gebhart/patrepeval huggingface dataset:
An information retrieval approach to concept location in source code (2005)

Concept location identifies parts of a software system that implement a specific concept that originates from the problem or the solution domain. Concept location is a very common software engineering activity that directly supports software maintenance and evolution tasks such as incremental change and reverse engineering. This work addresses the problem of concept location using an advanced information retrieval method, Latent Semantic Indexing (LSI). LSI is used to map concepts expressed in natural language by the programmer to the relevant parts of the source code. Results of a case study on NCSA Mosaic are presented and compared with previously published results of other static methods for concept location.
Using affinity chromatography to engineer and characterize pH‐dependent protein switches (2008)

Conformational changes play important roles in the regulation of many enzymatic reactions. Specific motions of side chains, secondary structures, or entire protein domains facilitate the precise control of substrate selection, binding, and catalysis. Likewise, the engineering of allostery into proteins is envisioned to enable unprecedented control of chemical reactions and molecular assembly processes. We here study the structural effects of engineered ionizable residues in the core of the glutathione-S-transferase to convert this protein into a pH-dependent allosteric protein. The underlying rational of these substitutions is that in the neutral state, an uncharged residue is compatible with the hydrophobic environment. In the charged state, however, the residue will invoke unfavorable interactions, which are likely to induce conformational changes that will affect the function of the enzyme. To test this hypothesis, we have engineered a single aspartate, cysteine, or histidine residue at a distance from the active site into the protein. All of the mutations exhibit a dramatic effect on the protein's affinity to bind glutathione. Whereas the aspartate or histidine mutations result in permanently nonbinding or binding versions of the protein, respectively, mutant GST50C exhibits distinct pH-dependent GSH-binding affinity. The crystal structures of the mutant protein GST50C under ionizing and nonionizing conditions reveal the recruitment of water molecules into the hydrophobic core to produce conformational changes that influence the protein's active site. The methodology described here to create and characterize engineered allosteric proteins through affinity chromatography may lead to a general approach to engineer effector-specific allostery into a protein structure.
A cannabinoid agonist, WIN 55,212-2, reduces neuropathic nociception induced by paclitaxel in rats (2005)

Paclitaxel is an effective antineoplastic drug treatment used as an anti-tumoral therapy. Unfortunately its use is associated with unwanted side effects, which include the development of peripheral neuropathies and neuropathic pain, greatly affecting the quality of life of patients. It is well known that agonists of the cannabinoid receptor are able to reduce hyperalgesia and allodynia that develop after nerve injury. Our aim was to evaluate the efficacy of the cannabinoid agonist WIN 55,212-2 to reduce the thermal hyperalgesia and the tactile allodynia induced by administration of paclitaxel in rats. Present results demonstrate that WIN 55,212-2 (1 mg/kg i.p.) significantly reduced the heat (P<0.0001) and the mechanical (P=0.0003) withdrawal thresholds, the dose being smaller than that required to reach similar effects in the sciatic nerve constriction model (1.5 mg/kg). When the cannabinoid tetrad test was evaluated to measure behavioral modifications, it was found that WIN 55,212-2 (1mg/kg) did not induce changes either in body temperature or in immobility time, and only a reduction in spontaneous motility was recorded. This effect was antagonized by SR 141716A, suggesting the involvement of the CB1 receptor, although the participation of CB2 receptors cannot be excluded from this study. When WIN 55,212-2 was administered intraplantar, no differences were observed between the injected paw and the contralateral paw, suggesting that systemic mechanisms are needed to reach effectiveness. From these results we suggest that cannabinoids may be an interesting alternative to reduce neuropathic symptoms induced by paclitaxel, however more work is required to assess this possibility.
An Experimental Study on the Effect of Oil Viscosity and Wear-Ring Clearance on the Performance of an Industrial Centrifugal Pump (2012)

The clearance of wear-rings in the impeller of centrifugal pumps has an important influence on the pump’s performance. Unfortunately, this effect has not been quite well documented, especially for the centrifugal pumps handling viscous oils. An industrial centrifugal pump with low specific speed was employed as a model to investigate the effect of the clearance on the performance of the pump. In this experimental study, the clearances of the wear-rings on the impeller shroud and hub were enlarged; the performances of the pump were measured when it pumped water and the viscous oils. The performance curves, the hydraulic parameters, and their relative variation ratios at best efficiency points were examined carefully for different clearances at various viscosities. The results showed that the flow rate is varied relatively in a range of −6% − +5%, the head −10% − +6%, the shaft-power + 2% −+8% and the efficiency −19% − +2%, respectively, when the clearance was enlarged from 0.25 mm to 0.85 mm at best efficiency points. The clearance of wear-rings on shroud has a more significant influence on the performance than on the hub. However, such an effect is weakened with increasing viscosity.
Human stearoyl-CoA desaturase: alternative transcripts generated from a single gene by usage of tandem polyadenylation sites (1999)

A critical step in the synthesis of unsaturated fatty acids is catalysed by stearoyl-CoA desaturase (Scd). To determine the regulation of human Scd, we characterized the gene and its transcripts. Screening a human keratinocyte cDNA library and analysis of 3'-RACE (rapid amplification of cDNA ends) products from various tissues yielded a 5.2 kb cDNA encoding a 359 amino acid protein with a calculated molecular mass of 41.5 kDa. Analysis of 3'-RACE products suggested that alternative usage of polyadenylation sites generates two transcripts of 3.9 and 5.2 kb, a result consistent with Northern analysis. Southern analysis demonstrated the existance of two SCD loci in the human genome. Chromosomal mapping localized one locus to chromosome 10, and the second locus to chromosome 17. Characterization of genomic clones isolated from chromosome-specific libraries revealed that only the locus on chromosome 10 contained introns. Sequence analysis of the intron-less locus displayed multiple nucleotide insertions and deletions, as well as in-frame stop codons. Reverse transcriptase-PCR analysis performed with primers specific to the intron-less locus failed to produce a PCR product from brain, liver and skin RNA, indicating that the locus on chromosome 17 is most likely a transcriptionally inactive, fully processed pseudogene. These results suggest strongly that there is one structural SCD gene in the human genome, and that it generates two transcripts by use of alternative polyadenyation sites. Although the primary sequence and intron-exon structure of SCD is phylogenetically conserved, divergence between rodent and human is seen in the number of SCD genes and in the generation of alternative transcripts, suggesting a species-specific component of SCD regulation and function.
Evaluating the performance of Affymetrix SNP Array 6.0 platform with 400 Japanese individuals (2008)

Our results confirmed that the SNP Array 6.0 platform reached the level reported by the manufacturer, and thus genome-wide association studies using the SNP Array 6.0 platform have considerable potential to identify candidate susceptibility or resistance genetic factors for multifactorial diseases in the Japanese population, as well as in other populations.
Carrier detection and prenatal diagnosis in Duchenne and Becker muscular dystrophy families, using dinucleotide repeat polymorphisms. (1991)

To improve carrier detection and prenatal diagnosis for Duchenne and Becker muscular dystrophy families, we determined allele frequencies and measures of variation for four (dC-dA)n.(dG-dT)n loci identified within a deletion-prone region of the human dystrophin gene. The loci are highly polymorphic, with predicted heterozygosities of 71.6%-93.3%. Direct DNA sequence analysis of the (dC-dA)n.(dG-dT)n locus in intron 49 revealed an additional length polymorphism which varies by single-basepair increments, is adjacent to the dinucleotide repeat block, and enhances the polymorphic content of this marker. The four (dC-dA)n.(dG-dT)n loci are each easily amplified by PCR in two diplex reactions. The variability of allele lengths at these loci makes them ideal for carrier detection and prenatal diagnosis, often providing diagnostic information when RFLP analysis is uninformative. These markers have aided in identification of deletion mutations, exclusion of maternal cell contamination of chorionic villus samples, confirmation of paternity, and mapping of gene recombinations. The allele identification of these loci can be performed either with a radiolabel or with an automated, nonradioactive, fluorescent gel detection system.
The Linkage of Molecular Markers to a Gene Controlling the Symptom Response in Maize to Maize Dwarf Mosaic Virus (1989)

L'analyse du polymorphisme de longueur des fragments de restriction, a confirme la presence d'un gene implique dans la resistance au virus de la mosaique nanisante du mais (MDMV), sur le chromosome 6 de la lignee consanguine Pa405, pres du centromere et determine l'effet de ce gene sur le developpement des symptomes induits par MDMV
Computational Estimation and Experimental Verification of Off-Target Silencing during Posttranscriptional Gene Silencing in Plants (2006)

Successful application of posttranscriptional gene silencing (PTGS) for gene function study in both plants and animals depends on high target specificity and silencing efficiency. By computational analysis with genome and/or transcriptome sequences of 25 plant species, we predicted that about 50% to 70% of gene transcripts in plants have potential off-targets when used for PTGS that could obscure experimental results. We have developed a publicly available Web-based computational tool called siRNA Scan to identify potential off-targets during PTGS. Some of the potential off-targets obtained from this tool were tested by measuring the amount of off-target transcripts using quantitative reverse transcription-PCR. Up to 50% of the predicted off-target genes tested in plants were actually silenced when tested experimentally. Our results suggest that a high risk of off-target gene silencing exists during PTGS in plants. Our siRNA Scan tool is useful to design better constructs for PTGS by minimizing off-target gene silencing in both plants and animals.
CMOS-integrated high-speed MSM germanium waveguide photodetector (2010)

A compact waveguide-integrated Germanium-on-insulator (GOI) photodetector with 10 +/- 2fF capacitance and operating at 40Gbps is demonstrated. Monolithic integration of thin single-crystalline Ge into front-end CMOS stack was achieved by rapid melt growth during source-drain implant activation anneal.
Mobile Interfaces: Liquids as a Perfect Structural Material for Multifunctional, Antifouling Surfaces (2013)

Life creates some of its most robust, extreme surface materials not from solids but from liquids: a purely liquid interface, stabilized by underlying nanotexture, makes carnivorous plant leaves ultraslippery, the eye optically perfect and dirt-resistant, our knees lubricated and pressure-tolerant, and insect feet reversibly adhesive and shape-adaptive. Novel liquid surfaces based on this idea have recently been shown to display unprecedented omniphobic, self-healing, anti-ice, antifouling, optical, and adaptive properties. In this Perspective, we present a framework and a path forward for developing and designing such liquid surfaces into sophisticated, versatile multifunctional materials. Drawing on concepts from solid materials design and fluid dynamics, we outline how the continuous dynamics, responsiveness, and multiscale patternability of a liquid surface layer can be harnessed to create a wide range of unique, active interfacial functions—able to operate in harsh, changing environments—not achievable with static solids. We discuss how, in partnership with the underlying substrate, the liquid surface can be programmed to adaptively and reversibly reconfigure from a defect-free, molecularly smooth, transparent interface through a range of finely tuned liquid topographies in response to environmental stimuli. With nearly unlimited design possibilities and unmatched interfacial properties, liquid materials—as long-term stable interfaces yet in their fully liquid state—may potentially transform surface design everywhere from medicine to architecture to energy infrastructure.
Induced hypothermia after out-of-hospital cardiac arrest: one hospital’s experience (2009)

We found that induced hypothermia can be incorporated into routine care of patients admitted to an ICU after OHCA. For patients with an initial rhythm of VF or uVT, this seems to have significantly improved hospital survival and neurological outcome. We also found that rapid infusion of cold intravenous fluids was effective for inducing hypothermia.
Dynamics of porcine circovirus type 2 infection in a herd of pigs with postweaning multisystemic wasting syndrome (2002)

Infection with PCV2 coincided with severe clinical signs; however, infected 28-week-old pigs did not have evidence of disease. Immunity declined over time in young pigs. A long duration of PCV2 viremia was apparent in a high percentage of infected pigs, which may affect transmission and persistence of the virus in a herd.
Human Immunodeficiency Virus Type 1 Protease Inhibitors: Evaluation of Resistance Engendered by Amino Acid Substitutions in the Enzyme's Substrate Binding Site (1994)

The human immunodeficiency virus type 1 (HIV-1) protease is a homodimeric aspartyl endopeptidase that is required for virus replication. A number of specific, active-site inhibitors for this enzyme have been described. Many of the inhibitors exhibit significant differences in activity against the HIV-1 and HIV type 2 (HIV-2) enzymes. An initial study was conducted to ascertain the HIV-1 protease's potential to lose sensitivity to several test inhibitors while retaining full enzymatic activity. The substrate binding sites of the HIV-1 and HIV-2 enzymes are almost fully conserved, except for four amino acid residues at positions 32, 47, 76, and 82. Accordingly, recombinant mutant type 1 proteases were constructed that contained the cognate type 2 residue at each of these four positions. The substitution at position 32 resulted in a significant adverse effect on inhibitor potency. However, this substitution also mediated a noted increase in the Km of the substrate. Individual substitutions at the remaining three positions, as well as a combination of all four substitutions, had very little effect on enzyme activity or inhibitor susceptibility. Hence, the four studied active site residues are insufficient to be responsible for differences in inhibitor sensitivity between the HIV-1 and HIV-2 proteases and are unlikely to contribute to the generation of inhibitor-resistant mutant HIV-1 protease.
Ultrasound guided site specific gene delivery system using adenoviral vectors and commercial ultrasound contrast agents (2006)

We have evaluated if ultrasound imaging (US) and various commercially available contrast microbubbles can serve as a non-invasive systemically administered delivery vehicle for site-specific adenoviral-mediated gene transfer in vitro and in vivo. The contrast agents were tested for their ability to enclose and to protect an adenoviral vector carrying the GFP marker gene (Ad-GFP) into the microbubbles. We have also evaluated the ability of the innate immune system to inactivate free adenoviruses as well as unenclosed viruses adsorbed on the surface of the contrast agents and in turn the ability of the microbubbles to enclose and to protect the viral vectors from such agents. In vitro as well as in vivo, innate components of the immune system were able to serve as inactivating agents to clear free viral particles and unenclosed adenoviruses adsorbed on the microbubbles' surface. Systemic delivery of Ad-GFP enclosed into microbubbles in the tail vein of nude mice resulted in specific targeting of the GFP transgene. Both fluorescence microscopy and GFP immunohistochemistry demonstrated US guided specific transduction in the targeted cells only, with no uptake in either heart, lungs or liver using complement-pretreated Ad-GFP microbubbles. This approach enhances target specificity of US microbubble destruction as a delivery vehicle for viral-mediated gene transfer.
Conformational and Temperature-sensitive Stability Defects of the ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator in Post-endoplasmic Reticulum Compartments (2001)

Deletion of phenylalanine at position 508 (DeltaF508) is the most common cystic fibrosis (CF)-associated mutation in the CF transmembrane conductance regulator (CFTR), a cAMP-regulated chloride channel. The consensus notion is that DeltaF508 imposes a temperature-sensitive folding defect and targets newly synthesized CFTR for degradation at endoplasmic reticulum (ER). A limited amount of CFTR activity, however, appears at the cell surface in the epithelia of homozygous DeltaF508 CFTR mice and patients, suggesting that the ER retention is not absolute in native tissues. To further elucidate the reasons behind the inability of DeltaF508 CFTR to accumulate at the plasma membrane, its stability was determined subsequent to escape from the ER, induced by reduced temperature and glycerol. Biochemical and functional measurements show that rescued DeltaF508 CFTR has a temperature-sensitive stability defect in post-ER compartments, including the cell surface. The more than 4-20-fold accelerated degradation rate between 37 and 40 degrees C is, most likely, due to decreased conformational stability of the rescued DeltaF508 CFTR, demonstrated by in situ protease susceptibility and SDS-resistant thermoaggregation assays. We propose that the decreased stability of the spontaneously or pharmacologically rescued mutant may contribute to its inability to accumulate at the cell surface. Thus, therapeutic efforts to correct the folding defect should be combined with stabilization of the native DeltaF508 CFTR.
Bone marrow stromal fibroblasts secrete interleukin-6 and granulocyte- macrophage colony-stimulating factor in the absence of inflammatory stimulation: demonstration by serum-free bioassay, enzyme-linked immunosorbent assay, and reverse transcriptase polymerase chain reaction (1992)

Bone marrow (BM) stromal fibroblasts produce hematopoietic growth factors (HGFs) in response to inflammatory mediators such as tumor necrosis factor-alpha or interleukin-1 alpha (IL-1 alpha). In the absence of such inflammatory stimuli, production of HGFs by BM stromal cells has been problematic and controversial. In vivo, however, basal hematopoiesis maintains blood counts within a normal homeostatic range even in the absence of inflammation, and HGFs are required for progenitor cell differentiation in vitro. To better ascertain the contribution of BM stromal fibroblasts to basal hematopoiesis, we therefore studied HGF production in quiescent BM stromal fibroblasts by three sensitive assays: serum-free bioassay, enzyme-linked immunosorbent assay, and reverse transcriptase polymerase chain reaction. Stromal fibroblasts were cultured in the presence or absence of normal human serum to determine if serum factor(s) present in the noninflammatory (basal) state induce secretion of HGFs. Human serum was found to induce or enhance transcription and secretion of granulocyte- macrophage colony-stimulating factor (GM-CSF) and enhance secretion of constitutively expressed IL-6. In contrast, no secretion of either granulocyte-CSF (G-CSF) or IL-3 was found. These data indicate that factors in normal human serum are active in enhancing GM-CSF and IL-6 production by stromal fibroblasts and suggest that these growth factors contribute to the maintainance of normal, basal hematopoiesis in vivo.
Antineoplastic agents. 166. Isolation, structure, and synthesis of combretastatin C-1 (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAntineoplastic agents. 166. Isolation, structure, and synthesis of combretastatin C-1Sheo Bux Singh and George R. PettitCite this: J. Org. Chem. 1989, 54, 17, 4105–4114Publication Date (Print):August 1, 1989Publication History Published online1 May 2002Published inissue 1 August 1989https://pubs.acs.org/doi/10.1021/jo00278a023https://doi.org/10.1021/jo00278a023research-articleACS PublicationsRequest reuse permissionsArticle Views760Altmetric-Citations29LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Supportive care in marrow transplantation (1992)

Marrow transplantation is now an accepted form of therapy for patients with aplastic anemia, genetic diseases, and a variety of malignant diseases. Intensive chemotherapy and radiotherapy regimens are necessary to eradicate cancer cells and allow engraftment of the transplanted marrow. Patients undergoing such treatment suffer prolonged marrow aplasia and immunosuppression and experience significant nonmarrow toxicities. This requires maximum supportive care including hyperalimentation, fluid and blood transfusions, antibacterial and antiviral prophylaxis, and measures to reduce organ toxicities and accelerate engraftment. The use of drugs to suppress the production of antitumor necrosis factor-alpha has shown promise in reducing the nonmarrow toxicities of the conditioning regimen. Prophylactic antibiotics that reduce gastrointestinal colonization with aerobic bacteria yet preserve anaerobic flora may more effectively reduce not only systemic bacteria but fungal infections as well. The impact of infections due to cytomegalovirus has been reduced by more effective prevention in patients who are cytomegalovirus negative and reactivation in patients who are cytomegalovirus positive. The use of recombinant growth factors will significantly reduce morbidity after transplantation by reducing the period of marrow aplasia.