gebhart/patrepeval huggingface dataset:
Apolipoprotein E (1999)

Apolipoprotein E is a key regulator of plasma lipid levels. Our appreciation of its role continues to expand as additional aspects of its function are discovered. Apolipoprotein E affects the levels of all lipoproteins, either directly or indirectly by modulating their receptor-mediated clearance or lipolytic processing and the production of hepatic very low density lipoproteins. Furthermore, it plays a critical role in neurobiology. The apolipoprotein E4 allele is the major susceptibility gene related to the occurrence and early age of onset of Alzheimer's disease. It is probable that one of the major functions of apolipoprotein E in the central nervous system is to mediate neuronal repair, remodeling, and protection, with apolipoprotein E4 being less effective than the E3 and E2 alleles. The isoform-specific effects of apolipoprotein E are currently being unraveled through detailed structure and function studies of this protein.
Hämoglobin A1-Analyse mit dem Mikrosäuleverfahren und Ergebnisse der Ringversuche (1984)

Zusammenfassung: Das Mikrosuleverfahren ist ein in der methodischen Durchfhrung einfaches und in der Reproduzierbarkeit der Ergebnisse gutes Analysenverfahren. Es hat sich in Diagnose und auch in Therapiekontrolle des Diabetes bewhrt. Die interne und externe Qualittskontrolle weisen dieses
Stability and Transformations of bis-PNA/DNA Triplex Structural Isomers (2004)

Structurally isomeric complexes formed between homopyrimidine bis-PNAs (T(2)JT(2)JT(4)-linker-T(4)CT(2)CT(2)) and single- and double-stranded DNA targets were investigated. These complexes are triplexes designated S1, S2 and S3 in order of increased mobility by polyacrylamide gel electrophoresis. It is shown that the S3 isomer is formed only on double-stranded DNA and possesses highest stability. Isomers S2 and S1 are formed upon binding of bis-PNA to double-stranded as well as to single-stranded DNA. It was found that the stability of the isomer S1 increases dramatically in the presence of excess single-stranded oligonucleotide complementary to the bis-PNA. The structure of the stabilized S1 isomer is proposed to consist of two bis-PNA/DNA triplexes. The relationship between the yield of the isomer S1 formed on single-stranded DNA and the bis-PNA concentration was investigated and a kinetic model of the formation of S1 is presented.
Transphoresis and Isotachophoresis—Automatable Fast Analysis of Electrolytes, Proteins, and Cells, with Suppression of Gravitational Effects (1974)

Abstract Transphoresis and isotachophoresis are defined as related fast high-resolution displacement electrophoretic methods, in which there are sharply separated compartments of uniform concentration, without gaussian zones. Electrical detection allows simultaneous analog or digital expression of quantity and identity from a single staircase signal. Use of free solution or dilute colloid in a capillary allows mechanical sample introduction, flushing, and reloading. Microliters of sample and inexpensive stock solutions are used and subnanomole quantities may be analyzed in minutes or seconds. All ions of one sign are analyzed simultaneously without staining, chemical reaction, or elution. The method is suitable for body fluids, and possibly for use with serum proteins. Temperature effects are less severe than in zone methods; but for proteins and cells gravitational distortions must be circumvented by rotation, stirring density gradients, or isopycnic solvents. Results of small ion, protein, and cell separations are given, and a separation in zero-gravity in Skylab is referred to.
Evolving enzyme technology for pharmaceutical applications: case studies (1997)

The case studies focus on two types of enzyme applications for pharmaceutical development. Demethylmacrocin O-methyltransferase, macrocin O-methyltransferase (both putatively rate-limiting) and tylosin reductase were purified from Streptomyces fradiae, characterized and the genes manipulated for increasing tylosin biosynthesis in S. fradiae. The rate-limiting enzyme, deacetoxycephalosporin C (DAOC) synthase/hydroxylase (expandase/ hydroxylase), was purified from Cephalosporium acremonium, its gene over-expressed, and cephalosporin C biosynthesis improved in C. acremonium. Also, heterologous expression of penicillin N epimerase and DAOC synthase (expandase) genes of Streptomyces clavuligerus in Penicillium chrysogenum permitted DAOC production in the fungal strain. Second, serine hydroxymethyltransferase of Escherichia coli and phthalyl amidase of Xanthobacter agilis were employed in chemo-enzymatic synthesis of carbacephem. Similarly, echinocandin B deacylase of Actinoplanes utahensis was used in the second-type synthesis of the ECB antifungal agent.
SENDMAIL — An Internetwork Mail Router (1998)

Routing mail through a heterogenous internet presents many new problems. Among the worst of these is that of address mapping. Historically, this has been handled on an ad hoc basis. However, this approach has become unmanageable as internets grow. Sendmail acts a unified &amp;quot;post office&amp;quot; to which all mail can be submitted. Address interpretation is controlled by a production system, which can parse both domain-based addressing and old-style ad hoc addresses. The production system is powerful enough to rewrite addresses in the message header to conform to the standards of a number of common target networks, including old (NCP/RFC733) Arpanet, new (TCP/RFC822) Arpanet, UUCP, and Phonenet. Sendmail also implements an SMTP server, message queueing, and aliasing. Sendmail implements a general internetwork mail routing facility, featuring aliasing and forwarding, automatic routing to network gateways, and flexible configuration. In a simple network, each node has an address, and resources can ...
Development of a Monoclonal Anti-Immunoglobulin E Antibody (Omalizumab) for the Treatment of Allergic Respiratory Disorders (2001)

Immunoglobulin E (IgE) mediates many of the inflammatory processes that underlie the symptoms of asthma and other allergic respiratory disorders. Recently, a recombinant, humanized, monoclonal antibody (mAb) that binds to and neutralizes IgE has been developed for the treatment of these disorders. Preclinical and clinical studies have shown that this mAb, directed against IgE and known as omalizumab, inhibits the binding of IgE to its receptors on effector cells, reduces IgE synthesis by B cells in response to allergen exposure, decreases the expression of IgE receptors, and attenuates both immediate and delayed inflammatory airway responses following exposure to inhaled allergen. Omalizumab is nonanaphylactogenic, and clinical experience to date suggests that omalizumab is safe and well tolerated by patients. These results suggest that specific inhibition of IgE may be an important new therapeutic option for the treatment of asthma and related disorders.
Bacterial Community Morphogenesis Is Intimately Linked to the Intracellular Redox State (2013)

Many microbial species form multicellular structures comprising elaborate wrinkles and concentric rings, yet the rules governing their architecture are poorly understood. The opportunistic pathogen Pseudomonas aeruginosa produces phenazines, small molecules that act as alternate electron acceptors to oxygen and nitrate to oxidize the intracellular redox state and that influence biofilm morphogenesis. Here, we show that the depth occupied by cells within colony biofilms correlates well with electron acceptor availability. Perturbations in the environmental provision, endogenous production, and utilization of electron acceptors affect colony development in a manner consistent with redox control. Intracellular NADH levels peak before the induction of colony wrinkling. These results suggest that redox imbalance is a major factor driving the morphogenesis of P. aeruginosa biofilms and that wrinkling itself is an adaptation that maximizes oxygen accessibility and thereby supports metabolic homeostasis. This type of redox-driven morphological change is reminiscent of developmental processes that occur in metazoans.
Species specificity in the interaction of CD8 with the alpha 3 domain of MHC class I molecules (1992)

The alpha 1 and alpha 2 domains of the class I MHC molecule constitute the putative binding site for processed peptides and the TCR, although the alpha 3 domain has been implicated as a binding site for the CD8 molecule. Species specificity in the binding of CD8 to the alpha 3 domain has been suggested as an explanation for the low xenogeneic T cell response to class I molecules, but results on this point have been conflicting and controversial. We have addressed this issue using CTL lines from HLA-A2.1 transgenic mice that specifically recognize and lyse A2.1-expressing cells infected with influenza A/PR/8 or pulsed with influenza matrix peptide M1(57-68). Species specificity was examined using transfectants that expressed hybrid molecules containing the alpha 1 and alpha 2 domains from HLA-A2.1 and the alpha 3 domain from a murine class I molecule. Lower levels of M1(57-68) peptide were required to sensitize L cell transfectants expressing a chimera that contained an H-2Dd alpha 3 domain than targets expressing the intact A2.1 molecule. However, at high doses of peptide, lysis of these two targets was similar. However, no reproducible difference in sensitization was observed using EL4 or Jurkat transfectants expressing A2.1 or A2.1 chimeric molecules that contained an H-2Kb alpha 3 domain. In all cases, however, lysis of peptide-pulsed A2.1 expressing targets was more sensitive to inhibition with anti-CD8 mAb than lysis of cells expressing these chimeric molecules. Thus, under suboptimal conditions such as low Ag density or in the presence of anti-CD8 mAb, these CTL preferentially recognize class I molecules with a murine alpha 3 domain. This suggests that there is some species specificity in the interaction of CD8 with the alpha 3 domain of the class I molecule. However, CTL recognition was inhibited by point mutations in the alpha 3 domain of HLA-A2.1 that have been shown to inhibit binding of human CD8 and recognition by human CTL, suggesting that murine CD8 interacts to some degree with human alpha 3 domains, and that similar alpha 3 domain residues may be important for murine and human CD8 binding. The relevance of these results to an understanding of low xenogeneic responses is discussed.
Antibody to rheumatoid arthritis associated nuclear antigen (RANA) in familial rheumatoid arthritis. (1984)

A search was made for the presence of antibody to the rheumatoid arthritis (RA) associated nuclear antigen (RANA) in the sera of 57 affected and unaffected members of 10 families with multiple members affected with RA. While anti-RANA was frequently observed among the seropositive affected individuals with definite or classical RA (60%), it was less frequently observed among those family members who had incompletely expressed disease, and rarely among normal close family members including those sharing haplotypes with the affected index case. An HLA haplotype containing B8, DR3 was more frequently seen among anti-RANA positive (61%) than anti-RANA negative (44%) RA patients. These data do not support a primary early role for the Epstein-Barr virus related antigen RANA in the etiology of RA. They may indicate a possible influence of the complete haplotype HLA-B8, DR3 on the expression of anti-RANA in established RA.
Dexamethasone alters F‐actin architecture and promotes cross‐linked actin network formation in human trabecular meshwork tissue (2004)

Elevated intraocular pressure is an important risk factor for the development of glaucoma, a leading cause of irreversible blindness. This ocular hypertension is due to increased hydrodynamic resistance to the drainage of aqueous humor through specialized outflow tissues, including the trabecular meshwork (TM) and the endothelial lining of Schlemm's canal. We know that glucocorticoid therapy can cause increased outflow resistance and glaucoma in susceptible individuals, that the cytoskeleton helps regulate aqueous outflow resistance, and that glucocorticoid treatment alters the actin cytoskeleton of cultured TM cells. Our purpose was to characterize the actin cytoskeleton of cells in outflow pathway tissues in situ, to characterize changes in the cytoskeleton due to dexamethasone treatment in situ, and to compare these with changes observed in cell culture. Human ocular anterior segments were perfused with or without 10(-7) M dexamethasone, and F-actin architecture was investigated by confocal laser scanning microscopy. We found that outflow pathway cells contained stress fibers, peripheral actin staining, and occasional actin "tangles." Dexamethasone treatment caused elevated IOP in several eyes and increased overall actin staining, with more actin tangles and the formation of cross-linked actin networks (CLANs). The actin architecture in TM tissues was remarkably similar to that seen in cultured TM cells. Although CLANs have been reported previously in cultured cells, this is the first report of CLANs in tissue. These cytoskeletal changes may be associated with increased aqueous humor outflow resistance after ocular glucocorticoid treatment.
Increased serum level of vascular endothelial growth factor in Mycobacterium avium complex infection (2006)

This study suggests that VEGF may be associated with the pathogenesis of pulmonary MAC infection. Additionally, serum VEGF levels may be a useful surrogate marker for evaluating the extent of disease and of the response to treatment.
A Stromal Cell-Derived Factor 1α Analogue Improves Endothelial Cell Function in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome (2016)

Endothelial cell (EC) dysfunction is a critical mediator of the acute respiratory distress syndrome (ARDS). Recent studies have demonstrated that stromal cell-derived factor 1α (SDF-1α) promotes EC barrier integrity. Our previous studies used a SDF-1α analogue CTCE-0214 (CTCE) in experimental sepsis and demonstrated that it attenuated vascular leak and modulated microRNA (miR) levels. We examined the hypothesis that CTCE improves EC function in lipopolysaccharide (LPS)-induced ARDS through increasing miR-126 expression. Human microvascular endothelial cells (HMVECs) were treated with thrombin to disrupt the EC integrity followed by incubation with CTCE or SDF-1α. Barrier function was determined by trans-endothelial electrical resistance assay. CTCE-induced alterations in miRNA expression and signaling pathways involved in barrier function were determined. Thrombin-induced vascular leak was abrogated by both CTCE and SDF-1α. CTCE also prevented thrombin-induced decreases of vascular endothelial (VE)-cadherin cell surface expression and expansion of the intercellular space. CTCE increased miR-126 levels and induced activation of AKT/Rac 1 signaling. Cotreatment with a miR-126 inhibitor blocked the protective effects of CTCE on AKT activation and endothelial permeability. In subsequent <i>in vivo</i> studies, ARDS was induced by intratracheal instillation of LPS. Intravenous injection of CTCE diminished the injury severity as evidenced by significant reductions in protein, immune cells, inflammatory cytokines and chemokines in the bronchoalveolar lavage fluid, increased miR-126 expression and decreased pulmonary vascular leak and alveolar edema. Taken together, our data show that CTCE improves endothelial barrier integrity through increased expression of miR-126 and activation of Rac 1 signaling and represents an important potential therapeutic strategy in ARDS.
Theoretical study of the two-dimensional electron mobility in strained III-nitride heterostructures (2001)

We present calculations of the two-dimensional (2D) electron mobility in III-nitride heterojunction structures in the presence of spontaneous and piezoelectrically induced polarization effects. The calculations are made using a self-consistent solution of the Schrödinger, Poisson, charge and potential balance equations. It is found that the polarization fields act to significantly increase the 2D sheet charge concentration while reducing the mobility. The mobility reduction results from the enhanced band bending and subsequent attraction of the electrons to the heterointerface where they experience increased surface roughness scattering. Good agreement is obtained between the theoretical calculations and experimental measurements over the full temperature range examined. Comparison of the mobility in InGaN/GaN to AlGaN/GaN heterostructures is made. It is found that the mobility is significantly higher in the InGaN/GaN structure than in the AlGaN/GaN structure.
Myelodysplastic Syndromes (2011)

These suggested practice guidelines are based on extensive evaluation of the reviewed risk-based data and indicate useful current approaches for managing patients with MDS. Four drugs have recently been approved by the FDA for treating specific subtypes of MDS: lenalidomide for MDS patients with del(5q) cytogenetic abnormalities; azacytidine and decitabine for treating patients with higher-risk or nonresponsive MDS; and deferasirox for iron chelation of iron overloaded patients with MDS. However, because a substantial proportion of patient subsets with MDS lack effective treatment for their cytopenias or for altering disease natural history, clinical trials with these and other novel therapeutic agents along with supportive care remain the hallmark of management for this disease. The role of thrombopoietic cytokines for management of thrombocytopenia in MDS needs further evaluation. In addition, further determination of the effects of these therapeutic interventions on the patient's quality of life is important.(116,119,120,128,129) Progress toward improving management of MDS has occurred over the past few years, and more advances are anticipated using these guidelines as a framework for coordination of comparative clinical trials.
Recognizing Hand-Printed Letters and Digits Using Backpropagation Learning (1991)

We report on results of training backpropagation nets with samples of hand-printed digits scanned off of bank checks and hand-printed letters interactively entered into a computer through a stylus digitizer. Generalization results are reported as a function of training set size and network capacity. Given a large training set, and a net with sufficient capacity to achieve high performance on the training set, nets typically achieved error rates of 4-5% at a 0% reject rate and 1-2% at a 10% reject rate. The topology and capacity of the system, as measured by the number of connections in the net, have surprisingly little effect on generalization. For those developing hand-printed character recognition systems, these results suggest that a large and representative training sample may be the single, most important factor in achieving high recognition accuracy. Benefits of reducing the number of net connections, other than improving generalization, are discussed.
Return of FEV1 after pulmonary exacerbation in children with cystic fibrosis (2010)

Approximately one in four patients with CF failed to recover to baseline lung function after a pulmonary exacerbation despite treatment with intravenous antibiotics. Failure to recover to baseline was associated with the degree of decline in FEV(1) that had occurred prior to hospital admission, suggesting opportunities for earlier intervention to improve lung function outcomes. Additional studies are needed to determine how the failure to recover to baseline affects subsequent FEV(1) decline.
Two genes substitute for the mouse Y chromosome for spermatogenesis and reproduction (2016)

The mammalian Y chromosome is considered a symbol of maleness, as it encodes a gene driving male sex determination, Sry, as well as a battery of other genes important for male reproduction. We previously demonstrated in the mouse that successful assisted reproduction can be achieved when the Y gene contribution is limited to only two genes, Sry and spermatogonial proliferation factor Eif2s3y. Here, we replaced Sry by transgenic activation of its downstream target Sox9, and Eif2s3y, by transgenic overexpression of its X chromosome-encoded homolog Eif2s3x. The resulting males with no Y chromosome genes produced haploid male gametes and sired offspring after assisted reproduction. Our findings support the existence of functional redundancy between the Y chromosome genes and their homologs encoded on other chromosomes.
Chemical and Physical Structure of Polymers as Carriers for Controlled Release of Bioactive Agents: A Review (1983)

Abstract In a controlled release system a drug, pesticide, or other bio-active agent is incorporated into a carrier, generally a polymeric material. The rate of release of the substance is determined by the properties of the polymer itself and is only weakly dependent on environmental factors (such as the pH of bodily fluids). Controlled release systems are capable of delivering substances slowly and continuously for up to several years.
The Impact of Herbicide-Resistant Rice Technology on Phenotypic Diversity and Population Structure of United States Weedy Rice (2014)

The use of herbicide-resistant (HR) Clearfield rice (Oryza sativa) to control weedy rice has increased in the past 12 years to constitute about 60% of rice acreage in Arkansas, where most U.S. rice is grown. To assess the impact of HR cultivated rice on the herbicide resistance and population structure of weedy rice, weedy samples were collected from commercial fields with a history of Clearfield rice. Panicles from each weedy type were harvested and tested for resistance to imazethapyr. The majority of plants sampled had at least 20% resistant offspring. These resistant weeds were 97 to 199 cm tall and initiated flowering from 78 to 128 d, generally later than recorded for accessions collected prior to the widespread use of Clearfield rice (i.e. historical accessions). Whereas the majority (70%) of historical accessions had straw-colored hulls, only 30% of contemporary HR weedy rice had straw-colored hulls. Analysis of genotyping-by-sequencing data showed that HR weeds were not genetically structured according to hull color, whereas historical weedy rice was separated into straw-hull and black-hull populations. A significant portion of the local rice crop genome was introgressed into HR weedy rice, which was rare in historical weedy accessions. Admixture analyses showed that HR weeds tend to possess crop haplotypes in the portion of chromosome 2 containing the ACETOLACTATE SYNTHASE gene, which confers herbicide resistance to Clearfield rice. Thus, U.S. HR weedy rice is a distinct population relative to historical weedy rice and shows modifications in morphology and phenology that are relevant to weed management.