gebhart/patrepeval huggingface dataset:
Stroke prevention in elderly patients with atrial fibrillation. (2002)

The prevalence rate of atrial fibrillation in elderly inpatients was found to be 11.1%. Most of the elderly with atrial fibrillation had multiple concomitant risk factors for stroke and would benefit from anticoagulant therapy. However, in the majority, anticoagulation was withheld because of contraindications (78.6%) and patients' objection to anticoagulation (5.3%).
Virus-induced dysfunction of CD4+CD25+ T cells in patients with HTLV-I–associated neuroimmunological disease (2005)

CD4(+)CD25(+) Tregs are important in the maintenance of immunological self tolerance and in the prevention of autoimmune diseases. As the CD4(+)CD25(+) T cell population in patients with human T cell lymphotropic virus type I-associated (HTLV-I-associated) myelopathy/tropical spastic paraparesis (HAM/TSP) has been shown to be a major reservoir for this virus, it was of interest to determine whether the frequency and function of CD4(+)CD25(+) Tregs in HAM/TSP patients might be affected. In these cells, both mRNA and protein expression of the forkhead transcription factor Foxp3, a specific marker of Tregs, were lower than those in CD4(+)CD25(+) T cells from healthy individuals. The virus-encoded transactivating HTLV-I tax gene was demonstrated to have a direct inhibitory effect on Foxp3 expression and function of CD4(+)CD25(+) T cells. This is the first report to our knowledge demonstrating the role of a specific viral gene product (HTLV-I Tax) on the expression of genes associated with Tregs (in particular, foxp3) resulting in inhibition of Treg function. These results suggest that direct human retroviral infection of CD4(+)CD25(+) T cells may be associated with the pathogenesis of HTLV-I-associated neurologic disease.
History of the Administrative Committee of the Microwave Theory and Techniques Society (1984)

Although for the last several years the history of the Microwaves Theory and Techniques Society Administrative Committee (AdCom) has been carried on an issue-by-issue basis in the MTT Newsletter, I thought a short historical overview might be appropriate in this Special Centennial Issue of the Transactions on Microwave Theory and Techniques.
Phase III Trial Comparing 4-Day Chronomodulated Therapy Versus 2-Day Conventional Delivery of Fluorouracil, Leucovorin, and Oxaliplatin As First-Line Chemotherapy of Metastatic Colorectal Cancer: The European Organisation for Research and Treatment of Cancer Chronotherapy Group (2006)

Both regimens achieved similar median survival times more than 18 months with an acceptable toxicity. The chronomodulated schedule produced a survival advantage over FOLFOX in men. The strong sex dependency of optimal scheduling of fluorouracil, leucovorin, and oxaliplatin calls for translational investigations of determinants related to the patient's molecular clock.
Enhancer effect of bovine papillomavirus E2 protien in replication of polyomavirus DNA (1991)

In polyomavirus, both transcription from the early promoter and viral DNA replication initiated at the origin of DNA replication is controlled by binding of proteins to the enhancer region. We have developed a simple model system to study the role of an enhancer binding factor in the initiation of polyomavirus DNA replication. A reporter plasmid was constructed which has the enhancer region replaced by two binding sites for a transcription factor, the E2 protein encoded by bovine papillomavirus type 1. Co-transfection of COP 5 cells which express polyomavirus large T-antigen, with the reporter plasmid and an E2 expression plasmid, resulted in E2-dependent stimulation of replication of the reporter plasmid. The activity of several E2 mutants was also analysed. Mutant proteins with decreased activity in transcriptional trans-activation, resulting from impaired DNA binding or other defects, were found to have quantitatively similar reductions of activity in viral DNA replication. The results suggest that the E2 protein activates transcription and polyomavirus DNA replication by similar mechanism(s).
Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1) (2002)

Adaptive immunity necessitates the proliferation of lymphocytes. In the mouse, we have previously shown that antigen-experienced T cells that have lost their proliferative potential express the killer cell lectinlike receptor G1 (KLRG1). By using a newly generated monoclonal antibody specific for human KLRG1, we now demonstrate that expression of KLRG1 also identifies T cells in humans that are capable of secreting cytokines but that fail to proliferate after stimulation. Furthermore, our data show that proliferative incapacity of CD8 T cells correlates better with KLRG1 expression than with absence of the CD28 marker. In peripheral blood lymphocytes (PBLs) from healthy adult donors, KLRG1 was expressed on 44% +/- 14% of CD8 and 18% +/- 10% of CD4 T cells. KLRG1 expression was restricted to antigen-experienced T cells. Here, KLRG1(+) cells were preferentially found in the CCR7(-) effector T-cell pool. Besides T cells, a significant portion (approximately 50%) of human natural killer (NK) cells expressed KLRG1. Interestingly, these KLRG1(+) NK cells were found exclusively in the CD56(dim) NK-cell subset. Thus, the expression of KLRG1 identifies a subset of NK cells and antigen-experienced T cells in humans that lack proliferative capacity.
The first calcium-catalysed Nazarov cyclisation (2014)

The first calcium-catalysed Nazarov cyclisation is described. The Ca(NTf2)(PF6) complex is found to be a very active catalyst for 4π electrocyclisations. The remarkable catalytic activity of this complex is attributed to its increased Lewis acidity compared to other Ca complexes. Spectroscopic studies have provided an insight into the chelating interactions between the substrate and the Ca catalyst.
Highly efficient second, third and fourth harmonic generation from a two- branch femtosecond erbium fiber source (2006)

We report on highly efficient second, third and fourth harmonic generation from a femtosecond erbium-doped fiber source operating at 98 MHz repetition rate. By use of quasi-phase-matching in fan-out poled MgO:LiNbO(3), we generate pulses at 770 nm, 520 nm and 390 nm, with corresponding average powers of 120 mW, 55 mW and 6 mW, respectively. Our device can be employed as a two-color source providing radiation from ultraviolet to near infrared.
Hemodynamic and metabolic effects of vasopressin infusion in children with shock (2007)

The evidence is restricted. Most studies are retrospective and include a small number of patients. Nevertheless, there is significant experience concerning the use of vasopressin in Pediatrics. Vasopressin has a beneficial clinical effect in children and can be indicated in the treatment of refractory vasodilatory shock, after adequate volume resuscitation and when high doses of other vasopressors are not effective.
Application-driven processor design exploration for power-performance trade-off analysis (2002)

This paper presents an efficient design exploration environment for high-end core processors. The heart of the proposed design exploration framework is a two-level simulation engine that combines detailed simulation for critical portions of the code with fast profiling for the rest. Our two-level simulation methodology relies on the inherent clustered structure of application programs and is completely general and applicable to any microarchitectural power/performance simulation engine. The proposed simulation methodology is 3-17/spl times/ faster, while being sufficiently accurate (within 5%) when compared to the fully detailed simulator The design exploration environment is able to vary different microarchitectural configurations and find the optimal one as far as energy/spl times/delay product is concerned in a matter of minutes. The parameters that are found to affect drastically the core processor power/performance metrics are issue width, instruction window size, and pipeline depth, along with correlated clock frequency. For very high-end configurations for which balanced pipelining, may not be possible, opportunities for running faster stages at lower voltage exist. In such cases, by using up to 3 voltage levels, the energy/spl times/delay product is reduced by 23-30% when compared to the single voltage implementation.
Occurrence of novel verrucomicrobial species, endosymbiotic and associated with parthenogenesis in Xiphinema americanum-group species (Nematoda, Longidoridae). (2000)

Numerous micro-organisms have been described as cytoplasmic symbionts of eukaryotes. Many so-called obligate endosymbionts rely exclusively on maternal (vertical or transovarial) transmission to maintain themselves, rendering them dependent on the host sex ratio, which they would tend to manipulate to their own advantage. The latter phenomenon is often associated with the presence of Wolbachia pipientis (alpha-Proteobacteria) in arthropods and nematodes. A potentially similar situation was discovered involving members of a new clade of Verrucomicrobia, another main line of descent in the Bacteria. Nematode species of the Xiphinema americanum group (Nematoda, Longidoridae), viz. Xiphinema americanum, Xiphinema rivesi and Xiphinema brevicollum, each harbour their own specific verrucomicrobial endosymbionts. They are exclusively maternally inherited and their hosts reproduce by thelytokous (mother-to-daughter) parthenogenesis, males being extremely rare. A new genus, 'Candidatus Xiphinematobacter' gen. nov., along with three new candidate verrucomicrobial species, 'Candidatus Xiphinematobacter americani' sp. nov., 'Candidatus Xiphinematobacter rivesi' sp. nov. and 'Candidatus Xiphinematobacter brevicolli' sp. nov., are described on the basis of transmission electron microscopy, scanning electron microscopy, DAPI (4',6-diamidino-2-phenylindole) epifluorescence microscopy and 16S rDNA sequence analysis. These are the first endosymbiotic species described among the Verrucomicrobia. They share a mean 16S rDNA similarity of about 93%, whereas similarity to their closest relative, clone WCHD3-88, is less than 87%. Thus, the endosymbionts form a homogeneous clade for which the new candidate genus 'Candidatus Xiphinematobacter' gen. nov. is proposed. The type species is 'Candidatus Xiphinematobacter brevicolli' sp. nov.
In-line gain control of the erbium doped fiber amplifier using samarium doped inner-cladding in the 1.5 μm region (2002)

A new type of erbium doped fiber for optical amplifier was reported where erbium was doped in the center of the core and samarium doped in a ring in the cladding. By utilizing the spectral overlap of the absorption cross section of samarium in the inner-cladding and the emission cross section of erbium ion in the core, we demonstrated a new way of in-line control the gain spectrum of erbium doped amplifier pumped at 980 nm. The gain spectra in the conventional band were measured and we demonstrated potential of gain-flattening in the 1.5 mm region without external filters using the specially designed fiber. The effects of samarium doped inner-cladding on amplified spontaneous emission in the long band were also reported.
MicroRNA‐223 reversibly regulates erythroid and megakaryocytic differentiation of K562 cells (2008)

MicroRNAs (miRNAs) are thought to modulate a variety of cellular events. Several studies have revealed the functions of miR-223 in granulopoiesis. Here we analysed miR-223 expression in various human tissues, blood and leukaemia cells, and focused on its role in K562 erythroid and megakaryocytic differentiation. MiR-223 was detected not only in granulocytes but also in erythroid cells. In K562 cells, expression of miR-223 was down-regulated during haemin-induced erythroid differentiation but up-regulated during phorbol myristate acetate (PMA)-induced megakaryocytic differentiation. The overexpression of miR-223 resulted in significant decrease of gamma-globin mRNA and the fraction of benzidine-positive cells in K562 cells, suggesting a suppressive effect of miR-223 on erythroid differentiation. Peaks corresponding to 4N cells in stable transfectants overexpressing miR-223 were higher than that in control K562 cells during megakaryocytic differentiation, indicating that miR-223 increases megakaryocytic differentiation. The expression of LIM domain only 2 (LMO2) reporter was suppressed in NIH-3T3 when the expression of miR-223 was enforced by both the luciferase and fluorescence system. Furthermore, LMO2 mRNA and protein levels were significantly decreased in stable K562 transfectants overexpressing miR-223. These results indicate that LMO2 is a direct target of miR-223. Thus, our results suggest that miR-223 reversibly regulates erythroid and megakaryocytic differentiation of K562 cells via down-modulation of LMO2.
Efficacy of H5 Influenza Vaccines Produced by Reverse Genetics in a Lethal Mouse Model (2005)

We studied the efficacy, in mice, of 2 H5 influenza vaccine viruses produced by reverse genetics. Mice were immunized with inactivated viruses and then inoculated with a human H5N1 1997 or 2003 virus or an avian H5N1 2001 virus. Vaccine viruses that we tested raised high levels of hemagglutination-inhibiting (1:160-1:1280) and virus-neutralizing (1:900-1:1900) antibodies on day 21 after a single dose of vaccine and decreased or prevented virus replication in mouse lungs; 54.5%-100% of immunized mice survived, whereas all control mice died. Protection was achieved despite antigenic differences and incomplete matching of the vaccine strain and the challenge virus. Therefore, high levels of cross-protection are predicted in the mouse model.
Effects of Putative Hydroxylated Thalidomide Metabolites on Blood Vessel Density in the Chorioallantoic Membrane (CAM) Assay and on Tumor and Endothelial Cell Proliferation. (2002)

Angiogenesis, in particular anti-angiogenesis, is an area of particular therapeutic interest in cancer treatment. Several anti-angiogenic agents are in the final stages of clinical trials. One of these agents, thalidomide, best known for its teratogenic potential, is showing promise against several tumor types. Thalidomide has been shown previously to require bio-activation to exert its anti-angiogenic effect in isolated blood vessels and endothelial cells. In this work, we confirmed these findings using the in utero chicken embryo chorioallantoic membrane (CAM) system. In particular, the anti-angiogenic effect of thalidomide is significantly enhanced by activation by human but not by rat liver microsomes. We also showed in the CAM assay that hydroxylation of thalidomide at either the 1'- or 5-position retained anti-angiogenic activity whereas its hydroxylation at the 4-position led to an inactive compound. We further demonstrated that thalidomide shows weak anti-proliferative activity against MDA-MB-231 human breast cancer cells in culture. Thalidomide showed slightly more anti-proliferative activity, however, against the SH-SY5Y human neuroblastoma and human umbilical vein endothelial cell (HUVEC) types. Furthermore, incubation of thalidomide with human liver microsomes added no additional anti-proliferative effect in these cell types versus thalidomide given alone. Finally, we report that none of the thalidomide metabolites tested had any anti-proliferative effect against the breast or neuroblastoma cells, but do possess appreciable anti-proliferative activity against the endothelial cells. In summary, this work suggests that hydroxylated thalidomide analogs based on putative metabolites of the drug possess significant anti-angiogenic activity and that exploring further derivatives of these as potential anti-angiogenic agents warrants further merit.
Mild electrocatalytic hydrogenation and hydrodeoxygenation of bio-oil derived phenolic compounds using ruthenium supported on activated carbon cloth (2012)

Electrocatalytic hydrogenation (ECH) is an option for stabilizing or upgrading bio-oil that employs mild conditions (≤80 °C and ambient pressure) compared to hydrotreatment. In this study, phenol, guaiacol (2-methoxyphenol), and syringol (2,6-dimethoxyphenol) were chosen as model lignin-like substrates because of their abundance in bio-oil and their high resistance to hydrogenation relative to the carbonyl compounds. Cathodic reduction was catalyzed by ruthenium supported on activated carbon cloth (Ru/ACC), a novel electrocatalyst. Incipient wetness impregnation and cation exchange methods were employed to prepare the electrocatalyst using three different ruthenium precursors. Scanning electron microscopy revealed that ruthenium nanoparticles within the range of 10 to 20 nm were deposited on the support by both catalyst synthesis methods. Catalysts prepared by cation exchange were more active than those prepared using incipient wetness impregnation, presumably because of support surface functionalization by the oxidation pretreatment. When using incipient wetness impregnation, catalysts synthesized with precursor hexaammineruthenium(III) chloride showed the best activity and electrochemical efficiency, followed by catalysts prepared with ruthenium(III) chloride and ruthenium(III) nitrosyl nitrate. The Ru/ACC electrocatalyst reduced guaiacol, phenol and syringol with similar electrochemical efficiencies, but temperature was an important variable; the electrochemical efficiency for guaiacol reduction increased from 8% at 25 °C to 17% at 50 °C, but then dropped back to 10% at 80 °C. Solution pH also affected catalyst activity and product selectivity, with acidic conditions favoring guaiacol conversion, electrochemical efficiency and cyclohexanol selectivity.
Physics of Blob Displacement in a Two-Dimensional Porous Medium (1988)

Summary The evolution of the geometry of blobs is observed during displacements in a two-dimensional (2D) transparent micromodel, and such macroscopic parameters as pressure drop and recovery are monitored simultaneously. The results are in good agreement with experiments performed in real media and with theoretical calculations of the conditions required for blob mobilization when the presence of loops in the structure is taken into account.
Biglycan, a Danger Signal That Activates the NLRP3 Inflammasome via Toll-like and P2X Receptors (2009)

The role of endogenous inducers of inflammation is poorly understood. To produce the proinflammatory master cytokine interleukin (IL)-1beta, macrophages need double stimulation with ligands to both Toll-like receptors (TLRs) for IL-1beta gene transcription and nucleotide-binding oligomerization domain-like receptors for activation of the inflammasome. It is particularly intriguing to define how this complex regulation is mediated in the absence of an infectious trigger. Biglycan, a ubiquitous leucine-rich repeat proteoglycan of the extracellular matrix, interacts with TLR2/4 on macrophages. The objective of this study was to define the role of biglycan in the synthesis and activation of IL-1beta. Here we show that in macrophages, soluble biglycan induces the NLRP3/ASC inflammasome, activating caspase-1 and releasing mature IL-1beta without the need for additional costimulatory factors. This is brought about by the interaction of biglycan with TLR2/4 and purinergic P2X(4)/P2X(7) receptors, which induces receptor cooperativity. Furthermore, reactive oxygen species formation is involved in biglycan-mediated activation of the inflammasome. By signaling through TLR2/4, biglycan stimulates the expression of NLRP3 and pro-IL-1beta mRNA. Both in a model of non-infectious inflammatory renal injury (unilateral ureteral obstruction) and in lipopolysaccharide-induced sepsis, biglycan-deficient mice displayed lower levels of active caspase-1 and mature IL-1beta in the kidney, lung, and circulation. Our results provide evidence for direct activation of the NLRP3 inflammasome by biglycan and describe a fundamental paradigm of how tissue stress or injury is monitored by innate immune receptors detecting the release of the extracellular matrix components and turning such a signal into a robust inflammatory response.
Shear stress selectively upregulates intercellular adhesion molecule-1 expression in cultured human vascular endothelial cells. (1994)

Hemodynamic forces induce various functional changes in vascular endothelium, many of which reflect alterations in gene expression. We have recently identified a cis-acting transcriptional regulatory element, the shear stress response element (SSRE), present in the promoters of several genes, that may represent a common pathway by which biomechanical forces influence gene expression. In this study, we have examined the effect of shear stress on endothelial expression of three adhesion molecules: intercellular adhesion molecule-1 (ICAM-1), which contains the SSRE in its promoter, and E-selectin (ELAM-1) and vascular cell adhesion molecule-1 (VCAM-1), both of which lack the SSRE. Cultured human umbilical vein endothelial cells, subjected to a physiologically relevant range of laminar shear stresses (2.5-46 dyn/cm2) in a cone and plate apparatus for up to 48 h, showed time-dependent but force-independent increases in surface immunoreactive ICAM-1. Upregulated ICAM-1 expression was correlated with increased adhesion of the JY lymphocytic cell line. Northern blot analysis revealed increased ICAM-1 transcript as early as 2 h after the onset of shear stress. In contrast, E-selectin and vascular cell adhesion molecule-1 transcript and cell-surface protein were not upregulated at any time point examined. This selective regulation of adhesion molecule expression in vascular endothelium suggests that biomechanical forces, in addition to humoral stimuli, may contribute to differential endothelial gene expression and thus represent pathophysiologically relevant stimuli in inflammation and atherosclerosis.
Validation of the 2nd Generation Proteasome Inhibitor Oprozomib for Local Therapy of Pulmonary Fibrosis (2015)

Proteasome inhibition has been shown to prevent development of fibrosis in several organs including the lung. However, effects of proteasome inhibitors on lung fibrosis are controversial and cytotoxic side effects of the overall inhibition of proteasomal protein degradation cannot be excluded. Therefore, we hypothesized that local lung-specific application of a novel, selective proteasome inhibitor, oprozomib (OZ), provides antifibrotic effects without systemic toxicity in a mouse model of lung fibrosis. Oprozomib was first tested on the human alveolar epithelial cancer cell line A549 and in primary mouse alveolar epithelial type II cells regarding its cytotoxic effects on alveolar epithelial cells and compared to the FDA approved proteasome inhibitor bortezomib (BZ). OZ was less toxic than BZ and provided high selectivity for the chymotrypsin-like active site of the proteasome. In primary mouse lung fibroblasts, OZ showed significant anti-fibrotic effects, i.e. reduction of collagen I and α smooth muscle actin expression, in the absence of cytotoxicity. When applied locally into the lungs of healthy mice via instillation, OZ was well tolerated and effectively reduced proteasome activity in the lungs. In bleomycin challenged mice, however, locally applied OZ resulted in accelerated weight loss and increased mortality of treated mice. Further, OZ failed to reduce fibrosis in these mice. While upon systemic application OZ was well tolerated in healthy mice, it rather augmented instead of attenuated fibrotic remodelling of the lung in bleomycin challenged mice. To conclude, low toxicity and antifibrotic effects of OZ in pulmonary fibroblasts could not be confirmed for pulmonary fibrosis of bleomycin-treated mice. In light of these data, the use of proteasome inhibitors as therapeutic agents for the treatment of fibrotic lung diseases should thus be considered with caution.