gebhart/patrepeval huggingface dataset:
Heterozygous Screen in Saccharomyces cerevisiae Identifies Dosage-Sensitive Genes That Affect Chromosome Stability (2008)

Current techniques for identifying mutations that convey a small increased cancer risk or those that modify cancer risk in carriers of highly penetrant mutations are limited by the statistical power of epidemiologic studies, which require screening of large populations and candidate genes. To identify dosage-sensitive genes that mediate genomic stability, we performed a genomewide screen in Saccharomyces cerevisiae for heterozygous mutations that increase chromosome instability in a checkpoint-deficient diploid strain. We used two genome stability assays sensitive enough to detect the impact of heterozygous mutations and identified 172 heterozygous gene disruptions that affected chromosome fragment (CF) loss, 45% of which also conferred modest but statistically significant instability of endogenous chromosomes. Analysis of heterozygous deletion of 65 of these genes demonstrated that the majority increased genomic instability in both checkpoint-deficient and wild-type backgrounds. Strains heterozygous for COMA kinetochore complex genes were particularly unstable. Over 50% of the genes identified in this screen have putative human homologs, including CHEK2, ERCC4, and TOPBP1, which are already associated with inherited cancer susceptibility. These findings encourage the incorporation of this orthologous gene list into cancer epidemiology studies and suggest further analysis of heterozygous phenotypes in yeast as models of human disease resulting from haplo-insufficiency.
Acyclovir kinetics after intravenous infusion (1979)

The disposition and safety of the antiviral drug acyclovir were studied in 14 subjects with advanced malignancies. Acyclovir was administered by a 1-hr intravenous infusion at doses of 0.5, 1.0, 2.5, and 5.0 mg/kg. At the end of infusion, mean peak plasma levels (+/- SEM), determined by radioimmunoassay, were 6.4 +/- 0.7, 12.1 +/- 2.3, 14.9 +/- 2.7, and 33.7 +/- 7.1 microM. The plasma concentration-time profiles could be described by a biexponential equation. The half-life of acyclovir in the slow disposition phase ranged from 2.2 to 5 hr and the drug was detected in the plasma for at least 18 hr after infusion. The total body clearance ranged from 117 to 396 ml/min/1.73 m2. A proportionality between area under the curve and dose suggests that acyclovir exhibits dose-independent kinetics in the dose range studied. There was wide variation in cumulative urinary excretion of unchanged drug, ranging from 30 to 69% of the dose. From renal clearances of acyclovir, which were higher than creatinine clearances, it appears that both glomerular filtration and tubular secretion contribute to its renal excretion. Analysis of the urine by reverse-phase high-performance liquid chromatography revealed the presence of the metabolite 9-carboxymethoxymethylguanine. There was no indication of toxicity either clinically or from laboratory findings in any of the study subjects. This study demonstrates that in addition to selectivity and low toxicity, the kinetic profile and metabolic disposition of acyclovir make it an attractive candidate for therapy in a variety of herpes infections.
Effects of daptomycin and vancomycin on tobramycin nephrotoxicity in rats (1990)

Daptomycin is a new biosynthetic antibiotic which belongs to a new class of drugs known as lipopeptides. The objective of this study was to evaluate the effects of daptomycin and vancomycin on tobramycin-induced nephrotoxicity. Female Sprague-Dawley rats were treated during 4 and 10 days with either saline (NaCl, 0.9%) or tobramycin at doses of 4 and 40 mg/kg per day (given every 12 h [q12h] intraperitoneally). Each treatment was combined with saline, daptomycin at a dose of 20 mg/kg per day (given q12h subcutaneously), and ancomycin at a dose of 50 mg/kg per day (given q12h subcutaneously). Daptomycin and vancomycin had no effect on the intracortical accumulation of tobramycin. Daptomycin did not accumulate in renal tissue even after 10 days of treatment. Tobramycin given at a dose of 40 mg/kg per day during 10 days induced a significant inhibition of sphingomyelinase activity in the renal cortex (P less than 0.01) and increased cellular regeneration (P less than 0.01), as measured by the incorporation of [3H]thymidine into DNA of the renal cortex. These changes were minimal when daptomycin was combined with tobramycin. Histologically, signs of tobramycin toxicity were also less severe in the presence of daptomycin. The intracortical accumulation of vancomycin was not modified by tobramycin. The sphingomyelinase activity was significantly more inhibited (P less than 0.01) when vancomycin was associated with tobramycin (4 and 40 mg/kg) without affecting the rate of [3H]thymidine incorporation into DNA. Histologically, signs of tobramycin toxicity were not affected by vancomuycin, but the cellular vacuolizations which were also observed in vancomycin-treated animals were still present in the proximal tubular cells of animals that were treated with the combination vancomycin-tobramycin. This study strongly suggests that daptomycin protects animals from tobramycin-induced nephrotoxicity but that vancomycin may enhance the effect of tobramycin. We conclude that daptomycin is safe and protects kidney cells from tobramycin-induced nephrotoxicity.
Detection of three common translocation breakpoints in non‐Hodgkin's lymphomas by fluorescence in situ hybridization on routine paraffin‐embedded tissue sections (2002)

Non-random chromosomal translocations are specifically involved in the pathogenesis of many non-Hodgkin's lymphomas and have clinical implications as diagnostic and/or prognostic markers. Their detection is often impaired by technical problems, including the distribution of the breakpoints over large genomic areas. This study reports a fluorescence in situ hybridization (FISH) method which allows the detection of specific chromosomal breakpoints in tissue sections from routinely fixed, paraffin-embedded samples. Hybridization was performed after demasking the DNA. Previously validated locus-specific probes (cosmids, PACs) flanking the BCL1, BCL2 regions and similar new probes for the MYC breakpoint region were used. The cases studied were five mantle cell lymphomas (MCL) and five follicular lymphomas (FL), selected on the basis of a previously proved t(11;14) and t(14;18) and five randomly chosen Burkitt's lymphomas (BL), as well as 21 negative control samples. In all samples, hybridization signals of sufficient intensity were obtained. Three different algorithms were used to score the hybridization signals in tissue sections, two of them taking into account the nuclei and their signal distribution indicative of chromosomal break, and one only considering the colocalization or segregation of the signals. In control tissues, these algorithms resulted in cut-off levels of 9.1%, 1.3%, or 10.0%. In the 15 lymphoma samples the percentages of abnormal cells/signals ranged from 28% to 80%, 13% to 49%, and 40% to 70%, respectively. The results indicate that small locus-specific probes can be used in FISH for regular detection of translocation breakpoints on routine paraffin tissue sections.
The curvature-velocity method for local obstacle avoidance (2002)

We present a new method for local obstacle avoidance by indoor mobile robots that formulates the problem as one of constrained optimization in velocity space. Constraints that stem from physical limitations (velocities and accelerations) and the environment (the configuration of obstacles) are placed on the translational and rotational velocities of the robot. The robot chooses velocity commands that satisfy all the constraints and maximize an objective function that trades off speed, safety and goal-directedness. An efficient, real-time implementation of the method has been extensively tested, demonstrating reliable, smooth and speedy navigation in office environments. The obstacle avoidance method is used as the basis of more sophisticated navigation behaviors, ranging from simple wandering to map-based navigation.
Cationic antimicrobial peptides as novel cytotoxic agents for cancer treatment (2006)

Cancer treatment by conventional chemotherapy is hindered by toxic side effects and the frequent development of multi-drug resistance by cancer cells. Cationic antimicrobial peptides (CAPs) are a promising new class of natural-source drugs that may avoid the shortcomings of conventional chemotherapy because certain CAPs exhibit selective cytotoxicity against a broad spectrum of human cancer cells, including neoplastic cells that have acquired a multi-drug-resistant phenotype. Tumour cell killing by CAPs is usually by a cell membrane-lytic effect, although some CAPs can trigger apoptosis in cancer cells via mitochondrial membrane disruption. Furthermore, certain CAPs are potent inhibitors of blood vessel development (angiogenesis) that is associated with tumour progression. This article reviews the mechanisms by which CAPs exert anticancer activity and discusses the potential application of selected CAPs as therapeutic agents for the treatment of human cancers.
A semi-strong form evaluation of the efficiency of the wheat futures market. (1988)

Futures market efficiency is of concern to both market participants and non-participants. The practical problem is that inefficient futures markets can lead to resource allocation problems. The specific objective of this study is to perform a Fama (1970) semi-strong efficiency test on the Chicago Board of Trade's wheat futures market. In this study, three wheat price prediction models are used as a standard with which to compare, on the basis of root mean squared error and bias, the futures market. One of the models, an autoregressive integrated moving average model, succeeded in obtaining a semi-strong efficiency rejection. Returns from speculating with the autoregressive integrated moving average model are then examined to see if the incremental returns are sufficiently large to cover all costs of speculating. A 19.5 percent after cost return was generated by simulating speculation with this model. Since a risk premium is expected when using unproven methods to forecast price, it was not determined whether this return is large enough to compensate for the risks involved. The results of this study indicate that there exists a possibility that the Chicago Board of Trade's wheat futures market is not allocating resources efficiently, at least for the time frame examined and efficiency definition chosen. As to whether this detected inefficiency is just an anomaly caused by the time frame examined, efficiency definition chosen, or the examination method, little can be said. The results of this test are only strictly interpreted relative to the particular definition of efficiency and time period chosen, and are not used to infer that the futures market can be replaced by a "more efficient" marketing tool.
Assessment of clinical sepsis-associated biomarkers in a septic mouse model (2018)

Objective Clinical sepsis-associated biomarkers were utilized in a cecal ligation and puncture (CLP) septic mouse model to provide a reference for investigating pathophysiological mechanisms and evaluating novel therapeutic interventions for sepsis. Methods Sepsis in mice was induced by CLP, and clinical biomarkers were evaluated (survival rate, blood physiological and biochemical indices, cytokines, hepatorenal function parameters, and blood coagulation). Results The mortality rate was >70%. The body temperature, blood pressure, and heart rate decreased within 48 h. Low lactic acid was found at 8 h. The CLP mice showed typical inflammatory symptoms with decreased white blood cells and procalcitonin and increased levels of soluble triggering receptor expressed on myeloid cells-1, interleukin (IL)-6, IL-10, tumor necrosis factor-α, macrophage inflammatory protein (MIP)-1α, MIP-1β, and MIP-2. The platelet count and activated partial thromboplastin time significantly decreased, and the prothrombin time and prothrombin time-international normalized ratio markedly increased. Phenotypes of multiple organ dysfunction were found in the CLP model, including increased liver alanine aminotransferase and aspartate transaminase; significantly reduced total protein, globulin, and serum albumin; increased blood urea nitrogen and creatinine; and decreased blood glucose. Conclusion The clinical features of the CLP mouse model were similar to those of human patients with sepsis.
Resampling Methods: A Practical Guide to Data Analysis (2000)

The goal of this book is to introduce statistical methodology-estimation, hypothesis, testing and classification-to a wide applied audience through resampling from existing data via the bootstrap, and estimation or cross-validation methods. The book provides an accessible introduction and practical guide to the power, simplicity and veritability of the bootstrap, cross-validation and permutation tests. Industrial statistical consultants, professionals and researchers will find the book's methods and software imimediately helpful. (unvollstandig)) This Second edition is a practical guide to data analysis using the bootstrap, cross-validation, and permutation tests. It is an essential resource for industrial statisticians, statistical consultants, and research professionals in science, engineering, and technology. Only requiring minimal mathematics beyond algebra, it provides a table-free introduction to data analysis utilizing numerous exercizes, practical data sets, and freely available statistical shareware. Topics and features: *Thoroughly revised text features more practical examples plus an additional chapter devoted to regression and data mining techniques and their limitations *Uses resampling approach to introduction statistics *A Practical presentation that covers all three sampling methods - bootstrap, density-estimation, and permutations *Includes systematic guide to help one select correct procedure for a particular application *Detailed coverage of all three statistical methodologies - classification, estimation, and hypothesis testing *Suitable for classroom use and individual, self-study purposes *Numerous practical examples using popular computer programs such as SAS, Stata, and StatXact *Useful appendices with computer programs and code to develop own methods *Downloadable freeware from author's website: http://users.oco.net/drphilgood/resamp.htm With its accessable style and intuitive topic development, the book is an excellent basic resource and guide to the power, simplicity and versatility of bootstrap, cross-validation and permutation tests. Students, professionals, and researchers will find it a particularly useful guide to modern resampling methods and their applications.
Isolation and Characterization of Bacillus Cereus from Various Sources (1991)

セレウス菌(Bacillus cereus)の分離を,食品,香辛料,動物および土壌の計1,675検体について試み,820株を得た。それらの菌株について各種生物学的性状を調べたところ,セロビオース,サリシン,スクロースからの酸産生能およびエスクリンの加水分解能の4種の性状に基づいて16の生物型を設定することができた。820株の分離菌と2株の食中毒由来株について,本法による生物型別を行ったところ,14種の生物型に細分され,由来によって優勢する生物型もみられた。
Simultaneous determination of proteins using an element-tagged immunoassay coupled with ICP-MS detection (2002)

We report a novel method that suggests that multiple proteins can be quantified simultaneously in complex biological samples. The use of distinguishable element-tagged antibodies allows discriminant detection with an Inductively Coupled Plasma Mass Spectrometer (ICP-MS), providing a sensitive and accurate means of determining the concentrations of specific proteins in complex mixtures. It is demonstrated that this method can be used to detect the levels of at least two target proteins at the same time, yielding a linear response to both proteins in a concentration range of 2–100 ng mL−1 using a sample size of 0.5 mL.
Fine organization of Bombyx mori fibroin heavy chain gene (2000)

The complete sequence of the Bombyx mori fibroin gene has been determined by means of combining a shotgun sequencing strategy with physical map-based sequencing procedures. It consists of two exons (67 and 15 750 bp, respectively) and one intron (971 bp). The fibroin coding sequence presents a spectacular organization, with a highly repetitive and G-rich (approximately 45%) core flanked by non-repetitive 5' and 3' ends. This repetitive core is composed of alternate arrays of 12 repetitive and 11 amorphous domains. The sequences of the amorphous domains are evolutionarily conserved and the repetitive domains differ from each other in length by a variety of tandem repeats of subdomains of approximately 208 bp which are reminiscent of the repetitive nucleosome organization. A typical composition of a subdomain is a cluster of repetitive units, Ua, followed by a cluster of units, Ub, (with a Ua:Ub ratio of 2:1) flanked by conserved boundary elements at the 3' end. Moreover some repeats are also perfectly conserved at the peptide level indicating that the evolutionary pressure is not identical along the sequence. A tentative model for the constitution and evolution of this unusual gene is discussed.
Molecular analysis of the pathophysiological binding of the platelet aggregation‐inducing factor podoplanin to the C‐type lectin‐like receptor CLEC‐2 (2007)

The mucin-type sialoglycoprotein podoplanin (aggrus) is involved in tumor cell-induced platelet aggregation and tumor metastasis. C-type lectin-like receptor-2 (CLEC-2) was recently identified as an endogenous receptor of podoplanin on platelets. However, the pathophysiological importance and function of CLEC-2 have not been elucidated. Here we clarified the pathophysiological interaction between podoplanin and CLEC-2 in vitro and in vivo. Using several deletion mutants of CLEC-2 expressed as Fc chimeras, we first identified an important podoplanin-recognition domain in CLEC-2. Furthermore, the podoplanin-CLEC-2 interaction was confirmed using several deletion mutants of podoplanin expressed as Fc chimeras. Not only the disialyl-core1-attached glycopeptide but also the stereostructure of the podoplanin protein was found to be critical for the CLEC-2-binding activity of podoplanin. We next synthesized various glycopeptides of podoplanin that included both the platelet aggregation-stimulating domain and O-glycan on Thr52. Interestingly, a disialyl-core1-attached glycopeptide was recognized specifically by CLEC-2. Moreover, the anti-podoplanin monoclonal antibody NZ-1 suppressed both the podoplanin-CLEC-2 interaction and podoplanin-induced pulmonary metastasis, suggesting that CLEC-2 is the first pathophysiological receptor of podoplanin to be identified. In summary, we clarified the molecular interaction in vitro and in vivo between a platelet aggregation-inducing factor, podoplanin, and its specific pathophysiological receptor on platelets, CLEC-2. Podoplanin and CLEC-2 might represent promising therapeutic targets in cancer metastasis.
Studies on Antiinflammatory Agents. II. Synthesis and Pharmacological Properties of 2'-(Phenylthio)methanesulfonanilides and Related Derivatives. (1993)

The structure of the previously reported new antiinflammatory agent (1, FK3311) was chemically modified in an attempt to find novel compounds with more potent and broader-spectrum activities. Some 2'-(phenylthio) and 2'-(phenylamino)methanesulfonanilides (2 and 3), in particular those bearing an electron-attracting substituent at the 4'-position, potently inhibited adjuvant arthritis in rats as well as collagen-induced arthritis in mice when administered orally. 4'-Carbamoyl-2'-(2,4-difluorophenylthio)methanesulfonanilide (3b), which was selected as a candidate for further development from among the compounds synthesized herein, exhibited activity in reducing arthritis in a spontaneous autoimmune disease model (MRL/lpr mice) within the dose range of 10-100 mg/kg (p.o.).
Ultra-wideband optical amplification with 3 dB bandwidthof 65 nm using a gain-equalised two-stage erbium-doped fibre amplifier and Ramanamplification (1997)

A 3 dB gain-reduction bandwidth up to 65 nm (1549–1614 nm) is achieved using a two-stage erbium-doped fibre amplifier, together with an intermediate equaliser and Raman amplification in the transmission fibre.
Cooperative, Heparan Sulfate‐Dependent Cellular Uptake of Dimeric Guanidinoglycosides (2010)

Oligoarginine and guanidinium-rich molecular transporters have been shown to facilitate the intracellular delivery of a diverse range of biologically relevant cargos. Several such transporters have been suggested to interact with cell-surface heparan sulfate proteoglycans as part of their cell-entry pathway. Unlike for other guanidinium-rich transporters, the cellular uptake of guanidinoglycosides at nanomolar concentrations is exclusively heparan sulfate dependent. As distinct cells differ in their expression levels and/or the composition of cell-surface heparan sulfate proteoglycans, one might be able to exploit such differences to selectively target certain cell types. To systematically investigate the nature of their cell-surface interactions, monomeric and dimeric guanidinoglycosides were synthesized by using neomycin, paromomycin, and tobramycin as scaffolds. These transporters differ in the number and 3D arrangement of their guanidinium groups. Their cellular uptake was measured by flow cytometry in wild-type and mutant Chinese hamster ovary cells after the corresponding fluorescent streptavidin-phycoerythrin-Cy5 conjugates had been generated. All derivatives showed negligible uptake in mutant cells lacking heparan sulfate. Decreasing the number of guanidinium groups diminished uptake, but the three dimensional arrangement of these groups was less important for cellular delivery. Whereas conjugates prepared with the monomeric carriers showed significantly reduced uptake in mutant cells expressing heparan sulfate chains with altered patterns of sulfation, conjugates prepared with the dimeric guanidinoglycosides could overcome this deficiency and maintain high levels of uptake in such deficient cells. This finding suggests that cellular uptake depends on the valency of the transporter and both the content and arrangement of the sulfate groups on the cell-surface receptors. Competition studies with chemically desulfated or carboxy-reduced heparin derivatives corroborated these observations. Taken together, these findings show that increasing the valency of the transporters retains heparan sulfate specificity and provides reagents that could distinguish different cell types based on the specific composition of their cell-surface heparan sulfate proteoglycans.
Stable-isotope studies of glutamate catabolism in Fusobacterium nucleatum. (1995)

Catabolism of glutamate was investigated in Fusobacterium nucleatum, an anaerobic micro-organism that is strongly implicated in periodontal disease. The distribution of labels in acetate and butyrate derived from [13C]glutamates was determined by NMR spectroscopy and MS. The label from L-[5-13C]glutamate was not incorporated, whereas C-1 of acetate and butyrate were efficiently labelled by L-[1-13C]glutamate; these results indicated that the hydroxyglutarate pathway predominated. In butyrate, enrichment at C-3 was smaller than C-1; that this was not due to participation of the methylaspartate pathway was demonstrated by the incorporation of label from L-[4-13C]glutamate into only C-2 of acetate and C-4 (major)/C-2 (minor) of butyrate. The presence of label at a second site in butyrate was attributed to the synthesis of butyrate from acetate and verified by the incorporation of label from [1,2-13C2]- and [2H3]-acetate.