gebhart/patrepeval huggingface dataset:
Anti–tumor necrosis factor therapies (2001)

Recently published studies confirm that the long-term use of biologicals targeting tumor necrosis factor-alpha (TNF-alpha) in therapy for rheumatoid arthritis (RA) gives rise to sustained improvement in symptoms and signs of disease provided the anti-TNF agent is efficacious and of low immunogenicity. The current regimens for infliximab 3 or 10 mg/kg infusion in combination with weekly oral methotrexate, or of etanercept 25 mg subcutaneously twice per week, appear to fulfill these criteria. D2E7, a "human" antibody produced by phage display, has also been used for over a year. It has recently emerged that anti-TNF therapy protects joints from structural damage. The 1-year data for infliximab and methotrexate combination therapy suggest that this regimen reduces disability. In early RA, etanercept acts more rapidly than methotrexate to decrease symptoms and retard the progression of erosions. In conclusion, for patients with established and early RA, anti-TNF therapies set a new standard for symptom control and joint protection.
Tumor Necrosis Factor-α-Activated Cell Death Pathways in NIT-1 Insulinoma Cells and Primary Pancreatic β Cells* (1999)

Tumor necrosis factor-α (TNFα) is a potential mediator of β cell destruction in insulin-dependent diabetes mellitus. We have studied TNF-responsive pathways leading to apoptosis in β cells. Primary β cells express low levels of the type I TNF receptor (TNFR1) but do not express the type 2 receptor (TNFR2). Evidence for TNFR1 expression onβ cells came from flow cytometry using monoclonal antibodies specific for TNFR1 and TNFR2 and from RT-PCR of β cell RNA. NIT-1 insulinoma cells similarly expressed TNFR1 (at higher levels than primary β cells) as detected by flow cytometry and radio-binding studies. TNF induced NF-κB activation in both primary islet cells and NIT-1 cells. Apoptosis in response to TNFα was observed in NIT-1 cells whereas apoptosis of primary β cells required both TNFα and interferon-γ (IFNγ). Apoptosis could be prevented in NIT-1 cells by expression of dominant negative Fas-associating protein with death domain (dnFADD). Apoptosis in NIT-1 cells was increased by coincubation with IFNγ, which also increased caspase 1 expression. These data show that TNF-activated pathways capable of inducing apoptotic cell death are present in β cells. Caspase activation is the dominant pathway of TNF-induced cell death in NIT-1 cells and may be an important mechanism of β cell damage in insulin-dependent diabetes mellitus.
Dantrolene Inhibition of Ryanodine Receptor Ca2+Release Channels (2001)

As an inhibitor of Ca(2+) release through ryanodine receptor (RYR) channels, the skeletal muscle relaxant dantrolene has proven to be both a valuable experimental probe of intracellular Ca(2+) signaling and a lifesaving treatment for the pharmacogenetic disorder malignant hyperthermia. However, the molecular basis and specificity of the actions of dantrolene on RYR channels have remained in question. Here we utilize [(3)H]ryanodine binding to further investigate the actions of dantrolene on the three mammalian RYR isoforms. The inhibition of the pig skeletal muscle RYR1 by dantrolene (10 microm) was associated with a 3-fold increase in the K(d) of [(3)H]ryanodine binding to sarcoplasmic reticulum (SR) vesicles such that dantrolene effectively reversed the 3-fold decrease in the K(d) for [(3)H]ryanodine binding resulting from the malignant hyperthermia RYR1 Arg(615) --> Cys mutation. Dantrolene inhibition of the RYR1 was dependent on the presence of the adenine nucleotide and calmodulin and reflected a selective decrease in the apparent affinity of RYR1 activation sites for Ca(2+) relative to Mg(2+). In contrast to the RYR1 isoform, the cardiac RYR2 isoform was unaffected by dantrolene, both in native cardiac SR vesicles and when heterologously expressed in HEK-293 cells. By comparison, the RYR3 isoform expressed in HEK-293 cells was significantly inhibited by dantrolene, and the extent of RYR3 inhibition was similar to that displayed by the RYR1 in native SR vesicles. Our results thus indicate that both the RYR1 and the RYR3, but not the RYR2, may be targets for dantrolene inhibition in vivo.
Metabolism of oligosaccharides and aldehydes and production of organic acids in soymilk by probiotic bifidobacteria (2004)

Abstract Four strains of Bifidobacterium were assessed for α-galactosidase activity in MRS broth using p-nitrophenyl-α-d-galactopyranoside as substrate. Bifidobacteria were then used to ferment soymilk prepared from soy protein isolate (SPI), with and without d-glucose and l-cysteine supplementation. Measurements of pH and the quantification of oligosaccharides, organic acids and aldehydes in soymilk were done after 0, 12, 24, 36 and 48 h of incubation. The presence of d-raffinose stimulated the α-galactosidase activity of B. longum BB536 (BB536) and B. pseudolongum 20099 (BP20099). In soymilk, oligosaccharides and aldehydes were effectively metabolized by Bifidobacterium; d-glucose and l-cysteine supplementation enhanced the hydrolysis of raffinose and stachyose. BB536 and BP20099 degraded a significantly greater level of oligosaccharides and aldehydes than B. animalis Bb-12 and B. longum 1941 (P &amp;lt; 0.05). Raffinose and stachyose were completely metabolized by BB536 after 48 h. In soymilk without any supplementation, hexanal and pentanal were not detected after 12 h of fermentation with BB536 and BP20099. BB536 was the highest producer of organic acids, with an average acetic acid/l(+)-lactic acid ratio of 0.7.
Synthesis and structure of molecular tweezers containing active site functionality (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and structure of molecular tweezers containing active site functionalitySteven C. Zimmerman, Zijian Zeng, Weiming Wu, and David E. ReichertCite this: J. Am. Chem. Soc. 1991, 113, 1, 183–196Publication Date (Print):January 1, 1991Publication History Published online1 May 2002Published inissue 1 January 1991https://pubs.acs.org/doi/10.1021/ja00001a027https://doi.org/10.1021/ja00001a027research-articleACS PublicationsRequest reuse permissionsArticle Views1101Altmetric-Citations71LEARN 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
Purification of a cartilage-derived growth factor. (1980)

A growth factor was isolated from bovine cartilage and purified by a combination of gel filtration chromatography and isoelectric focusing. In the first step of the purification, growth factor activity as measured by stimulation of DNA synthesis in quiescent 3T3 cells or chondrocytes, was extracted by incubation of cartilage with 1 M guanidine hydrochloride, pH 6.0. The crude cartilage extract was analyzed by gel filtration on a column equilibrated with 4 M guanidine hydrochloride and 5 mM dithiothreitol. All of the cartilage-derived growth factor activity migrated in a region corresponding to molecular weights between 12,000 and 20,000. The low molecular weight fraction was analyzed by isoelectric focusing in the presence of 6 M urea. Two major active fractions were found, with isoelectric points of approximately 9 and 10. Purification to homogeneity was accomplished by several cycles of gel filtration of the pI 9 fraction on columns equilibrated with 4 M guanidine hydrochloride and 5 mM dithiothreitol. The purified growth factor migrated as a single polypeptide band in two polyacrylamide gel electrophoresis systems, sodium dodecyl sulfate polyacrylamide gel electrophoresis and acid-urea polyacrylamide gel electrophoresis. The molecular weight of the cartilage-derived growth factor was estimated to be between 16,000 and 18,000 by gel filtration and 16,400 by SDS polyacrylamide gel electrophoresis. Gel filtration chromatography of the pI 10 fraction also yielded an active purified 16,400 molecular weight growth factor. Approximately 1 to 2.5 micrograms/ml of purified cartilage-derived growth factor was necessary to half-maximally stimulate DNA synthesis in 3T3 cells and chondrocytes.
Abstract 10045: A Novel Approach to Define Type 4a Myocardial Infarction in Acute Coronary Syndrome Patients Undergoing Early Invasive Management: Insights From the CHAMPION PLATFORM Trial (2011)

Background: Early PCI in pts with nSTE-ACS challenges the diagnosis of PCI-related MI. In CHAMPION PLATFORM, PCI was performed a median of 7.9 hours after admission, which may have hindered sensiti...
C-C-A-G-G-C-m5C-T-G-G. Helical fine structure, hydration, and comparison with C-C-A-G-G-C-C-T-G-G. (1992)

The self-complementary DNA duplex C-C-A-G-G-C-m5C-T-G-G has been refined against 1.75-A x-ray diffraction data to an R value of 17.4%. In the crystal of space group P6, 10-base pair DNA fragments with characteristic sequence-related fine structure stack end to end to form long antiparallel B-type double helices. As shown by a structure analysis at lower resolution (Heinemann, U., and Alings, C. (1991) EMBO J. 10, 35-43), the overall geometry of C-C-A-G-G-C-m5C-T-G-G is similar to that of the unmethylated analog C-C-A-G-G-C-C-T-G-G despite a different crystal environment. The present high resolution structure analysis permits a detailed comparison of the two duplexes and their hydration spheres. Helical parameters are significantly correlated between both molecules, with the exception of the base pair propeller. Sugar pucker and backbone torsion angles alpha, gamma, delta, and chi show similar mean values, but their individual values deviate significantly between duplexes. In contrast, torsion angles beta, epsilon, and zeta change along the strands of both duplexes in much the same way. The effect of single-site methylation on DNA conformation appears to be small and limited to the base pairs directly involved. Methylation tends to push base pairs toward the minor groove of the helix. A regular minor groove hydration pattern involves dual hydrogen bonding of water molecules to O-4' and base atoms of C-C-A-G-G-C-m5C-T-G-G.
Monitoring changes in fat-free mass in HIV-positive men with hypotestosteronemia and AIDS wasting syndrome treated with gonadal hormone replacement therapy (1999)

DEXA, BIS and D2O techniques demonstrated increases in fat-free mass. The BIS method is less costly, more convenient to use, and had results that more closely matched those from nitrogen balance and retention methods. BIS may be the preferred method to monitor changes in fat-free mass in AIDS patients and patients with malnutrition.
Modulation of radiation response of human tumour cells by the differentiation inducers, phenylacetate and phenylbutyrate (1997)

The aromatic fatty acids phenylacetate (PA) and phenylbutyrate (PB) are novel antitumour agents currently under clinical evaluation. Their ability to induce tumour differentiation in laboratory models and their low clinical toxicity profile makes them promising candidates for combination with conventional therapies. In the present studies, we characterized the interactions between these aromatic fatty acids and radiation, using as a model cell lines derived from cancers of the prostate, breast, brain and colon. Analysis of the radiation response of the tumour lines using the linear-quadratic model, demonstrated that cellular exposure to pharmacological, non-toxic concentrations of either PA or PB resulted in time-dependent and contrasting changes in radiation response. While drug pretreatment for 24 h reduced radiation sensitivity (significant alterations in both alpha and beta parameters), pre treatment for 72 h significantly increased radiosensitivity (significant alterations in alpha and beta parameters). In replicating tumour cells, these changes were accompanied by a gradual G1-phase arrest. Cytostasis alone, however, could not explain radiosensitization, as similar alterations in radiation response were documented also in non-cycling cells. Modulation of tumour radiobiology by PA and PB was tightly correlated with early rise followed by decline in intracellular glutathione levels and the activity of antioxidant enzymes such as catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase and glutathione S-transferase. Although in vitro findings identify the aromatic fatty acids PA and PB as a new class of non-toxic modulators of radiation response, the antagonistic effect of these compounds on radiation response needs further examination. Our data strongly suggest that for PA or PB to have a role in clinical radiotherapy, appropriate scheduling of combination therapies must take into account their time-dependent effects in order to achieve clinical radiosensitization.
The Class A Macrophage Scavenger Receptor Is a Major Pattern Recognition Receptor for Neisseria meningitidis Which Is Independent of Lipopolysaccharide and Not Required for Secretory Responses (2002)

Macrophages (Mphi) play a key role in the pathogenesis of invasive meningococcal infections. The roles of two pattern recognition molecules, the Mphi scavenger receptor (SR-A) and Toll-like receptor 4 (TLR-4), have been investigated using bone marrow culture-derived Mphi (BMMphi). Surprisingly, a comparison of BMMphi from wild-type and SR-A knockout (SR-A(-/-)) mice showed that nonopsonic phagocytosis of meningococci was mediated almost exclusively via SR-A. Previous studies have demonstrated only a partial involvement of the receptor in the uptake of other bacteria, such as Escherichia coli. Interestingly, we also show that lipopolysaccharide (LPS) was not the ligand for the receptor on these organisms. Further study of the downstream events of SR-A-mediated ingestion of Neisseria meningitidis demonstrated that SR-A was not required for cytokine production. To determine the bacterial and host factors required to stimulate Mphi activation, we examined TLR-4-deficient Mphi from C3H/HeJ mice and LPS-deficient meningococci. TLR-4-deficient cells elaborated reduced amounts of tumor necrosis factor alpha, interleukin-12 (IL-12), and IL-10, even though ingestion via SR-A was unaffected in these cells. Similarly, although there was no change in SR-A-mediated ingestion of LPS-deficient meningococci, the mutant failed to stimulate a Mphi-dependent cytokine response. Thus, we show that Mphi SR-A mediates opsonin-independent uptake of N. meningitidis independently of lipid A and that this activity is uncoupled from the Mphi secretion of proinflammatory cytokines, which provides a basis for further investigation of the role of this receptor in meningococcal disease in humans.
Storage, Photosynthesis, and Growth: The Conditional Nature of Mutations Affecting Starch Synthesis and Structure in Chlamydomonas (1995)

Nathalie Libessart, Marie-Lise Maddelein, Nathalie van den Koornhuyse, , Brigitte Delrue, Gregory Mouille, Christophe D'Hulst, Steven Ball, Storage, Photosynthesis, and Growth: The Conditional Nature of Mutations Affecting Starch Synthesis and Structure in Chlamydomonas, The Plant Cell, Vol. 7, No. 8 (Aug., 1995), pp. 1117-1127
Salvage synthesis of purine nucleotides by Helicobacter pylori (1994)

The incorporation of purine nucleotide precursors into Helicobacter pylori and the activities of enzymes involved in nucleotide salvage biosynthetic pathways were investigated by radioactive tracer analysis and nuclear magnetic resonance spectroscopy. The organism took up the nucleobases adenine, guanine and hypoxanthine, and the nucleosides adenosine, guanosine and deoxyadenosine. Any incorporation of deoxyguanosine by the cells was below the detection limits of the methods employed. The activities of adenine-, guanine- and hypoxanthine-phosphoribosyl transferases were established. The bacterium showed high levels of adenosine and guanosine nucleosidase activities and lesser activity for deoxyadenosine; no hydrolysis of deoxyguanosine was detected. Phosphorylase activities were not observed with any of the nucleosides. Phosphotransferase activities with similar rates were demonstrated for adenosine, guanosine and deoxyadenosine; and a weaker activity was detected for deoxyguanosine. No nucleoside kinase activities were observed with any of the nucleosides. The presence of adenylate kinase was established, but no guanylate kinase activity was observed. The study provided evidence for the presence in H. pylori of salvage pathways for the biosynthesis of purine nucleotides.
Circadian systems. I. The driving oscillation and its assay in Drosophila pseudoobscura. (1967)

This series reports studies on circadian systems in insects and mammals.In constant darkness and temperature an organism may display one or more circadian rhythms in functions such as locomotion, drug sensitivity, or the specific activity of individual enzymes.The period, r, of such rhythms is about 24 hours; it is usually precise and always temperature-compensated.In discussing these phenomena we describe the whole cell or organism as a circadian system whose output manifests (a directly observable) circadian rhythm, which must, a priori, be the result of a periodicity in its physiological control systems.We restrict the term circadian oscillation to this periodic driving element in the system's controls.Clearly the total system comprises, in addition to the driving oscillation, a plethora of physio- logical subsystems driven by this pacemaker.These driven elements may or may not be themselves periodic; in either case they are not oscillations ultimately responsible for the total system's periodicity.The driving oscillation entrains to (locks onto) a restricted class of environmental cycles, principally that of light and, to a lesser extent, temperature.It is thus responsible for phasing the entire cir- cadian system to the daily cycle of change in the environment.Our interest is in the following general questions: (1) What is the nature of the driving oscillation?(2) What is the mechanism of its entrainment by environ- mental cycles?(3) How is it coupled to the peripheral subsystems which it drives?* This work was performed under contracts
Chitosan as Antimicrobial Agent:  Applications and Mode of Action (2003)

Chitosan, a hydrophilic biopolymer industrially obtained by N-deacetylation of chitin, can be applied as an antimicrobial agent. The current review of 129 references describes the biological activity of several chitosan derivatives and the modes of action that have been postulated in the literature. It highlights the applications of chitosan as an antimicrobial agent against fungi, bacteria, and viruses and as an elicitor of plant defense mechanisms.
Thermal Dependence of Thermally Induced Protein Spherulite Formation and Growth: Kinetics of β-lactoglobulin and Insulin (2007)

Amyloid fibril forming proteins have been related to some neurodegenerative diseases and are not fully understood. In some such systems, these amyloid fibrils have been found to form radially oriented spherulite structures. The thermal dependence of formation and growth of these spherulite structures in two model protein systems, beta-lactoglobulin and insulin at low pH aqueous and high temperature conditions, have been monitored with time-lapse optical microscopy and quantified. A population-based polymerization reaction model was developed and applied to the experimental data with excellent agreement. While spherulites in the insulin solutions formed and grew at approximately 25x the rate of spherulites in the beta-lactoglobulin solutions, the temperature dependence and activation energies of both systems were found to be very similar to one another, suggesting that the underlying rate-limiting mechanisms for both formation and growth are consistent across the two systems. The similarity of both of these amyloid fibril forming protein systems provides confidence in their use as model systems for extrapolating understanding to similar systems involved in neurodegenerative diseases.
Miniaturised Cutting Tool With Triaxial Force Sensing Capabilities for Minimally Invasive Surgery (2006)

This paper reports a miniaturised triaxial force sensorized cutting tool for minimally invasive robotic surgery. This device exploits a silicon based MEMS triaxial force sensor that acts as the core component of the system. The outer diameter of the proposed device is less than 3 mm, thus enabling the insertion through a 9 French catheter guide. Characterization tests are performed for both normal and tangential loadings. A linear transformation relating the sensor output to the external applied force is introduced in order to have a triaxial force output in real time. Normal force resolution is 8.2 bits over a force range between 0 N and 30 N, while tangential resolution is 8.1 over a range of 6 N. Force signals with frequencies up to 250 Hz can successfully be detected, enabling haptic feedback and tissue mechanical properties investigation. Preliminary ex vivo muscular tissue cutting experiments are introduced and discussed in order to evaluate the device overall performances.
A simple envelope model for nonlinear power amplifiers with memory effects based on volterra expansion (2010)

For wideband communication systems, memory effects in power amplifiers (PAs) always become significant, which commonly make intermodulation-distortions (IMDs) response asymmetric in a two-tone test. The Volterra series is a general method to analyze and model the nonlinear PAs with the memory effects, while the complexity in the large number parameters to be calculated is a major limitation. In this paper, we propose a simple envelope from the Volterra series to represent the nonlinearity and the memory effects in the PAs. The proposed model reduces the parameters number remarkably and can express the asymmetric IMDs easily. The simulation results show that the proposed PA model is efficient to represent the nonlinear PA behaviors considering the memory effects.
NEURONAL CIRCUITS OF THE NEOCORTEX (2004)

We explore the extent to which neocortical circuits generalize, i.e., to what extent can neocortical neurons and the circuits they form be considered as canonical? We find that, as has long been suspected by cortical neuroanatomists, the same basic laminar and tangential organization of the excitatory neurons of the neocortex is evident wherever it has been sought. Similarly, the inhibitory neurons show characteristic morphology and patterns of connections throughout the neocortex. We offer a simple model of cortical processing that is consistent with the major features of cortical circuits: The superficial layer neurons within local patches of cortex, and within areas, cooperate to explore all possible interpretations of different cortical input and cooperatively select an interpretation consistent with their various cortical and subcortical inputs.