gebhart/patrepeval huggingface dataset:
Strategies for the discovery of novel tyrosine kinase inhibitors with anticancer activity. (1994)

We present a general drug discovery strategy to find novel inhibitors of tyrosine kinases. This scheme includes the production of initial protein targets for primary screening, an evaluation of enzyme potency and specificity, biochemical and biological effects on various cellular processes in whole-cell models, and strategies for in vivo evaluation of antitumor activity. These aspects are illustrated using a newly discovered class of tyrosine kinase inhibitors, the 2-thioindoles. Certain members of this class of compounds inhibit specific tyrosine kinases at low micromolar concentrations and exhibit a distinct structure-activity relationship, as well as enzyme specificity depending on the chemical substitution. These compounds suppress growth factor-mediated tyrosine phosphorylation and mitogenesis in viable cells and, in some cases, exhibit marked specificity for these effects depending on the substituents on the indole ring system. The issue is stressed that since inhibitors of signal transduction pathways represent an entirely new class of potential antitumor agents, distinct from past and currently used cancer therapies, alternative in vivo tumor models may be needed as well as different requirements for dose levels, scheduling and endpoint evaluation. These inherent difficulties emphasize a need for more basic research at the in vivo stage of drug evaluation to enhance model development and provide a better understanding of the pharmacology for these newer classes of drugs.
Scalable, high performance ethernet forwarding with CuckooSwitch (2013)

Several emerging network trends and new architectural ideas are placing increasing demand on forwarding table sizes. From massive-scale datacenter networks running millions of virtual machines to flow-based software-defined networking, many intriguing design options require FIBs that can scale well beyond the thousands or tens of thousands possible using today's commodity switching chips.
Reoxygenation after severe hypoxia induces cardiomyocyte hypertrophy in vitro: activation of CREB downstream of GSK3β (2004)

In vivo, left ventricular remodeling after myocardial infarction involves hypertrophy generally attributed to increased cardiac workload. We hypothesized that hypoxia/reoxygenation directly induces cardiomyocyte hypertrophy and studied several participating kinases and transcription factors in isolated cardiomyocytes. Hypoxia for 6 h followed by 42 h reoxygenation induced cardiomyocyte hypertrophy assessed by 3H leucine incorporation and immunohistochemistry. Inhibition of reactive oxygen species (ROS), serine/threonine kinase AKT, and ERK abolished reoxygenation-induced hypertrophy. In addition, a beta2-adrenergic receptor (beta2-AR) antagonist, as well as Gi inhibitor pertussis toxin, blocked reoxygenation-induced hypertrophy. Hypoxia for 6 h increased transcription factors CREB, NF-kappaB, and GATA DNA binding activities. However, only CREB DNA-binding was sustained during reoxygenation. Inhibition of PI3-kinase, ERK, and PKA abrogated reoxygenation-induced CREB DNA-binding without affecting CREB serine-133 phosphorylation. These same pathways were found to regulate hypoxia/reoxygenation-induced GSK3beta kinase activity and CREB serine-129 de-phosphorylation. GSK3beta mutants resistant to phosphorylation blocked the stimulation of CRE-dependent transcription induced by hypoxia/reoxygenation. Transfection of cardiomyocytes with a dominant-negative mutant of CREB abrogated hypoxia/reoxygenation-induced hypertrophy. We suggest that hypoxia/reoxygenation induces cardiomyocyte hypertrophy through CREB activation. Inactivation of GSK3beta by hypoxia/reoxygenation, possibly integrating PI3-kinase and ERK pathways downstream of beta2-AR and ROS, is a prerequisite for CRE-dependent transcription. Transient hypoxia may contribute to cardiac hypertrophy in ischemic heart disease independent of cardiac workload.
Design and Synthesis of a Tag‐Free Chemical Probe for Photoaffinity Labeling (2007)

Abstract The novel aromatic diazirine‐containing benzoic acid 22 was prepared via the diazirine 11 as the key intermediate. After formylation of the aryl ring and cleavage of the methyl ether function of aldehyde 12 , the phenolic hydroxy group was converted into the ether 21 terminating in an alkyne function. Oxidation of the aldehyde to the carboxylic acid provided the chemical probe 22 designed for tag‐free photoaffinity labeling. In a proof‐of‐concept study it could be shown that irradiation of the simple ester 23 indeed yields the methanol insertion product 24 . A subsequent click reaction with benzyl azide 20 led to the triazole 25 . A more complicated example was realized with the esterification of bafilomycin A 1 ( 27 ) with acid 22 . (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)
PEAQ - The ITU Standard for Objective Measurement of Perceived Audio Quality (2000)

Perceptual coding of audio signals is increasingly used in the transmission and storage of high-quality digital audio, and there is a strong demand for an acceptable objective method to measure the quality of such signals. A new measurement method is described that combines ideas from several earlier methods. The method should meet the requirements of the user community, and it has been recommended by ITU Radiocommunication study groups.
Effects of Titanium Nitride Coatings on Surface and Corrosion Characteristics of Ni-Ti Alloy (1994)

The structure of a titanium nitride film coated by arc ion plating on a Ni-50Ti shape memory alloy was characterized by X-ray photoelectron spectroscopy (XPS). The corrosion behavior of the titanium nitride-coated Ni-50Ti alloy was examined in 0.9% NaCl solution by potentiodynamic polarization measurements and a polarization resistance method. XPS spectra showed that the titanium nitride film consisted of three layers, a top layer of TiO2, a middle layer of TiNx (x > 1), and an inner layer of TiN. The passive current density for the titanium nitride-coated alloy was approximately two orders of magnitude lower than that of the polished alloy in the potential range from the free corrosion potential to +500 mV (vs. Ag/AgCl). Pitting corrosion associated with breakdown of the coated film occurred above this potential. The polarization resistance data also indicated that the corrosion rate of the titanium nitride-coated alloy at the free corrosion potential (+50-+100 mV) was more than one order of magnitude lower than that for the polished alloy.
NK CELL RECEPTORS (1998)

NK cells are regulated by opposing signals from receptors that activate and inhibit effector function. While positive stimulation may be initiated by an array of costimulatory receptors, specificity is provided by inhibitory signals transduced by receptors for MHC class I. Three distinct receptor families, Ly49, CD94/NKG2, and KIR, are involved in NK cell recognition of polymorphic MHC class I molecules. A common pathway of inhibitory signaling is provided by ITIM sequences in the cytoplasmic domains of these otherwise structurally diverse receptors. Upon ligand binding and activation, the inhibitory NK cell receptors become tyrosine phosphorylated and recruit tyrosine phosphatases, SHP-1 and possibly SHP-2, resulting in inhibition of NK cell-mediated cytotoxicity and cytokine expression. Recent studies suggest these inhibitory NK cell receptors are members of a larger superfamily containing ITIM sequences, the inhibitory receptor superfamily (IRS).
The Viscosity of Aqueous Solutions of Bovine Serum Albumin between pH 4.3 and 10.5. (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Viscosity of Aqueous Solutions of Bovine Serum Albumin between pH 4.3 and 10.5.Charles Tanford and John G. BuzzellCite this: J. Phys. Chem. 1956, 60, 2, 225–231Publication Date (Print):February 1, 1956Publication History Published online1 May 2002Published inissue 1 February 1956https://pubs.acs.org/doi/10.1021/j150536a020https://doi.org/10.1021/j150536a020research-articleACS PublicationsRequest reuse permissionsArticle Views2741Altmetric-Citations181LEARN 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 options Get e-Alerts
P‐024: The pattern and severity of FDG pet abnormalities in Alzheimer's disease and amnestic mild cognitive impairment: Preliminary findings from the Alzheimer's disease neuroimaging initiative (2007)

Patients with Alzheimer's disease (AD) [18]F-fluorodeoxyglucose (FDG) positron emission tomography (PET) measurements of the cerebral metabolic rate for glucose (CMRgl) in posterior cingulate, precuneus, and parietotemporal regions, which are correlated with dementia severity. Patients with amnestic mild cognitive impairment (MCI) who subsequently convert AD also have abnormally reduced CMRgl in some of these same brain regions. In this study, we used PET images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu\ADNI) to directly compare the FDG PET images of patients with AD, patients with MCI and elderly normal controls (NC). To compare the pattern and magnitude of regional-to-whole brain CMRgl reductions in ADNI patients with AD and MCI. FDG PET images from 16 AD patients, 27 MCI patients and 27 NC were analyzed using SPM5. An ANOVA with pair-wise comparisons contrasted regional CMRgl in the three subject groups. A conjunction analysis characterized brain regions with significantly reduced CMRgl in both patient groups. A simple linear regression characterized the relationship between the magnitude of regional CMRgl reductions and clinical severity after assigning the NC, MCI and AD groups to clinical severity values of 0, 1 and 2, respectively. In comparison with the NC, the AD and MCI groups each had lower CMRgl in posterior cingulate, precuneus, and parietotemporal regions (P<0.05 after correction for multiple comparisons), search regions implicated in a previous PET study of AD; they also had lower CMRgl in occipital cortex, the hippocampus, parahippocampal gyrus and fusiform gyrus (P<0.005, uncorrected for multiple comparisons). Based on the conjunction analysis, the AD and MCI groups each had lower CMRgl than the NC in the same posterior cingulate-precuneus and parietotemporal regions. CMRgl reductions in the posterior cingulate, precuneus and parietotemporal regions were correlated with group-related increases in clinical severity (P<0.05 after correction for multiple comparisons in the whole brain using FWE). This direct comparison of three subject groups confirms the similar distribution of FDG PET abnormalities in patients with AD and MCI, and its correlation with clinical severity. It also supports the comparability of measurements from different sites and scanners in the ADNI.
ChemInform Abstract: Preparative Scale Syntheses of Isomerically Pure (10E,12E,14Z)‐ and (10E,12E,14E)‐Hexadeca‐10,12,14‐trienals, Sex Pheromone Components of Manduca sexta. (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Parasitism ofHeliothis zeaandH. virescens(Lepidoptera: Noctuidae) Larvae in Wild and Cultivated Host Plants in the Delta of Mississipp1 (1984)

Bollworm, Heliothis zea (Boddie), and tobacco budworm, H. virescens (F.) larvae were collected at weekly intervals from 6 April through 28 August 1981 from several species of wild and cultivated host plants in the delta of Mississippi. The species, seasonal occurrence, and abundance of Heliothis larvae and their larval parasites in each species of host plant were determined. Four species of parasites, Microplitts croceipes (Cresson), Cotesia (= Apanteles) marginiventris (Cresson), Cardiochiles nigriceps Vierick, and Campoletis sonorensis (Cameron) were reared from Heliothis larvae. The highest and lowest numbers of species of parasites and percentage of parasitism of Heliothis larvae occurred in species of early season wild host plants. M. croceipes parasitized larger numbers of Heliothis spp. larvae in more species of host plants and was active over a longer period than any other parasite species. The decline in the incidence of parasitism of Heliothis in cotton, Gossypium hirsutum L., and soybeans, Glycine max (L.) Merr., during mid- and late season may have resulted from the rapid and vast expansion in host plant habitat and from applications of insecticides.
Screening swallowing function of patients with acute stroke. Part two: detailed evaluation of the tool used by nurses (2001)

Stroke is a common problem and a major consumer of health and social care budgets in the UK. Dysphagia is a frequent accompaniment and its management has the potential to exert significant influence within the rehabilitation process. This study explores in detail the performance of a screening tool (based on the Standardized Swallowing Assessment) used by nurses. Based on 68 complete screening episodes by independently competent nurses, with the effects of chance removed, the tool demonstrated good agreement with summative clinical judgement of swallow function (kappa = 0.88). The accuracy of results supported the full training and education programme for nurses. Not all components of the tool were required; analyses suggested elimination of three variables but further exploration is warranted. As a component of evidence-based guidelines for nutritional support in acute stroke, the screening initiative contributed to improved patient outcomes.
Semivariograms from a forest transect gap model compared with remotely sensed data (1992)

Abstract. A spatially linked version of a forest gap model, ZELIG, parameterized for the H. J. Andrews Experimental Forest, Oregon, was used to generate structural properties (i.e. biomass, leaf area, and maximum tree height) of young (80 yr), mature (140 yr), and old‐growth (450 yr) Pseudotsuga menziesii (Douglas fir) forests. Semivariograms were produced at 10 and 30 m resolution to describe the spatio‐temporal patterns of variation of the simulated structural features along a 5 km transect of contiguous 10 m x 10 m grid cells. These semivariograms from the simulations were compared with semivariograms from matrices of pixel digital values obtained from aerial videography of similarly aged stands. Although autocorrelative spatial patterning was absent from both the remotely sensed imagery (except at &lt; 20 m for the 450 yr stand) and the model output, the pixel‐to‐pixel and plot‐to‐plot variances exhibited similar patterns across the chronosequence at both resolutions. This suggests that gap models are able to capture temporal aspects of landscape dynamics associated with canopy texture of Pacific Northwest forests.
Differentiation of peanut lectin positive suppressor T-cells from peanut lectin negative precursors in bovine cells by 12-O-tetradecanoylphorbol-13-acetate. (1987)

Although 12-O-tetradecanoylphorbol-13-acetate (TPA) can synergize with lectins to enhance lymphocyte proliferation, pretreatment of lymphocytes with TPA decreases their response. Pretreatment also inhibits the response to allogeneic cells in the mixed lymphocyte culture. In this study we determined that at least part of this inhibition was due to the generation of T-lymphocytes with the ability to suppress proliferation in vitro. By using populations enriched in lymphocytes or macrophages we determined that the interaction of TPA with lymphocytes, but not macrophages, was required to mediate the suppression. The number of macrophages present in culture (range, 0.5-10%) was irrelevant to the generation of inhibitory activity. Moreover, the TPA-induced suppressor activity copurified with T-cells. Furthermore, when peanut lectin (agglutinin) (PNA) was used to separate T-cells after treatment with TPA, essentially all of the activity copurified with the PNA positive cells. When PNA separations were carried out before treatment with TPA, the suppressor activity arose from the PNA negative fraction. Therefore, TPA appeared to cause phenotypically PNA negative T-cells to gain the PNA positive marker, as well as to function as suppressor cells in vitro. Suppressor activity was also found in the culture medium. Thus the suppression observed may be mediated through a soluble factor released by the TPA-treated cells. Although the suppressor cell activity induced by TPA can only partially account for its in vitro inhibition of lymphocyte proliferation, the development of suppressor cells merits further study with respect to lymphocyte phenotypic and functional differentiation. The results also suggest the possibility that similar processes could occur in vivo, possibly during the course of tumor promotion.
Development of Sendai Virus Vectors and their Potential Applications in Gene Therapy and Regenerative Medicine (2012)

Gene delivery/expression vectors have been used as fundamental technologies in gene therapy since the 1980s. These technologies are also being applied in regenerative medicine as tools to reprogram cell genomes to a pluripotent state and to other cell lineages. Rapid progress in these new research areas and expectations for their translation into clinical applications have facilitated the development of more sophisticated gene delivery/expression technologies. Since its isolation in 1953 in Japan, Sendai virus (SeV) has been widely used as a research tool in cell biology and in industry, but the application of SeV as a recombinant viral vector has been investigated only recently. Recombinant SeV vectors have various unique characteristics, such as low pathogenicity, powerful capacity for gene expression and a wide host range. In addition, the cytoplasmic gene expression mediated by this vector is advantageous for applications, in that chromosomal integration of exogenous genes can be undesirable. In this review, we introduce a brief historical background on the development of recombinant SeV vectors and describe their current applications in gene therapy. We also describe the application of SeV vectors in advanced nuclear reprogramming and introduce a defective and persistent SeV vector (SeVdp) optimized for such reprogramming.
Ethyl (4‐N‐acylaminopyridin‐3‐yl)glyoxylate and 5‐azaisatin as new synthons for a route to various new polyheterocycles (1997)

Abstract From 4‐ N ‐protected‐aminopyridines which were functionalized at their 3‐position, 5‐azaisatin and equivalent synthons where obtained. Via the use of the Pfitzinger reaction, these compounds provided an easy route to new and various polyheterocyclic compounds.
Protein-Protein Interactions between Hepatitis C Virus Nonstructural Proteins (2003)

Replication of the hepatitis C virus (HCV) genome has been proposed to take place close to the membrane of the endoplasmic reticulum in membrane-associated replicase complexes, as is the case with several other plus-strand RNA viruses, such as poliovirus and flaviviruses. The most obvious benefits of this property are the possibility of coupling functions residing in different polypeptidic chains and the sequestration of viral proteins and nucleic acids in a distinct cytoplasmic compartment with high local concentrations of viral components. Indeed, HCV nonstructural (NS) proteins were clearly colocalized in association with membranes derived from the endoplasmic reticulum. This observation, together with the demonstration of the existence of several physical interactions between HCV NS proteins, supports the idea of assembly of a highly ordered multisubunit protein complex(es) probably involved in the replication of the viral genome. The objective of this study, therefore, was to examine all potential interactions between HCV NS proteins which could result in the formation of a replication complex(es). We identified several interacting viral partners by using a glutathione S-transferase pull-down assay, by in vitro and ex vivo coimmunoprecipitation experiments in adenovirus-infected Huh-7 cells allowing the expression of HCV NS proteins, and, finally, by using the yeast two-hybrid system. In addition, by confocal laser scanning microscopy, NS proteins were clearly shown to colocalize when expressed together in Huh-7 cells. We have been able to demonstrate the existence of a complex network of interactions implicating all six NS proteins. Our observations confirm previously described associations and identify several novel homo- and heterodimerizations.
Induction of fos RNA by DNA-damaging agents. (1989)

We have found that a wide variety of DNA-damaging agents and heat shock increase fos RNA to different extents in Chinese hamster ovary cells. These include the monofunctional alkylating agents methylmethane sulfonate and N-methyl-N'-nitro-N-nitrosoguanidine, the cross-linking agents cis-Pt(II) diamminedichloride and mechlorethamine HCl, the DNA base-damaging agents 4-nitroquinoline-N-oxide and N-acetoxy-2-acetylaminofluorene, ultraviolet and near-ultraviolet radiation, hydrogen peroxide, and Adriamycin. Prolonged increases in fos RNA were observed, with persistence to 16 h following treatment. Variation in the amount of fos RNA induction by these agents and the diverse types and frequencies of cellular damage produced by them suggested that there might be several different mechanisms responsible for increased fos RNA.
The Chemical Modification of KCa Channels by Carbon Monoxide in Vascular Smooth Muscle Cells (1997)

The chemical modification of big conductance calcium-activated potassium (KCa) channels in rat tail artery smooth muscle cells by carbon monoxide (CO) was investigated using the cell-free single channel recording technique. Exposure of the internal surface of cell membranes to diethyl pyrocarbonate (DEPC) neither affected the characteristics of KCa channels nor modified the stimulatory effect of CO on KCa channels. However, when DEPC was applied to the external surface of cell membranes, the open probability of KCa channels was reduced. The pH and concentration dependence of the effect of DEPC indicated the specific modification of histidine residues. Kinetic analysis suggested that one externally located histidine residue was modified by DEPC. Treatment of the external surface of cell membranes with DEPC abolished the CO-induced increase in the open probability of KCa channels. Likewise, the presence of CO partially protected KCa channels from inhibition by DEPC. Moreover, photooxidation of the histidine residue located on the external membrane surface abolished the CO-induced activation of KCa channels. Our study demonstrates that the CO-induced increase in the open probability of KCa channels may rely specifically on the structure and topological locations of histidine residues.