gebhart/patrepeval huggingface dataset:
A Small Subset of Signal Peptidase Residues are Perturbed by Signal Peptide Binding (2008)

Perturbations of the chemical shifts of a small subset of residues in the catalytically active domain of Escherichia coli signal peptidase I (SPase I) upon binding signal peptide suggest the contact surface on the enzyme for the substrate. SPase I, an integral membrane protein, is vital to preprotein transport in prokaryotic and eukaryotic secretory systems; it binds and proteolyses the N-terminal signal peptide of the preprotein, permitting folding and localization of the mature protein. Employing isotopically labeled C-terminal E. coli SPase I Delta2-75 and an unlabeled soluble synthetic alkaline phosphatase signal peptide, SPase I Delta2-75 was titrated with the signal peptide and 2D (1)H-(15)N heteronuclear single-quantum correlation nuclear magnetic resonance spectra revealed chemical shifts of specific enzyme residues sensitive to substrate binding. These residues were identified by 3D HNCACB, 3D CBCA(CO)NH, and 3D HN(CO) experiments. Residues Ile80, Glu82, Gln85, Ile86, Ser88, Gly89, Ser90, Met91, Leu95, Ile101, Gly109, Val132, Lys134, Asp142, Ile144, Lys145, and Thr234, alter conformation and are likely all in, or adjacent to, the substrate binding site. The remainder of the enzyme structure is unperturbed. Ramifications for conformational changes for substrate docking and catalysis are discussed.
What’s Cookin’? Interpreting Cooking Videos using Text, Speech and Vision (2015)

Jonathan Malmaud, Jonathan Huang, Vivek Rathod, Nicholas Johnston, Andrew Rabinovich, Kevin Murphy. Proceedings of the 2015 Conference of the North American Chapter of the Association for Computational Linguistics: Human Language Technologies. 2015.
Nucleic Acids: Structures, Properties, and Functions (2000)

Providing a comprehensive account of the structures and physical chemistry properties of nucleic acids, with special emphasis on biological function, this text is for those with only a basic understanding of physical chemistry and molecular biology.
Heparan Sulfate Proteoglycans Are Ligands for Receptor Protein Tyrosine Phosphatase σ (2002)

RPTPsigma is a cell adhesion molecule-like receptor protein tyrosine phosphatase involved in nervous system development. Its avian orthologue, known as cPTPsigma or CRYPalpha, promotes intraretinal axon growth and controls the morphology of growth cones. The molecular mechanisms underlying the functions of cPTPsigma are still to be determined, since neither its physiological ligand(s) nor its substrates have been described. Nevertheless, a major class of ligand(s) is present in the retinal basal lamina and glial endfeet, the potent native growth substrate for retinal axons. We demonstrate here that cPTPsigma is a heparin-binding protein and that its basal lamina ligands include the heparan sulfate proteoglycans (HSPGs) agrin and collagen XVIII. These molecules interact with high affinity with cPTPsigma in vitro, and this binding is totally dependent upon their heparan sulfate chains. Using molecular modelling and site-directed mutagenesis, a binding site for heparin and heparan sulfate was identified in the first immunoglobulin-like domain of cPTPsigma. HSPGs are therefore a novel class of heterotypic ligand for cPTPsigma, suggesting that cPTPsigma signaling in axons and growth cones is directly responsive to matrix-associated cues.
A partial model of the erythropoietin receptor complex (1996)

A model of the structure of erythropoietin (Epo) is presented based on structural homology to other hemopoietic cytokines. A model of the erythropoietin receptor complex was made based on evidence that this includes a homodimer of the receptor chain with known sequence. Key interactions are noted which explain data from mutation experiments, although at not all residues believed to be important to binding of Epo are at the interface. This is consistent with the hypothesis that the Epo receptor complex includes proteins in addition to the cloned receptor chain that have been cross-linked to Epo (Todokoro et al., Proc. Natl. Acad. Sci. USA 84:4126-4130, 1987; Mayeux et al., J. Biol. Chem. 266:23380-23385, 1991) but not isolated.
Characterization of an Epstein-Barr virus-induced thymidine kinase (1986)

Previous work from our laboratory suggested that the selective inhibition of Epstein-Barr virus (EBV) replication by 1-beta-D-arabinofuranosylthymine in human lymphoid cell lines involved the induction of a new thymidine kinase (TK) able to phosphorylate the thymidine analog. We further characterized this enzyme induced in various EBV-positive cell lines after viral genome activation with a combination of sodium butyrate and 12-O-tetradecanoylphorbol-13-acetate. The following results confirmed the existence of an EBV-specific deoxypyrimidine kinase: induction of EBV-related TK was connected with the appearance of viral early antigens in EBV-carrying cells; unexpected behaviors of the enzyme activity upon different fractionating treatments led to the conclusion that EBV-induced TK was extracted as a complex molecular form, larger than other known cellular or viral isozymes; enzymatic properties distinguished EBV-induced TK from host lymphoid cell isozymes but made it resemble other herpesvirus-specific deoxypyrimidine kinases, i.e., by partial inhibition by dTTP or ammonium sulfate, insensitiveness to dCTP, and nonstringent specificity for normal TK substrates. Genetic evidence is required to definitively ensure that EBV-specific TK actually is virus coded in EBV-transformed human lymphoid cells.
Higher Amount of Free Circulating DNA in Serum than in Plasma Is Not Mainly Caused by Contaminated Extraneous DNA during Separation (2006)

Circulating DNA isolated from serum and plasma has been shown to be a useful biomarker in various diseases including cancer. Serum reportedly contains a higher amount of free circulating DNA than it does in plasma. The underlying reason for this is unclear, but important because it may have clinical implications in interpreting results and using the appropriate resource. Twenty-four pairs of serum and plasma samples were collected from patients with tumors, and free circulating DNA was quantified by real-time quantitative PCR (qPCR) for the ALU repeats, which had a sensitivity of 0.1 pg/microL of DNA in serum/plasma. The possibility of DNA loss was eliminated because ALU-qPCR does not require DNA purification from serum/plasma. The DNA concentrations of serum and plasma samples were 970 +/- 730 pg/microL and 180 +/- 150 pg/microL (mean +/- SD), respectively. The amount of DNA in paired serum and plasma specimens was positively correlated (R = 0.72 and P = 0.0002). An estimated 8.2% of total DNA in serum was extraneous; the concentration of DNA was 6.1 +/- 3.5 (mean +/- SD)-fold higher in serum than in paired plasma after subtraction of it. Contribution of extraneous DNA from cells in blood ruptured during the separation step was minor for explaining the difference between serum and plasma. A possible explanation was unequal distribution of DNA during separation from whole blood. We advocate that serum is a better specimen source for circulating cancer-related DNA as a biomarker.
Energy-Detection Model for Monaural Auditory Detection (1962)

In the auditory detection of a sinusoidal signal in the presence of random noise, it has previously been demonstrated that the presence of a “pedestal” or background sinusoid of the same frequency and phase as the signal increases detectability. This increase was confirmed in a two-interval forced choice experiment in which a 1000-cps sinusoid was present in one of two 0.1-sec intervals, and the noise plus pedestal were present in both intervals. Pedestals of moderate intensity in phase with the signal increased detectability. Pedestals in quadrature (90° out of phase) with the signal did not improve detectability. Very large pedestals decreased detectability irrespective of phase. A simple energy-detection model was developed and its performance compared with the experimental results. The model consists of a bandpass filter, a square-law element, and an integrator. The probability of correct detection varies with signal level in a manner similar to the auditory results. Detectability is improved by an in-phase pedestal and approaches that of a correlation detector in the limit of infinite pedestal. Detectability is not improved by quadrate pedestals. The model can be modified to predict the decreasing detectability with large pedestals.
Spaceflight and Bone Turnover: Correlation with a New Rat Model of Weightlessness (1979)

Earlier manned spaceflight studies have revealed that the near-weightless environment of orbital flight produce certain biological effects in humans, including abnormalities in mineral metabolism. The data collected were compatible with bone mineral loss. Cosmos 782 and 936 experiments have shown a decrease in rat bone formation rate. In this paper, a rat model of weightlessness is described, which is unique in that the animal is free to move about a 360-deg arc. The model meets the requirements for an acceptable system. Data from the model and spaceflight are presented. Many of the responses noted in suspended animals indicate that the model closely mimics results from rats and man exposed to near-weightlessness during orbital spaceflight.
Major Cancer Regressions in Mesothelioma After Treatment with an Anti-Mesothelin Immunotoxin and Immune Suppression (2013)

Immunotoxins are potent anticancer agents with an unusual mechanism of action: inhibition of protein synthesis resulting in apoptotic cell death. Immunotoxins have produced many durable complete responses in refractory hairy cell leukemia, where patients rarely form antibodies to the bacterial toxin component of the immunotoxin. Patients with mesothelioma, however, have normal immune systems and form antibodies after one cycle, and tumor responses to the immunotoxin have not been observed in this disease. We describe the results of a trial in which major antitumor responses were seen in patients with advanced mesothelioma who received the anti-mesothelin immunotoxin SS1P, together with pentostatin and cyclophosphamide, to deplete T and B cells. Of 10 patients with chemotherapy-refractory mesothelioma, 3 have had major tumor regressions with 2 ongoing at 15 months, and 2 others responded to chemotherapy after discontinuing immunotoxin therapy. Antibody formation was markedly delayed, allowing more SS1P cycles to be given, but this alone does not appear to account for the marked antitumor activity observed.
Advances in active appearance models (1999)

This paper presents advances in the construction and use of Active Appearance Models (AAMs) for image interpretation. AAMs are photo-realistic generative models of object appearance that can be used to rapidly locate deformable objects in images. We extend the AAM method to include coloured texture and present an enhanced search algorithm with the ability to locate partially occluded objects. Previously, AAMs have been limited by the need for good manual initialisation. In this paper, we describe a hierarchical search algorithm that overcomes this drawback. The extended AAM method provides a complete, unified scheme for model based image interpretation. We demonstrate the application of the scheme to the task of locating faces in images.
NPP4 is a procoagulant enzyme on the surface of vascular endothelium (2012)

Ap3A is a platelet-dense granule component released into the extracellular space during the second wave of platelet aggregation on activation. Here, we identify an uncharacterized enzyme, nucleotide pyrophosphatase/phosphodiesterase-4 (NPP4), as a potent hydrolase of Ap3A capable of stimulating platelet aggregation and secretion. We demonstrate that NPP4 is present on the surface of vascular endothelium, where it hydrolyzes Ap3A into AMP and ADP, and Ap4A into AMP and ATP. Platelet aggregation assays with citrated platelet-rich plasma reveal that the primary and secondary waves of aggregation and dense granule release are strongly induced by nanomolar NPP4 in a concentration-dependent manner in the presence of Ap3A, while Ap3A alone initiates a primary wave of aggregation followed by rapid disaggregation. NPP2 and an active site NPP4 mutant, neither of which appreciably hydrolyzes Ap3A, have no effect on platelet aggregation and secretion. Finally, by using ADP receptor blockade we confirm that NPP4 mediates platelet aggregation via release of ADP from Ap3A and activation of ADP receptors. Collectively, these studies define the biologic and enzymatic basis for NPP4 and Ap3A activity in platelet aggregation in vitro and suggest that NPP4 promotes hemostasis in vivo by augmenting ADP-mediated platelet aggregation at the site of vascular injury.
Functional and Ultrastructural Features of DNA‐Fragmented Human Sperm (2000)

The functional significance of deoxyribonucleic acid (DNA) fragmentation in ejaculated human sperm is unclear. In this study the extent of DNA strand breakage in swim-up selected spermatozoa was evaluated by terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling (TUNEL)-coupled flow cytometry and correlated with several functional and morphological sperm parameters. The extent of DNA fragmentation (mean = 11.07%+/-8.00%, range = 0.79%-42.64%, n = 140) was positively related to abnormal morphology and associated with defects of the sperm tail. A negative correlation was found between DNA breakage and progressive motility. When a stepwise multiple linear regression model was used to analyze the relationship between DNA fragmentation and the aforementioned parameters, only motility results were included in the model. The presence of spermatozoa showing submicroscopic characteristics resembling those of somatic apoptosis has been reported in human ejaculate. To verify whether sperm DNA fragmentation was associated with the presence of such apoptotic-like cells, we performed electron microscopy and TUNEL-coupled flow cytometry in a limited number of sperm samples (n = 24). Although we did not observe any significant relationship between DNA breakage and the characteristics that are suggestive of apoptosis, an association was found with several ultrastructural features, indicating an impaired motility. Hence, we conclude that in ejaculated sperm, DNA fragmentation does not correspond to the apoptosis-like phenomenon and that it is associated with defects of motility.
Clostridium difficile Cell Attachment Is Modified by Environmental Factors (1999)

ABSTRACT Adherence of Clostridium difficile to Vero cells under anaerobic conditions was increased by a high sodium concentration, calcium-rich medium, an acidic pH, and iron starvation. The level of adhesion of nontoxigenic strains was comparable to that of toxigenic strains. Depending on the bacterial culture conditions, Vero cells could bind to one, two, or three bacterial surface proteins with molecular masses of 70, 50, and 40 kDa.
Pivotal Role of Extended Linker 2 in the Activation of Gα by G Protein-coupled Receptor (2014)

G protein-coupled receptors (GPCRs) relay extracellular signals mainly to heterotrimeric G-proteins (Gαβγ) and they are the most successful drug targets. The mechanisms of G-protein activation by GPCRs are not well understood. Previous studies have revealed a signal relay route from a GPCR via the C-terminal α5-helix of Gα to the guanine nucleotide-binding pocket. Recent structural and biophysical studies uncover a role for the opening or rotating of the α-helical domain of Gα during the activation of Gα by a GPCR. Here we show that β-adrenergic receptors activate eight Gαs mutant proteins (from a screen of 66 Gαs mutants) that are unable to bind Gβγ subunits in cells. Five of these eight mutants are in the αF/Linker 2/β2 hinge region (extended Linker 2) that connects the Ras-like GTPase domain and the α-helical domain of Gαs. This extended Linker 2 is the target site of a natural product inhibitor of Gq. Our data show that the extended Linker 2 is critical for Gα activation by GPCRs. We propose that a GPCR via its intracellular loop 2 directly interacts with the β2/β3 loop of Gα to communicate to Linker 2, resulting in the opening and closing of the α-helical domain and the release of GDP during G-protein activation.
Transcriptional control, translation and function of the products of the five open reading frames of the Escherichia coli nir operon (1992)

Five open reading frames designated nirB, nirD, nirE, nirC and cysG have been identified from the DNA sequence of the Escherichia coli nir operon. Complementation experiments established that the NirB, NirD and CysG polypeptides are essential and sufficient for NADH-dependent nitrite reductase activity (EC 1.6.6.4). A series of plasmids has been constructed in which each of the open reading frames has been fused in-phase with the beta-galactosidase gene, lacZ. Rates of beta-galactosidase synthesis during growth in different media revealed that nirB, -D, -E and -C are transcribed from the FNR-dependent promoter, p-nirB, located just upstream of the nirB gene: expression is co-ordinately repressed by oxygen and induced during anaerobic growth. Although the nirB, -D and -C open reading frames are translated into protein, no translation of nirE mRNA was detected. The cysG gene product is expressed from both p-nirB and a second, FNR-independent promoter, p-cysG, located within the nirC gene. No NADH-dependent nitrite reductase activity was detected in extracts from bacteria lacking either NirB or NirD, but a mixture of the two was as active as an extract from wild-type bacteria. Reconstitution of enzyme activity in vitro required stoichiometric quantities of NirB and NirD and was rapid and independent of the temperature during mixing. NirD remained associated with NirB during the initial stages of purification of the active enzyme, suggesting that NirD is a second structural subunit of the enzyme.
Evaluation of Source Code with Item Response Theory (2015)

The analysis of source code produced by novice programmers could provide interesting insights into their learning progress, particularly in introductory programming courses. Yet, as the programming ability of a person is assumed to be quite complex, it is not likely that it would be observable directly in its total. Instead, we regard those abilities as latent psychometric constructs and apply the methodology of item response theory (IRT) to assess their manifestations. In preparatory work, we had identified a list of items that represent the central concepts of object-oriented programming. In this paper we propose a methodology that allows the evaluation of coding abilities by analyzing the application of those concepts. We demonstrate this methodology by exemplarily analyzing source code that was produced during programming projects. The results provide interesting information about the difficulty of the concepts' application and the distribution of the respective coding abilities among the students.
Analysis of Data From Viral DNA Microchips (2001)

Viral DNA microchips, arrays of viral genes printed over a glass slide, are powerful tools for rapidly characterizing the expression pattern of these genes in an infection. The chips are exposed to a solution of fluorescently labeled cDNAs prepared from either mock or true infected human fibroblast cells and the expression levels of the various genes are recorded with the objective of detecting which viral genes are expressed to a significantly higher degree when exposed to the true infection as compared to the mock infection. The data were initially examined visually via image plots and scatterplots. These reveal that analysis of such data presents many challenges owing to, among other problems, high interchip and intrachip variability with low signal-to-noise ratio, differential intensity scales that have to be adjusted nonlinearly, nonGaussian data, data for a large number of genes with little replication, scratches and dark spots on the chips, dust, outliers, and an inability to quantitate intensities below a detection limit, or above a threshold. The first step of the analysis was to standardize the chips to a single intensity scale using a photograph analogy. Next, the average expression level of each gene was estimated using a highly resistant repeated median estimator to avoid being misled by aberrant values. Finally, a simulation-based approach was used to make a distribution-free assessment of significance.
Diagnosis and management of dysplasia in patients with ulcerative colitis and Crohnʼs disease of the colon (2008)

To minimize the possibility of developing lethal colorectal cancer (CRC) in ulcerative colitis (UC) and Crohn's colitis, patients are usually enrolled in a program of dysplasia surveillance. The success of a surveillance program depends on the identification of patients with dysplasia and timely referral for colectomy. While a number of issues might stand in the way of a surveillance system achieving its maximal effect (less than ideal agreement in the interpretation of biopsy specimens, sampling error by endoscopists, delays in referral to surgery, and patient drop-out among others), circumstantial evidence supports the concept that colonoscopic dysplasia surveillance is an effective means of reducing CRC mortality and morbidity while minimizing the application of colectomy for cancer prevention. This review critically appraises key issues in the diagnosis and management of dysplasia in UC and Crohn's disease as well as adjunct efforts to prevent CRC in inflammatory bowel disease.
Effects of substitutions of amino acids on the thermal stability of the Fv fragments of antibodies (1994)

The thermal stability of Fv fragments was examined by circular dichroism (CD) spectrometry and high-performance liquid chromatography. We analyzed three Fv fragments: that of a monoclonal antibody D1.3 and two derivatives of it. After separation of wild-type VH and VL fragments, thermal denaturation of each fragment was monitored by CD spectrometry. The results indicated that the dissociation of Fv into VH and VL fragments seemed to be coupled with the denaturation of each fragment and that the thermal denaturation of VH and VL fragments was prevented when they were associated with one another. The analysis of the three Fv fragments also indicated that, in some cases, differences in amino acids even within the CDRs could have significant effects on the thermal stability of the complex between VH and VL fragments.
Waveglow: A Flow-based Generative Network for Speech Synthesis (2019)

In this paper we propose WaveGlow: a flow-based network capable of generating high quality speech from mel-spectrograms. WaveGlow combines insights from Glow [1] and WaveNet [2] in order to provide fast, efficient and high-quality audio synthesis, without the need for auto-regression. WaveGlow is implemented using only a single network, trained using only a single cost function: maximizing the likelihood of the training data, which makes the training procedure simple and stable. Our PyTorch implementation produces audio samples at a rate of more than 500 kHz on an NVIDIA V100 GPU. Mean Opinion Scores show that it delivers audio quality as good as the best publicly available WaveNet implementation. All code will be made publicly available online [3].