gebhart/patrepeval huggingface dataset:
Defective Assembly of Influenza A Virus due to a Mutation in the Polymerase Subunit PA (2005)

The RNA-dependent RNA polymerase of influenza A virus is composed of three subunits that together synthesize all viral mRNAs and also replicate the viral genomic RNA segments (vRNAs) through intermediates known as cRNAs. Here we describe functional characterization of 16 site-directed mutants of one polymerase subunit, termed PA. In accord with earlier studies, these mutants exhibited diverse, mainly quantitative impairments in expressing one or more classes of viral RNA, with associated infectivity defects of varying severity. One PA mutant, however, targeting residues 507 and 508, caused only modest perturbations of RNA expression yet completely eliminated the formation of plaque-forming virus. Polymerases incorporating this mutant, designated J10, proved capable of synthesizing translationally active mRNAs and of replicating diverse cRNA or vRNA templates at levels compatible with viral infectivity. Both the mutant protein and its RNA products were appropriately localized in the cytoplasm, where influenza virus assembly occurs. Nevertheless, J10 failed to generate infectious particles from cells in a plasmid-based influenza virus assembly assay, and hemagglutinating material from the supernatants of such cells contained little or no nuclease-resistant genomic RNA. These findings suggest that PA has a previously unrecognized role in assembly or release of influenza virus virions, perhaps influencing core structure or the packaging of vRNAs or other essential components into nascent influenza virus particles.
Pathogenesis and treatment of ANCA-associated vasculitides. (2015)

Recent studies have increased our insight into the pathogenesis of ANCA-associated vasculitis (AAV). Although many data from in vitro and in vivo experimental studies support the pathogenic role of the autoantibodies, cellular immunity seems involved as well. Besides, an amplification loop via the alternative pathway of complement is apparent. These new insights make a more targeted therapeutic approach possible. In particular, the B-cell depleting antibody rituximab has been shown non-inferior to cyclophosphamide for induction of remission, and even superior in patients with relapsing disease being positive for PR3-ANCA. Rituximab is also superior to cyclophosphamide for maintaining remission. Blocking the C5a-receptor seems promising as well as an alternative for high dose corticosteroids during induction of remission.
Regulation of pancreatic β-cell insulin secretion by actin cytoskeleton remodelling: role of gelsolin and cooperation with the MAPK signalling pathway (2006)

We have previously isolated two MIN6 beta-cell sublines, B1, highly responsive to glucose-stimulated insulin secretion, and C3, markedly refractory (Lilla, V., Webb, G., Rickenbach, K., Maturana, A., Steiner, D. F., Halban, P. A. and Irminger, J. C. (2003) Endocrinology 144, 1368-1379). We now demonstrate that C3 cells have substantially increased amounts of F-actin stress fibres whereas B1 cells have shorter cortical F-actin. Consistent with these data, B1 cells display glucose-dependent actin remodelling whereas, in C3 cells, F-actin is refractory to this secretagogue. Furthermore, F-actin depolymerisation with latrunculin B restores glucose-stimulated insulin secretion in C3 cells. In parallel, glucose-stimulated ERK1/2 activation is greater in B1 than in C3 cells, and is potentiated in both sublines following F-actin depolymerisation. Glucose-activated phosphoERK1/2 accumulates at actin filament tips adjacent to the plasma membrane, indicating that these are the main sites of action for this kinase during insulin secretion. In addition, B1 cell expression of the calcium-dependent F-actin severing protein gelsolin is >100-fold higher than that of C3 cells. Knock-down of gelsolin reduced glucose-stimulated insulin secretion, whereas gelsolin over-expression potentiated secretion from B1 cells. Gelsolin localised along depolymerised actin fibres after glucose stimulation. Taken together, these data demonstrate that F-actin reorganization prior to insulin secretion requires gelsolin and plays a role in the glucose-dependent MAPK signal transduction that regulates beta-cell insulin secretion.
Radial k‐t FOCUSS for high‐resolution cardiac cine MRI (2009)

A compressed sensing dynamic MR technique called k-t FOCUSS (k-t FOCal Underdetermined System Solver) has been recently proposed. It outperforms the conventional k-t BLAST/SENSE (Broad-use Linear Acquisition Speed-up Technique/SENSitivity Encoding) technique by exploiting the sparsity of x-f signals. This paper applies this idea to radial trajectories for high-resolution cardiac cine imaging. Radial trajectories are more suitable for high-resolution dynamic MRI than Cartesian trajectories since there is smaller tradeoff between spatial resolution and number of views if streaking artifacts due to limited views can be resolved. As shown for Cartesian trajectories, k-t FOCUSS algorithm efficiently removes artifacts while preserving high temporal resolution. k-t FOCUSS algorithm applied to radial trajectories is expected to enhance dynamic MRI quality. Rather than using an explicit gridding method, which transforms radial k-space sampling data to Cartesian grid prior to applying k-t FOCUSS algorithms, we use implicit gridding during FOCUSS iterations to prevent k-space sampling errors from being propagated. In addition, motion estimation and motion compensation after the first FOCUSS iteration were used to further sparsify the residual image. By applying an additional k-t FOCUSS step to the residual image, improved resolution was achieved. In vivo experimental results show that this new method can provide high spatiotemporal resolution even from a very limited radial data set.
In Vitro and In Vivo Prostate Cancer Metastasis and Chemoresistance Can Be Modulated by Expression of either CD44 or CD147 (2012)

CD44 and CD147 are associated with cancer metastasis and progression. Our purpose in the study was to investigate the effects of down-regulation of CD44 or CD147 on the metastatic ability of prostate cancer (CaP) cells, their docetaxel (DTX) responsiveness and potential mechanisms involved in vitro and in vivo. CD44 and CD147 were knocked down (KD) in PC-3M-luc CaP cells using short hairpin RNA (shRNA). Expression of CD44, CD147, MRP2 (multi-drug resistance protein-2) and MCT4 (monocarboxylate tranporter-4) was evaluated using immunofluorescence and Western blotting. The DTX dose-response and proliferation was measured by MTT and colony assays, respectively. The invasive potential was assessed using a matrigel chamber assay. Signal transduction proteins in PI3K/Akt and MAPK/Erk pathways were assessed by Western blotting. An in vivo subcutaneous (s.c.) xenograft model was established to assess CaP tumorigenecity, lymph node metastases and DTX response. Our results indicated that KD of CD44 or CD147 decreased MCT4 and MRP2 expression, reduced CaP proliferation and invasive potential and enhanced DTX sensitivity; and KD of CD44 or CD147 down-regulated p-Akt and p-Erk, the main signal modulators associated with cell growth and survival. In vivo, CD44 or CD147-KD PC-3M-luc xenografts displayed suppressed tumor growth with increased DTX responsiveness compared to control xenografts. Both CD44 and CD147 enhance metastatic capacity and chemoresistance of CaP cells, potentially mediated by activation of the PI3K and MAPK pathways. Selective targeting of CD44/CD147 alone or combined with DTX may limit CaP metastasis and increase chemosensitivity, with promise for future CaP treatment.
Coupling of a Surface Network With Reservoir Simulation (2003)

Abstract A controller providing a link between reservoir and network simulators has been developed to facilitate reservoir and production management. An optimizer included in the network simulator ensures that optimal management of the coupled system is achieved. The utility of the tool is first tested using a very simple reservoir model with one injector and a single smart producer, and subsequently demonstrated for water-alternating-gas (WAG) injection in two North Sea field cases. For the synthetic test case, various optimization scenarios are explored with the coupled system and compared to standalone flow simulation results. In the North Sea Field 1, optimum oil production is achieved by adjusting the settings of the surface valves as well as the downhole intelligent completion valves (ICVs); in Field 2, gas lift is optimized over time. The coupled system has given more accurate and realistic results in all cases. For the synthetic test case, the coupling gives a significantly higher production than the standalone reservoir simulator run whatever the optimization scenario. For the Field 1 smart well case, the coupled results match historic performance more closely because the pressure drop across the flow lines and surface facilities, the interaction among the wells in the production network, and the boundary conditions are all accounted for. For the gas lift optimization case, the coupled system gives more realistic results with respect to the potential for increased oil production and recovery than the standalone reservoir and network models.
Exon skipping for Duchenne muscular dystrophy: a systematic review and meta-analysis (2018)

Current available data do not show evidence that exon-skipping drugs are effective in DMD. Despite potential effectiveness when used at a specific dose, significant side effects were reported with drisapersen. The small number of RCTs with relatively small numbers of participants indicate the difficulty in conducting sufficiently powered studies of DMD. Prospectively planned meta-analysis and utilization of the real-world data may provide a more precise estimate of the effect of exon skipping in this disease.
Timing and Computation in Inner Retinal Circuitry (2006)

In the vertebrate inner retina, the second stage of the visual system, different components of the visual scene are transformed, discarded, or selected before visual information is transmitted through the optic nerve. This review discusses the connections between higher-level functions of visual processing, mathematical descriptions of the neural code, inner retinal circuitry, and visual computations. In the inner plexiform layer, bipolar cells deliver spatially and temporally filtered input to approximately ten anatomical strata. These layers receive a unique combination of excitation and inhibition, causing cells in different layers to respond with different kinetics to visual input. These distinct temporal channels interact through amacrine cells, a diverse class of inhibitory interneurons, which transmit signals within and between layers. In particular, wide-field amacrine cells transmit transient inhibition over long distances within a layer. These mechanisms and properties are combined into computations to detect the presence of differential motion and suppress the visual effects of eye movements.
KNN with TF-IDF based Framework for Text Categorization (2014)

KNN is a very popular algorithm for text classification. This paper presents the possibility of using KNN algorithm with TF-IDF method and framework for text classification. Framework enables classification according to various parameters, measurement and analysis of results. Evaluation of framework was focused on the speed and quality of classification. The results of testing showed the good and bad features of algorithm, providing guidance for the further development of similar frameworks.
Differential Leukotriene Constrictor Responses in Human Atherosclerotic Coronary Arteries (1998)

Atherosclerosis is associated with a specific leukotriene receptor(s) capable of inducing hyperreactivity of human epicardial coronary arteries in response to LTC4 and LTD4.
Determination of oxidase enzyme substrates using cross‐flow thin‐layer amperometry (1996)

Abstract Thin‐layer cross‐flow amperometric detectors with enzyme modified working electrodes were developed for the determination of oxidase substrates in flowing streams. The enzyme was covalently immobilized in an osmium redox polymer film on the electrode surface. Electrodes modified with glucose oxidase or lactate oxidase were prepared for the continuous monitoring of glucose or lactate. A peroxidase electrode coupled with oxidase enzyme reactors was also explored for the determination of glucose, lactate, and acetylcholine/choline in continuous monitoring systems or following liquid chromatography. The effects of interferences, oxygen, mass transfer limiting membrane, and perfusate composition on electrode performance are discussed.
Continuous tracking within and across camera streams (2003)

This paper presents a new approach for continuous tracking of moving objects observed by multiple, heterogeneous cameras. Our approach simultaneously processes video streams from stationary and pan-tilt-zoom cameras. The detection of moving objects from moving camera streams is performed by defining an adaptive background model that takes into account the camera motion approximated by an affine transformation. We address the tracking problem by separately modeling motion and appearance of the moving objects using two probabilistic models. For the appearance model, multiple color distribution components are proposed for ensuring a more detailed description of the object being tracked. The motion model is obtained using a Kalman filter (KF) process, which predicts the position of the moving object. The tracking is performed by the maximization of a joint probability model. The novelty of our approach consists in modeling the multiple trajectories observed by the moving and stationary cameras in the same KF framework. It allows deriving a more accurate motion measurement for objects simultaneously viewed by the two cameras and an automatic handling of occlusions, errors in the detection and camera handoff. We demonstrate the performances of the system on several video surveillance sequences.
Localization of kinesin superfamily proteins to the connecting cilium of fish photoreceptors (1996)

Kinesin superfamily proteins (KIFs) are probable motors in vesicular and non-vesicular transport along microtubular tracks. Since a variety of KIFs have been recently identified in the motile flagella of Chlamydomonas, we sought to ascertain whether KIFs are also associated with the connecting cilia of vertebrate rod photoreceptors. As the only structural link between the rod inner segment and the photosensitive rod outer segment, the connecting cilium is thought to be the channel through which all material passes into and out of the outer segment from the rod cell body. We have performed immunological tests on isolated sunfish rod inner-outer segments (RIS-ROS) using two antibodies that recognize the conserved motor domain of numerous KIFs (anti-LAGSE, a peptide antibody, and anti-Klp1 head, generated against the N terminus of Chlamydomonas Klp1) as well as an antibody specific to a neuronal KIF, KIF3A. On immunoblots of RIS-ROS, LAGSE antibody detected a prominent band at approximately 117 kDa, which is likely to be kinesin heavy chain, and Klp1 head antibody detected a single band at approximately 170 kDa; KIF3A antibody detected a polypeptide at approximately 85 kDa which co-migrated with mammalian KIF3A and displayed ATP-dependent release from rod cytoskeletons. Immunofluorescence localizations with anti-LAGSE and anti-Klp1 head antibodies detected epitopes in the axoneme and ellipsoid, and immunoelectron microscopy with the LAGSE antibody showed that the connecting cilium region was particularly antigenic. Immunofluorescence with anti-KIF3A showed prominent labelling of the connecting cilium and the area surrounding its basal body; the outer segment axoneme and parts of the inner segment coincident with microtubules were also labelled. We propose that these putative kinesin superfamily proteins may be involved in the translocation of material between the rod inner and outer segments.
Ability of Commercial Demineralized Freeze‐Dried Bone Allograft to Induce New Bone Formation (1996)

Demineralized freeze-dried bone allograft (DFDBA) has been used extensively in periodontal therapy. The rationale for use of DFDBA includes the fact that proteins capable of inducing new bone; i.e., bone morphogenetic proteins, can be isolated from bone grafts. Commercial bone banks have provided DFDBA to the dental practitioner for many years; however, these organizations have not verified the osteoinductive capacity of their DFDBA preparations. The aim of this study was to determine the ability of commercial DFDBA preparations to induce new bone formation. DFDBA with particle sizes ranging from 200 to 500 microns was received from six bone banks using various bone production methods. Different lots of DFDBA from the same tissue bank were sometimes available. A total of 14 lots were examined. The surface area of bone particles in each sample was measured morphometrically and the pH of a solution containing the particles after suspension in distilled water determined. Samples from each DFDBA lot were implanted intramuscularly (10 mg) or subcutaneously (20 mg) into three different animals and tissue biopsies harvested after 4 weeks. One sample from each tissue bank was implanted and harvested after 8 weeks. At harvest, each area where DFDBA had been implanted was excised and examined by light microscopy. The ability of DFDBA to produce new bone was evaluated and the amount of residual bone particles measured. The results show that bone particles from all tissue banks had a variety of shapes and sizes, both before implantation and after 1 or 2 months of implantation. The pH of particle suspensions also varied between batches, as well as between tissue banks. None of the DFDBA induced new bone formation when implanted subcutaneously. Intramuscular implants from three banks induced new bone formation after 1 and 2 months. DFDBA from two banks caused new bone formation only after 2 months. However, DFDBA from one bank did not induce new bone at all. Particle size before implantation correlated with particle size after implantation. However, particle size did not correlate with ability to induce bone. The results show that commercial DFDBA differs in both size and ability to induce new bone formation, but that the two are not related. The study also indicates that wide variation in commercial bone bank preparations of DFDBA exist and that ability to induce new bone formation also varies widely. Furthermore, the results suggest that methods or assays for evaluating the ability of DFDBA to induce new bone should be developed and standardized.
Diacylglycerol accumulation and microvascular abnormalities induced by elevated glucose levels. (1991)

The present experiments were undertaken to examine the hypothesis that glucose-induced increased de novo synthesis of 1,2-diacyl-sn-glycerol (which has been observed in a number of different tissues, including retinal capillary endothelial cells exposed to elevated glucose levels in vitro) and associated activation of protein kinase C may play a role in mediating glucose-induced vascular functional changes. We report here that twice daily instillation of 30 mM glucose over 10 d in a rat skin chamber granulation tissue model induces approximately a 2.7-fold increase in diacylglycerol (DAG) levels (versus tissues exposed to 5 mM glucose) in association with marked increases in vascular clearance of albumin and blood flow. The glucose-induced increase in DAG levels as well as the vascular functional changes are prevented by addition of 3 mM pyruvate. Pharmacological activation of protein kinase C with the phorbol ester TPA in the presence of 5 mM glucose increases microvascular albumin clearance and blood flow, and similar effects are observed with 1-monoolein (MOG), a pharmacological inhibitor of the catabolism of endogenous DAG. A pharmacological inhibitor of protein kinase C (staurosporine) greatly attenuates the rise in microvascular albumin clearance (but not the rise in blood flow) induced by glucose or by MOG. These findings are compatible with the hypothesis that elevated concentrations of glucose increase tissue DAG content via de novo synthesis, resulting in protein kinase C activation, and that these biochemical events are among the factors that generate the increased microvascular albumin clearance.
Synthesis of Potent and Orally Efficacious 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor HSD-016 (2011)

Cortisol and the glucocorticoid receptor (GR) signaling pathway has been linked to the development of diabetes and metabolic syndrome. In vivo, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive cortisone to its active form, cortisol. Existing clinical data have supported 11β-HSD1 as a valid therapeutic target for type 2 diabetes. In our research program, (R)-1,1,1-trifluoro-2-(3-((R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methylpiperazin-1-ylsulfonyl)phenyl)propan-2-ol (HSD-016) was discovered to be a potent, selective, and efficacious 11β-HSD1 inhibitor and advanced as a clinical candidate. Herein, a reliable and scalable synthesis of HSD-016 is described. Key transformations include an asymmetric synthesis of a chiral tertiary alcohol via Sharpless dihydroxylation, epoxide formation, and subsequent mild reduction. This route ensured multikilogram quantities of HSD-016 necessary for clinical studies.
Antioxidants Counteract Nicotine and Promote Migration via RacGTP in Oral Fibroblast Cells (2010)

Treatment with AO combinations clearly counteracted the effects of nicotine by restoring and increasing cell-migration rates. We found the combination of PFR was the most effective in HGFs, whereas, RFT was the most effective combination in HPDL fibroblast. These results clearly demonstrate that PF, RFT, and PFR counteract the negative effects of nicotine on cultured oral fibroblasts via the RacGTP signal-transduction pathway.