gebhart/patrepeval huggingface dataset:
IL6 sensitizes prostate cancer to the antiproliferative effect of IFNα2 through IRF9 (2013)

Development and progression of prostate cancer (PCa) are associated with chronic inflammation. The cytokine interleukin 6 (IL6) can influence progression, differentiation, survival, and angiogenesis of PCa. To identify novel pathways that are triggered by IL6, we performed a gene expression profiling of two PCa cell lines, LNCaP and MDA PCa 2b, treated with 5 ng/ml IL6. Interferon (IFN) regulatory factor 9 (IRF9) was identified as one of the most prevalent IL6-regulated genes in both cell lines. IRF9 is a mediator of type I IFN signaling and acts together with STAT1 and 2 to activate transcription of IFN-responsive genes. The IL6 regulation of IRF9 was confirmed at mRNA and protein levels by quantitative real-time PCR and western blot respectively in both cell lines and could be blocked by the anti-IL6 antibody Siltuximab. Three PCa cell lines, PC3, Du-145, and LNCaP-IL6+, with an autocrine IL6 loop displayed high expression of IRF9. A tissue microarray with 36 PCa tissues showed that IRF9 protein expression is moderately elevated in malignant areas and positively correlates with the tissue expression of IL6. Downregulation and overexpression of IRF9 provided evidence for an IFN-independent role of IRF9 in cellular proliferation of different PCa cell lines. Furthermore, expression of IRF9 was essential to mediate the antiproliferative effects of IFNα2. We concluded that IL6 is an inducer of IRF9 expression in PCa and a sensitizer for the antiproliferative effects of IFNα2.
Fluorescence imaging detection for capillary isoelectric focusing (1995)

Abstract A simple laser‐induced fluorescence (LIF) imaging detector and an ultrasensitive LIF imaging detector are described for capillary isoelectric focusing (CIEF). An argon ion laser beam of 496.5 nm is used as excitation source. In the simple LIF imaging detector, the excitation beam is directed into a capillary column by an optic fiber array. In the ultrasensitive LIF imaging detector, the laser beam is first expanded, then is focused into the 4.5 cm long capillary column by a cylindrical lens. Fluorescence emission is detected by a charge‐coupled device (CCD) camera. The feasibility and performance of the LIF imaging detector system for CIEF are first verified with a naturally fluorescent protein, b‐phycoerythrin. Then, the ultrasensitive LIF imaging system is used as a detector for CIEF of proteins labeled with fluorescein isothiocyanate (FITC). Three FITC‐labeled proteins (i) α‐ D ‐galatosylated FITC‐albumin, (ii) insulin‐FITC, and (iii) casein‐FITC, are used as model samples. Fluorescence images of the model samples are measured during the CIEF process. The focusing of the protein samples is complete in about 1.5 min. The ultrasensitive detector's detection limits for the FITC‐labeled proteins are at the level of 10 −10 M , and the mass detection limits are about 4.5 × 10 −17 mole, even though only 10% of the fluorescence emission is collected. Therefore, the method is capable of separating and detecting 10 −11 M or amole (10 −18 mole) level protein samples with a band‐pass filter more specific to the fluorescence light. Potential applications of the LIF imaging system in addition to quantitation of separated fluorescent species in various capillary electrophoresis methods can also include investigation of interaction between analytes focused in a capillary column.
Exploring the space of a human action (2005)

One of the fundamental challenges of recognizing actions is accounting for the variability that arises when arbitrary cameras capture humans performing actions. In this paper, we explicitly identify three important sources of variability: (1) viewpoint, (2) execution rate, and (3) anthropometry of actors, and propose a model of human actions that allows us to investigate all three. Our hypothesis is that the variability associated with the execution of an action can be closely approximated by a linear combination of action bases in joint spatio-temporal space. We demonstrate that such a model bounds the rank of a matrix of image measurements and that this bound can be used to achieve recognition of actions based only on imaged data. A test employing principal angles between subspaces that is robust to statistical fluctuations in measurement data is presented to find the membership of an instance of an action. The algorithm is applied to recognize several actions, and promising results have been obtained.
Mathematical Modelling and Control of Chemical Composition Distribution of Ethylene/α-Olefin Copolymers Made with Single and Combined Metallocene Catalysts (2000)

ABSTRACTThe single-site nature of metallocene catalysts permits the production of polyolefins with narrow distributions of molecular weight, chemical composition and comonomer sequence length. This enhanced control over polymer chain microstructure permits, in principle, the synthesis of polyolefins with well-controlled properties. In order to benefit from this enhanced control, one needs to understand how polymerization conditions and catalyst type affect polymer microstructure, as well as how the existing characterization techniques can be used to determine their microstructure. This manuscript investigates the effect of polymerization conditions and catalyst type on the chemical composition distribution (CCD) of ethylene/α-olefin copolymers made with single-site and Ziegler-Natta catalysts. Mathematical models will be used to describe CCD of polyolefins made on single- and multiple-site-type catalysts. Crystallization analysis fractionation (CRYSTAF) and temperature rising elution fractionation (TREF) are used to measure the CCD of these resins. It will be shown that the interpretation of CCDs with these mathematical models can be used to enhance our understanding on the nature of active sites present in metallocene and Ziegler-Natta catalysts.
Experimental evidence for amplitude death induced by dynamic coupling: van der Pol oscillators (2004)

Amplitude death is a coupling induced stabilization of a fixed point in nonlinear oscillators. This phenomenon cannot be observed in two identical nonlinear oscillators coupled by a diffusive connection. However, it has been analytically confirmed that a diffusive dynamic coupling can induce death. This study derives a necessary and sufficient condition for amplitude death in van der Pol oscillators coupled by a diffusive dynamic coupling. The well-known RC line (T-type) is used to implement the dynamic coupling.
Changes in the conformation of influenza virus hemagglutinin at the pH optimum of virus-mediated membrane fusion. (1982)

A conformational change in the hemagglutinin glycoprotein of influenza virus has been observed to occur to pH values corresponding to those optimal for the membrane fusion activity of the virus. CD, electron microscopic, and sedimentation analyses show that, in the pH range 5.2-4.9, bromelain-solubilized hemagglutinin (BHA) aggregates as protein-protein rosettes and acquires the ability to bind both lipid vesicles and nonionic detergent. Trypsin treatment of BHA in the pH 5.0-induced conformation indicates that aggregation is a property of the BHA2 component and that the conformation change also involves BHA1. The implications of these observations for the role of the glycoprotein in membrane fusion are discussed.
Improved MECP2 Gene Therapy Extends the Survival of MeCP2-Null Mice without Apparent Toxicity after Intracisternal Delivery (2017)

Intravenous administration of adeno-associated virus serotype 9 (AAV9)/<i>hMECP2</i> has been shown to extend the lifespan of <i>Mecp2</i><sup>-/y</sup> mice, but this delivery route induces liver toxicity in wild-type (WT) mice. To reduce peripheral transgene expression, we explored the safety and efficacy of AAV9/<i>hMECP2</i> injected into the cisterna magna (ICM). AAV9/<i>hMECP2</i> (1 × 10<sup>12</sup> viral genomes [vg]; ICM) extended <i>Mecp2</i><sup>-/y</sup> survival but aggravated hindlimb clasping and abnormal gait phenotypes. In WT mice, 1 × 10<sup>12</sup> vg of AAV9/<i>hMECP2</i> induced clasping and abnormal gait. A lower dose mitigated these adverse phenotypes but failed to extend survival of <i>Mecp2</i><sup>-/y</sup> mice. Thus, ICM delivery of this vector is impractical as a treatment for Rett syndrome (RTT). To improve the safety of MeCP2 gene therapy, the gene expression cassette was modified to include more endogenous regulatory elements believed to modulate MeCP2 expression in vivo. In <i>Mecp2</i><sup>-/y</sup> mice, ICM injection of the modified vector extended lifespan and was well tolerated by the liver but did not rescue RTT behavioral phenotypes. In WT mice, these same doses of the modified vector had no adverse effects on survival or neurological phenotypes. In summary, we identified limitations of the original vector and demonstrated that an improved vector design extends <i>Mecp2</i><sup>-/y</sup> survival, without apparent toxicity.
Virtual group dynamics. (2002)

The various forms of Internet groups share many similarities to groups that exist in the offline world, but there are also critical differences. The authors examine traditional definitions of groups and how Internet groups fit into those existing definitions. They provide an analysis of relevant aspects that make virtual groups similar to and different from nonelectronic groups, and they examine the ways in which Internet groups function. Individual motivations for joining online groups and the consequences of virtual group membership are also discussed. Over the past decade the number of individuals regularly accessing the Internet has increased exponentially. According to recent research by Nie and Erbring (2000) the number of Americans online has risen to 55%. Worldwide, the number of people using the Internet has risen above 450 million, and that number is expected to double within the next year. Interpersonal communication has become the primary use of the Internet at home (Kraut, Mukopadhyay, Szczypula, Kiesler, & Scherlis, 1998), and people are increasingly turning to the Internet to fulfill important social and psychological needs. One of the most basic interpersonal needs is to “belong,” to feel that one is a member of a group of others who share similar interests and goals, and to feel that one is a valued (and unique) member of that group (Baumeister & Leary, 1995; Brewer, 1991). On the Internet, there are a wealth of venues where one can connect with like-minded others who share core interests and values and thus fulfill this important need. Chat rooms, newsgroups, electronic mailing lists, message boards, interactive games, and major interactive Web sites provide individuals with the opportunity to join existing online groups or to create their own. The various forms of Internet groups share many similarities with groups that exist in the
Polymorphism in ospC gene of Borrelia burgdorferi and immunoreactivity of OspC protein: implications for taxonomy and for use of OspC protein as a diagnostic antigen (1993)

The nucleotide sequences of the ospC gene from five Danish human Borrelia burgdorferi isolates representing all three B. burgdorferi genospecies (B. burgdorferi sensu stricto, Borrelia garinii sp. nov., and group VS461) and from the American type strain B31 were determined and compared with the published ospC sequence from the German B. burgdorferi isolate PKo (R. Fuchs, S. Jauris, F. Lottspeich, V. Preac-Mursic, B. Wilske, and E. Soutschek, Mol. Microbiol. 6:503-509, 1992). The ospC gene was present in all isolates, regardless of the presence or absence of its product, OspC. The deduced amino acid sequences of OspC from the seven isolates were aligned and revealed pairwise sequence identities ranging from 60.5 to 100%. Differences were scattered throughout the amino acid sequences. A phylogenetic tree was constructed and revealed three distinct phenotypic groups OspCI to OspCIII corresponding to the three delineated genospecies. Immunoblot analysis revealed that the seven OspC proteins tested have both common and specific epitopes. There is significant epitope diversity, since even polyclonal antisera showed serotype-restricted specificity. Therefore, a serodiagnostic assay for Lyme borreliosis utilizing OspC as a test antigen should include all three OspC phenotypes in order to obtain a species-wide sensitivity.
Fenton chemistry. Amino acid oxidation. (1991)

The oxidation of amino acids by Fenton reagent (H2O2 + Fe(II] leads mainly to the formation of NH+4, alpha-ketoacids, CO2, oximes, and aldehydes or carboxylic acids containing one less carbon atom. Oxidation is almost completely dependent on the presence of bicarbonate ion and is stimulated by iron chelators at levels which are substoichiometric with respect to the iron concentration but is inhibited at higher concentrations. The stimulatory effect of chelators is not due merely to solubilization of catalytically inactive polymeric forms of Fe(OH)3 nor to the conversion of Fe(II) to complexes incapable of scavenging hydroxyl radicals. The results suggest that an iron chelate and another as yet unidentified form of iron are both required for maximal rates of amino acid oxidation. The metal ion-catalyzed oxidation of amino acids is likely a "caged" process, since the oxidation is not inhibited by hydroxyl radical scavengers, and the relative rates of oxidation of various amino acids by the Fenton system as well as the distribution of products formed (especially products of aromatic amino acids) are significantly different from those reported for amino acid oxidation by ionizing radiation. Several iron-binding proteins, peptides, and hemoglobin degradation products can replace Fe(II) or Fe(III) in the bicarbonate-dependent oxidation of amino acids. In view of their ability to sequester metal ions and their susceptibility to oxidation by H2O2 in the presence of physiological concentrations of bicarbonate, amino acids may serve an important role in antioxidant defense against tissue damage.
Complement, neutrophils and free radicals: mediators of reperfusion injury. (1994)

Myocardial ischemia of sufficient duration produces irreversible myocardial injury and cell death. Associated with the direct ischemic insult, there is the indirect attack on the jeopardized tissue through activation of the complement system. The latter, occurring in response to ischemia, facilitates neutrophil-endothelial cell interactions, neutrophil migration into and across the vascular wall, along with the formation of cytotoxic oxygen metabolites and release of proteolytic enzymes. The neutrophil dependent actions participate in extending the tissue injury beyond that due to ischemia alone. The invading neutrophils injure the myocardial vasculature and sarcolemma through the generation of oxygen free radicals. Components of the complement system can damage tissue indirectly through formation of neutrophil chemoattractants as well as directly through assembly of the "membrane attack complex." Pharmacologic interventions that prevent complement activation, modulate neutrophil function or scavenge oxygen radicals, can reduce the extent of myocardial injury associated with ischemia reperfusion. The inflammatory reaction of cell injury mediated by neutrophil invasion of the affected tissue is an important site for pharmacologic intervention. Specific adhesive glycoprotein receptors are expressed on the neutrophil in conjunction with corresponding endothelial cell ligands. Recognition of these events has led to the development of specific antibodies having the potential to prevent cell-cell interactions essential for promoting and maintaining the inflammatory response. Therefore, neutrophil-independent extension of irreversible cell death that occurs upon reperfusion, is additive to the component of cell death attributed to the ischemic interval. As is the situation with any organ, function and cellular viability are dependent upon a blood supply, which if interrupted for a sufficiently long period, will lead to irreversible cellular changes and necrosis. Reperfusion is essential for arresting the otherwise progressive injury due to ischemia. The accelerated inflammatory response upon reperfusion contributes to an extension of the injury, a phenomenon known as "reperfusion" or "reoxygenation" injury.
Accessory Molecule and Costimulation Requirements for CD4 T Cell Response (1997)

T cell activation is brought about by recognition of peptide/MHC complexes on an antigen-presenting cell (APC) by the T cell receptor (TCR). However, in general this appears to be insufficient for the full development of T cell responses and therefore additional signals are required, provided by ligation of counter-receptors on the T cell by APC accessory molecules. Although many studies have suggested that B7 molecules (CD80/CD86) binding to CD28 induce this second signal, it is now evident that any one of a number of molecules may provide accessory function and that efficient response is only generated following multiple interactions. It has also become clear that T cells exist in varying states of activation or differentiation, and that requirements for accessory molecules and costimuli are not always equivalent. This review covers much of the recent data regarding accessory molecule regulation of T cell responses. A modified version of the two signal model is presented, suggesting that the major function of accessory molecules during the initial stages of activation is to augment the ability to signal through the TCR, and that the primary role of costimulatory signals is to allow IL-2 secretion and growth. The requirement for multiple accessory molecules interactions is discussed in relation to activation of naive T cells and how such interactions are less critical at the memory and effector stages. Finally, this new information is related to how T cells interact with varying APC and how these interactions may modulate T cell response.
Alterations of the p53 tumor suppressor gene and its association with activation of the c-K-ras-2 protooncogene in premalignant and malignant lesions of the human uterine endometrium. (1993)

We previously reported (T. Enomoto et al., Cancer Res., 50: 6139-6145, 1990; T. Enomoto et al., Cancer Res., 51: 5308-5314, 1991) a significant frequency of activating point mutations in codon 12 of the c-K-ras-2 protooncogene in endometrial adenocarcinoma and its premalignant precursor lesions (series 1 and 2). To reveal the role of the p53 tumor suppressor gene in the development of endometrial adenocarcinoma and to study the association of p53 alterations with K-ras activation, an additional 28 endometrial adenocarcinomas and an additional 11 premalignant atypical uterine hyperplasias (series 3), as well as 12 cases of endometrial adenocarcinoma (10 having K- or N-ras activation) and 2 cases of atypical hyperplasia from series 1 and 2, were screened for the presence of p53 alterations. Allelic loss, recognized at the polymorphic site in codon 72 of the p53 gene, was detected in 6 of 19 (32%) informative cases of endometrial adenocarcinoma and 1 of 4 (25%) informative cases of endometrial atypical hyperplasia by restriction fragment length polymorphism analysis and by single-strand conformation polymorphism analysis of polymerase chain reaction (PCR)-amplified DNA fragments. Mutations in the highly conserved regions of the p53 gene were detected by single-strand conformation polymorphism analysis of PCR-amplified DNA fragments. Mutations were found in 9 of 40 (23%) endometrial adenocarcinomas and 1 of 13 (8%) atypical hyperplasias that were studied. Mutations in p53 were significantly more frequently found in clinical grade 3 (G3) cancers (6 of 14, 43%) than in G1-G2 cancers (3 of 26, 12%) (P = 0.033). Mutations were subsequently confirmed by direct sequencing. Single missense base substitutions were detected in 6 cases of endometrial carcinoma and in one case of atypical hyperplasia. Deletions of a single base and of 2 bases were each detected in single cases of endometrial carcinoma, and a single base insertion was found in a third case. Point mutations in K-ras were also identified in tumors of series 3 by direct sequencing of PCR-amplified DNA fragments of exons 1 and 2. Point mutations in codons 12 and 13 in K-ras were detected by direct sequencing of PCR-amplified DNA in 7 of 28 adenocarcinomas in series 3, but none were found in exon 2 (codons 59.63. The spectrum of point mutations in p53 in endometrial adenocarcinomas was almost identical to what we found in K-ras in series 1 and 2 and in series 3, suggesting the possible role of a mutagen that might be responsible for mutations in both K-ras and p53.(ABSTRACT TRUNCATED AT 400 WORDS)
Very High Growth Rate Epitaxy Processes with Chlorine Addition (2007)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
High Sensitivity Scanning of Colorectal Tumors and Matched Plasma DNA for Mutations in APC, TP53, K‐RAS, and BRAF Genes with a Novel DHPLC Fluorescence Detection Platform (2004)

Tumor-associated DNA has been detected in plasma of colorectal cancer (CRC) patients using various techniques but with limited gene or mutation coverage. We report a highly sensitive scanning methodology for mutational assessment of the APC and TP53 genes, which typically pose an analytical challenge because of their significant genotypic heterogeneity as well as specific mutational scoring assays for K-RAS and BRAF. Plasma DNA isolated from 20 CRC patients were scanned for mutations in these targets without knowledge of the molecular or pathological analyses of the matched primary tumors. We chose mutation scanning technology and these molecular targets to provide a comprehensive screen for somatic mutations known to be associated with sporadic CRC. Mutations were identified with a novel denaturing high-performance liquid chromatography (DHPLC) platform that uses post-separation fluorescence technology to enable the detection of variants that represent <0.1% of the total analyzed DNA. Mutant allele specific amplification (MASA) followed by detection with the same platform was used to identify low-level target mutations (mutation scoring) in K-RAS codons 12, 13, and 61, and BRAF codon 599. Using this combined scanning and scoring approach, we were able to identify at least one mutational event in 20/20 (100%) CRC patients. The thoroughness of a mutation scanning and scoring panel may have important implications for CRC screening and disease monitoring during and following therapy.
Current-voltage characteristics of molecular conductors: two versus three terminal (2002)

Addresses the question of whether a "rigid molecule" (one which does not deform in an external field) used as the conducting channel in a standard three-terminal MOSFET configuration can offer any performance advantage relative to a standard silicon MOSFET. A self-consistent solution of coupled quantum transport and Poisson's equations shows that even for extremely small channel lengths (about 1 nm), a "well-tempered" molecular FET demands much the same electrostatic considerations as a "well-tempered" conventional MOSFET. In other words, we show that just as in a conventional MOSFET, the gate oxide thickness needs to be much smaller than the channel length (length of the molecule) for the gate control to be effective. Furthermore, we show that a rigid molecule with metallic source and drain contacts has a temperature independent subthreshold slope much larger than 60 mV/decade, because the metal-induced gap states in the channel prevent it from turning off abruptly. However, this disadvantage can be overcome by using semiconductor contacts because of their band-limited nature.