gebhart/patrepeval huggingface dataset:
The role of intraalveolar fibrosis in the process of pulmonary structural remodeling in patients with diffuse alveolar damage. (1987)

For a study of the processes and mechanisms of pulmonary structural remodeling in fibrotic lungs and metaplastic squamous epithelial cells in fibrotic alveoli, immunohistochemical, ultrastructural, and light-microscopic morphometric observations were made of the lungs in acute and proliferative stages of diffuse alveolar damage (n = 40) obtained from biopsies and autopsies. Morphometry showed that intraalveolar fibrosis developed in the early proliferative stage and was more prominent than interstitial fibrosis. In the early proliferative stage, activated myofibroblasts migrated into intraalveolar spaces through gaps in the epithelial basement membrane. They then attached to the luminal side of epithelial basement membrane and produced intraalveolar fibrosis and coalescence of alveolar walls. This intraalveolar fibrosis was the essential factor in the remodeled lungs. Albumin, fibrinogen, immunoglobulins, and surfactant apoprotein were present throughout the hyaline membrane. Fibronectin was not found in hyaline membrane of the lesions in early acute stage but was demonstrated in later stages in outer layers of hyaline membranes and in the areas of intraalveolar fibrosis. Fibronectin may be responsible for the migration and proliferation of myofibroblasts in intraalveolar spaces. Metaplastic single-layered and stratified squamous epithelial cells were keratin-positive and surfactant apoprotein-negative. These metaplastic epithelial cells were frequently found in the alveoli with minimal Type II epithelial cell proliferation and in the grossly scarred alveoli.
Enhanced tumorigenesis of NR6 cells which express non-down-regulating epidermal growth factor receptors. (1991)

Sequences in the regulatory carboxyl terminus of the epidermal growth factor (EGF) receptor are required for ligand-induced internalization via a high-affinity saturable endocytic pathway and for receptor down-regulation. To investigate the role of down-regulation in attenuating mitogenic signals, we compared the ability of NR6 cells expressing holo and mutant down-regulation defective EGF receptors to form tumors in athymic mice. NR6 cells expressing mutant EGF receptors reproducibly formed rapidly growing tumors, whereas cells expressing holo EGF receptors had a low tumorigenic potential. Serial passage of tumors of NR6 cells expressing mutant EGF receptors resulted in an enhanced rate of tumor formation that directly correlated with increased expression of mutant receptors. Tumor growth was inhibited by a competitive antagonist anti-EGF receptor monoclonal antibody. Excessive signaling from the cell surface can result from lack of sequences required for endocytosis and from saturation of endocytic mechanisms. Non-down-regulating kinase-active EGF receptors provide an especially strong growth signal, manifested as rapid tumor growth in athymic mice.
Population genomics: a bridge from evolutionary history to genetic medicine (2001)

Studies of human genetic variation are making contributions in several key areas. Evolutionary genetic studies yield critical clues about the histories of human populations, and they provide substantial support for an African origin of modern humans. The analysis of genetic variation has formed a foundation for DNA-based forensic applications. And, as attention is focused on locating genes underlying complex diseases, it is becoming clear that a better understanding of genetic variation will help to guide gene-mapping efforts. Population genomics, the large-scale comparison of DNA sequences, is now beginning to provide new insights in these areas. We review some of the general patterns of human genetic variation, and we show how our knowledge of these patterns can aid in the mapping and cloning of disease-causing genes.
GENERATION, TRANSLOCATION, AND PRESENTATION OF MHC CLASS I-RESTRICTED PEPTIDES (1995)

The T lymphocytes of the vertebrate immune system look for changes that take place within the organism by examining a display of peptides at the cell surface. These peptides are presented by the products of the major histocompatibility complex (MHC). MHC class I products present peptides derived by proteolysis of cytosolic proteins by the multicatalytic protease, the proteasome. These peptides are translocated from the cytosol into the endoplasmic reticulum by a dedicated peptide transporter, the transporter associated with antigen presentation (TAP). TAP consists of two subunits, and translocates peptides that are approximately 8-12 residues in length. The COOH terminal residue of the peptide is a major determinant in the specificity of translocation. Following translocation, peptides bind to MHC class I molecules, which depend on the peptide ligand as well as on interactions with chaperonins for proper folding. These complexes then egress from the ER and are transported to their final destination, the cell surface.
Chlorobutanol: maternal serum levels and placental transfer in the mouse. (1997)

Chlorobutanol (CB) is a pharmaceutical preservative and the active ingredient in certain sedatives and anesthetics and produces adverse effects in adult tissues and mouse embryos in vitro. Chlorobutanol is slowly eliminated in humans, but little is known about its serum levels in other species or placental transfer in any species. Pregnant mice gavaged with 80 mg CB/kg on gestational day (gd) 9.5 provided serum at 10 min to 36 h post-dosing for a time course study. Additional mice gavaged with 0, 8, 40 or 80 mg CB/kg on gd 9.5 provided maternal serum and embryos 2 h post-dosing for a placental transfer study, and CB levels were measured using capillary gas chromatography with electron capture detection. Dosing with 80 mg CB/kg produced maternal serum levels between 30.8 micrograms/mL (10 min) and < 1 microgram/mL (36 h), with a half-life of 7.45 h. Embryonic CB levels increased with maternal dose and were correlated with maternal serum levels. Serum levels of CB in the mouse appeared to follow a time course similar to humans, with rapid absorption and slow elimination. Placental transfer, as demonstrated here in the mouse, may allow embryonic accumulation of CB to potentially toxic levels.
Genotype Imputation (2009)

Genotype imputation is now an essential tool in the analysis of genome-wide association scans. This technique allows geneticists to accurately evaluate the evidence for association at genetic markers that are not directly genotyped. Genotype imputation is particularly useful for combining results across studies that rely on different genotyping platforms but also increases the power of individual scans. Here, we review the history and theoretical underpinnings of the technique. To illustrate performance of the approach, we summarize results from several gene mapping studies. Finally, we preview the role of genotype imputation in an era when whole genome resequencing is becoming increasingly common.
5-Hydroxytryptamine (serotonin) in the gastrointestinal tract (2013)

New studies show that enteric 5-HT is a polyfunctional signalling molecule, acting both in developing and mature animals as a neurotransmitter paracrine factor, endocrine hormone and growth factor.
Easier Tissue Macroarray (???Microchop???) Production (2003)

Fernández, Pedro Luis MD; Nayach, Iracema LT; Fernández, Eva LT; Fresno, Lucila LT; Palacín, Antonio MD; Farré, Xavier MD; Campo, Elías MD; Cardesa, Antonio MD Author Information
Posttraumatic Osteoarthritis Caused by Battlefield Injuries (2012)

The Army Physical Evaluation Board results for wounded warriors from a previously described cohort were reviewed to identify permanently disabling conditions and whether the conditions were preexisting or caused by battlefield injury. Arthritis was the most common unfitting condition in this cohort, with 94.4% of cases attributed to combat injury and only 5.6% attributed to preexisting conditions or documented in the health records prior to battle injury. The most common causes of injury that resulted in arthritis were intra-articular fractures secondary to explosions, traumatic arthrotomies resulting from fragment projectiles, and gunshot wounds. Arthritis was recognized as a disabling condition an average of 19 ± 10 months after injury. Research is needed to enhance prevention and management of joint injuries in order to minimize the disabling effects of joint degeneration in this young patient population.
Glycosidase antibodies induced to a half-chair transition-state analog (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGlycosidase antibodies induced to a half-chair transition-state analogHiroaki Suga, Norihiko Tanimoto, Anthony J. Sinskey, and Satoru MasamuneCite this: J. Am. Chem. Soc. 1994, 116, 24, 11197–11198Publication Date (Print):November 1, 1994Publication History Published online1 May 2002Published inissue 1 November 1994https://pubs.acs.org/doi/10.1021/ja00103a061https://doi.org/10.1021/ja00103a061research-articleACS PublicationsRequest reuse permissionsArticle Views243Altmetric-Citations25LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Charges in the hydrophobic interior of proteins (2010)

Charges are inherently incompatible with hydrophobic environments. Presumably for this reason, ionizable residues are usually excluded from the hydrophobic interior of proteins and are found instead at the surface, where they can interact with bulk water. Paradoxically, ionizable groups buried in the hydrophobic interior of proteins play essential roles, especially in biological energy transduction. To examine the unusual properties of internal ionizable groups we measured the pK(a) of glutamic acid residues at 25 internal positions in a stable form of staphylococcal nuclease. Two of 25 Glu residues titrated with normal pK(a) near 4.5; the other 23 titrated with elevated pK(a) values ranging from 5.2-9.4, with an average value of 7.7. Trp fluorescence and far-UV circular dichroism were used to monitor the effects of internal charges on conformation. These data demonstrate that although charges buried in proteins are indeed destabilizing, charged side chains can be buried readily in the hydrophobic core of stable proteins without the need for specialized structural adaptations to stabilize them, and without inducing any major conformational reorganization. The apparent dielectric effect experienced by the internal charges is considerably higher than the low dielectric constants of hydrophobic matter used to represent the protein interior in electrostatic continuum models of proteins. The high thermodynamic stability required for proteins to withstand the presence of buried charges suggests a pathway for the evolution of enzymes, and it underscores the need to mind thermodynamic stability in any strategy for engineering novel or altered enzymatic active sites in proteins.
T cell immunity as a tool for studying epigenetic regulation of cellular differentiation (2013)

Cellular differentiation is regulated by the strict spatial and temporal control of gene expression. This is achieved, in part, by regulating changes in histone post-translational modifications (PTMs) and DNA methylation that in turn, impact transcriptional activity. Further, histone PTMs and DNA methylation are often propagated faithfully at cell division (termed epigenetic propagation), and thus contribute to maintaining cellular identity in the absence of signals driving differentiation. Cardinal features of adaptive T cell immunity include the ability to differentiate in response to infection, resulting in acquisition of immune functions required for pathogen clearance; and the ability to maintain this functional capacity in the long-term, allowing more rapid and effective pathogen elimination following re-infection. These characteristics underpin vaccination strategies by effectively establishing a long-lived T cell population that contributes to an immunologically protective state (termed immunological memory). As we discuss in this review, epigenetic mechanisms provide attractive and powerful explanations for key aspects of T cell-mediated immunity - most obviously and notably, immunological memory, because of the capacity of epigenetic circuits to perpetuate cellular identities in the absence of the initial signals that drive differentiation. Indeed, T cell responses to infection are an ideal model system for studying how epigenetic factors shape cellular differentiation and development generally. This review will examine how epigenetic mechanisms regulate T cell function and differentiation, and how these model systems are providing general insights into the epigenetic regulation of gene transcription during cellular differentiation.
Presenilin-dependent γ-secretase activity modulates thymocyte development (2001)

In neuronal cells, presenilin-dependent gamma-secretase activity cleaves amyloid precursor proteins to release Abeta peptides, and also catalyzes the release of the intracellular domain of the transmembrane receptor Notch. Accumulation of aberrant Abeta peptides appears to be causally related to Alzheimer's disease. Inhibition of Abeta peptide production is therefore a potential target for therapeutic intervention. Notch proteins play an important role in cell fate determination in many different organisms and at different stages of development, for example in mammalian T cell development. We therefore addressed whether structurally diverse gamma-secretase inhibitors impair Notch function by studying thymocyte development in murine fetal thymic organ cultures. Here we show that high concentrations of the most potent inhibitors blocked thymocyte development at the most immature stage. In contrast, lower concentrations or less potent inhibitors impaired differentiation at a later stage, most notably suppressing the development of CD8 single-positive T cells. These phenotypes are consistent with an impairment of Notch signaling by gamma-secretase inhibitors and define a strict Notch dose dependence of consecutive stages during thymocyte development.
Treatment of rosacea with doxycycline monohydrate. (2000)

Rosacea is one of the most commonly occurring inflammatory dermatoses treated by dermatologists today. Estimates suggest that at least 13 million Americans have recognized rosacea, and the clinical experience of most practitioners would add considerably more to that number. Rosacea is an inflammatory condition of the skin, classically presenting with a history of flushing and/or blushing along with the clinical findings of erythema, edema, telangiectasia, papules, pustules, and nodules of the face. Severity and distribution vary considerably. A patient may have only a few scattered papules and pustules of the central third of the face or there may be numerous inflammatory, painful, tender, large nodules. In some cases, only the face may be affected. In other cases, there may be lesions of the scalp, neck, and/or torso. Although the exact etiology is unknown, rosacea is thought by most experts to be an inflammatory process incited by vascular instability with subsequent leakage of fluid and inflammatory mediators into the dermis.
The triacylglycerol synthesis enzyme DGAT1 also catalyzes the synthesis of diacylglycerols, waxes, and retinyl esters (2005)

The final step of triacylglycerol biosynthesis is catalyzed by acyl CoA:diacylglycerol acyltransferase (DGAT) enzymes. The two known DGATs, DGAT1 and DGAT2, are encoded by unrelated genes. Although both DGAT1 and DGAT2 knockout mice have reduced tissue triacylglycerol contents, they have disparate phenotypes, prompting us to investigate whether the two enzymes have unrecognized functional differences. We now report that DGAT1 exhibits additional acyltransferase activities in vitro, including those of acyl CoA:monoacylglycerol acyltransferase (MGAT), wax monoester and wax diester synthases, and acyl CoA:retinol acyltransferase (ARAT), which catalyze the synthesis of diacylglycerols, wax esters, and retinyl esters, respectively. These activities were demonstrated in in vitro assays with membranes from insect cells or homogenates from COS7 cells overexpressing DGAT1. Wax synthase and ARAT activities were also demonstrated in intact COS7 cells expressing DGAT1. Additionally, cells and tissues from DGAT1-deficient mice exhibited reduced ARAT activity, and the mice had increased levels of unesterified retinol in their livers on a high-retinol diet. Our findings indicate that DGAT1 can utilize a variety of acyl acceptors as substrates in vitro and suggest that these activities may be relevant to the in vivo functions of DGAT1.
Potato Peel Waste: Stability and Antioxidant Activity of a Freeze‐Dried Extract (1994)

ABSTRACT Aqueous extracts of potato peel waste were freeze‐dried. High performance liquid chromatography (HPLC) of the freeze‐dried extracts revealed that chlorogenic (50.31%), gallic (41.67%), protocatechuic (7.81%), and caffeic (0.21%) acids were the major phenolics. During 15 days storage of the freeze‐dried extract, no degradation of phenolics occurred. After 4 days storage at 63°C, 5.00g of sunflower oil containing either the freeze‐dried extract (200 ppm) or butylated hydroxyanisole (BHA) (200 ppm) reached peroxide values (PV) of 37.38 and 37.47 meq kg ‐1 respectively. L‐ascorbic acid‐6‐palmitate was the best antioxidant (PV= 10.65 meq kg ‐1 ) but the freeze‐dried extract was as good as BHA.
Enumeration and Characterization of Memory Cells in the TH Compartment (1996)

There is a great deal of interest in understanding how helper T cells differentiate in vivo and exert their regulatory role on a developing, immune response. Essential to development of protective immunity is the development of memory T cells. To study memory T cells in vivo we first need the means to identify and characterize these cells as they develop in their complex microenvironments. We have developed a method which allows us to directly purify both primary and memory helper T cells from the draining lymph nodes of mice as they respond to pigeon cytochrome c in vivo. Junctional sequences from these populations and from individual T cells show a strong selection for CDR3 length and residues characteristic of antigen binding. Overall these studies support a model of progressive clonal maturation with the memory T cell repertoire being more homogeneous than that of the primary response. There is some suggestion that affinity maturation may take place after repeated immunization, but on a more modest scale than that seen for antibodies. Finally we present the use of two new technologies that promise to greatly expand the analysis of immune responses in vivo. The use of flow cytometry with simultaneous detection of five and six fluorescence parameters helps to reliably resolve rare subsets of antigen-specific cells in order to understand the progression of their differentiation in vivo. Lastly, we have developed peptide/MHC tetramers as a new class of staining reagent that has wide applicability in the study of T cell responses in vivo.
Proteomic analysis of the supernatant of red blood cell units: the effects of storage and leucoreduction (2013)

We conclude that a number of proteins increase with RBC storage, which is partially ameliorated with leucoreduction, and transfusion of stored RBCs may introduce mediators that result in adverse events in the transfused host.
A Fast Iterative Shrinkage-Thresholding Algorithm for Linear Inverse Problems (2009)

We consider the class of iterative shrinkage-thresholding algorithms (ISTA) for solving linear inverse problems arising in signal/image processing. This class of methods, which can be viewed as an extension of the classical gradient algorithm, is attractive due to its simplicity and thus is adequate for solving large-scale problems even with dense matrix data. However, such methods are also known to converge quite slowly. In this paper we present a new fast iterative shrinkage-thresholding algorithm (FISTA) which preserves the computational simplicity of ISTA but with a global rate of convergence which is proven to be significantly better, both theoretically and practically. Initial promising numerical results for wavelet-based image deblurring demonstrate the capabilities of FISTA which is shown to be faster than ISTA by several orders of magnitude.
Mesenchymal Stem Cell Therapy in Joint Disease (2003)

Mesenchymal stem cells have the capacity to differentiate into a variety of connective tissue cells including bone, cartilage, tendon, muscle and adipose tissue. These multipotent cells have been isolated from bone marrow and from other adult tissues including skeletal muscle, fat and synovium. Because of their multipotentiality and capacity for self renewal adult stem cells may represent units of active regeneration of tissues damaged as a result of trauma or disease. In certain degenerative diseases such as osteoarthritis (OA) stem cells are depleted, and have reduced proliferative capacity and reduced ability to differentiate. The delivery of stem cells to these individuals may therefore enhance repair or inhibit the progressive destruction of the joint. We have developed methods for the delivery of mesenchymal stem cell preparations taken from bone marrow to the injured knee joint. This treatment has the potential to stimulate regeneration of cartilage and retard the progressive destruction of the joint that typically occurs following injury.