gebhart/patrepeval huggingface dataset:
MICROWAVE TRANSISTOR OSCILLATORS : AN ANALYTIC APPROACH TO SIMPLIFY COMPUTER-AIDED DESIGN (1999)

Microwave oscillator design generally represents a complex problem. Depending on the technical requirements of the oscillator, it is necessary to define the configuration of the oscillation system and transistor type, evaluate and measure smalland large-signal parameters of the transistor equivalent circuit and use an appropriate nonlinear simulator to calculate the oscillator electrical and spectral characteristics. When a transistor is used, representing the circuit as a two-port network is the most suitable approach for computer-aided design of free-running microwave oscillators. In this case, the basic parameters of the equivalent circuit either can be directly measured or approximated on the basis of experimental data with sufficient accuracy over a wide frequency range.1–3 In large-signal operation, it is necessary to define the appropriate parameters of the active two-port network as well as the parameters of the oscillator circuit’s external elements. Initially, the values of the external circuit elements are unknown. In addition, it is difficult to directly choose the values for a given microwave oscillator with a required oscillation frequency without any preliminary calculation. This process can be sufficiently timeconsuming and, in a typical case, calls for much simulation. Therefore, it is convenient to use an analytic method of optimizing microwave oscillator design that incorporates explicit expressions for feedback elements and load impedance in terms of the transistor equivalent circuit elements and its static characteristics.4 A conventional analytic approach to derive explicit expressions for the optimum values of an oscillator circuit first was applied to a bipolar transistor oscillator using an ideal transformer for feedback.5 Later, an analytic approach was used with a GaAs FET oscillator using a simplified transistor model where the influence of internal feedback from the gatedrain capacitance had not been taken into account.6 Such an approach involves a two-step procedure. First, the optimum combination of feedback elements required to realize a smallsignal maximum negative resistance to permit oscillations at the largest amplitude is defined. Then, taking into account the large-signal nonlinearity of the transistor equivalent circuit elements, the realized small-signal negative resistance is characterized to determine the optimum load impedance when maximum output power is generated for a given oscillator circuit configuration.
Treatment of Melanoma by Electroporation of Bacillus Calmette-Guerin (2011)

Electrochemotherapy could be considering as a good method for treatment of cutaneous and subcutaneous tumor lesions. Here we report the case of 59 year-old woman with melanoma malignum cutis, who developed after axillary dissection, cutaneous metastasis not appropriate for surgical operation. Electrochemotherapy with BCG vaccine resulted in good local control of the disease, with a complete response of treated melanoma lesion.
Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation inCPS1 (1998)

Carbamoyl phosphate synthetase I (CPS1) deficiency is an autosomal recessive metabolic disorder affecting the first enzymatic step of urea cycle. We report a consanguineous family in which the index patient died at 11 days of age from a severe form of CPS1 deficiency. Initial diagnosis was based on clinical histopathological, and enzymatic investigations. Direct sequencing of the complete CPS1 coding region revealed a disease-associated homozygous Thr544Met mutation in CPS1. On the basis of the molecular data, prenatal diagnosis was established for genomic DNA and performed at gestational week 12, after chorionic villus sampling. The fetus was homozygous for the Thr544Met mutation, and termination of pregnancy was elected. Histopathological signs of the hepatocellular metabolic disorder similar to that of the index patient were found in fetal liver thus giving morphological evidence for this hereditary error of urea cycle function as early as gestational week 12.
Effects of dehydration and arginine vasopressin infusions on the production of milk and the morphology of the goat udder (1990)

Lactating goats were subjected to dehydration and to infusions of arginine vasopressin (AVP). Dehydration decreased milk production significantly but no changes were observed on the day of AVP infusion. The levels of AVP in plasma reached the same magnitude during both experimental procedures. AVP-immunoreactivity was immunocytochemically detected by light (peroxidase-antiperoxidase technique) and electron microscopy (immuno-Au technique on to glutaraldehyde-fixed, resin-embedded sections) in the mammary gland but not in the control experiments. In addition the cisternae of the rough endoplasmic reticulum in the secretory alveolar cells underwent significant swelling in response to the experimental procedures.
Talent Development and Grouping in the Middle Grades: Challenging the Brightest without Sacrificing the Rest (1995)

Success for all students has been a core commitment of the middle school credo since its formulation in t e early 1960s; it is, many would argue, the central tenet of the middle school concept. Criticism of the junior high leading to the birth of the middle focused on the junior high's lapse into an elitist institu tion where opportunities for success were too often limited to the best and the bright est (Lounsbury, 1960). It was charged that the organization and operation of the junior high having become a little high school, overwhelmingly favored a small group of students who were unusually mature, self-disciplined, exceptionally suc cessful in elementary and who came to school with strong parental support. This star system has been rejected by middle school educators, in academic classrooms and on the athletic field. Over the last 30 years, middle school educators have devoted much energy to ensuring that all students were successful academically— but this was not sufficient. Middle school educators have dedicated similar efforts to guaranteeing that all stu dents experience continuous personal development that results in higher self esteem and more positive citizenship. Middle school components like heteroge neous interdisciplinary teams; advisories; intramurals; active instruction; and an exploratory, needs-based integrated curricu lum sprang from this basic commitment to the success of all students (George & Alexander, 1993). Unfortunately, as the middle school concept quietly developed, slowly gaining success and momentum decade after decade, the national economy deteriorated. Since the early 1960s, the number of family farms has diminished. The American auto
Storing and querying multiversion XML documents using durable node numbers (2005)

Managing multiple versions of XML documents represents an important problem for many traditional applications, such as software configuration control, as well as new ones, such as link permanence of web documents. Research on managing multiversion XML documents seeks to provide efficient and robust techniques for storing, retrieving and querying such documents. In this paper we present a novel approach to version management that achieves these objectives by a scheme based on Durable Node Numbers and timestamps for the elements of XML documents. We first present efficient storage and retrieval techniques for multiversion documents. Then, we explore the indexing and clustering strategies needed to assure efficient support for complex queries on content and on document evolution.
Emergency Department Visits for Antibiotic‐Associated Adverse Events (2008)

Antibiotic-associated adverse events lead to many ED visits, and allergic reactions are the most common events. Minimizing unnecessary antibiotic use by even a small percentage could significantly reduce the immediate and direct risks of drug-related adverse events in individual patients.
Norepinephrine modulates the growth‐inhibitory effect of transforming growth factor‐beta in primary rat hepatocyte cultures (1988)

TGF-beta is a potent inhibitor of EGF-induced DNA synthesis in primary rat hepatocyte cultures. Norepinephrine (NE) was shown to modulate this inhibition of DNA synthesis. It produced a five-fold increase, from 2.8 pM to 14.4 pM, in the ID50 for TGF-beta. The effect was dose-dependent and was significant at concentrations of 10(-6)M NE and greater. The modulation by NE was mediated by the alpha 1-adrenergic receptor as shown by the ability of the alpha 1 antagonist prazosin to block the activity. This effect might be important during liver regeneration in allowing escape of hepatocytes from negative growth control exerted by TGF-beta.
Construction of a Complete Rabbit Cornea Substitute Using a Fibrin-Agarose Scaffold (2006)

These findings suggest that development of a full-thickness rabbit cornea model is possible in the laboratory and may open new avenues for research.
Metabolic regulation analysis of an ethanologenic Escherichia coli strain based on RT-PCR and enzymatic activities (2008)

Results suggest that a higher ethanol formation rate, caused by ahigher PDCZm and ADHZm activities induces a metabolic state that cells compensate through enhanced glucose transport, ATP synthesis, and NAD-NADH+H turnover rates. These results show that glycolytic enzymatic activities, present in E. coli W and C under fermentative conditions, are sufficient to contend with increases in glucose consumption and product formation rates.
Rapid endocytosis of the cystic fibrosis transmembrane conductance regulator chloride channel. (1994)

The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is found at the apical region of exocrine epithelial cells, both at the cell surface and in an apically localized intracellular compartment. To determine if this internal pool was due to endocytosis, a technique was developed that allows the rate of CFTR internalization from the cell surface to be monitored. A two-step periodate/hydrazide biotinylation procedure was used to derivatize cell surface glycoconjugates. Because both of these steps are required for derivatization and are conducted at 4 degrees C, the inclusion of a 37 degrees C incubation between the treatments resulted in an assay for the internalization of cell surface glycoconjugates. CFTR was found to be targeted to a rapidly recycling endocytic pathway, as approximately 50% of cell surface CFTR was internalized within minutes and unavailable for biotinylation. In contrast, the major glycoproteins of the apical surface were not significantly endocytosed during even longer incubations at 37 degrees C. Elevating cAMP levels either by forskolin or cAMP analogs, which has been shown to activate CFTR chloride channel activity, inhibited CFTR internalization. However, cAMP did not affect the internalization of G551D CFTR, a naturally occurring Gly-551-->Asp mutant that is expressed at the cell surface but lacks normal ion-channel function. In addition, the inhibition by cAMP of CFTR was not observed when cells were depleted of cellular chloride. The presence of CFTR in epithelial cells had previously been shown to confer a cAMP-mediated inhibition on the rate of fluid-phase endocytosis. This effect was not seen in chloride-depleted cells, suggesting that CFTR's ion-channel function and localization to incipient endosomes may be responsible for the observed inhibition. The finding that CFTR is targeted to the endocytic pathway may provide insight into the role of CFTR in normal exocrine function. In addition, these findings suggest that the expression of a regulated ion channel in a membranous subcellular compartment provides a mechanism by which a cell can regulate vesicular trafficking through that compartment.
Functional Analysis of Early Secreted Antigenic Target-6, the Dominant T-cell Antigen of Mycobacterium tuberculosis, Reveals Key Residues Involved in Secretion, Complex Formation, Virulence, and Immunogenicity (2005)

Proteins of the 6-kDa early secreted antigenic target (ESAT-6) secretion system-1 of Mycobacterium tuberculosis are not only strongly involved in the anti-mycobacterial Th1-host immune response but are also key players for virulence. In this study, protein engineering together with bioinformatic, immunological, and virulence analyses allowed us to pinpoint regions of the ESAT-6 molecule that are critical for its biological activity in M. tuberculosis. Mutation of the Trp-Xaa-Gly motif, conserved in a wide variety of ESAT-6-like proteins, abolished complex formation with the partner protein CFP-10, induction of specific T-cell responses, and virulence. Replacement of conserved Leu residues interfered with secretion, coiled-coil formation, and virulence, whereas certain mutations at the extreme C terminus did not affect secretion but caused attenuation, possibly because of altered ESAT-6 targeting or trafficking. In contrast, the mutation of several residues on the outer surface of the four-helical bundle structure of the ESAT-6.CFP-10 complex showed much less effect. Construction of recombinant BCG expressing ESAT-6 with a C-terminal hexahistidine tag allowed us to co-purify ESAT-6 and CFP-10, experimentally confirming their strong interaction both in and outside of the mycobacterial cell. The strain induced potent, antigen-specific T-cell responses and intermediate in vivo growth in mice, suggesting that it remained immunogenic and biologically active despite the tag. Together with previous NMR data, the results of this study have allowed a biologically relevant model of the ESAT-6.CFP-10 complex to be constructed that is critical for understanding the structure-function relationship in tuberculosis pathogenesis.
Arteether, a new antimalarial drug: synthesis and antimalarial properties (1988)

Arteether (6) has been prepared from dihydroquinghaosu (3) by etherification with ethanol in the presence of Lewis acid and separated from its chromatographically slower moving alpha-dihydroqinghaosu ethyl ether (7). The absolute stereochemistry at C-12 has been determined by 1H NMR data (J11,12, NOESY). Ethyl ethers 6 and 7 showed potent in vitro inhibition of Plasmodium falciparum, and both compounds were highly potent antimalarials in mice infected with a drug-sensitive strain of Plasmodium berghei. Crystalline arteether (6) and its oily epimer 7 were 2-3 times more potent schizontocides than quinghaosu (1), but deoxy compounds 8, 9, and 11 were 100-300 times less potent in vitro than their corresponding peroxy precursors. Pharmacological studies have shown arteether(6) to have antimalarial activity in animals comparable to artesunate (2) and artemether (4), both of which are fast-acting blood schizontocides in humans. Arteether (6) has now been chosen for a clinical evaluation in high-risk malaria patients.
A Glycoconjugate Antigen Based on the Recognition Motif of a Broadly Neutralizing Human Immunodeficiency Virus Antibody, 2G12, Is Immunogenic but Elicits Antibodies Unable To Bind to the Self Glycans of gp120 (2008)

The glycan shield of human immunodeficiency virus type 1 (HIV-1) gp120 contributes to viral evasion from humoral immune responses. However, the shield is recognized by the HIV-1 broadly neutralizing antibody (Ab), 2G12, at a relatively conserved cluster of oligomannose glycans. The discovery of 2G12 raises the possibility that a carbohydrate immunogen may be developed that could elicit 2G12-like neutralizing Abs and contribute to an AIDS vaccine. We have previously dissected the fine specificity of 2G12 and reported that the synthetic tetramannoside (Man(4)) that corresponds to the D1 arm of Man(9)GlcNAc(2) inhibits 2G12 binding to gp120 as efficiently as Man(9)GlcNAc(2) itself, indicating the potential use of Man(4) as a building block for creating immunogens. Here, we describe the development of neoglycoconjugates displaying variable copy numbers of Man(4) on bovine serum albumin (BSA) molecules by conjugation to Lys residues. The increased valency enhances the apparent affinity of 2G12 for Man(4) up to a limit which is achieved at approximately 10 copies per BSA molecule, beyond which no further enhancement is observed. Immunization of rabbits with BSA-(Man(4))(14) elicits significant serum Ab titers to Man(4). However, these Abs are unable to bind gp120. Further analysis reveals that the elicited Abs bind a variety of unbranched and, to a lesser extent, branched Man(9) derivatives but not natural N-linked oligomannose containing the chitobiose core. These results suggest that Abs can be readily elicited against the D1 arm; however, potential differences in the presentation of Man(4) on neoglycoconjugates, compared to glycoproteins, poses challenges for eliciting anti-mannose Abs capable of cross-reacting with gp120 and HIV-1.
Integration of single oocyte trapping, in vitro fertilization and embryo culture in a microwell-structured microfluidic device (2010)

In vitro fertilization (IVF) therapy is an important treatment for human infertility. However, the methods for clinical IVF have only changed slightly over decades: culture medium is held in oil-covered drops in Petri dishes and manipulation occurs by manual pipetting. Here we report a novel microwell-structured microfluidic device that integrates single oocyte trapping, fertilization and subsequent embryo culture. A microwell array was used to capture and hold individual oocytes during the flow-through process of oocyte and sperm loading, medium substitution and debris cleaning. Different microwell depths were compared by computational modeling and flow washing experiments for their effectiveness in oocyte trapping and debris removal. Fertilization was achieved in the microfluidic devices with similar fertilization rates to standard oil-covered drops in Petri dishes. Embryos could be cultured to blastocyst stages in our devices with developmental status individually monitored and tracked. The results suggest that the microfluidic device may bring several advantages to IVF practices by simplifying oocyte handling and manipulation, allowing rapid and convenient medium changing, and enabling automated tracking of any single embryo development.
Expression of a protective gene-prolongs survival of T cells in human immunodeficiency virus-infected patients. (1996)

The resistance of acquired immunodeficiency syndrome (AIDS) to traditional drug therapy has prompted a search for alternative treatments for this disease. One potential approach is to provide genetic resistance to viral replication to prolong latency. This strategy requires the definition of effective antiviral genes that extend the survival of T cells in human immunodeficiency virus (HIV)-infected individuals. We report the results of a human study designed to determine whether a genetic intervention can prolong the survival of T cells in HIV-infected individuals. Gene transfer was performed in enriched CD4+ cells with plasmid expression vectors encoding an inhibitory Rev protein, Rev M10, or a deletion mutant control, deltaRev M10, delivered by gold microparticles. Autologous cells separately transfected with each of the vectors were returned to each patient, and toxicity, gene expression, and survival of genetically modified cells were assessed. Cells that expressed Rev M10 were more resistant to HIV infection than those with deltaRev M10 in vitro. In HIV-infected subjects, Rev M10-transduced cells showed preferential survival compared to deltaRev M10 controls. Rev M10 can therefore act as a specific intracellular inhibitor that can prolong T-cell survival in HIV-1-infected individuals and potentially serve as a molecular genetic intervention which can contribute to the treatment of AIDS.
The BIS monitor: a review and technology assessment. (2001)

In the administration of anesthesia, clinicians have traditionally relied on a variety of autonomic signs to assess the pharmacologic effects of anesthetic agents on the central nervous system. As any experienced clinician knows, these signs can be misleading and lead to overdosing or underdosing of anesthetic drugs. The development of a monitor to measure the bispectral index (BIS) provides anesthetists with the first clinically tested and US Food and Drug Administration-approved monitor to assess the effects of anesthesia on the cerebral cortex. This article reviews the development of the BIS monitor, compares the BIS monitor with other commonly used clinical monitors, assesses the cost-benefit from the use of this monitor, and explores some of the possible uses for this monitor outside of the operating suite.
Anorexia/cachexia of chronic diseases: a role for the TGF‐β family cytokine MIC‐1/GDF15 (2012)

Anorexia/cachexia is a common and currently mostly untreatable complication of advanced cancer. It is also a feature of a number of chronic diseases and can also occur as part of the normal ageing process. Over recent years, two different, but sometimes overlapping, processes have been identified to mediate anorexia/cachexia: those that act primarily on muscle reducing its mass and function, and processes that decrease nutrition leading to loss of both fat and muscle. In the case of at least some cancers, the latter process is sometimes driven by marked overexpression of macrophage inhibitory cytokine-1/growth differentiation factor 15 (MIC-1/GDF15). MIC-1/GDF15 is a transforming growth factor beta (TGF-β) family cytokine that is found in the serum of all normal individuals at an average concentration of about 0.6 ng/ml. Its increased expression in both cancers and other diseases can result in 10-100-fold or more elevation of its serum levels. In experimental animals, serum MIC-1/GDF15 levels at the lower end of this range induce anorexia by direct actions of the circulating cytokine on feeding centres in the brain. Mice with tumours overexpressing MIC-1/GDF15 display decreased food intake, loss of lean and fat mass and cachexia. That this process also mediates anorexia/cachexia in humans is suggested by the fact that there is a direct correlation between the degree of serum MIC-1/GDF15 elevation and the amount of cancer-related weight loss, the first such relationship demonstrated. Further, in experimental animals, weight loss can be reversed by neutralisation of tumour-produced MIC-1/GDF15 with a specific monoclonal antibody, suggesting the possibility of effective therapy of patients with the devastating complication of anorexia/cachexia.
Hepatitis B virus as a gene delivery vector activating foreign antigenic T cell response that abrogates viral expression in mouse models # (2009)

For the first time, HBV was used as a gene delivery vector, which strongly triggered functional T cell response and subsequently controlled the viral expression in the liver of surrogate mouse models for HBV infection. It might represent an innovative and promising strategy of active immunotherapy during HBV persistent infection. This concept could even be more generally extended to other chronic viral diseases.