gebhart/patrepeval huggingface dataset:
Fas-mediated liver damage in MRL hemopoietic chimeras undergoing lpr -mediated graft-versus-host disease (1997)

Fas is an apoptosis-signaling receptor that triggers cell death upon binding to its ligand (FasL). Autoimmune-prone MRL/lpr mice, characterized by a spontaneous mutation of Fas, exhibit a defect in the activation-induced cell death of mature T cells through a Fas-mediated pathway. As a consequence of this defect, activated T cells accumulating in this strain overexpress the FasL and can therefore mediate in vitro Fas-dependent cytotoxicity. To determine whether hepatic injury could be the result of an interaction between T lymphocytes bearing FasL and Fas-expressing liver cells, the livers of lethally irradiated MRL+/+ recipients reconstituted with MRL/lpr lymphoid cells were studied. After transfer of MRL/lpr spleen cells, livers were infiltrated by polyclonal CD8+ T lymphocytes of lpr origin with a peak on day 21 postgrafting. These donor-derived intrahepatic lymphocytes overexpressed the FasL and exerted in vitro Fas-mediated cytotoxicity against Fas+ thymocytes, which was specifically inhibited by soluble recombinant Fas in a dose-dependent manner. These intrahepatic lymphocytes induced apoptosis in vitro, irrespective of MHC restriction, in Fas-expressing primary cultured hepatocytes. Histologic examination of the liver revealed severe endothelialitis as well as periportal and intralobular infiltrations of activated lymphocytes with apoptotic hepatocytes in their vicinity. Simultaneously, liver damage was ascertained by elevated serum transaminase levels. These observations support the notion that an Ag-independent mechanism involving FasL may play a role in certain liver pathologies.
Adenine nucleosides derived from 6-deoxyhexofuranoses (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAdenine nucleosides derived from 6-deoxyhexofuranosesLeon M. LernerCite this: J. Org. Chem. 1976, 41, 2, 306–310Publication Date (Print):January 1, 1976Publication History Published online1 May 2002Published inissue 1 January 1976https://pubs.acs.org/doi/10.1021/jo00864a026https://doi.org/10.1021/jo00864a026research-articleACS PublicationsRequest reuse permissionsArticle Views88Altmetric-Citations9LEARN 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
High Wnt Signaling Represses the Proapoptotic Proteoglycan syndecan-2 in Osteosarcoma Cells (2010)

Osteosarcoma is characterized by frequent relapse and metastatic disease associated with resistance to chemotherapy. We previously showed that syndecan-2 is a mediator of the antioncogenic effect of chemotherapeutic drugs. The purpose of this work was to elucidate molecular mechanisms responsible for the low expression of syndecan-2 in osteosarcoma. We compared the regulatory activity of cis-acting DNA sequences of the syndecan-2 gene in osteosarcoma and osteoblastic cell lines. We identified a DNA region that negatively regulates syndecan-2 transcription in the osteosarcoma cells. T-cell factors (TCF) bind to this sequence in vivo. Wnt3a stimulation, beta-catenin activation, and TCF overexpression resulted in syndecan-2 repression, whereas Wnt inhibition using sFRP-1 increased syndecan-2 expression in U2OS cells. RhoA activation blunted the stimulatory effect of sFRP-1 on syndecan-2 transcription, whereas RhoA inhibition enhanced syndecan-2 expression. These results indicate that Wnt/beta-catenin and Wnt/RhoA signaling contribute to syndecan-2 repression. The alteration of syndecan-2 expression in osteosarcoma cell lines also seemed to be related to a higher shedding, controlled by Wnt/RhoA. Conversely, syndecan-2 was found to activate its own expression in U2OS cells through RhoA inhibition. These data identify a molecular network that may contribute to the low expression of the proapoptotic proteoglycan syndecan-2 in osteosarcoma cells. The high activity of the canonical Wnt pathway in the different osteosarcoma cells induces a constitutive repression of syndecan-2 transcription, whereas Wnt/RhoA signaling blocks the amplification loop of syndecan-2 expression. Our results identify syndecan-2 as a Wnt target and bring new insights into a possible pathologic role of Wnt signaling in osteosarcoma.
Functional Characterization of Adenoviral/Retroviral Chimeric Vectors and Their Use for Efficient Screening of Retroviral Producer Cell Lines (1999)

We have generated three different E1-deleted replication-defective adenoviral vectors expressing either Moloney murine leukemia virus (Mo-MuLV) Gag-Pol core particle proteins, gibbon ape leukemia virus (GALV) envelope glycoproteins, or an MuLV-derived retroviral vector genome encoding mCD2 antigen, a murine cell surface marker easily detectable by flow cytometry. Each of the three vectors was first characterized individually by infection of cells providing the complementary retroviral function(s) and able to induce the production of retroviral vectors with an efficiency similar to or higher than that of FLY stable retroviral packaging cells [Cosset, F.-L., Takeuchi, Y., Battini, J.-L., Weiss, R.A., and Collins, M.K.L., (1995). J. Virol. 69, 7430-7436]. In small-scale pilot experiments, TE671 cells simultaneously coinfected with the three adenoviral vectors efficiently released helper-free retroviral vectors in their supernatant, with titers greater than 10(6) infectious particles per milliliter by end-point titrations. Our results also indicated that in contrast to retroviral vector-packageable RNAs, the adenovirus-mediated overexpression of both Gag-Pol and Env packaging functions had limited impact on retroviral titers. The primary mechanism suspected is the premature intracellular cleavage of the Pr65gag precursor that we found in gag-pol-expressing cells, which in turn may impair the normal incorporation of high loads of functional Env. Last, the characterization of the adenoviral/retroviral chimeric vectors allowed the screening of various primate cells for retroviral production and we found that three hepatocyte-derived cell lines were highly efficient in the assembly and release of infectious retroviral particles.
Ready separation of proteins from nucleoprotein complexes by reversible modification of lysine residues (1980)

Modification of proteins with citraconic anhydride altered the electrostatic relationship between cationic epsilon-NH3+ groups of lysine residues of proteins and anionic phosphate groups of nucleic acids, thereby destabilizing the nucleoprotein complex. This procedure facilitated the separation of proteins from nucleic acids at pH4-4.2. The modifying groups were then deacylated from the proteins under acidic conditions (pH3-6) at 30 degrees C.
Near-infrared Spectroscopic Method for Assessing the Tissue Oxygenation State of Living Lung (1997)

To quantify changes in tissue oxygenation of pathologic lungs, we applied a novel method using near-infrared spectroscopy (NIRs). In in vitro experiments, we assayed the effect of photon scattering on the absorption spectra of an in vitro system simulating structures of lung, which consists of test tube containing air in hematocrit tubes and red blood cell suspension with various predetermined hemoglobin concentrations. It was determined that photon scattering of the tissue containing air did not affect the absorption in the NIR region. In in vivo experiments, we tested the applicability of the NIRs technique in rat lungs under the following conditions: (1) hypoxic loading; (2) administration of an inhibitor (NaCN) of the mitochondrial respiratory chain; (3) hemorrhagic shock. We found that: (1) Changes in hemoglobin oxygenation state in the lung measured by NIRs depended on inspired oxygen concentrations; (2) NaCN-induced reduction of cytochrome oxidase a,a3 in the lung was observed; and (3) Total hemoglobin levels in the lung decreased after bleeding. Changes in the hemoglobin oxygenation state and cytochrome oxidase redox state in the lung were determined using the least-square-curve fitting for NIR absorption spectra. Our NIRs technique was capable of assessing the hemoglobin oxygenation and cytochrome oxidase redox state in the lung.
Evaluation of friction enhancement through soft polymer micro-patterns in active capsule endoscopy (2010)

Capsule endoscopy is an emerging field in medical technology. Despite very promising innovations, some critical issues are yet to be addressed, such as the management and possible exploitation of the friction in the gastrointestinal environment in order to control capsule locomotion more actively. This paper presents the fabrication and testing of bio-inspired polymeric micro-patterns, which are arrays of cylindrical pillars fabricated via soft lithography. The aim of the work is to develop structures that enhance the grip between an artificial device and the intestinal tissue, without injuring the mucosa. In fact, the patterns are intended to be mounted on microfabricated legs of a capsule robot that is able to move actively in the gastrointestinal tract, thus improving the robot's traction ability. The effect of micro-patterned surfaces on the leg-slipping behaviour on colon walls was investigated by considering both different pillar dimensions and the influence of tissue morphology. Several in vitro tests on biological samples demonstrated that micro-patterns of pillars made from a soft polymer with an aspect ratio close to 1 enhanced friction by 41.7% with regard to flat surfaces. This work presents preliminary modelling of the friction and adhesion forces in the gastrointestinal environment and some design guidelines for endoscopic devices.
Evaluation of a Neonatal Rat Model for Prediction of Mumps Virus Neurovirulence in Humans (2000)

Neurovirulence of several mumps virus strains was assessed in a prototype rat neurovirulence test and compared to results obtained in the monkey neurovirulence test. The relative human neurovirulence of these strains was proportional to the severity of hydrocephalus in rats but not to lesion scores in the monkeys.
Induction of Apoptosis in Human Pancreatic Cancer Cells by Docosahexaenoic Acid (2003)

Polyunsaturated fatty acids have been indicated to induce anti-proliferative and/or apoptotic effects in various tumor cells. We showed that, at a 200- micro M concentration, both alpha-linoleic (18:2 n-6; LA) or docosahexaenoic (22:6 n-3; DHA) acid inhibited cell growth, while only DHA induced apoptosis in the human Paca-44 pancreatic cancer cell line. Investigating the mechanism underlying DHA-induced apoptosis, we showed that DHA induced a rapid and dramatic (>60%) intracellular depletion of reduced glutathione (GSH), without affecting oxidized glutathione (GSSG). Moreover, using two specific inhibitors of carrier-mediated GSH extrusion, cystathionine or methionine, we observed that GSH depletion occurred via an active GSH extrusion, and that inhibition of GSH efflux completely reversed apoptosis. These results provide the first evidence for a possible causative role of GSH depletion in DHA-induced apoptosis.
Archiving scientific data (2004)

Archiving is important for scientific data, where it is necessary to record all past versions of a database in order to verify findings based upon a specific version. Much scientific data is held in a hierachical format and has a key structure that provides a canonical identification for each element of the hierarchy. In this article, we exploit these properties to develop an archiving technique that is both efficient in its use of space and preserves the continuity of elements through versions of the database, something that is not provided by traditional minimum-edit-distance diff approaches. The approach also uses timestamps. All versions of the data are merged into one hierarchy where an element appearing in multiple versions is stored only once along with a timestamp. By identifying the semantic continuity of elements and merging them into one data structure, our technique is capable of providing meaningful change descriptions, the archive allows us to easily answer certain temporal queries such as retrieval of any specific version from the archive and finding the history of an element. This is in contrast with approaches that store a sequence of deltas where such operations may require undoing a large number of changes or significant reasoning with the deltas. A suite of experiments also demonstrates that our archive does not incur any significant space overhead when contrasted with diff approaches. Another useful property of our approach is that we use XML format to represent hierarchical data and the resulting archive is also in XML. Hence, XML tools can be directly applied on our archive. In particular, we apply an XML compressor on our archive, and our experiments show that our compressed archive outperforms compressed diff-based repositories in space efficiency. We also show how we can extend our archiving tool to an external memory archiver for higher scalability and describe various index structures that can further improve the efficiency of some temporal queries on our archive.
Short Synthesis of Methylphenidate and Itsp-Methoxy Derivative (2000)

Abstract A short method for the preparation of racemic threo- and erythro-methylphenidate derivatives is described. Condensation between α-ethoxy carbamate 1 and silyl ketene acetals 2a-b in the presence of TESOTf (20 mol%) afforded a 1.5:1 mixture of carbamates 3a-b/4a-b. Hydrogenolysis in EtOH followed by treatment with 3N HCl/MeOH afforded the corresponding hydrochlorides 7a-b/8a-b in good yields.
Strontium as a Marker for Intestinal Calcium Absorption: The Stimulatory Effect of Calcitriol (2000)

Although the reproducibility of AUC(0-240) and its sensitivity to calcitriol were better than those of Fc(240), the Fc(240) of strontium is preferred for a clinical test because of its simplicity, requiring only two instead of five blood samples.
Magnetic stimulation for the measurement of respiratory and skeletal muscle function (2004)

Respiratory and skeletal muscle function is of interest in many areas of pulmonary and critical care medicine. The capacity of the respiratory muscle pump to respond to the load imposed by disease is the basis of an understanding of ventilatory failure. Over the last four decades, considerable progress has been made in quantifying the capacity of the respiratory muscles, in terms of strength, endurance and fatigue. With the development of magnetic stimulation, it has recently become possible to nonvolitionally assess the respiratory muscles in a clinically acceptable way. This is of particular interest in the investigation of patients receiving critical care, those with neuromuscular disease, and in children where volitional efforts are either not possible or likely to be sub-maximal. Furthermore, the adaptation of these techniques to quantify the strength of peripheral muscles, such as the quadriceps, has allowed the effects of muscle training or rehabilitation, uninfluenced by learning effect, to be assessed. This article focuses on the physiological basis of magnetic nerve stimulation, and reviews how the technique has been applied to measure muscle strength and fatigue, with particular emphasis upon the diaphragm. The translation of magnetic stimulation into a clinical tool is described, and how it may be of diagnostic, prognostic and therapeutic value in several areas of pulmonary medicine. In particular, the use of magnetic stimulation in neuromuscular disease, the intensive care setting, chronic obstructive pulmonary disease and paediatrics will be discussed.
Discrete-time adaptive control of systems with unknown nonsmooth input nonlinearities (2002)

A unified discrete-time adaptive inverse approach is developed for control of systems with unknown nonsmooth input nonlinearities such as dead-zone, backlash and hysteresis characteristics. The proposed controller structure consists of an adaptive inverse for cancelling the effect of an unknown nonlinearity and a fixed (or adaptive) linear part for a known (or unknown) linear dynamics, which leads to a linearly parametrized error system suitable for adaptation, improves tracking performance and ensures closed-loop signal boundedness.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Use of Systemic Treatment in the Maintenance of Patients with Non–Small Cell Lung Cancer: A Systematic Review (2016)

For patients with advanced, stable stage IIIB/IV NSCLC whose disease has not progressed after four to six cycles of platinum-based chemotherapy, the overall survival benefits were strongest for pemetrexed maintenance therapy followed by epidermal growth factor receptor tyrosine kinase inhibitor maintenance therapy.
Copolymers of Thiophene and Thiazole. Regioregulation in Synthesis, Stacking Structure, and Optical Properties (2003)

Palladium-catalyzed polycondensation between 2,5-dibromo-4-alkylthiazoles (alkyl = butyl thorough nonyl) and 2,5-bis(trimethylstannyl)thiophene gave charge-transferred-type alternating polymers, PTz(R)Th's. PTz(R)Th's had a high regioregularity as judged from their 1H NMR and X-ray diffraction (XRD) data, and the head-to-tail content was estimated to be higher than 90% from the 1H NMR data. The polymer forms a stacked structure, and the stacked structure is proposed based on the XRD data. The tendency of the polymer to form the stacked structure is considered to contribute to the regioregulation in the polymerization. The polymer was susceptible to both electrochemical oxidation (or p-doping) and reduction (or n-doping).
Tailoring the substrate specificity of secondary alcohol dehydrogenase (2002)

Our research with the thermophilic secondary-alcohol dehydrogenase (SADH) from Thermoanaerobacter ethanolicus has provided novel information regarding the physical basis of enzyme substrate specificity and stereospecificity. We demonstrated that oxidation of secondary alcohols catalyzed by T. ethanolicus SADH exhibits temperature-dependent enantiospecificity. In other studies, we found that the structure of co-factor analogs also significantly affects the stereochemistry of the SADH reaction. More recently, we demonstrated that pH can also have a modest effect on SADH enantiospecificity. Organic solvents have also been shown by others to affect the stereochemistry of SADH reactions. We designed and prepared S39T and C295A mutant forms of SADH by site-directed mutagenesis, and we evaluated the effects of the mutations by analysis of the temperature dependence of the enantiomeric ratio (E) for simple chiral alcohols such as 2-butanol. This procedure allows for the determination of the differential Eyring parameters (ΔΔH  and ΔΔS  ) for the reaction. We demonstrated that this technique is a sensitive method for analysis of the effects of mutation on enzyme stereospecificity. S39T and C295A SADH exhibit significant changes in substrate specificity and stereospecificity consistent with the changes in the volume of the alkyl-binding pockets. Thus, it is possible to alter the substrate specificity and stereospecificity of alcohol dehydrogenase by changing either the reaction medium or the protein structure.Key words: alcohol dehydrogenase, substrate specificity, stereospecificity, temperature dependence, site-directed mutagenesis.
Phosphorylation of Retinoblastoma-Related Protein by the Cyclin D/Cyclin-Dependent Kinase Complex Is Activated at the G1/S-Phase Transition in Tobacco (2002)

In mammals, D-type cyclin-associated kinases mainly regulate the G1/S transition by phosphorylating the retinoblastoma (Rb) protein. We previously demonstrated that in tobacco, cyclin D (Nicta; CycD3;3) is complexed with the PSTAIRE-containing cyclin-dependent kinase (CDKA) from tobacco. Here, we show that Nicta; CycD3;3-associated kinases phosphorylate both the tobacco Rb-related protein (NtRb1) and histone H1. Although NtRb1 kinase activity was detected only during the middle G1- to early S-phase, histone H1 kinase activity was observed as two peaks in G1- to S-phase and G2/M- to M-phase. Importantly, we show that the proportion of cells in the G1-phase was reduced in transgenic Bright Yellow-2 cells overexpressing Nicta; CycD3;3-GFP. Mutational analyses revealed that phosphorylation of Thr-191 in Nicta; CycD3;3 possibly is required for both full kinase activity and localization predominantly to the nucleus. These data suggest that Nicta; CycD3;3 acts as a rate-limiting regulator in the G1/S transition by forming active complexes with CDKA or its related kinases to phosphorylate Rb-related protein and potentially plays a novel role during G2/M and mitosis.
Preparation and Characterization of pH-Responsive Poly(methacrylic acid-g-ethylene glycol) Nanospheres (2002)

Poly(methacrylic acid-g-ethylene glycol) (P(MAA-g-EG)) has been studied extensively in our laboratory due to its extremely promising applications in the biomedical and pharmaceutical fields. It exhibits pH-responsive interpolymer complexes that make it a promising candidate as an oral carrier for peptide and protein drug. We have developed a photoinitiated free-radical precipitation polymerization method to produce P(MAA-g-EG) nanospheres with relatively narrow size distributions. The influence of various reaction parameters, such as total monomer concentration in water, comonomer molar feed ratios, cross-linking agent concentration, and polymerization time, on the particle size and size distribution was investigated. P(MAA-g-EG) nanospheres with a relatively narrow size distribution could be produced in the size range 150−650 nm depending on the monomer concentration and comonomer molar feed ratio. The P(MAA-g-EG) nanospheres exhibited a pH-responsive swelling behavior. Increasing the concentration of the cross-linking agent during polymerization produced P(MAA-g-EG) nanospheres that swelled to a lesser degree. The morphology of the P(MAA-g-EG) nanospheres was investigated using cryogenic scanning electron microscopy.
A large array of human monoclonal antibodies to type 1 human immunodeficiency virus from combinatorial libraries of asymptomatic seropositive individuals. (1991)

A panel of human monoclonal antibody Fab fragments has been generated against the surface glycoprotein gp120 of type 1 human immunodeficiency virus (HIV) by antigen selection from a random combinatorial library expressed on the surface of filamentous phage. The library was prepared from 5 ml of bone marrow from an asymptomatic individual who has been HIV-positive for 6 years. The antibodies have high affinity for antigen (mostly with affinity constants of greater than 10(8) M-1) and notable sequence diversity. Given appropriate donor selection, the methods described should allow the generation of antibodies for the evaluation of passive immunization as a therapy for AIDS.