gebhart/patrepeval huggingface dataset:
Asn 505 Mutation of the C-MPL Gene, A Cause of Familial Essential Thrombocythemia, Induces the Autonomous Homodimerizaton of the C-Mpl Independent of Ligand Stimulation. (2004)

Abstract The c-MPL gene and its ligand, thrombopoietin (TPO), regulate the proliferation and differentiation of megakaryocytes and platelets. We previously found a dominant-positive activating mutation of the c-MPL gene as a cause of familial essential thrombocythemia. This mutation (Ser505 to Asn505) was located in the transmembrane domain of the c-MPL. The Ba/F3 cells expressing the mutant allele of Asn505 acquired interleukin-3 (IL-3)-independent survival capacity and the autonomous phosphorylation of Mek1/2 and Stat5b in the absence of IL-3 (Blood 103; 4198, 2004). The mechanism underlying how c-Mpl with Asn505 induces constitutive phosphorylation of Mek and Stat5b remains unknown. However, it is assumed that dimerization of c-Mpl molecules may be accelerated as a result of this specific mutation, as in the cases of mutations of c-kit and Neu at their transmembrane domains. Thus we examined the status of dimer formation of the c-Mpl molecules in the Ba/F3 cells with the Asn505 cells in the presence and absence of IL-3 or Tpo using the cell surface chemical cross-linking assay. As a result, in wild-type (Ser505) c-Mpl-expressing Ba/F3 cells, homodimeric signals of the c-Mpl proteins were detected only in the presence of IL-3 or Tpo, whereas mutant (Asn505) c-Mpl-expressing Ba/F3 cells harbored constitutively homodimeric signals even in the absence of IL-3 or Tpo. These observations suggest that mutant c-Mpl with Asn505 can activate the downstream signals involved in the Tpo-c-Mpl signaling pathway mediated by the formation of autonomous homodimerizaton independent of ligand stimulation. As asparagine (Asn) is well known to provide a strong free energy of association by forming interhelical hydrogen bonds in a hydrophobic environment, the Asn505 mutation in the transmembrane domain of the c-MPL is thought to drive strong interactions (dimerizations) among the c-Mpl molecules, leading to the activation of the Tpo-c-Mpl signaling and consequently autonomously activated megakaryocytopoiesis with the excessive production of platelets. The disulfide-bonded homodimerization may be also induced by the Asn505 mutation. Further investigation of this issue is now in progress.
Preparation and characterization of crosslinked and heat-treated PVA-MA films (1996)

Two kinds of water-insoluble PVA-MA hydrogel films were prepared from PVA-MA, an esterification product of poly(vinyl alcohol) and maleic anhydride, by heat treatment and a crosslinking reaction, respectively. Both films changed their dimensions upon environmental pH changes. The crosslinked gel expanded to approximately 230% of its original length, with most changes occurring in the pH range of 2–7. The heat-treated PVA-MA film swelled stepwisely, with about 45% of the total expansion occurring at pH 2–7 and the remaining 55% at pH 9–12. Results from IR spectra analysis and acid-base titration suggest that the ionization of carboxylic acid accounts for the pH-induced gel swelling irrespective of the differences in the swelling behavior of these two gels. The pKa values of the heat-treated PVA-MA gel increased from 4 to 10 while the degree of dissociation varied from 0 to 80%, whereas that of the crosslinked PVA-MA film is limited in a range of 3.3–4.2. The permeability of glucose across the crosslinked PVA-MA film increased when pH was raised from 2 to 7. No significant change of permeability was noticed between pH 7 and 12. For the heat-treated PVA-MA film, glucose permeability increased when pH was changed from 2 to 7 and from 7 to 12. © 1996 John Wiley & Sons, Inc.
A systematic, ligation-based approach to study RNA modifications (2006)

Over 100 different chemical types of modifications have been identified in thousands of sites in tRNAs, rRNAs, mRNAs, small nuclear RNAs, and other RNAs. Some modifications are highly conserved, while others are more specialized. They include methylation of bases and the ribose backbone, rotation, and reduction of uridine, base deamination, elaborate addition of ring structures, carbohydrate moieties, and more. We have developed a systematic approach to detect and quantify the extent of known RNA modifications. The method is based on the enzymatic ligation of oligonucleotides using the modified or unmodified RNA as the template. The efficiency of ligation is very sensitive to the presence and the type of modifications. First, two oligo pairs for each type of modification are identified. One pair greatly prefers ligation using the unmodified RNA template over the modified RNA template or vice versa. The other pair has equal reactivity with unmodified and modified RNA. Second, separate ligations with each of the two oligo pairs and the total RNA mixture are performed to detect the presence or absence of modifications. Multiple modification sites can be examined in the same ligation reaction. The feasibility of this method is demonstrated for three 2'O-methyl modification sites in yeast rRNA.
Postprocessing algorithm based on the probabilistic and semantic method for Japanese OCR (2002)

A postprocessing algorithm for Japanese OCR based on the probabilistic and semantic method is described. It determines the reliability of each recognized character and word in OCR outputs with their recognition probability and appearance frequency in the text. Using these reliabilities, grammatical word paths are searched in each phrase. When it is necessary to select the most suitable word from a similar word set, an attempt is made to select a particular one by the semantic method with co-occurrence word dictionary. This method was applied to OCR outputs of current newspapers and technical documents including some unregistered words, and evaluated its performance. While error correction rate depends on the ratio of unregistered words in the texts, the error detection rate is almost 90%.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Interactive effects of cocaine on HIV infection: implication in HIV-associated neurocognitive disorder and neuroAIDS (2015)

Substantial epidemiological studies suggest that not only, being one of the reasons for the transmission of the human immunodeficiency virus (HIV), but drug abuse also serves its role in determining the disease progression and severity among the HIV infected population. This article focuses on the drug cocaine, and its role in facilitating entry of HIV into the CNS and mechanisms of development of neurologic complications in infected individuals. Cocaine is a powerfully addictive central nervous system stimulating drug, which increases the level of neurotransmitter dopamine (DA) in the brain, by blocking the dopamine transporters (DAT) which is critical for DA homeostasis and neurocognitive function. Tat protein of HIV acts as an allosteric modulator of DAT, where as cocaine acts as reuptake inhibitor. When macrophages in the CNS are exposed to DA, their number increases. These macrophages release inflammatory mediators and neurotoxins, causing chronic neuroinflammation. Cocaine abuse during HIV infection enhances the production of platelet monocyte complexes (PMCs), which may cross transendothelial barrier, and result in HIV-associated neurocognitive disorder (HAND). HAND is characterized by neuroinflammation, including astrogliosis, multinucleated giant cells, and neuronal apoptosis that is linked to progressive virus infection and immune deterioration. Cocaine and viral proteins are capable of eliciting signaling transduction pathways in neurons, involving in mitochondrial membrane potential loss, oxidative stress, activation of JNK, p38, and ERK/MAPK pathways, and results in downstream activation of NF-κB that leads to HAND. Tat-induced inflammation provokes permeability of the blood brain barrier (BBB) in the platelet dependent manner, which can potentially be the reason for progression to HAND during HIV infection. A better understanding on the role of cocaine in HIV infection can give a clue in developing novel therapeutic strategies against HIV-1 infection in cocaine using HIV infected population.
Mechanism of Mitogen-activated Protein Kinase Phosphatase-3 Activation by ERK2 (1999)

The mitogen-activated protein kinase phosphatase 3 (MKP3)-catalyzed hydrolysis of aryl phosphates in the absence and presence of extracellular signal-regulated kinase 2 (ERK2) was investigated in order to provide insights into the molecular basis of the ERK2-induced MKP3 activation. In the absence of ERK2, the MKP3-catalyzed hydrolysis of simple aryl phosphates does not display any dependence on pH, viscosity, and the nature of the leaving group. Increased catalytic activity and enhanced affinity for oxyanions are observed for MKP3 in the presence of ERK2. In addition, normal bell-shaped pH dependence on the reaction catalyzed by MKP3 is restored in the presence of ERK2. Collectively, these results suggest that the rate-limiting step in the absence of ERK2 for the MKP3 reaction corresponds to a substrate-induced conformational change in MKP3 involving active site rearrangement and general acid loop closure. The binding of ERK2 to the N-terminal domain of MKP3 facilitates the repositioning of active site residues and speeds up the loop closure in MKP3 such that chemistry becomes rate-limiting in the presence of ERK2. Remarkably, it is found that the extent of ERK2-induced MKP3 activation is substrate dependent, with smaller activation observed for bulkier substrates. Unlike simple aryl phosphates, the MKP3-catalyzed hydrolysis of bulky polycyclic substrates exhibits bell-shaped pH rate profiles in the absence of ERK2. Furthermore, it is found that glycerol can also activate the MKP3-catalyzed reaction, increase the affinity of MKP3 for oxyanion, and restore the bell-shaped pH rate profile for the MKP3-catalyzed reaction. Thus, the rate of repositioning of catalytic groups and the reorienting of the electrostatic environment in the MKP3 active site can be enhanced not only by ERK2 but also by high affinity substrates or by glycerol.
Carcinogenicity in Mice of Mutagenic Compounds from a Tryptophan Pyrolyzate (1981)

The compounds 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole, which are potent mutagens in a tryptophan pyrolyzate, ar hepatic carcinogens when given orally to mice at concentrations of 200 parts per million in a pellet diet. Female mice showed higher susceptibilities to both compounds than male mice.
Garcinol modulates tyrosine phosphorylation of FAK and subsequently induces apoptosis through down‐regulation of Src, ERK, and Akt survival signaling in human colon cancer cells (2005)

Garcinol, from the fruit rind of Garcinia indica and other species, has been reported to suppress colonic aberrant crypt foci (ACF) formation in rats. In this study, we investigate the beneficial effects of tumor prevention by garcinol on the human colorectal cancer cell line, HT-29. Focal adhesion kinase (FAK) is the major signaling mediator of integrin-mediated cell-matrix contact-regulated cellular proliferation, migration, and apoptosis in adherent cells. Results of Matrigel analysis show that exposure of HT-29 cells to 10 microM garcinol inhibited cell invasion, and decreased the dose-dependent tyrosine phosphorylation of FAK. We further demonstrate by Western blot analysis that garcinol inhibited activation of the Src, MAPK/ERK, and PI3K/Akt signaling pathways. To investigate whether the loss of integrin-mediated cell-matrix contact can induce apoptosis, we demonstrate that garcinol induced it in HT-29 cells. The apoptotic dose of garcinol (20 microM) changed the ratio of the anti-apoptotic Bcl-2 and proapoptotic BAX proteins within 12 h, which correlated with a release of cytochrome c from the mitochondria to the cytosol, and with PARP cleavage. Additionally, we demonstrate that a decreasing MMP-7 protein level in HT-29 cells results in sensitization to garcinol. Garcinol also significantly inhibited the expression of MMP-7 in IL-1beta-induced HT-29 cells. These results suggest that garcinol reduces cell invasion and survival through the inhibition of FAK's downstream signaling.
Evidence of the presence of calcium/calmodulin-dependent protein kinase IV in human sperm and its involvement in motility regulation (2005)

The mechanisms involved in the regulation of mammalian sperm motility are not well understood. Calcium ions (Ca(2+)) have been suggested to play a key role in the maintenance of motility; nevertheless, how Ca(2+) modulates this process has not yet been completely characterized. Ca(2+) can bind to calmodulin and this complex regulates the activity of multiple enzymes, including Ca(2+)/calmodulin-dependent protein kinases (CaM kinases). Results from this study confirmed that the presence of Ca(2+) in the incubation medium is essential for maintaining human sperm motility. The involvement of CaM kinases in Ca(2+) regulation of human sperm motility was evaluated using specific inhibitors (KN62 and KN93) or their inactive analogues (KN04 and KN92 respectively). Sperm incubation in the presence of KN62 or KN93 led to a progressive decrease in the percentage of motile cells; in particular, incubation with KN62 also reduced sperm motility parameters. These inhibitors did not alter sperm viability, protein tyrosine phosphorylation or the follicular fluid-induced acrosome reaction; however, KN62 decreased the total amount of ATP in human sperm. Immunological studies showed that Ca(2+)/calmodulin-dependent protein kinase IV (CaMKIV) is present and localizes to the human sperm flagellum. Moreover, CaMKIV activity increases during capacitation and is inhibited in the presence of KN62. This report is the first to demonstrate the presence of CaMKIV in mammalian sperm and suggests the involvement of this kinase in the regulation of human sperm motility.
Experience in diagnosing a remote, tele-controlled unit using the AITEST expert system (2002)

This paper describes our experience in using a diagnostic expert system (AITEST) for fault isolation, diagnosis and repair action recommendations for a remote, tele-controlled UUT (Unit Under Test). We identify the unique requirements of diagnosis in this class of problems, and explains how these requirements were met in less than three person-months by integrating the expert system with specially-developed tele-control software and test software to form a seamless and capable diagnostic system for a specific UUT. We describe the process we used in analyzing the problem, concurrent development of knowledge base and test software, and their integration into the complete solution. We conclude by presenting preliminary results.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
New York Counterpoint (1985) (2004)

This chapter presents Reich's thoughts about New York Counterpoint. He says that New York Counterpoint is a continuation of ideas found in Vermont Counterpoint (1982), in which a soloist plays against a prerecorded tape of him- or herself. In New York Counterpoint, the soloist prerecords ten clarinet and bass clarinet parts and then plays a final eleventh part live against the tape. The compositional procedures used include several that occur in my earlier music.
Towards Automatic Test Database Generation. (2008)

Reactive oxygen species (ROS) are produced as an inescapable consequence of aerobic life. Their levels are kept low enough to be harmless by specific enzymes, such as superoxide dismutase, which eliminate them. Expression of these defence enzymes is modulated depending on the environmental oxidative threat. This basic protection, however, is not sufficient to protect against sudden large increases in ROS production. To cope with oxidative stress, rapid global responses are induced that enable bacteria to survive the stress period by multiple means: elimination of ROS, repair of oxidative damage, bypass of damaged functions and induction of adapted metabolism. The soxRS response, which protects against superoxide (O2.-)-generating agents and nitric oxide (.NO), is triggered by activation of a sensor molecule, SoxR, containing two essential [2Fe-2S] clusters. The soxRS regulon is induced in a two-stage process. Upon activation, SoxR induces soxS expression and SoxS, in turn, activates transcription of genes of the regulon. The mechanism of signalling has been under debate for years. Evidence for several pathways of SoxR activation, mediated by the modifications of [2Fe-2S] centres, has emerged from recent data. The direct oxidation of [2Fe-2S] centres, any event that may interfere with the pathway maintaining SoxR in a reduced inactive form, and direct nitrosylation by .NO can trigger SoxR activation. The multiple possibilities for SoxR activation, along with signal amplification via the two-stage process, constitute a unique, and particularly sensitive, system enabling cells to induce rapidly a protective response to a broad range of environmental changes indicative of possible oxidative stress.
Equilibrium phase compositions, phase densities, and interfacial tensions for carbon dioxide + hydrocarbon systems. 1. Carbon dioxide + n-butane (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEquilibrium phase compositions, phase densities, and interfacial tensions for carbon dioxide + hydrocarbon systems. 1. Carbon dioxide + n-butaneJack J. C. Hsu, N. Nagarajan, and R. L. Robinson Jr.Cite this: J. Chem. Eng. Data 1985, 30, 4, 485–491Publication Date (Print):October 1, 1985Publication History Published online1 May 2002Published inissue 1 October 1985https://pubs.acs.org/doi/10.1021/je00042a036https://doi.org/10.1021/je00042a036research-articleACS PublicationsRequest reuse permissionsArticle Views695Altmetric-Citations145LEARN 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
CD40–CD40L cross-talk integrates strong antigenic signals and microbial stimuli to induce development of IL-17-producing CD4 <sup>+</sup> T cells (2009)

IL-17-producing CD4(+) T cells have been recognized as key players in organ-related autoimmune disease; however, the parameters that govern their development are yet to be elucidated fully. By using both in vivo and in vitro systems, we have investigated the role of antigen dose, pathogen-associated molecular patterns, and CD40-CD40 ligand (CD40L) cross-talk in Th17 differentiation. We found that the strength of antigenic stimulation critically influenced the extent of Th17 differentiation, because high, but not low or intermediate, antigen concentrations led to IL-17 production. Strong antigenic stimulation of T cells up-regulated CD40L expression, which in concert with certain microbial stimuli (i.e., cytosine phosphate guanine, curdlan, and zymosan) synergistically increased dendritic cell (DC) IL-6 production and Th17 polarization. CD40-deficient DCs exhibited reduced cytokine release and failed to drive Th17 development in vitro. These results were confirmed in vivo where the absence of CD40-CD40L cross-talk was found to prevent the expansion of IL-17-producing cells and accordingly the development of experimental autoimmune encephalitis. Our data demonstrate that CD40-CD40L cross-talk is important for Th17 development by translating strong T cell receptor and microbial stimuli into IL-6 production.
Refactoring an Automotive Embedded Software Stack using the Component-Based Paradigm (2007)

The number of electronic systems in cars is continuously growing. Electronic systems, consisting of so-called electronic control units (ECUs) interconnected by a communication network, account for up to 30% of a modern car's worth. Consequently, software plays an ever more important role, both for the implementation of functions and the infrastructure. In order to benefit from the reuse of software modules, the major automotive companies have standardized a large number of these modules in the context of the AUTOSAR consortium. In this paper we propose the refactoring of the AUTOSAR stack of system software modules by applying the component-based paradigm in order to increase the scalability of the software stack according to the particular requirements of the application. We demonstrate the feasibility of this approach by performing the refactoring of the modules FlexRay Driver and FlexRay Interface as an example and by deploying the resulting refactored components in a sample automotive application. Finally, we measure the execution time as well as the memory consumption of the refactored components and compare these measures to the measures obtained from the corresponding ordinary AUTOSAR modules.
<title>Spectrum recovery from colorimetric data for color reproductions</title> (2001)

Colorimetric data can be readily computed from measured spectral data, however, as illustrated by metameric pairs, the mapping from spectral data to colorimetric values is many-to-one and therefore typically not invertible. In this paper, we investigate inversions of the spectrum-to-colorimetry mapping when the input is constrained to a single color reproduction medium. Under this constraint, accurate recovery of spectral data from colorimetric data is demonstrated for a number of different color reproduction processes. Applications of the spectrum reconstruction process are discussed and demonstrated through examples.
How COVID-19 induces cytokine storm with high mortality (2020)

The newly emerging coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, but has rapidly spread all over the world. Some COVID-19 patients encounter a severe symptom of acute respiratory distress syndrome (ARDS) with high mortality. This high severity is dependent on a cytokine storm, most likely induced by the interleukin-6 (IL-6) amplifier, which is hyper-activation machinery that regulates the nuclear factor kappa B (NF-κB) pathway and stimulated by the simultaneous activation of IL-6-signal transducer and activator of transcription 3 (STAT3) and NF-κB signaling in non-immune cells including alveolar epithelial cells and endothelial cells. We hypothesize that IL-6-STAT3 signaling is a promising therapeutic target for the cytokine storm in COVID-19, because IL-6 is a major STAT3 stimulator, particularly during inflammation. We herein review the pathogenic mechanism and potential therapeutic targets of ARDS in COVID-19 patients.
An Introduction to the Consensus Model of Engineering Design Decision Making (1998)

Abstract This paper presents an introduction1 to a model of a collaborative working environment which supports distributed team argumentation, negotiation, consensus building and rationale capture. Based on a natural model of team deliberation, this model is the basis for the development of a system that enables team support and the capture of the design rationale in value added activities. The consensus model is the result of over fifteen years of studying and modeling design engineers by the authors and the integration of research results from the fields of negotiation and argumentation modeling, design rationale capture, decision theoretics, and engineering best practices.