gebhart/patrepeval huggingface dataset:
Non-nucleoside adenosine deaminase inhibitors: 2000 – 2004 (2005)

Adenosine deaminase (ADA) is a crucial enzyme in purine metabolism that irreversibly deaminates adenosine to form inosine. ADA is ubiquitous in human tissues and plays a crucial role in immune system development. ADA inhibitors may be useful for the treatment of ischaemic injury, hypertension, lymphomas and leukaemia. Furthermore, ADA inhibitors have recently also been considered as anti-inflammatory drugs. Most ADA inhibitors to date are purine nucleosides or alkyladenine analogues that have poor pharmacokinetics and/or several toxicities. ADA inhibitors without these problems may improve the treatment of leukaemia and also have potential for use in many other clinical conditions. This hypothesis has generated considerable interest in the development of non-nucleoside ADA inhibitors. Recently, a Fujisawa non-nucleoside ADA inhibitor demonstrated in vivo efficacy in inflammation and lymphoma models after oral administration. This review describes recent advances in the development of non-nucleoside ADA inhibitors, based on the patent literature from January 2000 to December 2004.
High-Level Production of γ-Linolenic Acid in Brassica juncea Using a Δ6 Desaturase from Pythium irregulare (2002)

gamma-Linolenic acid (GLA), a nutritionally important fatty acid in mammals, is synthesized by a delta6 desaturase. Here, we report identification of PiD6, a new cDNA from the oleaginous fungus, Pythium irregulare, encoding a 459-amino acid protein that shares sequence similarity to carboxyl-directed desaturases from various species. Expression of PiD6 in yeast (Saccharomyces cerevisiae) revealed that it converts exogenously supplied linoleic acid into GLA, indicating that it encodes a delta6 fatty acid desaturase. Expression of the desaturase in Brassica juncea under the control of the Brassica napus napin promoter resulted in production of three delta6 unsaturated fatty acids (18:2-6, 9; 18:3-6, 9, 12; and 18:4-6, 9, 12, 15) in seeds. Among them, GLA (18:3-6, 9, 12) is the most abundant and accounts for up to 40% of the total seed fatty acids. Lipid class and positional analysis indicated that GLA is almost exclusively incorporated into triacylglycerol (98.5%) with only trace amounts found in the other lipids. Within triacylglycerols, GLA is more abundant at the sn-2 position.
Study of protein characteristics that influence entry into the cerebrospinal fluid of normal mice and mice with encephalitis. (1982)

Entry of proteins into the cerebrospinal (CSF) from the blood is partially determined by the size of the protein. To determine whether other characteristics of proteins influence CSF entry, proteins or protein fragments were iodinated, inoculated intravenously, and serum and CSF were sampled at later times. The Fc fragment of immunoglobulin G (IgG) did not enter the CSF significantly better than the Fab fragment suggesting that choroidal Fc receptors are not of importance for selective immunoglobulin entry. To determine the role of protein charge on entry, bovine serum albumin [isoelectric point (pI) = 3.9] was chemically altered to provide an albumin with an average pI of 6 (A-6) and another with a pI of 8.5 (A-8). All albumins were of the same size on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A-8 entered the CSF approximately 10-fold better than the native albumin. A-6 was intermediate, entering approximately twofold better. At the time of increased CSF protein concentration during an acute viral encephalitis these differences were narrowed but not eliminated. It is concluded that charge is an important determinant of protein entry into the CSF.
Analytical and Clinical Validation of a Digital Sequencing Panel for Quantitative, Highly Accurate Evaluation of Cell-Free Circulating Tumor DNA (2015)

Next-generation sequencing of cell-free circulating solid tumor DNA addresses two challenges in contemporary cancer care. First this method of massively parallel and deep sequencing enables assessment of a comprehensive panel of genomic targets from a single sample, and second, it obviates the need for repeat invasive tissue biopsies. Digital Sequencing™ is a novel method for high-quality sequencing of circulating tumor DNA simultaneously across a comprehensive panel of over 50 cancer-related genes with a simple blood test. Here we report the analytic and clinical validation of the gene panel. Analytic sensitivity down to 0.1% mutant allele fraction is demonstrated via serial dilution studies of known samples. Near-perfect analytic specificity (> 99.9999%) enables complete coverage of many genes without the false positives typically seen with traditional sequencing assays at mutant allele frequencies or fractions below 5%. We compared digital sequencing of plasma-derived cell-free DNA to tissue-based sequencing on 165 consecutive matched samples from five outside centers in patients with stage III-IV solid tumor cancers. Clinical sensitivity of plasma-derived NGS was 85.0%, comparable to 80.7% sensitivity for tissue. The assay success rate on 1,000 consecutive samples in clinical practice was 99.8%. Digital sequencing of plasma-derived DNA is indicated in advanced cancer patients to prevent repeated invasive biopsies when the initial biopsy is inadequate, unobtainable for genomic testing, or uninformative, or when the patient's cancer has progressed despite treatment. Its clinical utility is derived from reduction in the costs, complications and delays associated with invasive tissue biopsies for genomic testing.
Scribe characterization vehicle test chip for ultra fast product wafer yield monitoring (2006)

Sub 100nm technology nodes face more wafer to wafer and lot to lot variability. 300mm wafer manufacturing also faces larger within wafer spatial trends. Monitoring those issues on a per layer basis as well as correlating them to the product yield is key for significant yield improvements. A novel characterization vehicle/spl reg/ (CV/spl reg/) has been developed, which is being used in the scribe line of product wafers. The scribe CV test chip achieves an extremely efficient placement of defect sensitive test structures by arranging those in all layers underneath probing pads that are implemented in the top metal layer only. Placed next to product chips all scribe CV test chips on a wafer can be tested in less than 10 minutes per 300mm wafer. Data analysis unveils layer specific defect densities and fail rates, spatial wafer trends, excursion wafers, and more.
Synthesis of 4′-C-Ethynyl-β-D-ribo-pentofuranosyl Pyrimidines (1999)

The 4'-C-ethynyl-β-D-ribo-pentofuranosylpyrimidines were prepared from D-glucose through properly protected 4'-C-formyl-D-ribo-ribofuranose as the key intermediate, and preliminary biological tests against some viruses and tumor cells showed that the compounds were not active.
Deficiency in the Nuclear Factor E2-related Factor-2 Transcription Factor Results in Impaired Adipogenesis and Protects against Diet-induced Obesity (2010)

Nuclear factor E2-related factor 2 (Nrf2) is a cap-n-collar basic leucine zipper (CNC-bZIP) transcription factor that is well established as a master regulator of phase II detoxification and antioxidant gene expression and is strongly expressed in tissues involved in xenobiotic metabolism including liver and kidney. Nrf2 is also abundantly expressed in adipose tissue; however, the exact function of Nrf2 in adipocyte biology is unclear. In the current study we show that targeted knock-out of Nrf2 in mice decreases adipose tissue mass, promotes formation of small adipocytes, and protects against weight gain and obesity otherwise induced by a high fat diet. In mouse embryonic fibroblasts, 3T3-L1 cells, and human subcutaneous preadipocytes, selective deficiency of Nrf2 impairs adipocyte differentiation. Deficiency of Nrf2 also leads to decreased expression of peroxisome proliferator-activated receptor gamma (PPARgamma), CCAAT enhancer-binding protein alpha (C/EBPalpha), and their downstream targets during adipocyte differentiation. Conversely, activation of Nrf2 in 3T3-L1 cells by stable knockdown of its negative regulator Keap1 enhances and accelerates hormone-induced adipocyte differentiation. Transfection of Nrf2 stimulates Ppargamma promoter activity, and stable knockdown of Keap1 enhances PPARgamma expression in 3T3-L1 cells. In addition, chromatin immunoprecipitation studies show that Nrf2 associates with consensus binding sites for Nrf2 in the Ppargamma promoter. These findings demonstrate a novel biologic role for Nrf2 beyond its participation in detoxification and antioxidant pathways and place Nrf2 within the limited network of transcription factors that control adipocyte differentiation by regulating expression of PPARgamma.
Site-specific mutagenesis of Drosophila alcohol dehydrogenase: Evidence for involvement of tyrosine-152 and lysine-156 in catalysis (1993)

Amino acid sequence comparisons reveal that tyrosine-152 and lysine-156 of Drosophila alcohol dehydrogenase (ADH) are conserved in homologous dehydrogenases, suggesting that these residues are important in catalysis. To test this hypothesis, we used site-directed mutagenesis to substitute tyrosine-152 with phenylalanine, histidine, or glutamic acid or to substitute lysine-156 with isoleucine. All of these mutants are catalytically inactive. Two mutants were active: A cysteine mutation of tyrosine-152 has 0.25% of wild-type ADH activity, while an arginine substitution of lysine-156 retains 2.2% of wild-type ADH activity. Kinetic analysis shows that the cysteine mutant increases Km(ethanol) 56-fold and Km(propan-2-ol) 100-fold, while Km(NAD) values are essentially unaltered. The arginine mutant also shows the significant enlargement of Km(ethanol), but not of Km(NAD). Furthermore, the cysteine mutant and arginine mutant have different substrate specificity and behave differently on competitive inhibition than wild-type ADH. These results suggest that both tyrosine-152 and lysine-156 have essential roles in catalysis by Drosophila ADH.
The preliminary results of docetaxel-prednisolone combination therapy for the Japanese patients with hormone-refractory prostate cancer. (2007)

Between April 2004 and August 2005, we used docetaxel in combination with prednisolone to treat 14 patients with hormone-refractory prostate cancer (HRPC). Docetaxel was administered at a dose of 70 mg/m2 once every 21 days and oral prednisolone 5 mg was administered twice daily concurrently on days 1-21. The treatment was continued until disease progression or unacceptable adverse events occurred. Prostate specific antigen (PSA) was used as a tumor marker. PSA response was defined as a reduction from baseline of at least 50% that was maintained for 4 weeks. Five patients had measurable soft tissue lesions, which were nodal metastases in 4 and liver metastasis in 1. The median follow-up was 8.4 months. During follow-up, 5 patients died. The median treatment cycle was 7 cycles. Manifestations of hematologic toxicity included 11 patients (78%) with grade 3/4 neutropenia and only I with febrile neutropenia. Two patients with gastric hemorrhage and febrile neutropenia needed hospitalization. During follow-up, 8 patients (57%) achieved a PSA reduction from baseline of at least 50%. Three patients with nodal metastases and 1 patient with liver metastasis had partial response. Combined docetaxel and prednisolone was shown to be effective and feasible in Japanese patients.
The impact of visual contextualization on UI localization (2014)

Translating the text in an interface is a challenging task. Besides the jargon and technical terms, many of the strings are often very short, such as those shown in buttons and pull-down menus. Then, as a result of the lack of visual context in the traditional localization process, an important ambiguity problem arises. We study three approaches to solve this problem: using plain gettext (baseline condition), using gettext plus being able to operate the UI, and translating the UI in-place. We found that translators are substantially faster with plain gettext but commit a significantly higher number of errors in comparison to the other approaches. Unexpectedly, the mixed condition was slower and more error-prone than in-place translation. The latter was found to be comparable to plain gettext in terms of time, although some strings passed unnoticed as the UI was operated. Based on our results, we arrive at a set of recommendations to augment localization tools to improve translator's productivity.
Intraperitoneal Cisplatin and Paclitaxel in Ovarian Cancer (2006)

As compared with intravenous paclitaxel plus cisplatin, intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel improves survival in patients with optimally debulked stage III ovarian cancer.
Mutants of Saccharomyces cerevisiae unresponsive to cell division control by polypeptide mating hormone. (1980)

Temperature-sensitive mutations that produce insensitivity to division arrest by alpha-factor, a mating pheromone, were isolated in an MATa strain of Saccharomyces cerevisiae and shown by complementation studies to difine eight genes. All of these mutations (designated ste) produce sterility at the restrictive temperature in MATa cells, and mutations in seven of the genes produce sterility in MAT alpha cells. In no case was the sterility associated with these mutations coorectible by including wild-type cells of the same mating type in the mating test nor did nay of the mutants inhibit mating of the wild-type cells; the defect appears to be intrinsic to the cell for mutations in each of the genes. Apparently, none of the mutants is defective exclusively in division arrest by alpha-factor, as the sterility of none is suppressed by a temperature-sensitive cdc 28 mutation (the latter imposes division arrest at the correct cell cycle stage for mating). The mutants were examined for features that are inducible in MATa cells by alpha-factor (agglutinin synthesis as well as division arrest) and for the characteristics that constitutively distinguish MATa from MAT alpha cells (a-factor production, alpha-factor destruction). ste2 Mutants are defective specifically in the two inducible properties, whereas ste4, 5, 7, 8, 9, 11, and 12 mutants are defective, to varying degrees, in constitutive as well as inducible aspects. Mutations in ste8 and 9 assume a polar budding pattern unlike either MATa or MAT alpha cells but characteristic of MATa/alpha cells. This study defines seven genes that function in two cell types (MATa and alpha) to control the differentiation of cell type and one gene, ste2, that functions exclusively in MATa cells to mediate responsiveness to polypeptide hormone.
Amortised MAP Inference for Image Super-resolution (2016)

Image super-resolution (SR) is an underdetermined inverse problem, where a large number of plausible high-resolution images can explain the same downsampled image. Most current single image SR methods use empirical risk minimisation, often with a pixel-wise mean squared error (MSE) loss. However, the outputs from such methods tend to be blurry, over-smoothed and generally appear implausible. A more desirable approach would employ Maximum a Posteriori (MAP) inference, preferring solutions that always have a high probability under the image prior, and thus appear more plausible. Direct MAP estimation for SR is non-trivial, as it requires us to build a model for the image prior from samples. Furthermore, MAP inference is often performed via optimisation-based iterative algorithms which don't compare well with the efficiency of neural-network-based alternatives. Here we introduce new methods for amortised MAP inference whereby we calculate the MAP estimate directly using a convolutional neural network. We first introduce a novel neural network architecture that performs a projection to the affine subspace of valid SR solutions ensuring that the high resolution output of the network is always consistent with the low resolution input. We show that, using this architecture, the amortised MAP inference problem reduces to minimising the cross-entropy between two distributions, similar to training generative models. We propose three methods to solve this optimisation problem: (1) Generative Adversarial Networks (GAN) (2) denoiser-guided SR which backpropagates gradient-estimates from denoising to train the network, and (3) a baseline method using a maximum-likelihood-trained image prior. Our experiments show that the GAN based approach performs best on real image data. Lastly, we establish a connection between GANs and amortised variational inference as in e.g. variational autoencoders.
Effect of calcitriol treatment and withdrawal on hyperparathyroidism in haemodialysis patients with hypocalcaemia (2001)

In haemodialysis patients with hypocalcaemia, (i) moderate to severe hyperparathyroidism responded well to treatment with calcitriol, (ii) reductions in maximal PTH were calcitriol dependent while reductions in basal PTH were affected by the ionized calcium and serum phosphate concentrations, (iii) changes in the basal/maximal PTH ratio and the set point of calcium were calcium dependent, and (iv) the delayed rebound in basal PTH levels after withdrawal of calcitriol treatment may have been due to the long duration of treatment and the marked PTH suppression during treatment.
Tetragonal Li10GeP2S12 and Li7GePS8 – exploring the Li ion dynamics in LGPS Li electrolytes (2013)

Tetragonal Li10GeP2S12 (LGPS) is the best solid Li electrolyte reported in the literature. In this study we present the first in-depth study on the structure and Li ion dynamics of this structure type. We prepared two different tetragonal LGPS samples, Li10GeP2S12 and the new compound Li7GePS8. The Li ion dynamics and the structure of these materials were characterized using a multitude of complementary techniques, including impedance spectroscopy, 7Li PFG NMR, 7Li NMR relaxometry, X-ray diffraction, electron diffraction, and 31P MAS NMR. The exceptionally high ionic conductivity of tetragonal LGPS of ∼10−2 S cm−1 is traced back to nearly isotropic Li hopping processes in the bulk lattice of LGPS with EA ≈ 0.22 eV.
Inhibition of protein kinase C μ by various inhibitors. Inhibition from protein kinase c isoenzymes (1996)

Various inhibitors were tested for their potential to suppress the kinase activity of protein kinase C mu (PKC mu) in vitro and in vivo. Among the staurosporine-derived, rather selective PKC inhibitors the indolocarbazole Gö 6976 previously shown to inhibit preferentially cPKC isotypes proved to be a potent inhibitor of PKC mu with an IC50 of 20 nM, whereas the bisindolylmaleimide Gö 6983 was extremely ineffective in suppressing PKC mu kinase activity with a thousand-fold higher IC50 of 20 microM. Other strong inhibitors of PKC mu were the rather unspecific inhibitors staurosporine and K252a. Contrary to the poor inhibition of PKC mu by Gö 6983, this compound was found to suppress in vitro kinase activity of PKC isoenzymes from all three subgroups very effectively with IC50 values from 7 to 60 nM. Thus, Gö 6983 was able to differentiate between PKC mu and other PKC isoenzymes being useful for selective determination of PKC mu kinase activity in the presence of other PKC isoenzymes.
The Signal Peptide Anchors Apolipoprotein M in Plasma Lipoproteins and Prevents Rapid Clearance of Apolipoprotein M from Plasma (2008)

Lipoproteins consist of lipids solubilized by apolipoproteins. The lipid-binding structural motifs of apolipoproteins include amphipathic alpha-helixes and beta-sheets. Plasma apolipoprotein (apo) M lacks an external amphipathic motif but, nevertheless, is exclusively associated with lipoproteins (mainly high density lipoprotein). Uniquely, however, apoM is secreted to plasma without cleavage of its hydrophobic NH(2)-terminal signal peptide. To test whether the signal peptide serves as a lipoprotein anchor for apoM in plasma, we generated mice expressing a mutated apoM(Q22A) cDNA in the liver (apoM(Q22A)-Tg mice (transgenic mice)) and compared them with mice expressing wild-type human apoM (apoM-Tg mice). The substitution of the amino acid glutamine 22 with alanine in apoM(Q22A) results in secretion of human apoM without a signal peptide. The human apoM mRNA level in liver and the amount of human apoM protein secretion from hepatocytes were similar in apoM-Tg and apoM(Q22A)-Tg mice. Nevertheless, human apoM was not detectable in plasma of apoM(Q22A)-Tg mice, whereas it was easily measured in the apoM-Tg mice. To examine the plasma metabolism, recombinant apoM lacking the signal peptide was produced in Escherichia coli and injected into wild-type mice. The apoM without signal peptide did not associate with lipoproteins and was rapidly cleared in the kidney. Accordingly, ligation of the kidney arteries in apoM(Q22A)-Tg mice resulted in rapid accumulation of human apoM in plasma. The data suggest that hydrophobic signal peptide sequences, if preserved upon secretion, can anchor plasma proteins in lipoproteins. In the case of apoM, this mechanism prevents rapid loss by filtration in the kidney.
Reduction of Brochothrix thermosphacta on beef surfaces following immobilization of nisin in calcium alginate gels (1996)

Lean and adipose beef carcass tissues inoculated with Brochothrix thermosphacta (BT) (approx. 4.50 log10 cfu cm-2) were left untreated (U) or treated with 100 micrograms ml-1 nisin (N), calcium alginate (A) or 100 micrograms ml-1 nisin immobilized in a calcium alginate gel (AN). Tissue samples were refrigerated after treatments and bacterial populations and nisin activity were determined at 0, 1, 2 and 7 d. U, A and N treatments of lean and adipose tissues did not suppress bacterial growth ( > 6 log10 cfu cm-2 by day 7) while treatments of lean and adipose tissues with AN suppressed bacteria ( > 2.42 log10 cfu cm-2 by day 7). Bacteriocin titres from both tissues were higher in AN vs N samples after the 7 d incubation. This study demonstrates that immobilization of nisin in a gel may be a more effective delivery system of a bacteriocin to the carcass surface than direct application.
Peptide-Regulated Gene Depletion System Developed for Use in Streptococcus pneumoniae (2011)

To facilitate the study of pneumococcal genes that are essential for viability or normal cell growth, we sought to develop a tightly regulated, titratable gene depletion system that interferes minimally with normal cellular functions. A possible candidate for such a system is the recently discovered signal transduction pathway regulating competence for natural transformation in Streptococcus thermophilus. This pathway, which is unrelated to the ComCDE pathway used for competence regulation in Streptococcus pneumoniae, has not been fully elucidated, but it is known to include a short unmodified signaling peptide, ComS*, an oligopeptide transport system, Ami, and a transcriptional activator, ComR. The transcriptional activator is thought to bind to an inverted repeat sequence termed the ECom box. We introduced the ComR protein and the ECom box into the genome of S. pneumoniae R6 and demonstrated that addition of synthetic ComS* peptide induced the transcription of a luciferase gene inserted downstream of the ECom box. To determine whether the ComRS system could be used for gene depletion studies, the licD1 gene was inserted behind the chromosomally located ECom box promoter by using the Janus cassette. Then, the native versions of licD1 and licD2 were deleted, and the resulting mutant was recovered in the presence of ComS*. Cultivation of the licD1 licD2 double mutant in the absence of ComS* gradually affected its ability to grow and propagate, demonstrating that the ComRS system functions as intended. In the present study, the ComRS system was developed for use in S. pneumoniae. In principle, however, it should work equally well in many other Gram-positive species.