gebhart/patrepeval huggingface dataset:
Genome-Wide Detection of Single-Nucleotide and Copy-Number Variations of a Single Human Cell (2012)

Kindred cells can have different genomes because of dynamic changes in DNA. Single-cell sequencing is needed to characterize these genomic differences but has been hindered by whole-genome amplification bias, resulting in low genome coverage. Here, we report on a new amplification method-multiple annealing and looping-based amplification cycles (MALBAC)-that offers high uniformity across the genome. Sequencing MALBAC-amplified DNA achieves 93% genome coverage ≥1x for a single human cell at 25x mean sequencing depth. We detected digitized copy-number variations (CNVs) of a single cancer cell. By sequencing three kindred cells, we were able to identify individual single-nucleotide variations (SNVs), with no false positives detected. We directly measured the genome-wide mutation rate of a cancer cell line and found that purine-pyrimidine exchanges occurred unusually frequently among the newly acquired SNVs.
Approaching the AWGN channel capacity without active shaping (2002)

It is shown that the capacity of the AWGN channel can be approached via a multilevel coding scheme with the output of each encoder mapped into an independent signal constellation. No active shaping is required in this scheme, regardless of the signal-to-noise ratio. Moreover, shifted linear codes can be used.
Modeling temporal coherence for optical flow (2011)

Despite the fact that temporal coherence is undeniably one of the key aspects when processing video data, this concept has hardly been exploited in recent optical flow methods. In this paper, we will present a novel parametrization for multi-frame optical flow computation that naturally enables us to embed the assumption of a temporally coherent spatial flow structure, as well as the assumption that the optical flow is smooth along motion trajectories. While the first assumption is realized by expanding spatial regularization over multiple frames, the second assumption is imposed by two novel first- and second-order trajectorial smoothness terms. With respect to the latter, we investigate an adaptive decision scheme that makes a local (per pixel) or global (per sequence) selection of the most appropriate model possible. Experiments show the clear superiority of our approach when compared to existing strategies for imposing temporal coherence. Moreover, we demonstrate the state-of-the-art performance of our method by achieving Top 3 results at the widely used Middlebury benchmark.
Predicting the Functional, Molecular, and Phenotypic Consequences of Amino Acid Substitutions using Hidden Markov Models (2012)

The rate at which nonsynonymous single nucleotide polymorphisms (nsSNPs) are being identified in the human genome is increasing dramatically owing to advances in whole-genome/whole-exome sequencing technologies. Automated methods capable of accurately and reliably distinguishing between pathogenic and functionally neutral nsSNPs are therefore assuming ever-increasing importance. Here, we describe the Functional Analysis Through Hidden Markov Models (FATHMM) software and server: a species-independent method with optional species-specific weightings for the prediction of the functional effects of protein missense variants. Using a model weighted for human mutations, we obtained performance accuracies that outperformed traditional prediction methods (i.e., SIFT, PolyPhen, and PANTHER) on two separate benchmarks. Furthermore, in one benchmark, we achieve performance accuracies that outperform current state-of-the-art prediction methods (i.e., SNPs&GO and MutPred). We demonstrate that FATHMM can be efficiently applied to high-throughput/large-scale human and nonhuman genome sequencing projects with the added benefit of phenotypic outcome associations. To illustrate this, we evaluated nsSNPs in wheat (Triticum spp.) to identify some of the important genetic variants responsible for the phenotypic differences introduced by intense selection during domestication. A Web-based implementation of FATHMM, including a high-throughput batch facility and a downloadable standalone package, is available at http://fathmm.biocompute.org.uk.
Self-taught learning (2007)

We present a new machine learning framework called "self-taught learning" for using unlabeled data in supervised classification tasks. We do not assume that the unlabeled data follows the same class labels or generative distribution as the labeled data. Thus, we would like to use a large number of unlabeled images (or audio samples, or text documents) randomly downloaded from the Internet to improve performance on a given image (or audio, or text) classification task. Such unlabeled data is significantly easier to obtain than in typical semi-supervised or transfer learning settings, making self-taught learning widely applicable to many practical learning problems. We describe an approach to self-taught learning that uses sparse coding to construct higher-level features using the unlabeled data. These features form a succinct input representation and significantly improve classification performance. When using an SVM for classification, we further show how a Fisher kernel can be learned for this representation.
Stokes shift spectroscopy pilot study for cancerous and normal prostate tissues (2012)

Stokes shift spectroscopy (S3) is an emerging approach toward cancer detection. The goal of this paper is to evaluate the diagnostic potential of the S3 technique for the detection and characterization of normal and cancerous prostate tissues. Pairs of cancerous and normal prostate tissue samples were taken from each of eight patients. Stokes shift spectra were measured by simultaneously scanning both the excitation and emission wavelengths while keeping a fixed wavelength interval &#x394;&#x3BB;=20&#x2009;&#x2009;nm between them. The salient features of this technique are the highly resolved emission peaks and significant spectral differences between the normal and cancerous prostate tissues, as observed in the wavelength region of 250 to 600&#xA0;nm. The Stokes shift spectra of cancerous and normal prostate tissues revealed distinct peaks around 300, 345, 440, and 510&#xA0;nm, which are attributed to tryptophan, collagen, NADH, and flavin, respectively. To quantify the spectral differences between the normal and cancerous prostate tissues, two spectral ratios were computed. The findings revealed that both ratio parameters R1=I297/I345 and R2=I307/I345 were excellent diagnostic ratio parameters giving 100% specificity and 100% sensitivity for distinguishing cancerous tissue from the normal tissue. Our results demonstrate that S3 is a sensitive and specific technique for detecting cancerous prostate tissue.
The important role of neuropeptides in complex regional pain syndrome (2001)

Increased systemic CGRP levels in patients with acute CRPS suggest neurogenic inflammation as a pathophysiologic mechanism contributing to vasodilation, edema, and increased sweating. However, pain and hyperalgesia, in particular in chronic stages, were independent of increased neuropeptide concentration.
The Role of Electrostatics in Siderophore Recognition by the Immunoprotein Siderocalin1 (2008)

Iron is required for virulence of most bacterial pathogens, many of which rely on siderophores, small-molecule chelators, to scavenge iron in mammalian hosts. As an immune response, the human protein Siderocalin binds both apo and ferric siderophores in order to intercept delivery of iron to the bacterium, impeding virulence. The introduction of steric clashes into the siderophore structure is an important mechanism of evading sequestration. However, in the absence of steric incompatibilities, electrostatic interactions determine siderophore strength of binding by Siderocalin. By using a series of isosteric enterobactin analogues, the contribution of electrostatic interactions, including both charge-charge and cation-pi, to the recognition of 2,3-catecholate siderophores has been deconvoluted. The analogues used in the study incorporate a systematic combination of 2,3-catecholamide (CAM) and N-hydroxypyridinonate (1,2-HOPO) binding units on a tris(2-aminoethyl)amine (tren) backbone, [tren(CAM)(m)(1,2-HOPO)(n), where m = 0, 1, 2, or 3 and n = 3 - m]. The shape complementarity of the synthetic analogue series was determined through small-molecule crystallography, and the binding interactions were investigated through a fluorescence-based binding assay. These results were modeled and correlated through ab initio calculations of the electrostatic properties of the binding units. Although all the analogues are accommodated in the binding pocket of Siderocalin, the ferric complexes incorporating decreasing numbers of CAM units are bound with decreasing affinities (K(d) = >600, 43, 0.8, and 0.3 nM for m = 0-3). These results elucidate the role of electrostatics in the mechanism of siderophore recognition by Siderocalin.
Interaction of HIV Tat model peptides with tRNA and 5S rRNA. (1997)

New data are presented on the interaction of model synthetic peptides containing an arginine-rich region of human immunodeficiency virus (HIV-Tat), with native RNA molecules: tRNA(Phe) of Saccharomyces cerevisiae and 5S rRNA from Lupinus luteus. Both RNA species form complexes with the Tat1 (GRKKRRQRRRA) and Tat2 (GRKKRRQRRRAPQDSQTHQASLSKQPA) peptides, as shown by electrophoretic gel shift and RNase footprint assays, and CD measurements. The nucleotide sequence UGGG located in the dihydrouridine loop of tRNAPhe as well as in the loop D of 5S rRNA is specifically protected against RNases. Our data indicate direct interactions of guanine of RNA moieties with arginine residues. These interactions seem similar to those observed in DNA-protein complexes, but different from those previously observed in the TAR RNA-Tat complexes.
Advances in Antibody Design (2015)

The use of monoclonal antibodies as therapeutics requires optimizing several of their key attributes. These include binding affinity and specificity, folding stability, solubility, pharmacokinetics, effector functions, and compatibility with the attachment of additional antibody domains (bispecific antibodies) and cytotoxic drugs (antibody-drug conjugates). Addressing these and other challenges requires the use of systematic design methods that complement powerful immunization and in vitro screening methods. We review advances in designing the binding loops, scaffolds, domain interfaces, constant regions, post-translational and chemical modifications, and bispecific architectures of antibodies and fragments thereof to improve their bioactivity. We also highlight unmet challenges in antibody design that must be overcome to generate potent antibody therapeutics.
Molecular mechanisms and mode of tamoxifen resistance in breast cancer (2016)

Breast cancer is one of the most common cancers in women around the globe Tamoxifen is used for the last 40 years as an endocrine therapy for breast cancer. This resulted in the reduction of mortality rate by 30% and it still remains one of the most effective therapies against breast cancer. However, resistance against tamoxifen is still one of the major hurdles in the effective management of breast cancer. Intense research has been conducted in the past decade to further explore its resistance mechanism, but still a lot of research will be needed to effectively alleviate this problem. Several biochemical factors and molecular pathways, such as the modulation of ER signaling, upregulation of growth factors had been observed as key factors for tamoxifen resistance (TR). After, initial therapy of five to ten years, breast cancer patients develops resistance towards this drug. The resistance leads to the development of other cancers like uterine cancer. Here, we briefly explore all the molecular events related to tamoxifen resistance and focus on its mechanism of action as well as other pharmacological approaches to better its beneficial effects in the treatment of breast carcinoma.
Purification and properties of an endo-alpha-N-acetyl-D-galactosaminidase from Diplococcus pneumoniae (1977)

An enzyme that hydrolyzes the O-glycosidic linkage between alpha-N-acetyl-D-galactosamine and serine or threonine in mucins and mucin-type glycoproteins was purified by chromatography on an Affi-Gel 202 column or isoelectric focusing from filtrates of Diplococcus pneumoniae cultures. The final preparations were free of protease and a wide range of other glycosidase activities. The preparation obtained by isoelectric focusing was shown to consist of a single protein by gel filtration and sodium dodecyl sulfate-gel electrophoresis. This preparation had an apparent molecular weight of about 160,000, determined by gel filtration, an optimum pH of 7.6, and an isoelectric point in the range pH 8 to 9. The enzyme releases the disaccharide Gal-GalNAc from a variety of glycopeptide and glycoprotein substrates and appears to have a specific requirement for an unsubstituted galactose in the nonreducing terminus and an alpha linkage between N-acetylgalactosamine and the aglycone. This is the only endoenzyme known capable of cleaving the linkage between a carbohydrate and serine or threonine residues in glycoproteins. The ability of this enzyme to act on macromolecular substrates and its pH optimum makes it ideally suited to explore the distribution and function of mucin-type glycoproteins on normal and cancer cell surfaces.
Expression of erythropoietin in cats treated with a recombinant adeno-associated viral vector (2005)

Gene therapy may be an effective treatment for cats with hypoproliferative anemia. However, rAAV2-fEPO vector administration may result in pure RBC aplasia or pathologic erythrocytosis, and injection site removal does not consistently abolish the biological response.
Site-Selective N-Methylation of Peptides on Solid Support (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSite-Selective N-Methylation of Peptides on Solid SupportStephen C. Miller and Thomas S. ScanlanView Author Information Department of Pharmaceutical Chemistry University of California San Francisco, California 94143-0446 Cite this: J. Am. Chem. Soc. 1997, 119, 9, 2301–2302Publication Date (Web):March 5, 1997Publication History Received10 October 1996Published online5 March 1997Published inissue 1 March 1997https://doi.org/10.1021/ja9635443Copyright © 1997 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views4794Altmetric-Citations192LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (57 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Anions,Monomers,Peptides and proteins,Solid phase synthesis,Sulfones Get e-Alerts
Hemoglobin A1C by isoelectric focusing. (1982)

We separated the hemoglobins in an unwashed erythrocyte hemolysate according to their isoelectric points on a thin-layer horizontal polyacrylamide gel containing ampholyte (40 g/L) over a pH gradient of 6-8. We scanned the fixed, unstained gels by microdensitometry and calculated the percentage of hemoglobin A1C. The overall CV (between-run imprecision) for a normal hemolysate (mean, 5.2% of total hemoglobin) stored at -70 degrees C was 12.6%. An above-normal pooled specimen (mean 8.5%) showed an overall CV of 8.4%. We confirmed that hemoglobins S, C, and F do not interfere; acetylated F co-migrates with A1C. The mean A1C percentage in non-diabetic adults was 4.9%, the reference interval 3.9-6.4%. The mean values for diabetics in various degrees of control were 7.6% in the group rated "good," 9.9% in the "fair" group, and 12.2% in the "poor" group. Results for patients' samples (y) were compared with results by cation-exchange chromatography (x). The slope was 1.0 and the intercept was 2.2%. The percentage of hemoglobin A1C in erythrocytes remains constant for seven days in samples stored at 30 degrees C.
Rhein affects arylamineN-acetyltransferase activity inHelicobacter pylori from peptic ulcer patients (1998)

Arylamine N-acetyltransferase (NAT) activities with 2-aminofluorene and p-aminobenzoic acid were determined in the bacterium Helicobacter pylori collected from peptic ulcer patients. Cytosols or suspensions of H. pylori with or without specific concentrations of rhein co-treatment showed different percentages of 2-aminofluorene and p-aminobenzoic acid acetylation. The data indicate that there was decreased NAT activity associated with increased levels of rhein in H. pylori cytosols. Inhibition of growth studies from H. pylori demonstrated that rhein elicited dose-dependent bacteriostatic activity in H. pylori cultures: i.e. the greater the concentration of rhein, the greater the inhibition of growth to H. pylori. For the cytosol and intact bacteria examination, the apparent values of Km and Vmax were decreased after co-treatment with 40 microM rhein. This report is the first demonstration of rhein inhibition of arylamine N-acetyltransferase activity and rhein inhibition of growth in the bacterium H. pylori.
Prevention of Rhinovirus Infection in Chimpanzees by Soluble Intercellular Adhesion Molecule-1 (1997)

Intercellular adhesion molecule-1 (ICAM-1) is the cell surface receptor for the major class of human rhinoviruses, and tICAM453, a truncated, soluble form of ICAM-1, has been shown previously to be a potent in vitro inhibitor of rhinovirus. In this report, we have investigated the in vivo efficacy of tICAM453 for the prophylaxis of rhinovirus serotype 16 infection in the chimpanzee. Because chimpanzees do not show clinical symptoms of infection after rhinovirus challenge, infection was followed by measuring antirhinovirus serum antibody responses and detection of virus shedding. By both of these measures, intranasal application of tICAM453 was efficacious in preventing rhinovirus infection in chimpanzees subsequently challenged with infectious doses of virus. These results suggest that the use of soluble rhinovirus receptor to inhibit virus binding to host cells should be feasible in humans.
Enhancement of neural stem cell survival, proliferation and differentiation by IGF-1 delivery in graphene oxide-incorporated PLGA electrospun nanofibrous mats (2019)

The mammalian central nervous system has a limited ability for self-repair under injury conditions. The treatment of nerve injuries has been revolutionised with the development of tissue engineering techniques. However, the lack of bioactivity has severely restricted the application of biodegradable implants for neurogenesis. Therefore, surface modification of biomaterials is crucial to improve their bioactivity and promote endogenous repair mechanisms for nerve regeneration. Insulin-like growth factor 1 (IGF-1) is a growth factor for neuroprotection and neurogenesis. In this study, IGF-1 was successfully immobilised on graphene oxide (GO)-incorporated poly(lactic-<i>co</i>-glycolic acid) (PLGA) biodegradable electrospun nanofibres. For the <i>in vitro</i> investigation, neural stem cells (NSCs) were cultured on different nanofibres to observe various cellular activities. GO enhanced NSC survival under H<sub>2</sub>O<sub>2</sub> pre-treatment and neuronal differentiation to some extent. More importantly, the immobilisation of IGF-1 onto the PLGA/GO nanofibres resulted in significantly increased NSC survival, proliferation, and differentiation. Findings from this study revealed that using PLGA/GO electrospun nanofibres to immobilise IGF-1 has excellent potential for the enhancement of the neuroprotective and neurogenic effects of nerve implants.
A study of ion suppression effects in electrospray ionization from mobile phase additives and solid‐phase extracts (2003)

Since the wide adoption of liquid chromatography/tandem mass spectrometry (LC/MS/MS), the ion suppression/enhancement phenomenon is the latest barrier to high-throughput analysis. This consequence of a nonoptimized analytical method can lead to adverse effects during quantitation (i.e. poor accuracy and precision). Previous papers have reported that ion suppression is a direct result of endogenous material present in biological samples. However, in the case of a solid-phase liquid chromatography/tandem mass spectrometry (SPE/LC/MS/MS) system, the measured result is the combination of several operating conditions and parameters. Little has been done to effectively monitor and/or choose optimized conditions for the complete sequence of extraction, clean up, separation and analysis. This paper describes a simple setup for quantification of ion suppression/enhancement. Several mobile phase additives, ion-pairing agents and SPE extracts were measured and compared against a standard reference. The results demonstrated that a clean up of plasma extracts based on ion exchange leads to minimal ion suppression/enhancement for the compounds that were investigated.
Antibodies directed against the peroxisomal targeting signal of firefly luciferase recognize multiple mammalian peroxisomal proteins. (1990)

We have previously shown that the peroxisomal targeting signal in firefly luciferase consists of the COOH-terminal three amino acids of the protein, serine-lysine-leucine (Gould, S.J., G.A. Keller, N. Hosken, J. Wilkinson, and S. Subramani, 1989. J. Cell Biol. 108:1657-1664). Antibodies were raised against a synthetic peptide that contained this tripeptide at its COOH terminus. Immunofluorescence and immunocryoelectron microscopy revealed that the anti-peptide antibodies specifically detected peroxisomes in mammalian cells. Further characterization revealed that the antibodies were primarily directed against the COOH-terminal three amino acids of the peptide. In Western blot experiments, the antibodies recognized 15-20 rat liver peroxisomal proteins, but reacted with only a few proteins from other subcellular compartments. These results provide independent immunological evidence that the peroxisomal targeting signal identified in firefly luciferase is present in many peroxisomal proteins.
Quantitative method to determine mRNA levels by reverse transcriptase-polymerase chain reaction from leukocyte subsets purified by fluorescence-activated cell sorting: Application to peripheral cannabinoid receptors (1999)

This method allows precise measurement of the mRNA of CB2-r performed on cell numbers as low as 10(5) after sorting. Its performance, high accuracy, reproducibility, and reliability make it a valuable tool for assaying proteins weakly expressed in cells.
Barrett's Esophagus: A New Look at Surveillance Based on Emerging Estimates of Cancer Risk (1999)

Surveillance of Barrett's patients should extend life, with incremental cost-utility ratios that compare favorably with some accepted medical practices. Policy makers can compare the cost of surveillance to that of other accepted practices to determine their willingness to fund surveillance.