell proton exchange membrane (PEM) fuel cell measurements. Cathodic catalyst layers were prepared from inks with different alcohols (1-propanol or 2-propanol) and varying water content (16-65 wt% H 2 O). The H 2 /air performance of cathode catalyst layers prepared from the different inks with 700 EW ionomer differed drastically, particularly under wet operating conditions, whereby the best performance was obtained for an ink based on 16 wt% H 2 O in 1-propanol. This was successfully correlated with the observation of ionomer patches at the cathode electrode surface (i.e., the surface facing the diffusion medium) determined by scanning electron microscopy (SEM), with N 2 adsorption analysis of the electrodes using a QSDFT model, and with dynamic light scattering data of ionomer/solvent mixtures. No correlation could be obtained between H 2 /air performance and the proton conductivity of the cathodes obtained by electrochemical impedance spectroscopy, and a model to rationalize this behavior will be proposed.
Increased fetal lung T2 signal is not due to increasing surfactant concentration: an in vitro T2 mapping analysis (2016)

The increasing lung/liver T2 signal ratio seen in fetal lungs with increasing gestational age is not due to increasing surfactant concentration. © 2016 John Wiley & Sons, Ltd.
Angiosarcoma of elderly patients treated with weekly low-dose docetaxel in combination with radiotherapy (2013)

血管肉腫は手術療法，化学療法，放射線療法，免疫療法を組み合わせて治療するが，高齢者では全身状態や合併症のため治療法の選択に苦慮することが多い。我々は，低用量docetaxel（DTX）による化学療法と放射線療法（RT）の併用（以下DTX＋RT）で加療した80歳以上の血管肉腫患者4例を経験したため，治療効果や合併症，予後などを報告する。DTXを低用量で投与したが，腫瘍は縮小し，4例の平均生存期間は17.1ヵ月であった。副作用として骨髄抑制は生じなかったが，食欲不振や胸水貯留がみられた。副作用に注意が必要であるが，低用量DTX＋RTでの治療は高齢者にとってQuality of Life（QOL）を維持しつつ効果が期待できる治療法と考えられた。
Human Rhinovirus Attenuates the Type I Interferon Response by Disrupting Activation of Interferon Regulatory Factor 3 (2006)

The type I interferon (IFN) response requires the coordinated activation of the latent transcription factors NF-kappaB, interferon regulatory factor 3 (IRF-3), and ATF-2, which in turn activate transcription from the IFN-beta promoter. Synthesis and subsequent secretion of IFN-beta activate the Jak/STAT signaling pathway, resulting in the transcriptional induction of the full spectrum of antiviral gene products. We utilized high-density microarrays to examine the transcriptional response to rhinovirus type 14 (RV14) infection in HeLa cells, with particular emphasis on the type I interferon response and production of IFN-beta. We found that, although RV14 infection results in altered levels of a wide variety of host mRNAs, induction of IFN-beta mRNA or activation of the Jak/STAT pathway is not seen. Prior work has shown, and our results have confirmed, that NF-kappaB and ATF-2 are activated following infection. Since many viruses are known to target IRF-3 to inhibit the induction of IFN-beta mRNA, we analyzed the status of IRF-3 in infected cells. IRF-3 was translocated to the nucleus and phosphorylated in RV14-infected cells. Despite this apparent activation, very little homodimerization of IRF-3 was evident following infection. Similar results in A549 lung alveolar epithelial cells demonstrated the biological relevance of these findings to RV14 pathogenesis. In addition, prior infection of cells with RV14 prevented the induction of IFN-beta mRNA following treatment with double-stranded RNA, indicating that RV14 encodes an activity that specifically inhibits this innate host defense pathway. Collectively, these results indicate that RV14 infection inhibits the host type I interferon response by interfering with IRF-3 activation.
Anti-DHAV-1 reproduction and immuno-regulatory effects of a flavonoid prescription on duck virus hepatitis (2017)

BLIN inhibits DHAV-1 reproduction by suppressing its adsorption and release. Additionally, BLIN promoted the duckling antiviral response.
Synthesis of Polysilazane from Isocyanato (methyl) silane; Toriisoshianato (mechiru) shiran karano porishirazan no gosei (1999)

The reaction of triisocyanato (methyl) silane with ammonia in diethyl ether, tetrahydrofuran or pyridine was investigated. Isocyanato (methyl) silazanes was isolated as a white powder soluble in organic solvents after removal of the oligomers by means of reprecipitation. The isolated polysilazane was unstable and easily polymerizable and was composed of the unit structures of MeSi(NH){sub x/2}(NCO){sub 3-x}(x=1,2,3) with a number average molecular weight of 500. However, the reaction of methylisocyanatopolysilazane with amine provided silylurea derivatives of polysilazane with a softening point, spinnability, and stability against condensation. (author)
Towards Adapting ImageNet to Reality: Scalable Domain Adaptation with\n Implicit Low-rank Transformations (2013)

Images seen during test time are often not from the same distribution as\nimages used for learning. This problem, known as domain shift, occurs when\ntraining classifiers from object-centric internet image databases and trying to\napply them directly to scene understanding tasks. The consequence is often\nsevere performance degradation and is one of the major barriers for the\napplication of classifiers in real-world systems. In this paper, we show how to\nlearn transform-based domain adaptation classifiers in a scalable manner. The\nkey idea is to exploit an implicit rank constraint, originated from a\nmax-margin domain adaptation formulation, to make optimization tractable.\nExperiments show that the transformation between domains can be very\nefficiently learned from data and easily applied to new categories. This begins\nto bridge the gap between large-scale internet image collections and object\nimages captured in everyday life environments.\n