gebhart/patrepeval huggingface dataset:
Co-Administration of Etomoxir and RU-486 Mitigates Insulin Resistance in Hepatic and Muscular Tissues of STZ-Induced Diabetic Rats (2001)

Insulin resistance is a condition of central importance in a cluster of clinical disorders including diabetes mellitus, hypertension, dyslipidemia, central obesity and coronary heart disease. Despite its association with numerous health problems, the mechanism responsible for the development of this phenomenon remains to be established. A novel theory has proposed that insulin resistance in diabetes stems, at least in part, from enhanced free fatty acid (FFA) oxidation and/or excessive production of glucocorticoids (GCs). Several key predictions of this premise were subjected to experimental testing using streptozotocin (STZ)-treated rats as a model for insulin-dependent diabetes mellitus and euglycemic-hyperinsulinemic clamp technique for the in vivo measurement of insulin actions. Euglycemic clamp studies with an insulin infusion index of 5 mU/kg/min were used to measure endogenous glucose production (EGP), glucose infusion rate (GIR), glucose disposal rate (GDR) and skeletal muscle glucose utilization index (GUI). Post-absorptive basal EGP and plasma levels of glucose and free fatty acids (FFA) were elevated in the STZ diabetic rats compared to their corresponding control values. In contrast, hypoinsulinemia was evident in these animals. Steady-state GIR and GDR during euglycemic-hyperinsulinemic clamp were markedly decreased in the STZ diabetic rats. Similarly, insulin-mediated suppression of EGP and plasma FFA concentration was also impaired in these animals. GUI, a measure of 2-deoxyglucose (2-DG) uptake, was increased in response to insulin in the order of white gastrocnemus (WG), red gastrocnemus (RG), extensor digitorum longus and soleus muscles. This parallels the percentage of red fibers in these muscles. Diabetes interferes with insulin's ability to increase 2-DG uptake in all of the above muscles with the exception of WG. Nullification of the associated hyperlipidemic and hypercortisolemic states of diabetes with etomoxir (hyperlipidemic) and the glucocorticoid receptor blocker RU-486 (hypercortisolemic) ameliorated the diabetes-related impairment of the in vivo insulin action. Overall these results together with those garnered from the literature support the notion that hypercortisolemia and the enhancement of FFA oxidation are involved, at least in part, in the development of hepatic and skeletal muscle insulin resistance in poorly controlled type I diabetes.
Challenges in the development of advanced Li-ion batteries: a review (2011)

Li-ion battery technology has become very important in recent years as these batteries show great promise as power sources that can lead us to the electric vehicle (EV) revolution. The development of new materials for Li-ion batteries is the focus of research in prominent groups in the field of materials science throughout the world. Li-ion batteries can be considered to be the most impressive success story of modern electrochemistry in the last two decades. They power most of today's portable devices, and seem to overcome the psychological barriers against the use of such high energy density devices on a larger scale for more demanding applications, such as EV. Since this field is advancing rapidly and attracting an increasing number of researchers, it is important to provide current and timely updates of this constantly changing technology. In this review, we describe the key aspects of Li-ion batteries: the basic science behind their operation, the most relevant components, anodes, cathodes, electrolyte solutions, as well as important future directions for R&D of advanced Li-ion batteries for demanding use, such as EV and load-leveling applications.
Cell surface characteristics of coagulase-negative staphylococci and their adherence to fluorinated poly(ethylenepropylene) (1986)

The ability of 21 nonencapsulated and 15 encapsulated coagulase-negative staphylococci (CNS) to adhere to xylene in xylene-water emulsions and to fluorinated poly(ethylenepropylene) (FEP) films revealed remarkable differences. Nonencapsulated CNS strains adhered well to FEP, whereas their adherence to xylene ranged widely. Encapsulated strains with low adherence to xylene showed slight adherence to FEP. Encapsulated strains which adhered well to xylene ranged widely in their adherence to FEP. It was concluded that results obtained from the xylene adherence test were not predictive of the adherence of CNS to the hydrophobic FEP surface. The number of nonwashed, slime-producing CNS strains adhering to FEP was similar to that of washed bacteria of the same strains. Bacterial adherence to FEP was decreased when FEP films were exposed to a solution containing extracellular products (EP) obtained from a slime-producing CNS strain. Bacterial adherence to xylene also decreased when the bacterial suspensions contained EP. Apparently, initial adherence of CNS to FEP and xylene is hampered by EP. Nonencapsulated and encapsulated CNS pretreated with proteolytic enzymes failed to adhere to xylene and FEP, indicating that intact surface proteins or constituents associated with surface proteins mediated their adherence to xylene and FEP. Freeze-etch replicas of a CNS strain adhering to FEP showed a smooth, flattened area on the bacterial surface at the contact site of the bacteria with the FEP, indicating that an external layer was present at the bacterial surface.
Activation of nuclear factor erythroid 2-related factor 2 and PPARγ plays a role in the genistein-mediated attenuation of oxidative stress-induced endothelial cell injury (2012)

We investigate the cytoprotective effects and the molecular mechanism of genistein in oxidative stress-induced injury using an endothelial cell line (EA.hy926). An oxidative stress model was established by incubating endothelial cells with H₂O₂. According to the present results, genistein pretreatment protected endothelial cells against H₂O₂-induced decreases in cell viability and increases in apoptosis. Genistein also prevented the inhibition of B-cell lymphoma 2 and the activation of caspase-3 induced by H₂O₂. Genistein increased superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels and attenuated the decrease in these antioxidants during oxidative stress. We also found that genistein induced the promoter activity of both nuclear factor erythroid 2-related factor 2 (Nrf2) and PPARγ. Additionally, genistein induced the nuclear translocation of Nrf2 and PPARγ. While genistein caused the up-regulation of both Nrf2 and PPARγ, it also activated and up-regulated the protein expression and transcription of a downstream protein, haem oxygenase-1 (HO-1). Moreover, the use of Nrf2 small interfering RNA transfection and HO-1- or PPARγ-specific antagonists (Znpp and GW9662, respectively) blocked the protective effects of genistein on endothelial cell viability during oxidative stress. Therefore, we conclude that oxidative stress-induced endothelial cell injury can be attenuated by treatment with genistein, which functions via the regulation of the Nrf2 and PPARγ signalling pathway. Additionally, the endogenous antioxidants SOD, CAT and GSH appear to play a role in the antioxidant activity of genistein. The present findings suggest that the beneficial effects of genistein involving the activation of cytoprotective antioxidant genes may represent a novel strategy in the prevention and treatment of cardiovascular endothelial damage.
Chronic relapsing experimental autoimmune encephalomyelitis (CREAE) in mice: enhancement by monoclonal antibodies against interferon‐γ (1996)

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated inflammatory and demyelinating disorder of the central nervous system. Depending on the experimental conditions, it takes an acute monophasic or a chronic relapsing-remitting course. We have previously reported that the incidence and severity of acute EAE in mice are reduced by administration of interferon (IFN)-gamma and augmented by treatment with neutralizing antibodies against IFN-gamma. Here, we investigated the role of IFN-gamma in chronic relapsing models of EAE (CREAE) in SJL/J and Biozzi ABH mice. Spontaneous relapses in Biozzi mice as well as induced relapses in SJL/J mice were facilitated by administration of neutralizing monoclonal antibody (mAb) against IFN-gamma in the disease-free interval. The enhancing effect of anti-IFN-gamma mAb given before and during the primary attack did not carry over to the relapses. However, early administration of IFN-gamma in Biozzi mice, which developed spontaneous relapses in a high proportion, provided partial protection not only against the first attack, but also against subsequent relapses. Administration of exogenous IFN-gamma during the remission phase provided some protection against subsequent relapses. These results indicate that in both types of relapses, IFN-gamma is produced and does provide a certain degree of protection against disease progression.
Development of the human dispermic embryo (1999)

In a recent CD-ROM, we portrayed the microstructure of the pre-implantation human embryo (Sathananthan et al., 1999), which was a multimedia production with computer colour-enhanced electron micrographs of mainly monospermic embryos. This disk portrays light and electron micrographs of over 250 tripronuclear (3PN), dispermic, human embryos during pre-implantation development, viewed in thick and thin Araldite sections, as well as appearances of whole embryos flat embedded in Araldite blocks visualized with the light microscope. The 100 figures were computerized (IBM TIFF format), edited and labelled using Adobe Photoshop 5. Some of the figures were coloured on computer. The early development of 3PN embryos overtly resembles that of normal embryos but there are important differences in their microstructure which are portrayed in this presentation. This is a multicentric study involving researchers from four IVF centres.
Imploding argon plasma experiments (1979)

The Pithon pulsed electron beam accelerator was used to implode an argon plasma at 4 TW. The plasma was prepared by microwave preionization of an annular column of gas injected between the output electrodes of the pulser. The electrodynamic behavior implied that most of the gas was involved in the pinch. The plasma conditions were inferred from hydrogenlike and heliumlike x-ray emission spectra. Final pinch dimensions were determined from x-ray pinhole photographs and laser shadowgraphs.
Nucleic Acid Sequence Bank (1980)

In the report by T. Kakunaga and J. D. Crow (25 July, p. 505), Fig. 1 on page 506 should have been printed as follows: [See figure in the PDF file]
Comparison of restriction endonuclease analysis, ribotyping, and pulsed-field gel electrophoresis for molecular differentiation of Clostridium difficile strains (1994)

A combined clinical and molecular epidemiologic analysis of 46 strains of Clostridium difficile, including 16 nosocomial isolates from one ward (outbreak ward) plus 17 other nosocomial isolates and 13 community-acquired isolates, was performed. HindIII digests of total cellular DNA were analyzed by restriction enzyme analysis (REA) and ribotyping; SmaI digests were analyzed by pulsed-field gel electrophoresis (PFGE). Isolates were assigned to typing groups on the basis of the profiles detected; isolates with closely related profiles were assigned to subgroups. The 16 isolates from the outbreak ward were resolved by both REA and PFGE into five distinct groups; 13 isolates represented two REA groups and three PFGE groups and two isolates were resolved as distinct groups by both techniques. DNA obtained from one isolate was persistently partially degraded, precluding analysis by PFGE. Seventeen sporadic nosocomial isolates were resolved by REA and PFGE into comparable numbers of groups (i.e., nine groups) and subgroups (i.e., 15 and 14 subgroups, respectively), with two isolates not evaluable by PFGE. The 13 epidemiologically unrelated community-acquired isolates were assigned to 11 groups by REA and to 12 groups by PFGE. Overall, ribotyping identified only nine groups among the 46 isolates. We conclude that REA and PFGE have comparable discriminatory powers for epidemiologic typing of C. difficile isolates and that ribotyping is appreciably less discriminatory. For a few isolates, partial DNA degradation prevented analysis by PFGE but not by REA or ribotyping; the cause of the degradation is unknown.
Development of Targeted, Polymeric Delivery Vehicles for Camptothesin and siRNA Via Boronic Acid-Diol Complexation (2013)

Our research lab has developed polymer-based nanoparticle delivery systems for the anticancer drug, camptothecin (CPT), CRLX101; and for the small interfering RNA (siRNA), CALAA-01. CRLX101 has shown great success in both animal studies and clinical trials. However, it is incapable of achieving targeted delivery. CALAA-01 has demonstrated effectiveness in a phase I clinical trial. However, it suffers from its rapid in vivo clearance. To address the issues of targeting in the anticancer drug delivery system and the short circulation time in the siRNA delivery system, we have created a new delivery platform involving the use of boronic acid-diol complexation. This thesis is divided into two parts to discuss CPT delivery and siRNA delivery separately. In Part I, the targeted delivery of CPT via boronic acid-diol complexation is described. CPT was conjugated to a copolymer of mucic acid and PEG (MAP) and self-assembled into MAP-CPT nanoparticles. The targeting agent, Herceptin antibody was attached to boronic acid (BA), this was then complexed with the diol-containing MAP to form a targeted nanoparticle carrying ca. 60 CPT, with a 40 nm diameter and a slightly negative surface charge. The attachment of a single Herceptin per nanoparticle was sufficient to enhance cellular uptake of nanoparticles into BT-474, a HER2 overexpressing cell line by 70% compared to the non-targeted version. Nude mice bearing BT-474 xenograft tumors treated with targeted MAP-CPT nanoparticles resulted in all mice revealing complete tumor regression. In Part II, the boronic acid-diol complexation delivery platform is applied for the delivery of siRNA. First, the CALAA-01 delivery system for siRNA was further characterized and optimized. Then, a copolymer of mucic acid and dimethylsuberimidate (MAD) was synthesized and used in condensing the anionic siRNA into nanoparticles. Nanoparticles were stabilized by placing a surface PEG layer through boronic acid-diol complexation. Targeting was achieved by conjugating the distal end of the BA-PEG with a targeting agent, Herceptin antibody. MAD/siRNA nanoparticles effectively entered cells and demonstrated low cellular toxicity. MAD/siRNA nanoparticles stabilized with nitroPBA-PEG resulted in a diameter of 130 nm with a slightly negative surface charge. Pharmacokinetic studies in mice demonstrated improved circulation compared to CALAA-01.
Predicting amino acid residues responsible for enzyme specificity solely from protein sequences (2002)

We describe a general, modular method for developing protocols to identify the amino acid residues that most likely define the division of a protein superfamily into two subsets. As one possibility, we use PROBE to gather superfamily members and perform an ungapped alignment. We then use a modified BLOSUM62 substitution matrix to determine the discriminating power of each column of aligned residues. The overall method is particularly useful for predicting amino acids responsible for substrate or binding specificity when no structures are available. We apply our method to three pairs of protein classes in three different superfamilies, and present our results, some of which have been experimentally verified. This approach may accelerate the elucidation of enzymic substrate specificity, which is critical for both mechanistic insights into biocatalysis and ultimate application.
An Animal Model of MERS Produced by Infection of Rhesus Macaques With MERS Coronavirus (2013)

In 2012, a novel coronavirus (CoV) associated with severe respiratory disease, Middle East respiratory syndrome (MERS-CoV; previously known as human coronavirus-Erasmus Medical Center or hCoV-EMC), emerged in the Arabian Peninsula. To date, 114 human cases of MERS-CoV have been reported, with 54 fatalities. Animal models for MERS-CoV infection of humans are needed to elucidate MERS pathogenesis and to develop vaccines and antivirals. In this study, we developed rhesus macaques as a model for MERS-CoV using intratracheal inoculation. The infected monkeys showed clinical signs of disease, virus replication, histological lesions, and neutralizing antibody production, indicating that this monkey model is suitable for studies of MERS-CoV infection.
Configuration Estimates Improve Pedestrian Finding (2007)

Fair discriminative pedestrian finders are now available. However, these pedestrian finders make most errors on pedestrians in configurations that are uncommon in the training data, for example, mounting a bicycle. This is undesirable. However, the human configuration can itself be estimated discriminatively using structure learning. We demonstrate a pedestrian finder which first finds the most likely human pose in the window using a discriminative procedure trained with structure learning on a small dataset. We then present features (local histogram of oriented gradient and local PCA of gradient) based on that configuration to an SVM classifier. We show, using the INRIA Person dataset, that estimates of configuration significantly improve the accuracy of a discriminative pedestrian finder but require fewer training examples.
Dynamic reciprocity: how do extracellular matrix and hormones direct gene expression? (1987)

Using mouse mammary epithelial cells (MME) as a model, we show that extracellular matrix (ECM) plays a fundamental role in the maintenance of tissue-specific function in culture. The ECM affects both the level of mRNA and the rates of synthesis and secretion of milk proteins. Casein gene expression by primary mammary epithelial cells and cell strains is controlled by both ECM and lactogenic hormones (insulin, hydrocortisone and prolactin). In the case of transferrin, the major iron-binding protein of mouse milk, the ECM rather than prolactin, appears to modulate the level of its mRNA. We further show that both ECM and lactogenic hormones influence cell shape and polarity of mammary epithelial cells. The data are consistent with a model of "Dynamic Reciprocity" (Bissell et al. 1982) where the ECM is postulated to exert an influence on gene expression via transmembrane proteins and cytoskeletal components. Cytoskeleton, in turn, is associated with polyribosomes, affecting mRNA stability and rates of protein synthesis, and with the nuclear matrix, affecting mRNA processing and, possibly, rates of transcription. We postulate that hormones and ECM act synergistically to complete the 'reciprocity' loop.
The cellular receptor (CD4) of the human immunodeficiency virus is expressed on neurons and glial cells in human brain. (1987)

The expression of the CD4 antigen in normal human brain was investigated in parallel by immunohistochemical and Northern blot analyses. With anti-CD4 antibodies detecting different epitopes of the molecule, CD4+ neurons were defined in the cerebellum, thalamus, and pons. CD4+ glial cells were identified in the thalamus and pons. CD4-specific mRNA was detected in all three subareas and in the hippocampus, while other subareas were negative. The CD4+ cells were negative with anti-T cell antibodies (anti-CD2 and anti-CD8), as well as with antimonocyte antibodies (M-M 522 and M-M 42).
On the performance of multicarrier RAKE systems (2002)

We integrate the multicarrier signaling technique and the RAKE receiver to design a DS CDMA system with the capability to increase the data rate, mitigate the effect of correlation among the various subcarriers, and suppress partial-band interference. In the proposed system, a data sequence is serial-to-parallel converted, and multicarrier DS CDMA is used on each of the parallel data streams, The receiver provides a RAKE for each subcarrier, and the outputs of the RAKEs are combined by a maximal-ratio combiner. We derive the average probability of error of the system and compare the results with those of both a single carrier RAKE system and a multicarrier DS CDMA system, when multiple access interference, partial-band interference and multipath interference are present.
Emerging drugs for hepatitis C (2008)

Early preclinical studies using these compounds produced encouraging results, but the initial enthusiasm has been hampered by toxicity issues and rapid selection of resistance. Therefore, combination therapy with a backbone of pegIFN/RBV, or perhaps in the future using several of these small molecules, preferably having distinct modes of action and resistance profiles, will be required.
Juxtaposition of domains homologous to protein kinases and histidyl-tRNA synthetases in GCN2 protein suggests a mechanism for coupling GCN4 expression to amino acid availability. (1989)

The GCN2 protein of Saccharomyces cerevisiae stimulates the expression of amino acid biosynthetic genes under conditions of amino acid starvation by derepressing GCN4, a transcriptional activator of these genes. GCN2 contains sequences homologous to the catalytic domain of protein kinases. We show here that substitution of a highly conserved lysine in the presumed ATP-binding site of this domain impairs the derepression of histidine biosynthetic genes under GCN4 control. This result supports the idea that protein kinase activity is required for GCN2 positive regulatory function. Determination of the nucleotide sequence of the entire GCN2 complementation unit, and measurement of the molecular weight of GCN2 protein expressed in vivo, indicate that GCN2 is a Mr approximately 180,000 protein and contains a Mr approximately 60,000 segment homologous to histidyl-tRNA synthetases (HisRSs) juxtaposed to the protein kinase domain. Several two-codon insertion mutations in the HisRS-related coding sequences inactivate GCN2 regulatory function. Based on these results, we propose that the GCN2 HisRS domain responds to the presence of uncharged tRNA by activating the adjacent protein kinase moiety, thus providing a means of coupling GCN2-mediated derepression of GCN4 expression to the availability of amino acids.
Total synthesis of (+)-duocarmycin SA (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal synthesis of (+)-duocarmycin SADale L. Boger and Kozo MachiyaCite this: J. Am. Chem. Soc. 1992, 114, 25, 10056–10058Publication Date (Print):December 1, 1992Publication History Published online1 May 2002Published inissue 1 December 1992https://pubs.acs.org/doi/10.1021/ja00051a045https://doi.org/10.1021/ja00051a045research-articleACS PublicationsRequest reuse permissionsArticle Views1360Altmetric-Citations70LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts