gebhart/patrepeval huggingface dataset:
Association of methotrexate and corticosteroids in the treatment of patients with rheumatoid arthritis. (1997)

The association of MTX and corticosteroids seems to bring about a greater improvement in the different clinical activity parameters of RA than MTX alone, without any significant increase in the frequency of side effects. These results need to be confirmed in larger scale prospective studies.
Directions in the immune targeting of cancer: Lessons learned from the cancer‐testis Ag NY‐ESO‐1 (2006)

Since the early 1990s, numerous cancer Ag have been defined and for a handful of these there is now some clinical experience, which has made it possible to assess their value as targets for cancer immunotherapy. The cancer-testis Ag have been particularly attractive because their expression is limited to cancer and virtually no non-malignant cells apart from germ cells and trophoblast. Among these, NY-ESO-1 has been the focus of our attention. The exceptional immunogenicity of this Ag coupled with its widespread distribution among many cancer types make it a very good vaccine candidate, with the potential to be used in vaccines against many types of malignancies. This article reviews emerging knowledge about the biology of NY-ESO-1 and experience with the early clinical development of vaccines directed against NY-ESO-1. These early studies have yielded a wealth of information about the immunology of NY-ESO-1 and set the scene for future clinical strategies for immune targeting of cancer.
Doxorubicin‐induced oxygen free radical formation in sensitive and doxorubicin‐resistant variants of rat glioblastoma cell lines (1993)

We have studied the formation of hydroxyl radical (OH.) induced by doxorubicin in a series of doxorubicin- or vincristine-selected variants of C6 rat glioblastoma cells in culture by electron-spin resonance spectroscopy using 5,5'-dimethyl-1-pyrroline-1-oxide as a spin trap. Wild-type cells, sensitive to doxorubicin, exhibited in the presence of this drug a concentration-dependent OH. formation which could be inhibited by preincubation with superoxide dismutase, catalase or an antibody against cytochrome P450-reductase. In highly doxorubicin-resistant cells, OH. formation was reduced to about 20% of the level obtained in sensitive cells. In cells presenting a very low level of resistance to doxorubicin or in cells selected with vincristine, both presenting a pure multidrug-resistant phenotype, OH. formation was identical to that obtained in sensitive cells. In cells of intermediate resistance or in revertant cells, intermediate levels of OH. formation were obtained. Protection against OH. formation and action can be identified at the levels of superoxide dismutase and glutathione peroxidase activities, which are both enhanced in the resistant cells.
Immune complexes formed following the binding of anti–platelet factor 4 (CXCL4) antibodies to CXCL4 stimulate human neutrophil activation and cell adhesion (2008)

We tested the possibility that immune complexes formed following platelet factor 4 (PF4/CXCL4) binding to anti-PF4 antibody can stimulate neutrophil activation, similar to previous reports with platelets. Monoclonal Abs against PF4 and IgG from a heparin-induced thrombocytopenia (HIT) patient were applied. We observed that although PF4 or anti-PF4 antibody alone did not alter neutrophil function, costimulation with both reagents resulted in approximately 3-fold increase in cell surface Mac-1 expression, enhanced cell adhesion via L-selectin and CD18 integrins, and degranulation of secondary and tertiary granules. The level of Mac-1 up-regulation peaked at an intermediate PF4 dose, suggesting that functional response varies with antigen-antibody stoichiometry. PF4 binding to neutrophils was blocked by chondroitinase ABC. Cell activation was inhibited by both chondroitinase ABC and anti-CD32/FcgammaRII blocking mAb, IV.3. Confocal microscopy demonstrated that immune complexes colocalize with CD32a. Studies with HIT IgG demonstrated that neutrophils could be activated in the absence of exogenous heparin. These data, together, show that leukocyte surface chondroitin sulfates promote neutrophil activation by enhancing immune-complex binding to CD32a. Studies with recombinant PF4 suggest a role for arginine 49 in stabilizing PF4-chondroitin binding. Neutrophils activated via this mechanism may contribute to thrombosis and inflammation in patients mounting an immune response to PF4-heparin.
Detection of Tumors with 19F Magnetic Resonance Imaging (1988)

Previous 19F magnetic resonance imaging studies showed that the reticuloendothelial system can be imaged with an emulsion of perfluorooctyl bromide (PFOB). Similar techniques can be used to detect previously implanted RIF-1 tumors in mice after intravenous PFOB administration. Accumulation of PFOB within these neoplasms is due to egress of the emulsion through tumor capillary fenestrations. This is the first report in which 19F MRI and PFOB are used to detect tumors. This technique may allow clinical detection of cancer with 19F MRI.
Aminoacyl tRNA synthetases as targets for new anti‐infectives (1998)

Because resistance has developed to mainline antibiotics, including vancomycin, new antibiotics are now being aggressively sought. For this purpose, aminoacyl tRNA synthetases are being pursued as targets for new drugs. These enzymes are universal and are essential for cell viability. The key to their usefulness lies in being able to find drugs that inhibit a pathogen synthetase but not its human cell counterpart. The possibility for species-specific inhibition was originally demonstrated with a natural product and has now been demonstrated with prototypical drugs that are based on the structure of an intermediate of the aminoacylation reaction. Efficacy of a rationally designed inhibitor has been shown in vivo with a pathogen infection established in an animal model. Although many challenges remain, these early results suggest that synthetases will continue to be of major interest for development of new anti-infectives.
The p14ARF Tumor Suppressor Protein Facilitates Nucleolar Sequestration of Hypoxia-inducible Factor-1α (HIF-1α) and Inhibits HIF-1-mediated Transcription (2001)

Oncogenic alterations can influence tumor cell survival partly by affecting the activity of the hypoxia-inducible factor-1 (HIF-1) transcription factor. The alpha subunit of HIF-1 was found to be frequently overexpressed in advanced tumors, which was proposed to help the adaptation of tumor cells to hypoxia. Here we show that an important tumor suppressor protein, p14ARF (alternative reading frame product of the INK4A locus) can directly inhibit the transcriptional activity of HIF-1 by sequestering its alpha subunit into the nucleolus. The interaction requires neither p53 nor HDM2. This is one of the first reports that describe the interaction of p14ARF with a protein besides HDM2, which may define a p53-independent tumor suppressor activity for p14ARF.
Mini-sternotomy for aortic valve replacement reduces the length of stay in the cardiac intensive care unit: meta-analysis of randomised controlled trials (2011)

Background Mini-sternotomy for isolated aortic valve replacement aims to reduce operative trauma hastening recovery and improving the cosmetic outcome of cardiac surgery. The short-term clinical benefits from the mini-sternotomy are presumed to arise because the incision is less extensive and the lower half of the chest cage remains intact. The basic conduct of virtually all other aspects of the aortic valve replacement procedure remains the same. Therefore, similar long-term outcomes are to be expected. Objectives To conduct a meta-analysis of the only available randomised controlled trials (RCT) in the published English literature. Data sources Electronic search for relevant publications in MEDLINE, EMBASE and CENTRAL databases were performed. Four studies met the criteria. Study eligibility criteria RCT comparing minimally invasive (inverted C or L (J)-shaped) hemi-sternotomy versus conventional sternotomy for adults undergoing isolated aortic valve replacement using standard cardiopulmonary bypass technique. Methods Outcome measures were the length of positive pressure ventilation, blood loss, intensive care unit (ICU) and hospital stay. Results The length of ICU stay was significantly shorter by 0.57 days in favour of the mini-sternotomy group (CI -0.95 to -0.2; p=0.003). There was no advantage in terms of duration of ventilation (CI -3.48 to 0.36; p=0.11). However, there was some evidence to suggest a reduction in blood loss and the length of stay in hospital in the mini-sternotomy group. This did not prove to be statistically significant (154.17 ml reduction (CI -324.51 to 16.17; p=0.08) and 2.03 days less (CI -4.12 to 0.05; p=0.06), respectively). Limitations This study includes a relatively small number of subjects (n=220) and outcome variables. The risk of bias was not assessed during this meta-analysis. Conclusion Mini-sternotomy for isolated aortic valve replacement significantly reduces the length of stay in the cardiac ICU. Other short-term benefits may include a reduction in blood loss or the length of hospital stay.
Genomic RNAs of influenza viruses are held in a circular conformation in virions and in infected cells by a terminal panhandle. (1987)

The viral RNA segments in influenza virions were shown to be circular in conformation by using psoralen crosslinking methods. Electron microscopy of purified RNA following treatment of virus with the psoralen reagent 4'-aminomethyltrioxsalen (AMT) revealed circles with lengths corresponding to the individual segments. RNA blot analysis using polyacrylamide gels demonstrated that RNA from AMT-treated virus had a slowed migration, consistent with it being a single-stranded circle. Furthermore, nuclease S1 protection assays indicated that the termini of the RNA segments form an approximately 15-base-pair-long panhandle. This structure is consistent with the partial sequence complementarity that has been observed for the termini of all influenza virus RNAs. By RNA blot analysis, circular structures of viral sense RNA were also found in influenza virus-infected cells at early and late time points. The circular RNA was the predominant species at the time when the major transcription product is message RNA. This finding and the observation that the termination signal for mRNA synthesis directly abuts the panhandle suggest that a panhandle in the template viral RNA is a cis regulatory signal promoting the synthesis of mRNA instead of plus-sense template. Also, since the panhandle is present in high concentration in virions, we suggest that it is required for packaging and that the input RNA after infection is in the proper conformation for synthesis of primary transcripts.
Toxicity of Trichome Exudates of Nicotiana and Petunia Species to Tobacco Hornworm1 Larvae2 (1970)

Journal Article Toxicity of Trichome Exudates of Nicotiana and Petunia Species to Tobacco Hornworm Larvae Get access Richard Thurston Richard Thurston 3 University of Kentucky, Lexington 40506 3Professor of Entomology Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Economic Entomology, Volume 63, Issue 1, 1 February 1970, Pages 272–274, https://doi.org/10.1093/jee/63.1.272 Published: 01 February 1970 Article history Received: 06 June 1969 Published: 01 February 1970
Comparison of two different cell topologies for a multilevel power supply to achieve high efficiency envelope amplifier (2009)

A solution combining a multilevel converter in series with a linear regulator to obtain an envelope amplifier was presented recently in [1] for EER. Two possible implementations of the multilevel cell are compared. In [1], a two-state topology for the multilevel cell is proposed for the envelope amplifier. The three-state cell topology, proposed in this paper, has two main advantages: less number of cells and inputs and a simpler electrical and physical design. The comparison of the energy handled by each cell topology confirms several advantages of the three-state cell. Considerations to optimize the design of the multilevel converter for both cell topologies and experimental comparison between both cell architectures are enclosed.
Glyphosate-Resistant Goosegrass. Identification of a Mutation in the Target Enzyme 5-Enolpyruvylshikimate-3-Phosphate Synthase (2002)

The spontaneous occurrence of resistance to the herbicide glyphosate in weed species has been an extremely infrequent event, despite over 20 years of extensive use. Recently, a glyphosate-resistant biotype of goosegrass (Eleusine indica) was identified in Malaysia exhibiting an LD(50) value approximately 2- to 4-fold greater than the sensitive biotype collected from the same region. A comparison of the inhibition of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) activity by glyphosate in extracts prepared from the resistant (R) and sensitive (S) biotypes revealed an approximately 5-fold higher IC(50)(glyphosate) for the (R) biotype. Sequence comparisons of the predicted EPSPS mature protein coding regions from both biotypes revealed four single-nucleotide differences, two of which result in amino acid changes. One of these changes, a proline to serine substitution at position 106 in the (R) biotype, corresponds to a substitution previously identified in a glyphosate-insensitive EPSPS enzyme from Salmonella typhimurium. Kinetic data generated for the recombinant enzymes suggests that the second substitution identified in the (R) EPSPS does not contribute significantly to its reduced glyphosate sensitivity. Escherichia coli aroA- (EPSPS deficient) strains expressing the mature EPSPS enzyme from the (R) biotype exhibited an approximately 3-fold increase in glyphosate tolerance relative to strains expressing the mature EPSPS from the (S) biotype. These results provide the first evidence for an altered EPSPS enzyme as an underlying component of evolved glyphosate resistance in any plant species.
A New Algorithm for Computing Inertial Altitude and Vertical Velocity (1971)

Inertial navigators determine inertial altitude and vertical velocity by a closed feedback loop in which the vertical accelerometer output is mixed with a pressure altitude reference. Pressure altitude is determined as a function of presure based on the standard atmosphere models. Since the atmosphere is almost always nonstandard, large inertial altitude and vertical velocity errors may result. A unique algorithm has been devised to compute a dynamically corrected altitude reference by numerically integrating the physical relation for a column of air as a function of pressure, gravity, and absolute temperature. The new algorithm has been flight tested and has been shown to yield accurate results.
Thermoelectric Properties of Molecular Nanowires (2011)

Recently there has been an increasing interest in using organic materials for thermoelectric applications due to the noteworthy advantages of mechanical flexibility, low-cost synthesis, and solution processability. While the thermal conductivity of organic semiconductors is known to be small, very few theoretical works are available to predict thermoelectric properties of organic semiconductors and guide experimental efforts. In this work, we studied the thermoelectric properties (electrical conductivity, Seebeck coefficient, and power factor) of quasi-one-dimensional (Q1D) self-assembled molecular nanowires (NWs) based on a rigorous evaluation of the Kubo formula using the Holstein model. The molecular NWs are composed of either one-dimensional conducting polymer chains, coupled by covalent bonds, or linear stacks of planar building blocks, held together by van der Waals or π–π interactions; these are also known as molecule metals (or semiconductors), charge transfer salts, or π-stacked organic semiconductors. The dependence of thermoelectric properties on a variety of physical parameters, including intersite coupling, electron–phonon interaction, chemical potential (doping concentration), and temperature, are systematically studied. We found that the thermoelectric properties are strongly affected by the intersite coupling and the dielectric constant. If the phonon thermal conductivity is assumed to be 0.2 W/mK, the thermoelectric figure of merit (ZT) of a molecular NW can reach 15.2, which is much larger than the best known inorganic thermoelectric materials obtained so far. Finally, we applied our model to study the thermoelectric properties of 1D polymer chains of P3HT and PEDOT:PSS. The power factor reaches 500 μW/cmK for a PEDOT:PSS chain. This study indicates that low-dimensional conducting polymers could be promising high-ZT materials. The theoretical study presented in this work could be useful for guiding the searchfor high-efficiency thermoelectric materials that are potentially low-cost and compatible with environmental-friendly processing.
Extended-stopband bandpass filter using both half- and quarter-wavelength resonators (2005)

A novel quasielliptic microstrip bandpass filter (BPF) using both half- and quarter-wavelength resonators is proposed. With the quarter-wavelength (/spl lambda//4) resonators placed in the interstage, the filter spurious passband can be pushed up to 3 f/sub 0/ where f/sub 0/ stands for the passband center frequency. To improve the stopband characteristics, a modified stopband-extended filter is implemented, utilizing the multiple transmission zeros placed at specified frequencies to achieve good frequency selectivity and out-of-band rejection. The modified filter provides a 22.5-dB rejection level from 1.14 f/sub 0/ to 5.2 f/sub 0/.
GOLDEN 2: A Novel Transcriptional Regulator of Cellular Differentiation in the Maize Leaf (1998)

The differentiation of distinct cell types within the leaf is essential for normal plant development. We characterized previously a transposon-induced mutant of maize (bundle sheath defective1) that disrupts the differentiation of a single photosynthetic cell type in the leaf. In this study, we show that this mutation is allelic to golden2 (g2), a lesion first reported 70 years ago. We cloned G2 by using Suppressor-mutator as a molecular tag. The gene encodes a 2. 2-kb transcript that is present throughout the wild-type leaf but is most abundant in C4 leaf blade tissue. Gene sequence data showed the existence of a bipartite nuclear localization signal encoded by the first exon, and we determined that G2 reporter gene fusions are targeted to the nucleus in onion epidermal cells. Further sequence analysis indicated the presence of a novel motif within the deduced protein sequence that shares features with TEA DNA binding domains. Therefore, we propose that G2 acts as a novel transcriptional regulator of cellular differentiation in the maize leaf.
Three-dimensional experimental analysis of the near-field and far-field radiation of planar millimeter-wave transmitters (1997)

An experimental study of the electric near-field distribution of two different types of planar transmitters for the 76.5 GHz frequency regime important for automotive applications is presented. Three-dimensional field mapping is performed with a novel stroboscopic optoelectronic technique combining electrooptic testing (near-field measurements) with photoconductive probing (far-field). The detected mode patterns give a detailed insight into the operation of the devices under test and allow tracing back mode anomalies to misdesigned parts of the structure for improved and direct failure analysis.
Role of PI3Kδ and PI3Kγ in inflammatory arthritis and tissue localization of neutrophils (2008)

The p110delta isoform of class I phosphoinositide 3-kinase (PI3K) plays a major role in B cell receptor signaling, while its p110gamma counterpart is thought to predominate in leukocyte chemotaxis. Consequently, emphasis has been placed on developing PI3Kgamma selective inhibitors to treat disease states that result from inappropriate tissue accumulation of leukocytes. We now demonstrate that PI3Kdelta blockade is effective in treating an autoimmune disorder in which neutrophil infiltration is required for tissue injury. Using the K/BxN serum transfer model of arthritis, in which neutrophils and leukotriene B(4) (LTB(4)) participate, we show that genetic deletion or selective inhibition of PI3Kdelta diminishes joint erosion to a level comparable to its PI3Kgamma counterpart. Moreover, the induction and progression of joint destruction was profoundly reduced in the absence of both PI3K isoforms and correlated with a limited ability of neutrophils to migrate into tissue in response to LTB(4). However, the dynamic interplay between these isoforms is not pervasive, as fMLP-induced neutrophil extravasation was primarily reliant on PI3Kgamma. Our results not only demonstrate that blockade of PI3Kdelta has potential therapeutic value in the treatment of chronic inflammatory conditions, but also provide evidence that dual inhibition of these lipid kinases may yield superior clinical results.
Dystonia and parkinsonism in GM1 type 3 gangliosidosis (2005)

GM1 gangliosidosis is due to beta-galactosidase deficiency. Only patients with type 3 disease survive into adulthood and develop movement disorders. Clinical descriptions of this form are rare, particularly in non-Japanese patients. We describe four new patients and systematically analyze all previous reports found by a literature search and contacts with the authors for additional information. Generalized dystonia remained the predominant feature throughout the disease course and was often associated with akinetic-rigid parkinsonism. GM1 gangliosidosis must be considered as a cause of early-onset generalized dystonia, particularly in patients with short stature and skeletal dysplasia.
Control of TFH cell numbers: why and how? (2013)

T follicular helper (TFH) cells are essential for formation of germinal centres (GCs) and selection of mutated GC B cells. It has become clear over the last decade that precise control of TFH cell numbers is important to produce optimally affinity-matured antibody responses that are devoid of self-reactivity. Indeed, limiting the number of TFH cells appears important to impose competition amongst B-cell clones and set a selection threshold that will favour survival of high affinity clones. In contrast, excessive number of TFH cells appears to lower the selection threshold and allow survival of low affinity or self-reactive clones. Here, we review the cell-intrinsic and cell-extrinsic mechanisms that influence TFH cell homeostasis, including recent insights into novel modes of regulation by T-cell costimulators, toxic metabolites, microRNAs, RNA-binding proteins and regulatory cells.
The data locality of work stealing (2000)

This paper studies the data locality of the work-stealing scheduling algorithm on hardware-controlled shared-memory machines. We present lower and upper bounds on the number of cache misses using work stealing, and introduce a locality-guided work-stealing algorithm along with experimental validation.