gebhart/patrepeval huggingface dataset:
Application of a new approach for the quantitation of drug synergism to the combination of cis-diamminedichloroplatinum and 1-beta-D-arabinofuranosylcytosine. (1990)

This report describes the application of a new approach, the universal response surface approach, to the quantitative assessment of drug interaction, i.e., the determination of synergism, antagonism, additivity, potentiation, inhibition, and coalitive action. The specific drug combination and experimental growth system for this introductory application was that of 1-beta-D-arabinofuranosylcytosine (ara-C) and cisplatin with simultaneous drug exposure (1, 3, 6, 12, or 48 h) against L1210 leukemia in vitro. To quantitate the type and degree of drug interaction, a model was fitted using nonlinear regression to the data from each separate experiment, and parameters were estimated (K. C. Syracuse and W. R. Greco, Proc. Biopharm. Sect. Am. Stat. Assoc., 127-132, 1986). The parameters included the maximum cell density over background in absence of drug, the background cell density in presence of infinite drug, the 50% inhibitory concentrations and concentration-effect slopes for each drug, and a synergism-antagonism parameter, alpha. A positive alpha indicates synergism, a negative alpha, antagonism, and a zero alpha, additivity. Maximal synergy was found with a 3-h exposure of ara-C + cisplatin, with alpha = 3.08 +/- 0.96 (SE) and 2.44 +/- 0.70 in two separate experiments. Four different graphic representations of the raw data and fitted curves provide visual indications of goodness of fit of the estimated dose-response surface to the data and visual indications of the intensity of drug interaction. The universal response surface approach is mathematically consistent with the traditional isobologram approach but is more objective, is more quantitative, and is more easily automated. Although specifically developed for in vitro cancer chemotherapy applications, the universal response surface approach should prove to be useful in the fields of pharmacology, toxicology, epidemiology, and biomedical science in general.
Non-invasive measurement of mRNA decay reveals translation initiation as the major determinant of mRNA stability (2018)

The cytoplasmic abundance of mRNAs is strictly controlled through a balance of production and degradation. Whereas the control of mRNA synthesis through transcription has been well characterized, less is known about the regulation of mRNA turnover, and a consensus model explaining the wide variations in mRNA decay rates remains elusive. Here, we combine non-invasive transcriptome-wide mRNA production and stability measurements with selective and acute perturbations to demonstrate that mRNA degradation is tightly coupled to the regulation of translation, and that a competition between translation initiation and mRNA decay -but not codon optimality or elongation- is the major determinant of mRNA stability in yeast. Our refined measurements also reveal a remarkably dynamic transcriptome with an average mRNA half-life of only 4.8 min - much shorter than previously thought. Furthermore, global mRNA destabilization by inhibition of translation initiation induces a dose-dependent formation of processing bodies in which mRNAs can decay over time.
A Significant Number of Human Immunodeficiency Virus Epitope-Specific Cytotoxic T Lymphocytes Detected by Tetramer Binding Do Not Produce Gamma Interferon (2000)

Despite the seemingly important role of cytotoxic T-lymphocyte (CTL) responses in human immunodeficiency virus (HIV) disease pathogenesis, their measurement has relied on a variety of different techniques. We utilized three separate methodologies for the detection of CTLs in a cohort of HIV-infected individuals who were also human leukocyte antigen A2 (HLA-A2) positive. Among the different CTL assays, a correlation was seen only when the Gag epitope-specific HLA A*0201-restricted tetramer assay was compared with the ELISPOT assay performed after stimulation with the Gag epitope; however, this correlation was of borderline statistical significance. On average, the tetramer reagent detected a 10-fold-higher number of cells than were seen to produce gamma interferon by the ELISPOT assay. The implications of this CTL assay comparison and the possibility of phenotypic differences in HIV-specific CD8(+) T lymphocytes are discussed.
Speech formant frequency and bandwidth tracking using multiband energy demodulation (2002)

The AM-FM modulation model and a multiband analysis/demodulation scheme is applied to speech formant frequency and bandwidth tracking. Filtering is performed by a bank of Gabor bandpass filters. Each band is demodulated to amplitude envelope and instantaneous frequency signals using the energy separation algorithm. Short-time formant frequency and bandwidth estimates are obtained from the instantaneous amplitude and frequency signals and their merits are presented. The estimates are used to determine the formant locations and bandwidths. Performance and computational issues (frequency domain implementation) are discussed. Overall, the multiband demodulation approach to formant tracking is easy to implement, provides accurate formant frequency and realistic bandwidth estimates, and performs well in the presence of nasalization.
Jasmonic Acid Is a Key Regulator of Spider Mite-Induced Volatile Terpenoid and Methyl Salicylate Emission in Tomato (2004)

The tomato (Lycopersicon esculentum) mutant def-1, which is deficient in induced jasmonic acid (JA) accumulation upon wounding or herbivory, was used to study the role of JA in the direct and indirect defense responses to phytophagous mites (Tetranychus urticae). In contrast to earlier reports, spider mites laid as many eggs and caused as much damage on def-1 as on wild-type plants, even though def-1 lacked induction of proteinase inhibitor activity. However, the hatching-rate of eggs on def-1 was significantly higher, suggesting that JA-dependent direct defenses enhanced egg mortality or increased the time needed for embryonic development. As to gene expression, def-1 had lower levels of JA-related transcripts but higher levels of salicylic acid (SA) related transcripts after 1 d of spider mite infestation. Furthermore, the indirect defense response was absent in def-1, since the five typical spider mite-induced tomato-volatiles (methyl salicylate [MeSA], 4,8,12-trimethyltrideca-1,3,7,11-tetraene [TMTT], linalool, trans-nerolidol, and trans-beta-ocimene) were not induced and the predatory mite Phytoseiulus persimilis did not discriminate between infested and uninfested def-1 tomatoes as it did with wild-type tomatoes. Similarly, the expression of the MeSA biosynthetic gene salicylic acid methyltransferase (SAMT) was induced by spider mites in wild type but not in def-1. Exogenous application of JA to def-1 induced the accumulation of SAMT and putative geranylgeranyl diphosphate synthase transcripts and restored MeSA- and TMTT-emission upon herbivory. JA is therefore necessary to induce the enzymatic conversion of SA into MeSA. We conclude that JA is essential for establishing the spider mite-induced indirect defense response in tomato.
Cache index-aware memory allocation (2011)

Poor placement of data blocks in memory may negatively impact application performance because of an increase in the cache conflict miss rate [18]. For dynamically allocated structures this placement is typically determined by the memory allocator. Cache index-oblivious allocators may inadvertently place blocks on a restricted fraction of the available cache indexes, artificially and needlessly increasing the conflict miss rate. While some allocators are less vulnerable to this phenomena, no general-purpose malloc allocator is index-aware and methodologically addresses this concern. We demonstrate that many existing state-of-the-art allocators are index-oblivious, admitting performance pathologies for certain block sizes. We show that a simple adjustment within the allocator to control the spacing of blocks can provide better index coverage, which in turn reduces the superfluous conflict miss rate in various applications, improving performance with no observed negative consequences. The result is an index-aware allocator. Our technique is general and can easily be applied to most memory allocators and to various processor architectures.
Twist1 Regulates Ifng Expression in Th1 Cells by Interfering with Runx3 Function (2012)

A transcription factor network that includes STAT4, T-bet, and Runx3 promotes the differentiation of Th1 cells and inflammatory immune responses. How additional transcription factors regulate the function of Th1 cells has not been defined. In this study we show that the negative regulatory factor Twist1 decreases expression of T-bet, Runx3, and IL-12Rβ2 as it inhibits IFN-γ production. Ectopic expression of Runx3, but not T-bet or IL-12Rβ2, compensates for the effects of Twist1 on IFN-γ production, and Twist1 regulation of Ifng depends on complex formation with Runx3. Twist1 decreases Runx3 and T-bet binding at the Ifng locus, and it decreases chromatin looping within the Ifng locus. These data define an IL-12/STAT4-induced negative regulatory loop that impacts multiple components of the Th1 transcriptional network and provide further insight into regulation of Th1 differentiation.
The location of the first AUG codons in cowpea mosaic virus RNAs (1982)

We have made use of the known sequence of the 5' ends of both CPMV RNAs to synthesise an oligodeoxynucleotide which can prime second-strand DNA synthesis on full-length cDNA copies of both RNAs. By priming synthesis in the presence of dideoxynucleoside triphosphates, we have determined the positions of the first AUG codons in each RNA. These occur at positions 115 and 207 on M and B RNA respectively. By using a cloned double-stranded DNA fragment derived from near the 5' end of M RNA as a primer additional sequence from the 5' terminal region of M RNA has been obtained.
Lipocalin-Type Prostaglandin D Synthase in Human Male Reproductive Organs and Seminal Plasma1 (1998)

Prostaglandin D synthase (PGDS) activity was detected in human seminal plasma (0.05-1.83 nmol/min per milligram protein). The enzyme was purified from human seminal plasma by immunoaffinity chromatography and found to be 27 kDa in size and N-glycosylated, similar to PGDS in the cerebrospinal fluid. The N-terminal amino acid sequence of 16 residues of the seminal enzyme, APEAQVSVQPNFQQDK, was identical to that of the cerebrospinal fluid PGDS. Although PGDS activity and the content determined by the immunoassay each highly varied in the seminal plasma, the concentration was significantly (p < 0.001) lower in the oligozoospermic group (2.47 +/- 0.51 microg/ml) than in the normozoospermic group (9.75 +/- 1.49 microg/ml). Prostaglandin (PG) D2 was detected in the seminal plasma (5.00 +/- 0.65 ng/ml) with a positive correlation to the PGDS concentration (p < 0.05). PGD2 was converted to the J series of PGs in the seminal plasma with a half-life of 6.5 h. Northern blot analysis revealed that mRNA for PGDS was expressed in the testis, prostate, and epididymis. Through immunohistochemistry, PGDS was localized in Leydig cells of the testis and in epithelial cells of the prostate and ductus epididymidis.
Isolation, characterization, and interactions (2009)

Preface Contributors Introduction Section 1. Bacteriophage Isolation 1. Methods for the Isolation of Viruses from Environmental Samples K. Eric Wommack, Kurt E. Williamson, Rebekah R. Helton, Shellie R. Bench, and Danielle M. Winget 2. Bacteriophage Enrichment from Water and Soil Rohan Van Twest and Andrew M. Kropinski 3. Isolation of Phage via Induction of Lysogens Raul R. Raya and Elvira M. Hebert 4. Isolation of Cyanophages from Aquatic Environments Andrew D. Millard 5. Isolation of Viruses from High Temperature Environments Jennifer Fulton, Trevor Douglas, and Mark Young 6. Isolation of Novel Large and Aggregating Bacteriophages Philip Serwer, Shirley J. Hayes, Julie Thomas, Borries Demeler, and Stephen C. Hardies Section 2. Bacteriophage Characterization 7. Enumeration of Bacteriophages by Double Agar Overlay Plaque Assay Andrew M. Kropinski, Amanda Mazzocco, Tom Waddell, Erika Lingohr, and Roger P. Johnson 8. Enumeration of Bacteriophages by the Direct Plating Plaque Assay Amanda Mazzocco, Tom Waddell, Erika Lingohr, and Roger P. Johnson 9. Enumeration of Bacteriophages Using the Small Drop Plaque Assay System Amanda Mazzocco, Tom Waddell, Erika Lingohr, and Roger P. Johnson 10. Determination of Virus Abundance by Epifluorescence Microscopy Alice C. Ortmann and Curtis A. Suttle 11. Enumeration of Bacteriophages Using Flow Cytometry Corina P. D. Brussaard 12. Basic Phage Electron Microscopy Hans-W. Ackermann 13. Phage Classification and Characterization Hans-W. Ackermann 14. Phage Host Range and Efficiency of Plating Elizabeth Kutter 15. Measurementof the Rate of Attachment of Bacteriophage to Cells Andrew M. Kropinski 16. Measurement of the Bacteriophage Inactivation Kinetics with Purified Receptors Andrew M. Kropinski 17. Bacteriophage Plaques: Theory and Analysis Stephen T. Abedon and John Yin 18. Practical Methods for Determining Phage Growth Parameters Paul Hyman and Stephen T. Abedon 19. Phage Production and Maintenance of Stocks, Including Expected Stock Lifetimes Louis-Charles Fortier and Sylvain Moineau Section 3. Bacteriophage-Host Interactions 20. Construction of Phage Mutants (General) Robert Villafane 21. Modifying Bacteriophage l with Recombineering Lynn C. Thomason, Amos B. Oppenheim, and Donald L. Court 22. Identification and Isolation of Lysogens with Induced Prophage Jonathan Livny, Christopher N. LaRock, and David I. Friedman 23. Generalized Transduction Anne Thierauf, Gerardo Perez, and Stanley Maloy 24. Preparation and Characterization of Polyclonal Anti-Phage Serum Thomas E. Waddell, Kristyn Franklin, Amanda Mazzocco, and Roger P. Johnson 25. Generalized Transduction by Lytic Bacteriophages Thomas E. Waddell, Kristyn Franklin, Amanda Mazzocco, Andrew M. Kropinski, and Roger P. Johnson
Cloning and cDNA sequence of the dihydrolipoamide dehydrogenase component human alpha-ketoacid dehydrogenase complexes. (1988)

cDNA clones comprising the entire coding region for human dihydrolipoamide dehydrogenase (dihydrolipoamide:NAD+ oxidoreductase, EC 1.8.1.4) have been isolated from a human liver cDNA library. The cDNA sequence of the largest clone consisted of 2082 base pairs and contained a 1527-base open reading frame that encodes a precursor dihydrolipoamide dehydrogenase of 509 amino acid residues. The first 35-amino acid residues of the open reading frame probably correspond to a typical mitochondrial import leader sequence. The predicted amino acid sequence of the mature protein, starting at the residue number 36 of the open reading frame, is almost identical (greater than 98% homology) with the known partial amino acid sequence of the pig heart dihydrolipoamide dehydrogenase. The cDNA clone also contains a 3' untranslated region of 505 bases with an unusual polyadenylylation signal (TATAAA) and a short poly(A) track. By blot-hybridization analysis with the cDNA as probe, two mRNAs, 2.2 and 2.4 kilobases in size, have been detected in human tissues and fibroblasts, whereas only one mRNA (2.4 kilobases) was detected in rat tissues.
Proteomics--a new way for drug target discovery. (1998)

The results of the genome projects and the obvious problems with handling, storing and interpretation of generated data pose a lot of pressure on existing strategies in drug target discovery and development of new therapeutic concepts. Genomic data, i.e. DNA/RNA sequences identified by subtractive expression pattern analysis, are not enough per se for a clear identification of a therapeutic target, mainly because proteins and not DNA/RNA are the loci for drug mode-of-action. The effects seen on the gene expression level are only a response to drug effects on the protein level. In addition, there is not always a direct correlation between gene expression and protein expression. Therefore, the major focus of current efforts in drug discovery is the linkage between the genes and the function. One of the most powerful technologies for this purpose is now evolving and has been designated as Proteomics.
Differential Cold Tolerance, Starch, Sugar, Protein, and Lipid of Yellow and Purple Nutsedge Tubers (1975)

From measurements of viability after exposure of tubers to natural overwintering in the soil and 6 weeks exposure at 2 C, species cold tolerance of the tubers was ranked in decreasing order: yellow nutsedge ;I' (Cyperus esculentus L.), an ecotype originating in Illinois; yellow nutsedge ;G', an ecotype originating in Georgia; and purple nutsedge (Cyperus rotundus L.). The ratios of unsaturated-saturated fatty acids in tuber triglycerides, tuber polar lipids, and leaf polar lipids followed the same order as the cold tolerance rankings, with the most cold-hardy species having the highest ratios. Lipid content was less than 1% of dry weight in purple nutsedge tubers, but was from 5 to 7% in both yellow nutsedge tubers. Starch, sugar, and lipid contents increased significantly in the hardy yellow nutsedge ;I' tubers during a 6-week exposure to 2 C, but did not change in the susceptible purple nutsedge tubers; only sugar increased in yellow nutsedge ;G' tubers after this treatment. Protein content was not altered by the 2 C treatment in any of the tubers. Apparently, several factors involving starch, sugar, lipids, and fatty acids are related to the differences in tolerance to cold in these species.
Platelet Microbicidal Protein 1: Structural Themes of a Multifunctional Antimicrobial Peptide (2004)

Mammalian platelets release platelet microbicidal proteins (PMPs) as components of their antimicrobial armamentarium. The present studies defined the structure of PMP-1 and examined its structure-activity relationships. Amino acid sequencing and mass spectroscopy demonstrated that distinct N-terminal polymorphism variants of PMP-1 isolated from nonstimulated or thrombin-stimulated platelets arise from a single PMP-1 propeptide. Sequence data (NH(2)-[S]D(1)DPKE(5)SEGDL(10)HCVCV(15)KTTSL(20) . . .) enabled cloning of PMP-1 from bone marrow and characterization of its full-length cDNA. PMP-1 is translated as a 106-amino-acid precursor and is processed to yield 73-residue (8,053 Da) and 72-residue (7,951-Da) variants. Searches with the BLAST program and sequence alignments demonstrated the homology of PMP-1 to members of the mammalian platelet factor 4 (PF-4) family of proteins. On the basis of phylogenetic relatedness, congruent sequence motifs, and predicted three-dimensional structures, PMP-1 shares the greatest homology with human PF-4 (hPF-4). By integration of its structural and antimicrobial properties, these results establish the identity of PMP-1 as a novel rabbit analogue of the microbicidal chemokine (kinocidin) hPF-4. These findings advance the hypothesis that stimuli in the setting of infection prompt platelets to release PF-4-class or related kinocidins, which have structures consistent with their likely multiple roles that bridge molecular and cellular mechanisms of antimicrobial host defense.
Sphingosine inhibition of protein kinase C activity and of phorbol dibutyrate binding in vitro and in human platelets. (1986)

Sphingosine inhibited protein kinase C activity and phorbol dibutyrate binding. When the mechanism of inhibition of activity and phorbol dibutyrate binding was investigated in vitro using Triton X-100 mixed micellar methods, sphingosine inhibition was subject to surface dilution; 50% inhibition occurred when sphingosine was equimolar with sn-1,2-dioleoylglycerol (diC18:1) or 40% of the phosphatidylserine (PS) present. Sphingosine inhibition was modulated by Ca2+ and by the mole percent of diC18:1 and PS present. Sphingosine was a competitive inhibitor with respect to diC18:1, phorbol dibutyrate, and Ca2+. Increasing levels of PS markedly reduced inhibition by sphingosine. Since protein kinase C activity shows a cooperative dependence on PS, the kinetic analysis of competitive inhibition was only suggestive. Sphingosine inhibited phorbol dibutyrate binding to protein kinase C but did not cause protein kinase C to dissociate from the mixed micelle surface. Sphingosine addition to human platelets blocked thrombin and sn-1,2-dioctanoylglycerol-dependent phosphorylation of the 40-kDa (47 kDa) dalton protein. Moreover, sphingosine was subject to surface dilution in platelets. The mechanism of sphingosine inhibition is discussed in relation to a previously proposed model of protein kinase C activation. The possible physiological role of sphingosine as a negative effector of protein kinase C is suggested and a plausible cycle for its generation is presented. The potential physiological significance of sphingosine inhibition of protein kinase C is further established in accompanying papers on HL-60 cells (Merrill, A. H., Jr., Sereni, A. M., Stevens, V. L., Hannun, Y. A., Bell, R. M., Kinkade, J. M., Jr. (1986) J. Biol. Chem. 261, 12010-12615) and human neutrophils (Wilson, E., Olcott, M. C., Bell, R. M., Merrill, A. H., Jr., and Lambeth, J. D. (1986) J. Biol. Chem. 261, 12616-12623). These results also suggest that sphingosine will be a useful inhibitor for investigating the function of protein kinase C in vitro and in living cells.
Prolonged cardiac preservation. Evaluation of the University of Wisconsin preservation solution by comparison with the St. Thomas' Hospital cardioplegic solutions in the rat. (1990)

The University of Wisconsin solution differs from other types of solutions used for organ preservation because it contains high-energy phosphate precursors (adenosine and phosphate), impermeants (lactobionate and raffinose), an oncotic agent (pentafraction), and antioxidants (allopurinol and glutathione). These components have the potential to enhance the preservation of ATP, reduce intracellular and extracellular edema, and attenuate free-radical-mediated injury. The University of Wisconsin solution has been demonstrated to enhance and extend the preservation of the liver, pancreas, and kidney, but its potential role in the heart remains unproven. We have evaluated the University of Wisconsin solution (Du Pont) by comparing it with the St. Thomas' Hospital cardioplegic solutions No. 1 and No. 2 (Plegisol), which are used in Europe and the United States for routine cardiac surgery and transplantation. For each solution, 10 isolated working rat hearts were arrested by 10 ml of the solution (at 4 degrees C) and then maintained immersed in the same solution for 4 hours at 4 degrees C. Mean recovery of functional indexes (expressed as a percentage of their preischemic control values) after use of the University of Wisconsin solution were as follows: peak aortic pressure, 90.6 +/- 1.0; dP/dt, 71.5 +/- 5.5; aortic flow, 81.6 +/- 4.7; coronary flow, 87.5 +/- 3.5; and cardiac output, 82.6 +/- 3.5. In contrast, the mean recoveries after St. Thomas' Hospital solution No. 1 were as follows: peak aortic pressure, 82.8 +/- 1.3; dP/dt, 49.7 +/- 3.0; aortic flow, 58.4 +/- 5.3; coronary flow, 79.6 +/- 5.9; and cardiac output, 63.0 +/- 4.9. In contrast still, mean recoveries after St. Thomas' Hospital solution No. 2 were as follows: peak aortic pressure, 83.1 +/- 1.2; dP/dt, 40.7 +/- 6.1; aortic flow, 37.0 +/- 5.1; coronary flow, 65.8 +/- 3.6; and cardiac output, 43.1 +/- 5.6. The recovery of all indexes were significantly superior (p less than 0.005) after preservation with University of Wisconsin solution compared with either of the St. Thomas' Hospital solutions.(ABSTRACT TRUNCATED AT 250 WORDS)