gebhart/patrepeval huggingface dataset:
Sigma-1 receptors are essential for capsaicin-induced mechanical hypersensitivity: Studies with selective sigma-1 ligands and sigma-1 knockout mice (2009)

We evaluated the role of sigma(1) receptors on capsaicin-induced mechanical hypersensitivity and on nociceptive pain induced by punctate mechanical stimuli, using wild-type and sigma(1) receptor knockout (sigma(1)-KO) mice and selective sigma(1) receptor-acting drugs. Mutation in sigma(1)-KO mice was confirmed by PCR analysis of genomic DNA and, at the protein level, by [(3)H](+)-pentazocine binding assays. Both wild-type and sigma(1)-KO mice not treated with capsaicin showed similar responses to different intensities of mechanical stimuli (0.05-8 g force), ranging from innocuous to noxious, applied to the hind paw. This indicates that sigma(1) gene inactivation does not modify the perception of punctate mechanical stimuli. The intraplantar (i.pl.) administration of capsaicin induced dose-dependent mechanical allodynia in wild-type mice (markedly reducing both the threshold force necessary to induce paw withdrawal and the latency to paw withdrawal induced by a given force). In contrast, capsaicin was completely unable to induce mechanical hypersensitivity in sigma(1)-KO mice. The high-affinity and selective sigma(1) antagonists BD-1063, BD-1047 and NE-100, administered subcutaneously (s.c.), dose-dependently inhibited mechanical allodynia induced by capsaicin (1 microg,i.pl.), yielding ED(50) (mg/kg) values of 15.80+/-0.93, 29.31+/-1.65 and 40.74+/-7.20, respectively. The effects of the sigma(1) antagonists were reversed by the sigma(1) agonist PRE-084 (32 mg/kg, s.c.). None of the drugs tested modified the responses induced by a painful mechanical punctate stimulus (4 g force) in nonsensitized animals. These results suggest that sigma(1) receptors are essential for capsaicin-induced mechanical hypersensitivity, but are not involved in mechanical nociceptive pain.
Albuminuria, impaired kidney function and cardiovascular outcomes or mortality in the elderly (2009)

Elevated cystatin C and albuminuria are common, identify different subsets of the older population, and are independent, graded risk factors for cardiovascular disease and mortality.
A New Fungal Immunomodulatory Protein, FIP-fve Isolated from the Edible Mushroom, Flammulina velutipes and its Complete Amino Acid Sequence (1995)

A new fungal immunomodulatory protein (FIP-fve) has been isolated and purified from the edible golden needle mushroom (Flammulina velutipes). The apparent molecular mass of FIP-fve determined by SDS/PAGE agrees well with the value of 12704 Da calculated from its amino acid composition and sequence. The complete amino acid sequence of FIP-fve was elucidated by protein sequencing techniques. FIP-fve consists of 114 amino acid residues with an acetylated amino end, and lacks methionine, half-cystine and histidine residues. FIP-fve was able to hemagglutinate human red blood cells. The immunomodulatory activity of FIP-fve was demonstrated by its stimulatory activity toward human peripheral blood lymphocytes, and its suppression of systemic anaphylaxis reactions and local swelling of mouse footpads. FIP-fve was found to enhance the transcriptional expression of interleukin-2 and interferon-gamma.
Structure/permeability relationships of polyimide membranes. Applications to the separation of gas mixtures (1989)

Abstract The permeability of nine different polyimide membranes to H 2 , N 2 , O 2 , CH 4 , and CO 2 has been determined at 35°C and at applied pressures of up to 9 atm. The dianhydride monomers used for the synthesis of the polymides were PMDA and 6FDA, whereas the diamine monomers were ODA, BDAF, and p ‐PDA. The selectivities of the 6FDA polymides toward CO 2 relative to CH 4 are higher than those of the PMDA polyimides at comparable CO 2 permeabilities. Both types of polyimides exhibit significantly higher CO 2 /CH 4 selectivities than more common glassy polymers, such as cellulose acetate, polysulfone, and polycarbonate. The selectivities of the PMDA and 6FDA polyimides to O 2 relative to N 2 are of the same magnitude and generally higher than those of common glassy polymers with similar O 2 permeabilities. The polymides are more permeable to N 2 than to CH 4 , whereas the opposite is true for many other glassy polymers. Possible factors responsible for the above behavior, such as segmental mobility, mean interchain distance, and formation of charge transfer complexes, are examined. The relevance of the study to the development of more highly gas‐selective and permeable membranes for the separation of gas mixtures is also discussed.
Faithful Completion of Images of Scenic Landmarks Using Internet Images (2015)

Previous works on image completion typically aim to produce visually plausible results rather than factually correct ones. In this paper, we propose an approach to faithfully complete the missing regions of an image. We assume that the input image is taken at a well-known landmark, so similar images taken at the same location can be easily found on the Internet. We first download thousands of images from the Internet using a text label provided by the user. Next, we apply two-step filtering to reduce them to a small set of candidate images for use as source images for completion. For each candidate image, a co-matching algorithm is used to find correspondences of both points and lines between the candidate image and the input image. These are used to find an optimal warp relating the two images. A completion result is obtained by blending the warped candidate image into the missing region of the input image. The completion results are ranked according to combination score, which considers both warping and blending energy, and the highest ranked ones are shown to the user. Experiments and results demonstrate that our method can faithfully complete images.
Could transcranial direct current stimulation have unexpected additional benefits in the treatment of depressed patients? (2012)

The application of novel brain stimulation techniques to treat depression, and pos-sibly other neuropsychiatric disorders, is a new and rapidly growing field. Among these techniques, transcranial direct cur-rent stimulation (tDCS) is emerging as one of the most promising approaches because of its relative ease of use, safety and neurobiological effects. tDCS involves the use of weak electric currents (1–2 mA), passed through brain tissue via electrodes placed on the scalp. The stimulation is too weak to directly cause neuronal firing, but is thought to interact with the neuronal membrane and background neural activ-ity, resulting in modification of synaptic strength
SSME Parameter Modeling with Neural Networks (1994)

&lt;div class="htmlview paragraph"&gt;The High Pressure Oxidizer Turbine (HPOT) discharge temperature of the Space Shuttle Main Engine (SSME) was estimated using Radial Basis Function Neural Networks (RBFNN) during the startup transient. Estimation was performed for both nominal engine operation and during simulated input sensor failures. The K-means clustering algorithm was used on the data to determine the location of the basis function centers. The performance of the RBFNN is compared with that of a feedforward neural network trained with the Quickprop learning algorithm.&lt;/div&gt;
Image processing in the Alexandria Digital Library project (2002)

The management of images, video, and in general, multimedia data, is an important issue in the design of digital libraries. In particular, the following problems stand out: efficient storage, fast retrieval, and protection of intellectual property. We outline below some of the recent advances in image processing in the context of the UCSB Alexandria Digital Library (ADL) project whose goal is to create a database of spatially indexed data. Maps and satellite images are among the main data sets in this project. The focus of this overview is on image retrieval using texture and on digital watermarking. A texture thesaurus for browsing aerial photographs and a wavelet based digital watermarking scheme are presented.
The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding (1998)

We recently reported the positional cloning of a candidate gene for hereditary hemochromatosis called HFE. The gene product, a member of the major histocompatibility complex class I-like family, was found to have a mutation, Cys-282 --> Tyr (C282Y), in 85% of patient chromosomes. This mutation eliminates the ability of HFE to associate with beta2-microglobulin (beta2m) and prevents cell-surface expression. A second mutation that has no effect on beta2m association, H63D, was found in eight out of nine patients heterozygous for the C282Y mutant. In this report, we demonstrate in cultured 293 cells overexpressing wild-type or mutant HFE proteins that both the wild-type and H63D HFE proteins form stable complexes with the transferrin receptor (TfR). The C282Y mutation nearly completely prevents the association of the mutant HFE protein with the TfR. Studies on cell-associated transferrin at 37 degrees C suggest that the overexpressed wild-type HFE protein decreases the affinity of the TfR for transferrin. The overexpressed H63D protein does not have this effect, providing the first direct evidence for a functional consequence of the H63D mutation. Addition of soluble wild-type HFE/beta2m heterodimers to cultured cells also decreased the apparent affinity of the TfR for its ligand under steady-state conditions, both in 293 cells and in HeLa cells. Furthermore, at 4 degrees C, the added soluble complex of HFE/beta2m inhibited binding of transferrin to HeLa cell TfR in a concentration-dependent manner. Scatchard plots of these data indicate that the added heterodimer substantially reduced the affinity of TfR for transferrin. These results establish a molecular link between HFE and a key protein involved in iron transport, the TfR, and raise the possibility that alterations in this regulatory mechanism may play a role in the pathogenesis of hereditary hemochromatosis.
An E. coli promoter induced by the cessation of growth (1987)

The production of the bacterial DNA replication inhibitor Microcin B17 is induced as cultures enter stationary phase. Using S1 nuclease protection assays we have shown that this induction is the result of increased levels of transcription initiation from a promoter located upstream from mcbA, the structural gene for Microcin B17. Upstream from the start site of transcription there is a rather typical -35 region. However, there is no good homology to the consensus -10 region. While most of the cell's transcription is shut off as a result of the cessation of growth, transcription from the mcbA promoter continues for several hours in stationary phase. A single-copy gene fusion between mcbA and lacZ was used to monitor the response of the promoter to different nutritional conditions and in different host backgrounds altered in metabolic regulatory loci. Starvation for nitrogen, phosphate or carbon sources all induced transcription from the promoter. Levels of transcription were reduced in ompR backgrounds. In contrast, mutations in other global regulatory loci, fnr, relA and cya had little or no effect.
Derivatives of 10,11‐dihydro‐5H‐dibenzo[a,d] cycloheptene and related compounds. III. Azaketones (1971)

Abstract The preparation and properties of four isomeric azadibenzoeycloheptenones 3 and their 10,11‐dihydro derivatives 2 are described. The ketones 2 were prepared by cyclization of appropriately substituted phenethylpyridine carboxylic acids and dehydrogenated to 3 . Four monochloro derivatives 24 of the 4‐azaketone 2d are also described.
Simultaneous optimization of supply and threshold voltages for low-power and high-performance circuits in the leakage dominant era (2004)

Electrothermal couplings between supply voltage, operating frequency, power dissipation and die temperature have been shown to significantly impact the energy-delay-product (EDP) based simultaneous optimization of supply (Vdd) and threshold (Vth) voltages. We present for the first time, the implications of an electrothermally aware EDP optimization on circuit operation in leakage dominant nanometer scale CMOS technologies. It is demonstrated that electrothermal EDP (EEDP) optimization restricts the operation of the circuit to a certain region in the Vdd-Vth plane. Also, the significance of EEDP optimization has been shown to increase with increase in leakage power and/or process variations.
Purification and characterization of the yeast-expressed erythropoietin mutant Epo (R103A), a specific inhibitor of human primary hematopoietic cell erythropoiesis (2002)

A drug that specifically inhibits erythropoiesis would be clinically useful. The erythropoietin (Epo) mutant Epo (R103A) could potentially be used for this purpose. Epo (R103A) has a single amino acid substitution of alanine for arginine at position 103. Because of this mutation, Epo (R103A) is only able to bind to one of the 2 subunits of the erythropoietin receptor (EpoR) homodimer and is thus a competitive inhibitor of Epo activity. To produce large quantities of Epo (R103A) to test in animal models of thalassemia and sickle cell disease, we expressed and purified recombinant Epo (R103A) from the yeast Pichia pastoris. Using this method milligram quantities of highly purified Epo (R103A) are obtained. The yeast-expressed Epo (R103A) is properly processed and glycosylated and specifically inhibits Epo-dependent cell growth and (125)I-Epo binding. Epo (R103A) does not, however, directly induce apoptosis in 32D cells expressing EpoR. Epo (R103A) inhibits erythropoiesis of human CD34(+) hematopoietic cells and completely blocks erythroid burst-forming unit formation in normal human bone marrow colony assays. Yeast-expressed Epo (R103A) is a specific inhibitor of primary erythropoiesis suitable for testing in animal models.
The CTG repeat expansion size correlates with the splicing defects observed in muscles from myotonic dystrophy type 1 patients (2008)

The CTG repeat length plays a key role in the extent of splicing misregulation and foci formation, thus providing a useful link between the genotype and the molecular cellular phenotype in DM1.
Effect of inhibitors of eicosanoid metabolism in murine collagen‐induced arthritis (1988)

The dual inhibitors of arachidonic acid metabolism, Smith Kline & French (SK&F) 86002, SK&F 104351, and phenidone; the corticosteroid, dexamethasone; and the selective cyclooxygenase inhibitors, ibuprofen, indomethacin, naproxen, and piroxicam were evaluated for their antiarthritic potency in the murine, collagen-induced arthritis model. The ability of these compounds to alter the severity of arthritic lesions and to reduce serum levels of the acute-phase reactant, serum amyloid P component (SAP) were monitored. Serum concentrations of SAP were found to correlate strongly (r = 0.985) with disease severity at day 35 postimmunization. Treatment with SK&F 86002, SK&F 104351, phenidone, or dexamethasone significantly reduced disease severity, as judged by clinical score (55%, 72%, 41%, and 45% inhibition, respectively) and SAP levels (62%, 94%, 52%, and 94% inhibition, respectively) in arthritic mice. This profile of activity was not shared by the selective cyclooxygenase inhibitors, which did not uniformly inhibit disease activity by both parameters. The results suggest that dual inhibitors of 5-lipoxygenase and cyclooxygenase may prove more effective than selective cyclooxygenase inhibitors as anti-arthritic agents.
FIR filter design via semidefinite programming and spectral factorization (2002)

We present a semidefinite programming approach to FIR filter design with arbitrary upper and lower bounds on the frequency response magnitude. It is shown that the constraints can be expressed as linear matrix inequalities (LMIs), and hence they can be easily handled by interior-point methods. Using this LMI formulation, we can cast several interesting filter design problems as convex or quasi-convex optimization problems, e.g. minimizing the length of the FIR filter and computing the Chebychev approximation of a desired power spectrum or a desired frequency response magnitude on a logarithmic scale.
Approximate Aggregates in Oracle 12C (2016)

New generation of analytic applications emerged to process data generated from non conventional sources. The challenge for the traditional database systems is that the data sets are very large and keep increasing at a very high rate while the application users have higher performance expectations. The most straightforward response to this challenge is to deploy larger hardware configurations making the solution very expensive and not acceptable for most cases. Alternative solutions fall into two categories: reduce the data set using sampling techniques or reduce the computational complexity of expensive database operations by using alternative algorithms. Alternative algorithms considered in this paper are approximate aggregates that perform a lot better at the cost of reduced and tolerable accuracy. In Oracle 12C we introduced approximate aggregates of expensive aggregate functions that are very common in analytic applications, that is, approximate count distinct and approximate percentile. The performance is improved in two ways. First, the approximate aggregates use bounded memory, often eliminating the need to use temporary storage which results in significant performance improvement over the exact aggregates. Second, we provide materialized view support that allows users to store pre-computed results of approximate aggregates. These results can be rolled up to answer queries on different dimensions (such rollup is not possible for exact aggregates).
Multiplexing a High-Throughput Liability Assay to Leverage Efficiencies (2009)

In order to identify potential cytochrome P-450 3A4 (drug-metabolizing enzyme) inducers at an early stage of the drug discovery process, a cell-based transactivation high-throughput luciferase reporter assay for the human pregnane X receptor (PXR) in HepG2 cells has been implemented and multiplexed with a viability end point for data interpretation, as part of a Lead Profiling portfolio of assays. As a routine part of Lead Profiling operations, assays are periodically evaluated for utility as well as for potential improvements in technology or process. We used a recent evaluation of our PXR-transactivation assay as a model for the application of Lean Thinking-based process analysis to lab-bench assay optimization and automation. This resulted in the development of a 384-well multiplexed homogeneous assay simultaneously detecting PXR transactivation and HepG2 cell cytotoxicity. In order to multiplex fluorescent and luminescent read-outs, modifications to each assay were necessary, which included optimization of multiple assay parameters such as cell density, plate type, and reagent concentrations. Subsequently, a set of compounds including known cytotoxic compounds and PXR inducers were used to validate the multiplexed assay. Results from the multiplexed assay correlate well with those from the singleplexed assay formats measuring PXR transactivation and viability separately. Implementation of the multiplexed assay for routine compound profiling provides improved data quality, sample conservation, cost savings, and resource efficiencies.
Bevacizumab and Erlotinib: A Promising New Approach to the Treatment of Advanced NSCLC (2008)

Biologic agents that target molecules involved in tumor growth, progression, and pathological angiogenesis--such as the human epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF)--have demonstrated efficacy in patients with non-small cell lung cancer (NSCLC). Erlotinib (Tarceva); OSI Pharmaceuticals, Inc., Melville, NY, Genentech, Inc., South San Francisco, CA, and F. Hoffmann-La Roche Ltd, Basel, Switzerland), a highly selective tyrosine kinase inhibitor that inhibits EGFR, and bevacizumab (Avastin); Genentech, Inc., South San Francisco, CA, and F. Hoffmann-La Roche Ltd, Basel, Switzerland), a VEGF-targeted recombinant humanized monoclonal antibody, have displayed very encouraging activity in a randomized phase II trial in patients with previously treated NSCLC. Because erlotinib and bevacizumab act on two different pathways critical to tumor growth and dissemination, administering these drugs concomitantly may confer additional clinical benefits to cancer patients with advanced disease, by virtue of their complementary (or additive) antitumor activity. The combination of bevacizumab plus erlotinib may prove to be a viable second-line alternative to chemotherapy or erlotinib monotherapy in patients with NSCLC. The benefits of the combination may be further enhanced by selecting for patients who are likely to respond to this therapy. While a number of potential predictive markers have been identified for erlotinib, their value remains to be confirmed in prospective trials. In addition, the application of such personalized therapy will also depend on the availability of validated screening methods.
Major Histocompatibility Complex Class I and Class II Expression in Renal Cell Carcinoma and Modulation by Interferon Gamma (1996)

(i) Like normal kidney, virtually all primary human renal cell carcinomas express MHC class I antigens and retain this phenotype even during tumor progression and metastasis; (ii) class II expression on normal and RCC cells appears more limited but occurs frequently in both primary and metastatic lesions; and (iii) in most continuous RCC cell lines expression of MHC class I and II can effectively be stimulated by IFN-gamma. Since expression of MHC molecules might determine the immunogenicity of human RCC, its constitutive expression and augmentation could play an important role for the immunotherapy and prognosis of human renal cancer.
Glutamine Repeats and Neurodegeneration (2000)

A growing number of neurodegenerative diseases have been found to result from the expansion of an unstable trinucleotide repeat. Over the past 6 years, researchers have focused on identifying the mechanism by which the expanded polyglutamine tract renders a protein toxic to a subset of vulnerable neurons. In this review, we summarize the clinicopathologic features of these disorders (spinobulbar muscular atrophy, Huntington disease, and the spinocerebellar ataxias, including dentatorubropallidoluysian atrophy), describe the genes involved and what is known about their products, and discuss the model systems that have lent insight into pathogenesis. The review concludes with a model for pathogenesis that illuminates the unifying features of these polyglutamine disorders. This model may prove relevant to other neurodegenerative disorders as well.
Role of hypoxia-inducible factor-1α as a cancer therapy target (2006)

Hypoxia occurs in solid tumours due to a mismatch between tumour growth and angiogenesis. Hypoxia in solid tumours is associated with an aggressive phenotype and resistance to radiation therapy and chemotherapy leading to poor patient prognosis. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor, which is activated in response to intratumoural hypoxia and as a result of genetic alterations that activate oncogenes and inactivate tumour suppressor genes. It plays a key role in the adaptation of tumour cells to hypoxia by activating the transcription of genes, which regulate several biological processes including angiogenesis, cell proliferation and survival, glucose metabolism, pH regulation and migration. This makes HIF-1 an attractive target for the development of anticancer agents. The success of these agents depends on reliable methods to identify those patients most likely to benefit from HIF-1-targeted therapy. Several novel small molecule inhibitors of HIF-1 have been identified and are moving towards clinical trials, but none of these are specific for HIF-1. Further work is ongoing to identify more selective HIF-1 inhibitors.