gebhart/patrepeval huggingface dataset:
Characterization of a Trypanosoma cruzi C3 binding protein with functional and genetic similarities to the human complement regulatory protein, decay-accelerating factor (1991)

Evasion of the complement system by microorganisms is an essential event in the establishment of infection. In the case of Trypanosoma cruzi, the causative agent of Chagas disease, resistance to complement-mediated lysis is a developmentally regulated characteristic. Infectious trypomastigotes are resistant to complement-mediated lysis in the absence of immune antibodies, whereas the insect forms (epimastigotes) are sensitive to lysis via the alternative complement pathway. We have purified a developmentally regulated, trypomastigote glycoprotein, gp160, and shown that it has complement regulatory activity. The T. cruzi gp160 restricts complement activation by binding the complement component C3b and inhibiting C3 convertase formation. The protein is anchored in the parasite membrane via a glycosyl phosphatidylinositol linkage, similar to the human complement regulatory protein, decay-accelerating factor. Using anti-gp160 antibodies we have isolated a bacteriophage lgt11 clone expressing a portion of the gp160 gene that shares significant DNA sequence homology with the human DAF gene. These results provide functional, biochemical, and genetic evidence that the T. cruzi gp160 is a member of the C3/C4 binding family of complement regulatory proteins, and that gp160 may provide the infectious trypomastigotes with a means of evading the destructive effects of complement.
Effect of small changes in orientation on reaction rate (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffect of small changes in orientation on reaction rateDan R. Storm and D. E. Koshland Jr.Cite this: J. Am. Chem. Soc. 1972, 94, 16, 5815–5825Publication Date (Print):August 1, 1972Publication History Published online1 May 2002Published inissue 1 August 1972https://pubs.acs.org/doi/10.1021/ja00771a046https://doi.org/10.1021/ja00771a046research-articleACS PublicationsRequest reuse permissionsArticle Views413Altmetric-Citations56LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Risk factors for hospital-acquired candidemia. A matched case-control study. (1989)

Nosocomial candidemia has become an important infection not only because of an apparently increasing incidence but also because of its high fatality rate. We studied 28 risk factors through a matched case-control study that included 88 pairs of patients hospitalized between July 1983 and December 1986. The strongest single risk factor found in the univariate analysis was the number of prior antibiotics administered: the exposure odds ratio (OR) was 12.50 when patients who received three to five antibiotics were compared with those who received none to two antibiotics. A multiple logistic regression analysis using a conditional likelihood method was performed to evaluate several risk factors simultaneously. The final model selected by a stepwise procedure included the following variables: number of antibiotics received prior to infection (OR, 1.73 per unit increase), isolation of Candida species from sites other than blood (OR, 10.37), prior hemodialysis (OR, 18.13), and prior use of a Hickman catheter (OR, 7.23). It remains to be shown in controlled clinical trials whether limiting the number of antibiotics or instituting prophylaxis and/or early treatment for high-risk patients will reduce the incidence of nosocomial candidemia.
Network supercomputing (1992)

The High Performance Parallel Interface (HIPPI), American National Standards Institute (ANSI) draft standard X3T9, which is likely to become the backbone for interconnecting high-performance computing components into a single unit, is reviewed. The current HIPPI operating environment is described, and preliminary performance measurements obtained while transmitting data between Cray-2 and CM-2 computer systems are reported. The use of HIPPI for computationally intensive applications to reduce their total execution time is discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Antiplasmin-cleaving enzyme is a soluble form of fibroblast activation protein (2005)

Circulating antiplasmin-cleaving enzyme (APCE) has a role in fibrinolysis and appears structurally similar to fibroblast activation protein (FAP), a cell-surface proteinase that promotes invasiveness of certain epithelial cancers. To explore this potential relationship, we performed comparative structure/function analyses of the 2 enzymes. APCE from human plasma and recombinant FAP (rFAP) exhibited identical pH optima of 7.5, extinction coefficients (in(280 nm)(1%)) of 20.2 and 20.5, common sequences of tryptic peptides, and cross-reactivity with FAP antibody. APCE and rFAP are homodimers with monomeric subunits of 97 and 93 kDa. Only homodimers appear to have enzymatic activity, with essentially identical kinetics toward Met-alpha2-antiplasmin (Met-alpha2AP) and peptide substrates. APCE and rFAP cleave both Pro3-Leu4 and Pro12-Asn13 bonds of Met-alpha2AP, but relative kcat/Km values for Pro12-Asn13 are about 16-fold higher than for Pro3-Leu4. APCE and rFAP demonstrate higher kcat/Km values toward a peptide modeled on P4-P4' sequence surrounding the Pro12-Asn13 primary cleavage site than for Z-Gly-Pro-AMC and Ala-Pro-AFC substrates. These data support APCE as a soluble derivative of FAP and Met-alpha2AP as its physiologic substrate. Conversion of Met-alpha2AP by membrane or soluble FAP to the more easily fibrin-incorporable form, Asn-alpha2AP, may increase plasmin inhibition within fibrin surrounding certain neoplasms and have an impact on growth and therapeutic susceptibility.
14nm metal gate film stack development and challenges (2017)

As IC technology advances to 16/14 nm and beyond, FinFET architecture with advantage of excellent leakage performance becomes main stream in IC industry. However, it also brings big challenges for integration and processes due to its very aggressive structure and profile, CD shrinkage, shadow effect and gap-fill difficulty. In this work, atomic layer deposition (ALD) metal films, including TaN, TiN (TiSiN), TiAl and CVD W, were studied for replacement metal gate application. Challenges of step coverage & gap-fill, loading effect and tunable range of work function will be discussed and addressed. Thickness of high K capping layer (TiN or TaN), work function metal (TiN & TiAl), W barrier layer (TiN) all show strong effect on N/P MOS device Vt, and more than 300 mv tunable range of work function can be achieved. Besides, higher Al : Ti ratio process, interfacial special treatment between TiAl & W barrier TiN and different W process can lower down NMOS Vt. At the last, ALD and CVD process ensure good gap-fill performance when CD opening is larger than 5nm (aspect ratio is about 20:1).
Detecting web page structure for adaptive viewing on small form factor devices (2003)

Mobile devices have already been widely used to access the Web. However, because most available web pages are designed for desktop PC in mind, it is inconvenient to browse these large web pages on a mobile device with a small screen. In this paper, we propose a new browsing convention to facilitate navigation and reading on a small-form-factor device. A web page is organized into a two level hierarchy with a thumbnail representation at the top level for providing a global view and index to a set of sub-pages at the bottom level for detail information. A page adaptation technique is also developed to analyze the structure of an existing web page and split it into small and logically related units that fit into the screen of a mobile device. For a web page not suitable for splitting, auto-positioning or scrolling-by-block is used to assist the browsing as an alterative. Our experimental results show that our proposed browsing convention and developed page adaptation scheme greatly improve the user's browsing experiences on a device with a small display.
The Roles of Proteinase-Activated Receptors in the Vascular Physiology and Pathophysiology (2006)

Proteinase-activated receptors (PARs) belong to a family of G protein-coupled receptors, thus mediating the cellular effects of proteinases. In the vascular system, thrombin and other proteinases in the coagulation-fibrinolysis system are considered to be the physiologically relevant agonists, whereas PARs are among the most important mechanisms mediating the interaction between the coagulation-fibrinolysis system and the vascular wall. Under physiological conditions, PARs are mainly expressed in endothelial cells, and participate in the regulation of vascular tone, mostly by inducing endothelium-dependent relaxation. PARs in endothelial cells are also suggested to contribute to a proinflammatory phenotypic conversion and an increase in the permeability of vascular lesions. In smooth muscle cells, PARs mediate contraction, migration, proliferation, hypertrophy, and production of the extracellular matrix, thereby contributing to the development of vascular lesions and the pathophysiology of such vascular diseases as atherosclerosis. However, the expression of PARs in the smooth muscle of normal arteries is limited. The upregulation of PARs in the smooth muscle is thus considered to be a key step for PARs to participate in the pathogenesis of vascular lesions. Elucidating the molecular mechanism regulating the PARs expression is therefore important to develop new strategies for the prevention and treatment of vascular diseases.
GLYCEMIC EFFECTS OF SOLANINE IN RATS (1967)

It has been widely recognized that solanine (Fig. 1) is contained in Solarium species, especially in fresh potato sprouts as a toxic alkaloid. There have been reports concerning sola n i ne, namely, Kline et al. (1) reported that potato sprouts were shown to be toxic to pregnant rats when fed at a level of 10% of the diet. Solanine and solanidine, aglycon of solanine, inhibit human plasma cholinesterase in vitro (2, 3). No other pharmacological and biochemical studies on toxicities of solanine have been published. The present investigation was undertaken to determine the alteration of blood sugar level of rat treated with solanine. Hyperglycemia has been reported as one feature of poisoning by some toxic substances, i.e., guthion (4), paracetamol (5), parathion (6) and amphetamine (7). It seemed possible, therefore, that changes of disturbance of carbohydrate metabolism.
Critical Role of Endogenous Heme Oxygenase 1 as a Tuner of the Invasive Potential of Prostate Cancer Cells (2009)

Prostate cancer (PCa) is the second leading cause of cancer-associated death in men. Inflammation has been recognized as a risk factor for this disease. Heme oxygenase 1 (HO-1), the inducible isoform of the rate-limiting enzyme in heme degradation, counteracts oxidative and inflammatory damage. Here, we investigated the regulated expression of HO-1 and its functional consequences in PCa. We studied the effect of genetic and pharmacologic disruption of HO-1 in the growth, invasion, and migration in androgen-sensitive (MDA PCa2b and LNCaP) and androgen-insensitive (PC3) PCa cell lines. Our results show that HO-1 levels are markedly decreased in PC3 compared with MDA PCa2b and LNCaP. Hemin treatment increased HO-1 at both protein and mRNA levels in all cell lines and decreased cell proliferation and invasion. Furthermore, overexpression of HO-1 in PC3 resulted in markedly reduced cell proliferation and migration. Accordingly, small interfering RNA-mediated silencing of HO-1 expression in MDA PCa2b cells resulted in increased proliferation and invasion. Using reverse transcription-quantitative PCR-generated gene array, a set of inflammatory and angiogenic genes were upregulated or downregulated in response to HO-1 overexpression identifying matrix metalloprotease 9 (MMP9) as a novel downstream target of HO-1. MMP9 production and activity was downregulated by HO-1 overexpression. Furthermore, PC3 cells stably transfected with HO-1 (PC3HO-1) and controls were injected into nu/nu mice for analysis of in vivo tumor xenograft phenotype. Tumor growth and MMP9 expression was significantly reduced in PC3HO-1 tumors compared with control xenografts. Taken together, these results implicate HO-1 in PCa cell migration and proliferation suggesting its potential role as a therapeutic target in clinical settings.
miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells (2008)

microRNA-124 and microRNA-137 induce differentiation of adult mouse neural stem cells, mouse oligodendroglioma-derived stem cells and human glioblastoma multiforme-derived stem cells and induce glioblastoma multiforme cell cycle arrest. These results suggest that targeted delivery of microRNA-124 and/or microRNA-137 to glioblastoma multiforme tumor cells may be therapeutically efficacious for the treatment of this disease.
Use of Drug Carriers To Ameliorate the Therapeutic Index of Anthracycline Antibiotics (1994)

Anthracycline antibiotics are some of the most effective antitumor agents. However, their use is limited by lack of tumor specificity and natural or acquired resistance. Different tumor targeting strategies have been explored to enhance their therapeutic index by actively or passively target them to the tumor site. Immunoconjugates of doxorubicin and different anthracyclines incorporated into liposomes are being evaluated in clinical trials. Based on the preclinical studies, some of these agents have a definite potential of being superior antitumor agents for specific indications.
Novel Therapeutic Strategy Against Central Baroreflex Failure (1999)

These results suggest the feasibility of a BBS approach for central baroreflex failure.
Carbohydrate-based vaccines: challenges and opportunities (2010)

Advances in the synthesis of oligo- or polysaccharides and new technologies developed in glycobiology studies have opened a new avenue in carbohydrate vaccine design. In principle, various types of cell-surface epitopes, characteristic of the invading organism or related to aberrant growth of cells, can be applied to develop vaccines. Numerous promising carbohydrate-based vaccine candidates have been prepared in recent years. This article, primarily for general readers, briefly presents the recent advances involving carbohydrate-based vaccines, including antibacterial, antiparasite, anticancer and antivirus vaccines.
The effect of class II gene transfection on the tumourigenicity of the H-2K-negative mouse leukaemia cell line K36.16. (1991)

There is much evidence to suggest that potentially immunogenic tumour cells can escape cytolytic immune destruction by loss of class I antigen expression. Many tumours are allele-specific class I negative and, in murine systems, reconstitution of class I expression by gene transfection leads to an increase in tumour immunogenicity. In many systems where mice have rejected class I transfected tumour cells they are also immune to a subsequent challenge with the untransfected parent tumour. In this study we have examined the effect of stable class II antigen expression (induced by gene transfection) on a class I loss mutant (H-2Kk negative) murine cell line, K36.16. We show that H-2Ek expression is more effective at increasing tumour immunogenicity than the reconstitution of H-2Kk expression in these cells. This suggests that the induction of class II antigen expression on tumour cells may provide an effective way of enhancing tumour-specific immune responses in vivo.
Cleavage of the HER2 ectodomain is a pervanadate-activable process that is inhibited by the tissue inhibitor of metalloproteases-1 in breast cancer cells. (1999)

HER2/neu, a Mr 185,000 tyrosine kinase receptor that is overexpressed in breast cancer, undergoes proteolytic cleavage of its extracellular domain (ECD). In contrast with other membrane-bound proteins, including growth factor receptors, that are cleaved by a common machinery system, we show that HER2 cleavage is a slow process and is not activated by protein kinase C. Pervanadate, a general inhibitor of protein-tyrosine phosphatases, induces a rapid and potent shedding of HER2 ECD. The shedding of HER2 ECD is inhibited by the broad-spectrum metalloprotease inhibitors EDTA, TAPI-2, and batimastat. The tissue inhibitor of metalloproteases-1; an inhibitor of matrix metalloproteases that does not inhibit cleavage by the general protein kinase C-dependent shedding machinery, also inhibited HER2 ECD shedding, whereas tissue inhibitor of metalloproteases-2 did not. These data suggest that HER2 cleavage is a process regulated by an as-yet-unidentified distinct protease.
megaTALs: a rare-cleaving nuclease architecture for therapeutic genome engineering (2013)

Rare-cleaving endonucleases have emerged as important tools for making targeted genome modifications. While multiple platforms are now available to generate reagents for research applications, each existing platform has significant limitations in one or more of three key properties necessary for therapeutic application: efficiency of cleavage at the desired target site, specificity of cleavage (i.e. rate of cleavage at 'off-target' sites), and efficient/facile means for delivery to desired target cells. Here, we describe the development of a single-chain rare-cleaving nuclease architecture, which we designate 'megaTAL', in which the DNA binding region of a transcription activator-like (TAL) effector is used to 'address' a site-specific meganuclease adjacent to a single desired genomic target site. This architecture allows the generation of extremely active and hyper-specific compact nucleases that are compatible with all current viral and nonviral cell delivery methods.
Design and Instrumentation of a Measurement and Calibration System for an Acoustic Telemetry System (2010)

The Juvenile Salmon Acoustic Telemetry System (JSATS) is an active sensing technology developed by the U.S. Army Corps of Engineers, Portland District, for detecting and tracking small fish. It is used primarily for evaluating behavior and survival of juvenile salmonids migrating through the Federal Columbia River Power System to the Pacific Ocean. It provides critical data for salmon protection and development of more "fish-friendly" hydroelectric facilities. The objective of this study was to design and build a Measurement and Calibration System (MCS) for evaluating the JSATS components, because the JSATS requires comprehensive acceptance and performance testing in a controlled environment before it is deployed in the field. The MCS consists of a reference transducer, a water test tank lined with anechoic material, a motion control unit, a reference receiver, a signal conditioner and amplifier unit, a data acquisition board, MATLAB control and analysis interface, and a computer. The fully integrated MCS has been evaluated successfully at various simulated distances and using different encoded signals at frequencies within the bandwidth of the JSATS transmitter. The MCS provides accurate acoustic mapping capability in a controlled environment and automates the process that allows real-time measurements and evaluation of the piezoelectric transducers, sensors, or the acoustic fields. The MCS has been in use since 2009 for acceptance and performance testing of, and further improvements to, the JSATS.
Low Cost Tuberculosis Vaccine Antigens in Capsules: Expression in Chloroplasts, Bio-Encapsulation, Stability and Functional Evaluation In Vitro (2013)

Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the leading fatal infectious diseases. The development of TB vaccines has been recognized as a major public health priority by the World Health Organization. In this study, three candidate antigens, ESAT-6 (6 kDa early secretory antigenic target) and Mtb72F (a fusion polyprotein from two TB antigens, Mtb32 and Mtb39) fused with cholera toxin B-subunit (CTB) and LipY (a cell wall protein) were expressed in tobacco and/or lettuce chloroplasts to facilitate bioencapsulation/oral delivery. Site-specific transgene integration into the chloroplast genome was confirmed by Southern blot analysis. In transplastomic leaves, CTB fusion proteins existed in soluble monomeric or multimeric forms of expected sizes and their expression levels varied depending upon the developmental stage and time of leaf harvest, with the highest-level of accumulation in mature leaves harvested at 6PM. The CTB-ESAT6 and CTB-Mtb72F expression levels reached up to 7.5% and 1.2% of total soluble protein respectively in mature tobacco leaves. Transplastomic CTB-ESAT6 lettuce plants accumulated up to 0.75% of total leaf protein. Western blot analysis of lyophilized lettuce leaves stored at room temperature for up to six months showed that the CTB-ESAT6 fusion protein was stable and preserved proper folding, disulfide bonds and assembly into pentamers for prolonged periods. Also, antigen concentration per gram of leaf tissue was increased 22 fold after lyophilization. Hemolysis assay with purified CTB-ESAT6 protein showed partial hemolysis of red blood cells and confirmed functionality of the ESAT-6 antigen. GM1-binding assay demonstrated that the CTB-ESAT6 fusion protein formed pentamers to bind with the GM1-ganglioside receptor. The expression of functional Mycobacterium tuberculosis antigens in transplastomic plants should facilitate development of a cost-effective and orally deliverable TB booster vaccine with potential for long-term storage at room temperature. To our knowledge, this is the first report of expression of TB vaccine antigens in chloroplasts.
Thalidomide analogs as emerging anti-cancer drugs (2003)

Recently, it has been demonstrated that a number of novel thalidomide analogs possess anti-cancer properties due to their T cell co-stimulatory, anti-angiogenic and/or anti-inflammatory effects. Based on such effects, a class of thalidomide analogs known as Immunomodulatory Drugs (IMiDs) have recently entered into phase I clinical trials for the treatment of a number of cancers. The lead IMiD CC-5013 (referred to clinically as REVIMID) is now entering phase III clinical trials for multiple myeloma and metastatic melanoma, while CC-4047 (ACTIMID) is currently under investigation in phase I/II and II trials for multiple myeloma and prostate cancer, respectively. The other group of compounds, classified as Selective Cytokine Inhibitory Drugs (SelCIDs), do not co-stimulate T cells, but have anti-inflammatory and anti-angiogenic properties. Moreover, a subset of SelCIDs has been found to possess direct anti-tumor activity both in vitro and in vivo. This minireview highlights the various mechanisms of action associated with these compounds and their subsequent clinical development. The enhanced efficacy and lower side-effect profiles of the analogs in comparison to thalidomide make the use of these agents very attractive as novel anti-cancer agents.