gebhart/patrepeval huggingface dataset:
High performance damascene metal gate MOSFETs for 0.1 μm regime (2000)

A novel transistor formation process (damascene gate process) was developed in order to apply metal gates and high dielectric constant gate insulators to MOSFET fabrication and minimize plasma damage to gate insulators. In this process, the gate insulators and gate electrodes are formed after ion implantation and high temperature annealing (/spl sim/1000/spl deg/C) for source/drain formation, and the gate electrodes are fabricated by chemical mechanical polishing (CMP) of gate materials deposited in grooves. Metal gates and high dielectric constant gate insulators are applicable to the MOSFET, since the processing temperature after gate formation can be reduced to as low as 450/spl deg/C. Furthermore, process-damages on gate insulators are minimized because there is no plasma damage caused by source/drain ion implantation and gate reactive ion etching (RIE). By using this process, fully planarized metal (W/TiN or Al/TiN) gate transistors with SiO/sub 2/ or Ta/sub 2/O/sub 5/ as gate insulators were uniformly fabricated on an 8-in wafer. Further, the damascene metal gate transistors exhibited low gate sheet resistivity, no gate depletion and drastic improvement in gate oxide integrity, resulting in high transistor performance.
Measuring Functioning and Well-Being: The Medical Outcomes Study Approach (1992)

This book provides a set of ready-to-use generic measures that are applicable to all adults, including those well and chronically ill, as well as a methodological guide to collecting health data and constructing health measures.
Functional Consequences of Cysteine Modification in the Ligand Binding Sites of Peroxisome Proliferator Activated Receptors by GW9662 (2002)

In the course of a high throughput screen to search for ligands of peroxisome proliferator activated receptor-gamma (PPARgamma), we identified GW9662 using a competition binding assay against the human ligand binding domain. GW9662 had nanomolar IC(50) versus PPARgamma and was 10- and 600-fold less potent in binding experiments using PPARalpha and PPARdelta, respectively. Pretreatment of all three PPARs with GW9662 resulted in the irreversible loss of ligand binding as assessed by scintillation proximity assay. Incubation of PPAR with GW9662 resulted in a change in the absorbance spectra of the receptors consistent with covalent modification. Mass spectrometric analysis of the PPARgamma ligand binding domain treated with GW9662 established Cys(285) as the site of covalent modification. This cysteine is conserved among all three PPARs. In cell-based reporter assays, GW9662 was a potent and selective antagonist of full-length PPARgamma. The functional activity of GW9662 as an antagonist of PPARgamma was confirmed in an assay of adipocyte differentiation. GW9662 showed essentially no effect on transcription when tested using both full-length PPARdelta and PPARalpha. Time-resolved fluorescence assays of ligand-modulated receptor heterodimerization, coactivator binding, and corepressor binding were consistent with the effects observed in the reporter gene assays. Control activators increased PPAR:RXR heterodimer formation and coactivator binding to both PPARgamma and PPARdelta. Corepressor binding was decreased. In the case of PPARalpha, GW9662 treatment did not significantly increase heterodimerization and coactivator binding or decrease corepressor binding. The experimental data indicate that GW9662 modification of each of the three PPARs results in different functional consequences. The selective and irreversible nature of GW9662 treatment, and the observation that activity is maintained in cell culture experiments, suggests that this compound may be a useful tool for elucidation of the role of PPARgamma in biological processes.
Structural models for the protein family characterized by gamete surface protein Pfs230 ofPlasmodium falciparum (2005)

Ps230 is the largest representative of a 10-member family of proteins found in all Plasmodium species. The family is defined by partially conserved, cysteine-rich double domains that are approximately 350 aa in length and have one to three predicted disulfide bridges in each half. In Plasmodium falciparum, the most dangerous human malaria, Pf12 is the smallest member of the family, comprising just one double domain. Pfs230, with 7 double domains, and Pfs48/45 and Pfs47, with 1.5 double domains each, are found on the gamete surfaces and are thus potential candidates for a transmission-blocking vaccine. Fold prediction analyses of the double domains in Pfs230 reveal structural resemblance to SAG1 (surface antigen 1), a surface protein with a double beta-sandwich structure from another apicomplexan parasite, Toxoplasma gondii. Template-directed modeling onto SAG1 clearly establishes the structural link between SAG1 and Pfs230 and produces positions for the cysteines that accord with the disulfide-bonding arrangement predicted for the Pfs230 family in earlier work. A highly clustered region of polymorphisms within the second double domain in Pfs230 maps to one side of the sandwich surface. This observation suggests that this region may be functional and reinforces the validity of these molecular models for the core domains of the Pfs230 family of proteins.
PPARγ but not PPARα Ligands Are Potent Repressors of Major Histocompatibility Complex Class II Induction in Atheroma-Associated Cells (2002)

Peroxisome proliferator-activated receptors (PPARs) are essential in glucose and lipid metabolism and are implicated in metabolic disorders predisposing to atherosclerosis, such as diabetes and dyslipidemia. Conversely, antidiabetic glitazones and hypolipidemic fibrate drugs, known as PPARgamma and PPARalpha ligands, respectively, reduce the process of atherosclerotic lesion formation, which involves chronic immunoinflammatory processes. Major histocompatibility complex class II (MHC-II) molecules, expressed on the surface of specialized cells, are directly involved in the activation of T lymphocytes and in the control of the immune response. Interestingly, expression of MHC-II has recently been observed in atherosclerotic plaques, and it can be induced by the proinflammatory cytokine interferon-gamma (IFN-gamma) in vascular cells. To explore a possible role for PPAR ligands in the regulation of the immune response, we investigated whether PPAR activation affects MHC-II expression in atheroma-associated cells. In the present study, we demonstrate that PPARgamma but not PPARalpha ligands act as inhibitors of IFN-gamma-induced MHC-II expression and thus as repressors of MHC-II-mediated T-cell activation. All different types of PPARgamma ligands tested inhibit MHC-II. This effect of PPARgamma ligands is due to a specific inhibition of promoter IV of CIITA and does not concern constitutive expression of MHC-II. Thus, the beneficial effects of antidiabetic PPARgamma activators on atherosclerotic plaque development may be partly explained by their repression of MHC-II expression and subsequent inhibition of T-lymphocyte activation.
Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. (1993)

To compare the ability of different cytokines and other molecules to enhance the immunogenicity of tumor cells, we generated 10 retroviruses encoding potential immunomodulators and studied the vaccination properties of murine tumor cells transduced by the viruses. Using a B16 melanoma model, in which irradiated tumor cells alone do not stimulate significant anti-tumor immunity, we found that irradiated tumor cells expressing murine granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated potent, long-lasting, and specific anti-tumor immunity, requiring both CD4+ and CD8+ cells. Irradiated cells expressing interleukins 4 and 6 also stimulated detectable, but weaker, activity. In contrast to the B16 system, we found that in a number of other tumor models, the levels of anti-tumor immunity reported previously in cytokine gene transfer studies involving live, transduced cells could be achieved through the use of irradiated cells alone. Nevertheless, manipulation of the vaccine or challenge doses made it possible to demonstrate the activity of murine GM-CSF in those systems as well. Overall, our results have important implications for the clinical use of genetically modified tumor cells as therapeutic cancer vaccines.
Molecular cloning of complementary DNA encoding the lignin-forming peroxidase from tobacco: Molecular analysis and tissue-specific expression (1987)

Plant peroxidases play a major role in lignin formation and wound healing and are believed to be involved in auxin catabolism and defense to pathogen attack. The function of the anionic peroxidase isozymes is best understood in tobacco. These isozymes catalyze the formation of the lignin polymer and form rigid cross-links between lignin, cellulose, and extensin in the secondary plant cell wall. We report the purification of the anionic peroxidase isozymes from tobacco and their partial amino acid sequence. An oligonucleotide probe deduced from the amino acid sequence was used to screen a tobacco leaf cDNA library and a 1200-base-pair cDNA clone was isolated and sequenced in its entirety. The predicted amino acid sequence revealed a 22-amino acid signal peptide and a 302-amino acid mature protein (M(r), 32,311). The amino acid sequence was compared to that of the cationic peroxidases from horseradish and turnip and was found to be 52% and 46% homologous, respectively. By RNA blot analysis, the messenger for the tobacco isozyme was found to be abundant in stem tissue while expressed at very low levels in leaf and root tissue. Four distinguishable copies of the gene were found on genomic DNA blots. The gene copy number may reflect the allotetraploid nature of Nicotiana tabacum.
Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy (2007)

The intercalated disc (ID) of cardiac myocytes is emerging as a crucial structure in the heart. Loss of ID proteins like N-cadherin causes lethal cardiac abnormalities, and mutations in ID proteins cause human cardiomyopathy. A comprehensive screen for novel mechanisms in failing hearts demonstrated that expression of the lysosomal integral membrane protein 2 (LIMP-2) is increased in cardiac hypertrophy and heart failure in both rat and human myocardium. Complete loss of LIMP-2 in genetically engineered mice did not affect cardiac development; however, these LIMP-2 null mice failed to mount a hypertrophic response to increased blood pressure but developed cardiomyopathy. Disturbed cadherin localization in these hearts suggested that LIMP-2 has important functions outside lysosomes. Indeed, we also find LIMP-2 in the ID, where it associates with cadherin. RNAi-mediated knockdown of LIMP-2 decreases the binding of phosphorylated beta-catenin to cadherin, whereas overexpression of LIMP-2 has the opposite effect. Collectively, our data show that LIMP-2 is crucial to mount the adaptive hypertrophic response to cardiac loading. We demonstrate a novel role for LIMP-2 as an important mediator of the ID.
Adjusting intraocular lens power for sulcus fixation (2003)

For sulcus fixation in eyes with a normal axial length, the IOL power should be 1.00 D less than the power for in-the-bag fixation.
HIGH-DOSE THERAPY AND TRANSPLANTATION FOR LOW-GRADE LYMPHOMA (1997)

Because of the indolent natural history of low-grade lymphomas, long follow-up is needed to assess the overall success of high-dose therapy and autografting. Results to date suggest that patients with brief first or second remission with chemotherapy or those who attain only a partial remission with second-line or subsequent chemotherapy, but remain drug sensitive, may enjoy prolonged remissions relative to conventional treatment. The role of autografting in first remission is uncertain because the data from clinical trials are not mature. Furthermore, the risk of myelodysplasia after transplantation, the broad range of therapeutic alternatives available, and the option to give high-dose therapy upon relapse argue against autografting as primary treatment. Although purging the autograft of residual lymphoma as assessed by molecular methods has been associated with longer remission duration in one major center, the data from published series are remarkably similar, whether the graft was purged or not. Promising anecdotal data suggest that allogeneic transplantation for low-grade lymphoma deserves further study in prospective clinical trials.
Hysteroscopy: Textbook and Atlas (1994)

Hysteroscopy is a method of endoscopic viewing of the uterus. This book provides basic information on the technical fundamentals, the various indications for hysterscopy, hysteroscopic findings of physiological and pathological changes in the endometrium, hysteroscopic differential diagnosis, and on correlations to histology. Indications and contraindications are also stated. More and more, hysteroscopy is being performed in the doctor's office. The work gives a detailed account of the morphological confirmation of the endoscopic findings (streak curretage, endometrium cytology), and includes operative hystersocopy.
The Language of Judges (1993)

Since many legal disputes are battles over the meaning of a statute, contract, testimony, or the Constitution, judges must interpret language in order to decide why one proposed meaning overrides another. And in making their decisions about meaning appear authoritative and fair, judges often write about the nature of linguistic interpretation. In the first book to examine the linguistic analysis of law, Lawrence M. Solan shows that judges sometimes inaccurately portray the way we use language, creating inconsistencies in their decisions and threatening the fairness of the judicial system. Solan uses a wealth of examples to illustrate the way linguistics enters the process of judicial decision making: a death penalty case that the Supreme Court decided by analyzing the use of adjectives in a jury instruction; criminal cases whose outcomes depend on the Supreme Court's analysis of the relationship between adverbs and prepositional phrases; and cases focused on the meaning of certain words in the Constitution. Solan finds that judges often describe our use of language poorly because there is no clear relationship between the principles of linguistics and the jurisprudential goals that the judge wishes to promote. A major contribution to the growing interdisciplinary scholarship on law and its social and cultural context, Solan's lucid, engaging book is equally accessible to linguists, lawyers, philosophers, anthropologists, literary theorists, and political scientists.
Assembly of the enveloped bacteriophage ϕ6 in environments which perturb the host cell membranes (1975)

The effects of known membrane-perturbing agents (pH, Na+, Ca2+, and a small lipid-soluble molecule) on the enveloped bacteriophage phi 6 host cell system were investigated at the levels of cellular growth, virus assembly and stability, and the physical and chemical properties of host cell membranes. Spin-label probes of cellular membranes indicate that growth in high levels of Na+ or the small spherical hydrophobic molecule adamantanone results in membranes having increased "fluidity," while growth in high levels of Ca2+ results in slightly greater rigidity of the membranes. In addition, the phospholipid composition of the cellular membranes is dependent on the NaCl concentration in the growth medium. None of these membrane alterations, however, prevent the production of infectious phi 6 virus particles.
Endowing T cells with antibody specificity using chimeric T cell receptors (1992)

T cells recognize antigen in the form of a peptide associated with a cell surface molecule encoded by the major histocompatibility gene complex (MHC). The elaborate requirements for the T cell receptor (TCR)-antigen interaction stand in contrast to the simple and defined nature of the antigenic determinants recognized by antibodies. The similarity in the molecular structure and gene organization between antibodies and the TCR has prompted attempts to interchange the antigen-binding, variable regions of these molecules. To this end, chimeric TCR (cTCR) genes, composed of the variable domains of antibodies linked to TCR constant regions, have been used to confer antibody-type specificity on T cells. cTCR-expressing T cells respond to stimulator cells as well as to immobilized antigen in an MHC unrestricted and independent manner. The antibody-like specificity of the resulting T cells has been exploited, using defined ligands, to elucidate the physicochemical parameters that govern TCR-mediated signaling, and to provide a useful experimental system to study the role of MHC and cell-adhesion/accessory molecules in T cell activation. The successful expression of such cTCR in transgenic mice opens new avenues to explore the role of the MHC in T cell development and maturation. Eventually, chimeric receptors specific to tumor or viral antigens might be used for in vivo targeting of T cells in the framework of immuno- and gene therapy.
Generation of Streptomyces globisporus SMY622 Strain with Increased Landomycin E Production and It's Initial Characterization (2004)

Landomycin E (LaE) overproducing strain Streptomyces globisporus SMY6222 has been developed using UV induced mutagenesis and selection for streptomycin resistance. SMY622 has been shown by HPLC to produce 200-fold higher amounts of LaE when comparing with parental strain. The levels of transcription of regulatory gene lndI and oxygenase gene lndE are two times higher in the mutant than in the wild type. Gene rpsL for ribosomal protein S12 from SMY622 was shown to contain point mutation K43R. Possible reasons for increased LaE synthesis in SMY622 are discussed.
Site specific enzymatic cleavage of RNA (1979)

The hybridization of a DNA oligonucleotide a specific tetramer or longer) will direct a cleavage by RNase H (EC 3.1.4.34) to a specific site in RNA. The resulting fragments can then be labeled at their 5' or 3' ends, purified, and sequenced directly. This procedure is demonstrated with two RNA molecules of known sequence: 5.8S rRNA from yeast (158 nucleotides) and satellite tobacco necrosis virus (STNV) RNA (1240 nucleotides).
Multiple page size support in the Linux kernel (2002)

The Linux kernel currently supports a single user space page size, usually the minimum dic-tated by the architecture. This paper describes the ongoing modifications to the Linux kernel to allow applications to vary the size of pages used to map their address spaces and to reap the performance benefits associated with the use of large pages. The results from our implementation of mul-tiple page size support in the Linux kernel are very encouraging. Namely, we find that the performance improvement of applications written in various modern programming lan-guages range from 10 % to over 35%. The ob-served performance improvements are consis-tent with those reported by other researchers. Considering that memory latencies continue to grow and represent a barrier for achieving scal-able performance on faster processors, we ar-gue that multiple page size support is a neces-sary and important addition to the OS kernel and the Linux kernel in particular. 1
The role of hepatitis C virus-specific cytotoxic T lymphocytes in chronic hepatitis C (1997)

Cellular immune responses, particularly those mediated by CD8+ CTL, may be important in the pathogenesis and control of hepatitis C virus (HCV) infection. To define the role of HCV-specific CTL in chronic hepatitis C, HCV-specific CTL activity in liver and peripheral blood was assessed in 35 patients with chronic HCV infection and 5 non-HCV controls. HCV-specific CTL activity of expanded CD8+ cells was evaluated against autologous lymphoblastoid cells transduced with recombinant vaccinia virus vectors expressing HCV genotype 1a Ags. CTL activity was detected in unprimed bulk-expanded CD8+ cells derived from the liver in 16 of the 35 patients, but not in peripheral circulation. Three patients infected with non-type 1 HCV were found to have HCV-specific CTL activity against HCV type 1a epitopes, all directed toward HCV core region. Compared with patients without detectable HCV-specific CTL activity based on our assay, those exhibiting CTL activity had lower levels of viremia (p < 0.01 for both branched DNA version 1.0 and 2.0 assays) and more active disease, as reflected by a higher histologic activity index (p = 0.006) and serum alanine aminotransferase levels (p = 0.03). It is concluded that 1) with nonspecific stimulation, HCV-specific CTL activity is found more commonly in the liver than in peripheral circulation, suggesting a tissue-specific localization with HCV-specific CTL and/or its precursors; 2) cross-genotype CTL activity exists, especially toward HCV core, which is relatively conserved across genotypes; and 3) patients with intrahepatic HCV-specific CTL activity had lower levels of viremia and more active liver disease.
pH-Responsive Poly(styrene-alt-maleic anhydride) Alkylamide Copolymers for Intracellular Drug Delivery (2006)

Many macromolecular therapeutics such as peptides, proteins, antisense oligodeoxynucleotides (ASODN), and short interfering RNA (siRNA) are active only in the cytoplasm or nucleus of targeted cells. Endocytosis is the primary route for cellular uptake of these molecules, which results in their accumulation in the endosomal-lysosomal trafficking pathway and loss of therapeutic activity. In this article, we describe the synthesis and pH-dependent membrane-destabilizing activity of a new "smart" polymer family that can be utilized to enhance the intracellular delivery of therapeutic macromolecules through the endosomal membrane barrier into the cytoplasm of targeted cells. These polymers are propylamine, butylamine, and pentylamine derivatives of poly(styrene-alt-maleic anhydride) (PSMA) copolymers. The PSMA-alkylamide derivatives are hydrophilic and membrane-inactive at physiological pH; however, they become hydrophobic and membrane-disruptive in response to endosomal pH values as measured by their hemolytic activity. Results show that the pH-dependent membrane-destabilizing activity of PSMA derivatives can be controlled by varying the length of the alkylamine group, the degree of modification of the copolymer, and the molecular weight of the PSMA copolymer backbone. Butylamine and pentylamine derivatives of PSMA copolymers exhibited more than 80% hemolysis at endosomal pH values, which suggests their potential as a platform of "smart" polymeric carriers for enhanced cytoplasmic delivery of a variety of therapeutic macromolecules.
Detection of barley chromatin added to wheat by genomic in situ hybridization (1991)

A technique for in situ hybridization is reported that can be used to detect barley chromatin in wheat background using total genomic DNA as a probe. A 1:2 ratio of biotin-labeled genomic DNA of barley to blocking (unlabeled, sheared) DNA of wheat was sufficient to reveal brownish labeled barley chromosome domains against bluish background of unlabeled wheat chromatin in metaphase, prophase, and interphase nuclei of wheat-barley addition lines. Using this procedure, the behavior of specific barley chromosomes was analyzed in interphase and prophase cells. In prophase cells, the 6H chromosome was always associated with a nucleolus. A genomic clone of α-amylase gene (gRAmy56) that contains a barley-specific dispersed repeat sequence was also used to detect barley chromosomes in a wheat background.Key words: Hordeum vulgare, Triticum aestivum, genomic in situ hybridization, biotin, nucleolar organizing region.