gebhart/patrepeval huggingface dataset:
The Pathogenesis and Therapy of Muscular Dystrophies (2015)

Current molecular genomic approaches to human genetic disorders have led to an explosion in the identification of the genes and their encoded proteins responsible for these disorders. The identification of the gene altered by mutations in Duchenne and Becker muscular dystrophy was one of the earliest examples of this paradigm. The nearly 30 years of research partly outlined here exemplifies the road that similar current gene discovery protocols will be expected to travel, albeit much more rapidly owing to improved diagnosis of genetic disorders and an understanding of the spectrum of mutations thought to cause them. The identification of the protein dystrophin has led to a new understanding of the muscle cell membrane and the proteins involved in membrane stability, as well as new candidate genes for additional forms of muscular dystrophy. Animal models identified with naturally occurring mutations and developed by genetic manipulation have furthered the understanding of disease progression and underlying pathology. The biochemistry and molecular analysis of patient samples have led to the different dystrophin-dependent and -independent therapies that are currently close to or in human clinical trials. The lessons learned from decades of research on dystrophin have benefited the field of human genetics.
Diagnostic Utility of Cytokine Biomarkers in the Evaluation of Acute Knee Pain (2009)

Intra-articular concentrations of four inflammatory cytokines IFN-gamma, IL-6, MCP-1, and MIP-1beta correlated to pain in patients with symptomatic meniscal tears in the knee but were markedly lower in asymptomatic normal knees and in asymptomatic knees with meniscal tears. These cytokines may be involved in the generation of pain following meniscal injury.
Local gradient pattern - A novel feature representation for facial expression recognition (2014)

Many researchers adopt Local Binary Pattern for pattern analysis. However, the long histogram created by Local Binary Pattern is not suitable for large-scale facial database. This paper presents a simple facial pattern descriptor for facial expression recognition. Local pattern is computed based on local gradient flow from one side to another side through the center pixel in a 3x3 pixels region. The center pixel of that region is represented by two separate two-bit binary patterns, named as Local Gradient Pattern-LGP for that pixel. LGP pattern is extracted from each pixel. Facial image is divided into 81 equal sized blocks and the histograms of local LGP features for all 81 blocks are concatenated to build the feature vector. Experimental results prove that the proposed technique along with Support Vector Machine is effective for facial expression recognition.
Roles of N-Linked Glycans in the Endoplasmic Reticulum (2004)

From a process involved in cell wall synthesis in archaea and some bacteria, N-linked glycosylation has evolved into the most common covalent protein modification in eukaryotic cells. The sugars are added to nascent proteins as a core oligosaccharide unit, which is then extensively modified by removal and addition of sugar residues in the endoplasmic reticulum (ER) and the Golgi complex. It has become evident that the modifications that take place in the ER reflect a spectrum of functions related to glycoprotein folding, quality control, sorting, degradation, and secretion. The glycans not only promote folding directly by stabilizing polypeptide structures but also indirectly by serving as recognition "tags" that allow glycoproteins to interact with a variety of lectins, glycosidases, and glycosyltranferases. Some of these (such as glucosidases I and II, calnexin, and calreticulin) have a central role in folding and retention, while others (such as alpha-mannosidases and EDEM) target unsalvageable glycoproteins for ER-associated degradation. Each residue in the core oligosaccharide and each step in the modification program have significance for the fate of newly synthesized glycoproteins.
The Role of PPARs in Lung Fibrosis (2007)

Pulmonary fibrosis is a group of disorders characterized by accumulation of scar tissue in the lung interstitium, resulting in loss of alveolar function, destruction of normal lung architecture, and respiratory distress. Some types of fibrosis respond to corticosteroids, but for many there are no effective treatments. Prognosis varies but can be poor. For example, patients with idiopathic pulmonary fibrosis (IPF) have a median survival of only 2.9 years. Prognosis may be better in patients with some other types of pulmonary fibrosis, and there is variability in survival even among individuals with biopsy-proven IPF. Evidence is accumulating that the peroxisome proliferator-activated receptors (PPARs) play important roles in regulating processes related to fibrogenesis, including cellular differentiation, inflammation, and wound healing. PPARalpha agonists, including the hypolidipemic fibrate drugs, inhibit the production of collagen by hepatic stellate cells and inhibit liver, kidney, and cardiac fibrosis in animal models. In the mouse model of lung fibrosis induced by bleomycin, a PPARalpha agonist significantly inhibited the fibrotic response, while PPARalpha knockout mice developed more serious fibrosis. PPARbeta/delta appears to play a critical role in regulating the transition from inflammation to wound healing. PPARbeta/delta agonists inhibit lung fibroblast proliferation and enhance the antifibrotic properties of PPARgamma agonists. PPARgamma ligands oppose the profibrotic effect of TGF-beta, which induces differentiation of fibroblasts to myofibroblasts, a critical effector cell in fibrosis. PPARgamma ligands, including the thiazolidinedione class of antidiabetic drugs, effectively inhibit lung fibrosis in vitro and in animal models. The clinical availability of potent and selective PPARalpha and PPARgamma agonists should facilitate rapid development of successful treatment strategies based on current and ongoing research.
Regulation of succinate dehydrogenase (sdhCDAB) operon expression in Escherichia coli in response to carbon supply and anaerobiosis: role of ArcA and Fnr (1995)

Succinate dehydrogenase (SDH) of Escherichia coli, the sole membrane-bound enzyme of the tricarboxylic acid cycle, participates in the aerobic electron-transport pathway to generate energy via oxidative phosphorylation reactions. Previous studies have established that succinate dehydrogenase (SDH) synthesis is elevated by aerobiosis and suppressed during growth with glucose. To examine how the sdhCDAB genes that encode SDH are regulated by changes in the environment, sdh-lacZ fusions were constructed and analysed in vivo following cell growth under a variety of alternative culture conditions. Expression of sdh-lacZ was highest under aerobic conditions and was decreased 10-fold in the absence of oxygen. The fnr and arcA gene products are required for this oxygen control and each acts to repress sdhC-lacZ expression. Expression of sdh-lacZ also varied 10- to 14-fold depending on the type of carbon substrate used or the medium richness. This control was shown to be independent of the crp and fruR gene products, and indicates that some other regulatory element exists in the cell to adjust SDH enzyme levels accordingly. Iron and haem availability affected sdhC-lacZ expression by two- to three-fold. Lastly, sdhC-lacZ expression was shown to vary with the cell growth rate during aerobic and anaerobic conditions.
HER‐2 pulsed dendritic cell vaccine can eliminate HER‐2 expression and impact ductal carcinoma in situ (2012)

Results suggest that vaccination against HER-2/neu is safe and well tolerated and induces decline and/or eradication of HER-2/neu expression. These findings warrant further exploration of HER-2/neu vaccination in estrogen-independent breast cancer and highlight the need to target additional tumor-associated antigens and pathways.
Epitope mapping of HLA-B27 and HLA-B7 antigens by using intradomain recombinants. (1988)

To study the HLA-B7 and HLA-B27 antigenic determinants, hybrid genes between these two alleles were constructed by in vivo recombination in Escherichia coli. After transfection of these genes into P815 (high transfection efficiency recipient) murine cells, the bindings of Bw6, HLA-B7, and HLA-B27 allele-specific mAb were studied, as well as that of human anti-HLA-B7 and anti-HLA-B27 monospecific alloantisera. Most of the HLA-B7 antigenic determinants were assigned to the first external domain of the molecule. Four different epitopic areas could be defined: the Bw6 epitope was associated with residues 82 and 83; the BB7.1 epitope to amino acids 63, 67, and 70; the MB40.2 and MB40.3 epitope to amino acid sequence 177-180, and human alloantisera identified as an epitope associated with residue 9. HLA-B27 antigenicity studied by TM-1 mAb was found to involve residues 77 and 80 in the alpha-1 domain. Results obtained with human monospecific alloantisera allowed the definition of an additional allospecific site associated with the NH2 terminal part on the alpha-1 domain of HLA-B27. Epitope mapping fits with data obtained by sequence comparisons and is discussed with reference to the crystallographic three-dimensional structure of the HLA-A2 molecule.
Sequential multiple‐step europium ion implantation and annealing of GaN (2014)

Abstract Sequential multiple Eu ion implantations at low fluence (1×10 13 cm ‐2 at 300 keV) and subsequent rapid thermal annealing (RTA) steps (30 s at 1000 °C or 1100 °C) were performed on high quality nominally undoped GaN films grown by metal organic chemical vapour deposition (MOCVD) and medium quality GaN:Mg grown by hydride vapour phase epitaxy (HVPE). Compared to samples implanted in a single step, multiple implantation/annealing shows only marginal structural improvement for the MOCVD samples, but a significant improvement of crystal quality and optical activation of Eu was achieved in the HVPE films. This improvement is attributed to the lower crystalline quality of the starting material, which probably enhances the diffusion of defects and acts to facilitate the annealing of implantation damage and the effective incorporation of the Eu ions in the crystal structure. Optical activation of Eu 3+ ions in the HVPE samples was further improved by high temperature and high pressure annealing (HTHP) up to 1400 °C. After HTHP annealing the main room temperature cathodo‐ and photoluminescence line in Mg‐doped samples lies at ∼ 619 nm, characteristic of a known Mg‐related Eu 3+ centre, while after RTA treatment the dominant line lies at ∼ 622 nm, typical for undoped GaN:Eu. (© 2014 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
A study of residual stress distribution through the thickness of p/sup +/ silicon films (thermal oxidation effects) (1993)

The effect of thermal oxidation on the residual stress distribution throughout the thickness of heavily-boron-doped (p/sup +/) silicon films is studied. The deflection of p/sup +/ silicon cantilever beams due to residual stress variation throughout the film thickness is studied for as-diffused and thermally oxidized films. Cantilevers of as-diffused p/sup +/ silicon films display a positive curvature (or a negative bending moment), signified by bending up of the beams. Thermal oxidation of the films prior to cantilever fabrication by anisotropic etching modifies the residual stresses in the p/sup +/ film, specially in the near-surface region (i.e. the top 0.3 to 0.5 mu m for the oxidation times used here), and can result in beams with a negative curvature even when the oxide is removed from the p/sup +/ silicon cantilever surface subsequent to cantilever fabrication.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
piRNAs in the Germ Line (2007)

Small noncoding RNAs have emerged as potent regulators of gene expression at both transcriptional and posttranscriptional levels. Recently, a class of small RNAs that interact with Piwi proteins has been discovered in the mammalian germ line and Drosophila. These Piwi-interacting RNAs (piRNAs) represent a distinct small RNA pathway.
Frequency division multiplexing readout and simultaneous manipulation of an array of flux qubits (2012)

An important desired ingredient of superconducting quantum circuits is a readout scheme whose complexity does not increase with the number of qubits involved in the measurement. Here, we present a readout scheme employing a single microwave line, which enables simultaneous readout of multiple qubits. Consequently, scaling up superconducting qubit circuits is no longer limited by the readout apparatus. Parallel readout of 6 flux qubits using a frequency division multiplexing technique is demonstrated, as well as simultaneous manipulation and time resolved measurement of 3 qubits. We discuss how this technique can be scaled up to read out hundreds of qubits on a chip.
Photosensitive protecting groups (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotosensitive protecting groupsAbraham Patchornik, B. Amit, and R. B. WoodwardCite this: J. Am. Chem. Soc. 1970, 92, 21, 6333–6335Publication Date (Print):October 1, 1970Publication History Published online1 May 2002Published inissue 1 October 1970https://pubs.acs.org/doi/10.1021/ja00724a041https://doi.org/10.1021/ja00724a041research-articleACS PublicationsRequest reuse permissionsArticle Views4806Altmetric-Citations398LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Relation between weight and length at birth and body mass index in young adulthood: cohort study: Table 1 (1997)

Few studies have thoroughly examined the relation between weight in early childhood and the later risk of obesity, but recent studies have shown an association between low birth weight and cardiovascular disease in adulthood.1 High birth weight correlates with being overweight in late adolescence,2 and intrauterine growth retardation is associated with a higher ratio of waist to hip circumference (an indicator of abdominal fatness) in men.1 We examined the association between weight and length at birth and adult body mass index in Danish conscripts.

We conducted our study in the fifth conscription district of Denmark. Nearly all Danish men have to appear before the draft board when they are between 18 and 26. We studied all men born after 1 January 1973 …
Structural Identifiability of PBPK Models: Practical Consequences for Modeling Strategies and Study Designs (1997)

Physiologically based pharmacokinetic (PBPK) models usually contain unknown parameters that need to be estimated by calibration to concentration-time profiles from in vivo experiments. However, even with error-free data, the number of parameters that can be estimated in this way is limited, depending on the particular situation. This paper introduces the concept of structural identifiability of a model, a requirement to make the estimation of parameters by calibration a meaningful undertaking. We briefly discuss the techniques-available from systems analysis-for examining the identifiability of models. Two conditions of uniqueness are involved, one relating to the model's equations and its parameters, the other to the number of available observations in time. The assessment of the first uniqueness condition involves rather tedious matrix algebra, requiring the appropriate mathematical expertise. We therefore give some general results for a particular class of PBPK models, indicating in what situations the first uniqueness condition either holds or does not. The assessment of the second uniqueness condition does not require specialized skills, and the minimum number of observations in time necessary can be easily determined for any particular situation. The practical implications for both modeling strategies and experimental protocols are discussed.
Natural Mutations in a 2‘−5‘ Oligoadenylate Synthetase Transgene Revealed Residues Essential for Enzyme Activity (2005)

Unlike other RNA polymerases, 2'-5' oligoadenylate synthetases, a family of interferon-induced enzymes, catalyze the formation of 2'-5', not 3'-5', phosphodiester bonds. Moreover, to be active, these proteins require double-stranded RNA as a cofactor. We have been identifying the specific residues of these proteins that impart their novel properties. Here, we report the identity of three such residues that underwent natural mutations in a transgenic mouse line. When deliberately introduced into recombinant proteins, each of these mutations rendered the protein enzymatically inactive. In an effort to understand the roles of these residues in enzyme activity, new mutants carrying other residues in one of these three sites were generated. Detailed characterization of the properties of the mutant proteins revealed that Lys 404 is needed for proper binding of the acceptor substrate, Pro 500 provides structural flexibility to the protein, and Ser 471 is probably required for its proper folding. This study illustrates the power of using natural mutations in transgenes as guides for studying structure-function relationships of proteins.
Structures of Escherichia coli Branched-Chain Amino Acid Aminotransferase and Its Complexes with 4-Methylvalerate and 2-Methylleucine:  Induced Fit and Substrate Recognition of the Enzyme, (2001)

The following three-dimensional structures of three forms of Escherichia coli branched-chain amino acid aminotransferase (eBCAT) have been determined by the X-ray diffraction method: the unliganded pyridoxal 5'-phosphate (PLP) form at a 2.1 A resolution, and the two complexes with the substrate analogues, 4-methylvalerate (4-MeVA) as the Michaelis complex model and 2-methylleucine (2-MeLeu) as the external aldimine model at 2.4 A resolution. The enzyme is a trimer of dimers, and each subunit consists of small and large domains, and the interdomain loop. The active site is formed by the residues at the domain interface and those from two loops of the other subunit of the dimer unit, and binds one PLP with its re-face directed toward the protein side. Upon binding of a substrate, Arg40 changes its side-chain direction to interact with the interdomain loop, and the loop, which is disordered in the unliganded form, shows its ordered structure on the active-site cavity, interacts with the hydrophobic side chain of the substrate, and shields it from the solvent region. The substrate binds to the active-site pocket with its alpha-hydrogen toward the protein side, its side-chain on the side of O3 of PLP, and its alpha-carboxylate on the side of the phosphate group of PLP. The hydrophobic side-chain of the substrate is recognized by Phe36, Trp126, Tyr129, Tyr164, Tyr31*, and Val109*. The alpha-carboxylate of the substrate binds to the unique site constructed by three polar groups (two main-chain NH groups of the beta-turn at Thr257 and Ala258 and the hydroxy group of Tyr95) which are activated by the access of Arg40 to the main-chain C=O group of the beta-turn and the coordination of Arg97 to the hydroxy group. Since Arg40 is the only residue that significantly changes its side-chain conformation and directly interacts with the interdomain loop and the beta-turn, the residue plays important roles in the induced fit of the interdomain loop and the alpha-carboxylate recognition of the substrate.
Educational clinical case series in pediatric allergy and immunology (2007)

Eosinophilic inflammation may occur in any part of the intestinal tract from the esophagus to the rectum. Despite 70 yr having passed since the first reference to a case of eosinophilic gastroenteritis, the epidemiology and natural history of eosinophilic gastrointestinal disorders are still poorly known. Insights into their etiology and pathogenesis have revealed an important role for allergens; interleukins 4, 5, and 13; the eotaxin family of chemokines; and eosinophil-derived proteins. Diagnosis is confirmed by typical histologic features in a patient with a suggestive clinical phenotype. Treatment involves eliminating triggering allergens, making dietary restrictions the first choice of therapy in a compliant patient; corticosteroids [topical in eosinophilic esophagitis (EE)], despite the potential for serious side effects, are used with success in refractory and non-compliant patients. In this study we discuss EE and gastroduodenitis against the backdrop of clinical case presentations.
Hydrogel-Based Microreactors as a Functional Component of Microfluidic Systems (2002)

A simple two-step method for fabricating poly(ethylene glycol) (PEG) hydrogel-based microreactors and microsensors within microfluidic channels is described. The intrachannel micropatches contain either a dye, which can report the pH of a solution within a fluidic channel, or enzymes that are able to selectively catalyze specific reactions. Analytes present within the microfluidic channel are able to diffuse into the micropatches, encounter the enzymes, and undergo conversion to products, and then the products interact with the coencapsulated dye to signal the presence of the original substrate. The micropatches are prepared by photopolymerizing the PEG precursor within the channel of a microfluidic system consisting of a poly(dimethylsiloxane) mold and a glass plate. Exposure takes place through a slit mask oriented perpendicular to the channel, so the size of the resulting micropatch is defined by the channel dimensions and the width of the slit mask. Following polymerization, the mold is removed, leaving behind the micropatch(es) atop the glass substrate. The final microfluidic device is assembled by irreversibly binding the hydrogel-patterned glass slide to a second PDMS mold that contains a larger channel. Multiple micropatches containing the same or different enzymes can be fabricated within a single channel. The viability of this approach is demonstrated by sensing glucose using micropatches copolymerized with glucose oxidase, horseradish peroxidase, and a pH-sensitive dye.