gebhart/patrepeval huggingface dataset:
Interleukin 17 contributes to the chronicity of inflammatory diseases such as rheumatoid arthritis (2013)

Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction and bone resorption. The proinflammatory cytokine interleukin 17 (IL-17), primarily produced by Th17 cells, has been shown to be involved in all stages of the disease and to be an important contributor of RA chronicity. Three major processes drive the IL-17-mediated chronicity. Several epigenetic events, enhanced in RA patients, lead to the increased production of IL-17 by Th17 cells. IL-17 then induces the production of several inflammatory mediators in the diseased synovium, which are further synergistically enhanced via combinations of IL-17 with other cytokines. IL-17 also promotes the survival of both the synoviocytes and inflammatory cells and promotes the maturation of these immune cells. This leads to an increased number of synoviocytes and inflammatory cells in the synovial fluid and in the synovium leading to the hyperplasia and exacerbated inflammation observed in joints of RA patients. Furthermore, these IL-17-driven events initiate several feedback-loop mechanisms leading to increased expansion of Th17 cells and thereby increased production of IL-17. In this review, we aim to depict a complete picture of the IL-17-driven vicious circle leading to RA chronicity and to pinpoint the key aspects that require further exploration.
Inhibition of Calcineurin Phosphatase Activity by a Calcineurin B Homologous Protein (1999)

Calcineurin, a Ca(2+)/calmodulin-stimulated protein phosphatase, plays a key role in T-cell activation by regulating the activity of NFAT (nuclear factor of activated T cells), a family of transcription factors required for the synthesis of several cytokine genes. Calcineurin is the target of the immunosuppressive drugs cyclosporin A and FK506 complexed with their cytoplasmic receptors cyclophilin and FKBP12, respectively. In this study we report that calcineurin is also the target of a recently identified Ca(2+)-binding protein, CHP (for calcineurin homologous protein), which shares a high degree of homology with the regulatory B subunit of calcineurin and with calmodulin. In Jurkat and HeLa cells, overexpression of CHP specifically impaired the nuclear translocation and transcriptional activity of NFAT but had no effect on AP-1 transcriptional activity and only a small (<25%) inhibitory effect on the transcriptional activity of NFkappaB. Further study indicated that CHP inhibits calcineurin activity. In cells overexpressing CHP, the phosphatase activity of immunoprecipitated calcineurin was inhibited by approximately 50%; and in a reconstituted assay, the activity of purified calcineurin was inhibited up to 97% by the addition of purified recombinant CHP in a dose-dependent manner. Moreover, prolonged activation of Jurkat cells was associated with a decreased abundance of CHP, suggesting a possible regulatory mechanism allowing activation of calcineurin. CHP, therefore, is a previously unrecognized endogenous inhibitor of calcineurin activity.
A Soluble Polymer-Bound Ruthenium Carbene Complex: A Robust and Reusable Catalyst for Ring-Closing Olefin Metathesis (2000)

Poly(ethylene glycol)(PEG)-bound Ru carbene complex 3, prepared from functionalized styrene 1 and Grubbs catalyst 2, exhibits remarkable stability and catalyzes the ring-closing metathesis of a variety of α,ω-dienes, and leads to the formation of five-, six-, seven-, and eight-membered carbo- and heterocycles. The catalyst can be completely recovered and repeatedly reused (up to eight runs) with minimal loss of activity.
Reversing adipocyte differentiation: Implications for treatment of obesity (1999)

Conventional treatment of obesity reduces fat in mature adipocytes but leaves them with lipogenic enzymes capable of rapid resynthesis of fat, a likely factor in treatment failure. Adenovirus-induced hyperleptinemia in normal rats results in rapid nonketotic fat loss that persists after hyperleptinemia disappears, whereas pair-fed controls regain their weight in 2 weeks. We report here that the hyperleptinemia depletes adipocyte fat while profoundly down-regulating lipogenic enzymes and their transcription factor, peroxisome proliferator-activated receptor (PPAR)γ in epididymal fat; enzymes of fatty acid oxidation and their transcription factor, PPARα, normally low in adipocytes, are up-regulated, as are uncoupling proteins 1 and 2. This transformation of adipocytes from cells that store triglycerides to fatty acid-oxidizing cells is accompanied by loss of the adipocyte markers, adipocyte fatty acid-binding protein 2, tumor necrosis factor α, and leptin, and by the appearance of the preadipocyte marker Pref-1. These findings suggest a strategy for the treatment of obesity by alteration of the adipocyte phenotype.
Mechanisms of Methicillin Resistance in Staphylococcus aureus (2015)

Staphylococcus aureus is a major human and veterinary pathogen worldwide. Methicillin-resistant S. aureus (MRSA) poses a significant and enduring problem to the treatment of infection by such strains. Resistance is usually conferred by the acquisition of a nonnative gene encoding a penicillin-binding protein (PBP2a), with significantly lower affinity for β-lactams. This resistance allows cell-wall biosynthesis, the target of β-lactams, to continue even in the presence of typically inhibitory concentrations of antibiotic. PBP2a is encoded by the mecA gene, which is carried on a distinct mobile genetic element (SCCmec), the expression of which is controlled through a proteolytic signal transduction pathway comprising a sensor protein (MecR1) and a repressor (MecI). Many of the molecular and biochemical mechanisms underlying methicillin resistance in S. aureus have been elucidated, including regulatory events and the structure of key proteins. Here we review recent advances in this area.
Inducible expression of the P, V, and NP genes of the paramyxovirus simian virus 5 in cell lines and an examination of NP-P and NP-V interactions (1995)

The P, V, and NP genes of the paramyxovirus simian virus 5 (SV5) were cloned such that their expression was regulated by the tetracycline-controlled transactivator (M. Gossen and H. Bujard, Proc. Natl. Acad. Sci. USA 89:5547-5551, 1992), and mammalian cell lines that inducibly expressed individually the P, V, or NP protein or coexpressed the P plus NP or V plus NP proteins were isolated. A plasmid that expresses the tetracycline-controlled transactivator linked, via the foot-and-mouth disease virus 2A cleavage peptide sequence, to the neomycin aminoglycoside phosphotransferase gene was constructed. Cells were cotransfected with this plasmid, and the appropriate responder plasmids and clonies were selected on the basis of their resistance to Geneticin (via the neomycin aminoglycoside phosphotransferase gene). The properties of these cell lines, in terms of the induction of the P, V, and NP genes, are described in detail. Both the P and V proteins were phosphorylated when expressed alone. In immunoprecipitation studies using a monoclonal antibody that recognizes both the P and V proteins, a nonphosphorylated host cell protein with an estimated molecular weight of 150,000 was coprecipitated with V but not P. Immunofluorescence data demonstrated that when expressed separately, the P protein had a diffuse cytoplasmic distribution, but the related V protein had both a nuclear and cytoplasmic distribution. The NP protein had a granular cytoplasmic distribution, giving rise to punctate and granular fluorescence. Coexpression of the NP and P proteins resulted in the accumulation of large cytoplasmic inclusion aggregates, similar to those visualized at late times in SV5-infected cells. Coexpression of V with NP led to a partial redistribution of the NP protein in that the NP protein had both a diffuse cytoplasmic and nuclear distribution in the presence of V, but no NP-V aggregates or inclusion bodies were visualized. Direct binding studies also revealed that NP bound to both P and V. For SV5, these studies suggest that V may have a role in keeping NP soluble prior to encapsidation.
ChemInform Abstract: Possible Antineoplastic Agents. Part 2. (1977)

Abstract Zur Untersuchung einiger Glutarimide auf antineoplastische Aktivität werden die Glutarsäureanhydride (I) mit entsprechenden primären Aminen zu den Glutarimiden (III) umgesetzt, Saccharinnatrium (IV) wird mit 2‐Bromglutarimid (V) kondensiert und die Sulfonamidoglutarsäuren (VII) werden über die Säurechloride in Ester und Amide umgewandelt, von denen sich die letzteren durch Erhitzen zu Glutarimiden cyclisieren lassen.
[Active constituents lowering blood-lipid in beeswax]. (1996)

Three compounds were isolated from the active fraction Lowering blood-lipid in the traditional Chinese beeswax (Apis cerana or A. mellifera). They were identified as dotriacontanol, triacontanol and octacosanol by chemical and spectroscopic methods.
Neuronal apoptosis does not correlate with dementia in HIV infection but is related to microglial activation and axonal damage (1999)

To characterize the distribution of apoptotic neurons and their relationships with the stage of disease, a history of HIV-dementia, and the degree of productive HIV infection, microglial activation and axonal damage, we examined the brains of 40 patients. Samples of frontal and temporal cortex, basal ganglia and brain stem were taken post-mortem from 20 patients with AIDS (including three with HIV-dementia, and eight with cognitive disorders that did not fulfil the criteria for HIV-dementia), 10 HIV-positive asymptomatic cases and 10 seronegative controls. Neuronal apoptosis was demonstrated by in situ end labelling in 18 AIDS cases and two pre-AIDS cases; a single apoptotic neuron was present in the temporal cortex of a control. Semiquantitative evaluation showed that the severity of neuronal apoptosis in the cerebral cortex correlated with the presence of cerebral atrophy, but not with a history of HIV dementia. There was no global quantitative correlation between neuronal apoptosis and HIV encephalitis or microglial activation. However, there was some topographical correlation between these changes. In the basal ganglia, apoptotic neurons were much more abundant in the vicinity of multinucleated giant cells and/or p24 expressing cells. Microglial activation was constantly present in these areas. Axonal damage was identified using beta-amyloid-precursor protein (betaAPP) immunostaining in 17 AIDS and eight pre-AIDS brains. Although no global quantitative correlation could be established between axonal damage and neuronal apoptosis there was an obvious topographic correlation supporting the view that axonal damage, either secondary to local microglial activation or due to the intervention of systemic factors, may also contribute to neuronal apoptosis.
SLV-308. Solvay. (2003)

Solvay is developing SLV-308 (SME-308), a partial dopamine D2 agonist and noradrenergic agonist with serotonin 5-HT1A agonist properties, for the potential oral treatment of Parkinson's disease (PD), panic and depression. By January 2001, SLV-308 had entered phase II trials for PD and phase I trials for anxiety and depression.
Immune Responses in Interleukin-2-Deficient Mice (1993)

The role of costimulatory signals in T cell induction was evaluated in mice lacking the interleukin-2 (IL-2) gene. In vitro secondary antiviral T cell responses were absent unless IL-2 was added, confirming the crucial role of IL-2 in vitro. In vivo, primary and secondary cytotoxic T cell responses against vaccinia and lymphocytic choriomeningitis virus were within normal ranges. B cell reactivity to vesicular stomatitis virus was not impaired. T helper cell responses were delayed but biologically functional. Natural killer cell activity was markedly reduced but inducible. These normal in vivo immune responses in IL-2-deficient mice question the importance of IL-2 as defined by in vitro studies.
A Field Study on the Impact of Variations in Short-Term Memory Demands on Drivers’ Visual Attention and Driving Performance Across Three Age Groups (2012)

Drivers' awareness of vehicle surroundings is incrementally affected by increases in cognitive demand. Developers of more advanced driver support systems should consider gaze concentration as a measure of driver cognitive workload. This recommendation is particularly relevant in light of the added benefits of gaze measurements for detecting visual demand.
Expectativas, sentimentos e vivências do pai durante o parto e nascimento de seu filho (2000)

Trata-se de um estudo qualitativo, do tipo exploratorio, que
busca conhecer as expectativas, sentimentos e vivencias do
pai durante o processo de parto e nascimento de seu bebe. A analise de conteudo, de acordo com Bardin (1977), revelou
os temas: “Eu esperava que eu pudesse estar junto com ela, no decorrer de tudo” e “Muita emocao, tem que se segurar ...”. Conclui-se que o pai tem o desejo de estar presente em todos os momentos relacionados ao parto e nascimento do bebe.
[Status and developmental prospects of the medical proton channel in the synchrocyclotron in Gatchina]. (1983)

The medical proton beam on the synchrocyclotron in Gatchina modernized in 1980, is characterized by a simplicity of the beam adjustment that amounts to standard operations, the time of adjustment reduced considerably. The optical scheme ensures a good reproducibility of all the beam parameters from session to session. A large "zone of convergence" makes it possible to select a necessary irradiation field size with the diameter from 3 to 10 mm. A new medical complex with a 2-room premises for irradiation is envisaged on the basis of the "second beam" to expand the medical program. The piercing technique of moving field irradiation with protons at an energy of 1 Gy and the utilization of the convergent beam ensure the ratio of the focal dose to the surface dose 200:1.
Functional studies on the MRP1 multidrug transporter: characterization of ABC-signature mutant variants. (2004)

Our results reinforce the notion that a single mutation in one of the ABC-signature regions affects the function of the whole protein. The relative role of the conservative leucines and glycines in MRP1 indicates a similar three-dimensional structure within the catalytic center of various ABC proteins.
Immunoglobulin D(H) recombination signal sequence targeting: effect of D(H) coding and flanking regions and recombination partner (1996)

V(D)J recombination is targeted by recombination signal sequences (RSS) located immediately adjacent to immune receptor gene segments. While the RSS flanking D(H) segments appear to be equivalent, they are not randomly utilized. During D(H) to J(H) rearrangement, the 3' D(H) RSS is virtually exclusively utilized, suggesting that the 3' D(H) RSS could simply be a better target for the recombinase. However, when we examined V(H) to D(H) (without J(H)) rearrangements, we found that the preference for D(H) RSS use changes, so that the 5' D(H) RSS are preferred. This suggests that the 3' D(H) RSS are not simply superior targets for the V(D)J recombinase, but instead that certain 12/23-bp spacer RSS combinations work better together to target recombination than do others. We have analyzed a series of artificial recombination substrates to delineate cis sequences that affect D(H) RSS selection. Our data suggest that coding sequences adjacent to the D(H) RSS, flanking sequences outside the D(H) gene segment itself, and recombination partner all affect D(H) RSS targeting.
Linearly and nonlinearly chirped Bragg gratings fabricated on curved fibers (1995)

We can introduce chirping, or a variation in the periodicity of a Bragg grating, into an optical fiber by writing gratings on curved optical fibers. By precisely specifying the curvature, we can obtain linear, quadratic, and square-root chirped gratings. Experimental and numerical verifications of the relationships between curvature and grating characteristics are presented.
CI/FSK: Bandwidth-Efficient Multicarrier FSK for High Performance, High Throughput, and Enhanced Applicability (2004)

In traditional binary frequency-shift keying (BFSK), two distinct carrier frequencies are used to represent binary data. In this letter, we propose transmitting multiple orthogonal, in-phase subcarriers around two distinct carrier frequencies to represent binary information. The envelope of the resulting FSK signal is a carrier interferometry pattern, and hence, the name carrier interferometry (CI/) FSK. We demonstrate that this technique is spectrally efficient when compared to traditional BFSK. Performance and data-rate benefits are also demonstrated with the use of a novel coherent reception technique. Moreover, while it is difficult to employ traditional BFSK in multipath channels, we show how the new CI/FSK scheme exploits frequency-diversity benefits when used in such channels.
Chemical Reactor Analysis and Optimal Digestion (1986)

Journal Article Chemical Reactor Analysis and Optimal Digestion: An optimal digestion theory can be readily derived from basic principles of chemical reactor analysis and design Get access Deborah L. Penry, Deborah L. Penry Search for other works by this author on: Oxford Academic Google Scholar Peter A. Jumars Peter A. Jumars Search for other works by this author on: Oxford Academic Google Scholar BioScience, Volume 36, Issue 5, May 1986, Pages 310–315, https://doi.org/10.2307/1310235 Published: 01 May 1986
Vanadium‐Catalyzed Asymmetric Oxidation of Sulfides Using Schiff Base Ligands Derived from β‐Amino Alcohols with Two Stereogenic Centers (2009)

Abstract Novel Schiff base ligands derived from β‐amino alcohols with two stereogenic centers were prepared and used in the preparation of optically pure sulfoxides by using aqueous hydrogen peroxide as the oxidant. A variety of sulfides were smoothly converted into the corresponding sulfoxides catalyzed by the chiral vanadium–Schiff base complex. Good yields (&gt;80 %) with excellent enantioselectivities (&gt;99 % ee ) were obtained in most cases. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)
Construction of a Large Signature-Tagged Mini-Tn 5 Transposon Library and Its Application to Mutagenesis of Sinorhizobium meliloti (2006)

Sinorhizobium meliloti genome sequence determination has provided the basis for different approaches of functional genomics for this symbiotic nitrogen-fixing alpha-proteobacterium. One of these approaches is gene disruption with subsequent analysis of mutant phenotypes. This method is efficient for single genes; however, it is laborious and time-consuming if it is used on a large scale. Here, we used a signature-tagged transposon mutagenesis method that allowed analysis of the survival and competitiveness of many mutants in a single experiment. A novel set of signature tags characterized by similar melting temperatures and G+C contents of the tag sequences was developed. The efficiencies of amplification of all tags were expected to be similar. Thus, no preselection of the tags was necessary to create a library of 412 signature-tagged transposons. To achieve high specificity of tag detection, each transposon was bar coded by two signature tags. In order to generate defined, nonredundant sets of signature-tagged S. meliloti mutants for subsequent experiments, 12,000 mutants were constructed, and insertion sites for more than 5,000 mutants were determined. One set consisting of 378 mutants was used in a validation experiment to identify mutants showing altered growth patterns.
Vacuum-Assisted Closure: Microdeformations of Wounds and Cell Proliferation (2004)

The mechanism of action of the Vacuum Assisted Closure Therapy (VAC; KCI, San Antonio, Texas), a recent novel innovation in the care of wounds, remains unknown. In vitro studies have revealed that cells allowed to stretch tend to divide and proliferate in the presence of soluble mitogens, whereas retracted cells remain quiescent. The authors hypothesize that application of micromechanical forces to wounds in vivo can promote wound healing through this cell shape-dependent, mechanical control mechanism. The authors created a computer model (finite element) of a wound and simulated VAC application. Finite element modeling is commonly used to engineer complex systems by breaking them down into simple discrete elements. In this model, the authors altered the pressure, pore diameter, and pore volume fraction to study the effects of vacuum-induced material deformations. The authors compared the morphology of deformation of this wound model with histologic sections of wounds treated with the VAC. The finite element model showed that most elements stretched by VAC application experienced deformations of 5 to 20 percent strain, which are similar to in vitro strain levels shown to promote cellular proliferation. Importantly, the deformation predicted by the model also was similar in morphology to the surface undulations observed in histologic cross-sections of the wounds. The authors hypothesize that this tissue deformation stretches individual cells, thereby promoting proliferation in the wound microenvironment. The application of micromechanical forces may be a useful method with which to stimulate wound healing through promotion of cell division, angiogenesis, and local elaboration of growth factors. Finite element modeling of the VAC device is consistent with this mechanism of action.
A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells (2005)

Bacterial type IV secretion (T4S) systems mediate the transfer of macromolecular substrates into various target cells, e.g., the conjugative transfer of DNA into bacteria or the transfer of virulence proteins into eukaryotic host cells. The T4S apparatus VirB of the vascular tumor-inducing pathogen Bartonella henselae causes subversion of human endothelial cell (HEC) function. Here we report the identification of multiple protein substrates of VirB, which, upon translocation into HEC, mediate all known VirB-dependent cellular changes. These Bartonella-translocated effector proteins (Beps) A-G are encoded together with the VirB system and the T4S coupling protein VirD4 on a Bartonella-specific pathogenicity island. The Beps display a modular architecture, suggesting an evolution by extensive domain duplication and reshuffling. The C terminus of each Bep harbors at least one copy of the Bep-intracellular delivery domain and a short positively charged tail sequence. This biparte C terminus constitutes a transfer signal that is sufficient to mediate VirB/VirD4-dependent intracellular delivery of reporter protein fusions. The Bep-intracellular delivery domain is also present in conjugative relaxases of bacterial conjugation systems. We exemplarily show that the C terminus of such a conjugative relaxase mediates protein transfer through the Bartonella henselae VirB/VirD4 system into HEC. Conjugative relaxases may thus represent the evolutionary origin of the here defined T4S signal for protein transfer into human cells.
Preventing kinking of the peel-away sheath during insertion of a long term central venous catheter using percutaneous subclavicular venipuncture. (1991)

Kinking of the peel-away sheath can prevent placement of catheters by way of percutaneous subclavicular venipuncture. We described a technique for overcoming kinking of the peel-away sheath when changing patient position and repeatedly dilating the catheter insertion tract which do not allow placement of the catheter. This technique has been used successfully in three recent instances.