gebhart/patrepeval huggingface dataset:
Inheritance of Crippled Trifoliolate Leaves Occurring in Interracial Crosses of Common Bean and Its Relationship With Hybrid Dwarfism (1996)

Crippled trifoliolate leaves were observed in two lines from interracial populations of common bean (Phaseolus vulgaris L). The lines, WA 7807-305 and TY 5578-220, were F 2 -derived F 6 recombinant inbreds from populations Rio Tibagi/ABA 58 and Brasil 2/ICA L 23, respectively. Rio Tibagi and Brasil 2 are small-seeded, grow in tropical lowlands, and belong to the race Mesoamerica. In contrast, ABA 58 and ICA L 23 belong to the large-seeded Andean race Nueva Granada. The two lines were crossed with each other, with one of their normal parents, and with tester stocks. The normal parents and tester stocks carried either the DI1 or DI2 gene. These genes are complementary dominant, dosage dependent lethal, and known to cause hybrid dwarfism or plant stunting. The recessive gene Icr causes trifoliolate leaf crippling in the presence of either DI1 or DI2. When both DI1 and DI2 are present, a dwarf-lethal or semilethal phenotype is produced, irrespective of the alleles at the Icr locus. Thus, the genotypes of the lines are, for WA 7807-305: DI1 DI1 dl2 dl2 Icr Icr, and for TY 5578-220: dl1 dl1 DI2 DI2 Icr Icr. Other reported cases of developmental abnormalities are reviewed and their significance for common bean improvement is discussed.
Application of a 16S rRNA PCR–High-Resolution Melt Analysis Assay for Rapid Detection of Salmonella Bacteremia (2011)

Current culture and phenotypic protocols for diagnosing Salmonella infections can be time-consuming. Here, we describe the application of a 16S rRNA PCR coupled to high-resolution melt analysis (HRMA) for species and serotype identification within 6 h of blood sample collection from a patient with Salmonella enterica serotype Enteritidis bacteremia.
Ultraviolet grating polarizers (1981)

Wet and dry processing technologies are applied to the development of high-aspect-ratio gratings in SiO2. Planar gratings having nearly vertical sidewalls and periods of 3000 Å are used as the basic structure for generating ultraviolet polarizers which perform at wavelengths well below 3000 Å. Extinction ratios of 0.5 at wavelengths of 2400 Å have been obtained. With new techniques available for generating fine-period surface gratings, it should be possible to fabricate planar polarizers with high polarization efficiencies at even shorter wavelengths.
Boosting antibody-dependant cellular cytotoxicity against tumor cells with a CD137 stimulatory antibody (2012)

Monoclonal antibodies (mAb) induce tumor regression through antibody-dependant cellular cytotoxicity (ADCC). We recently showed that an agonistic anti-CD137 mAb stimulates natural killer (NK) cells which have been activated by a tumor-specific mAb, resulting in increased ADCC against cancer cells.
Embedded DPCM for Variable Bit Rate Transmission (1980)

Within the bit stream of an embedded digital code is a stream that can be decoded to produce a reasonable replica of the analog source signal. Unlike pulse code modulation (PCM), differential PCM (DPCM), is not an embedded code. If C bits/sample are delected from the bit stream of a DPCM encoder with E bits/sample, the decoded analog signal is substantially noisier than the output of a DPCM codec with D = E - C bits/sample. The penalty is 4-10 dB in signal-to-noise ratio (snr). However, with minor modifications to the encoder and decoder, DPCM becomes an embedded code. Embedded DPCM with E bits/ sample at the encoder and D bits/sample transmitted produces exactly the same output as embedded DPCM with D bits/sample encoding and perfect transmission. The snr of embedded DPCM is slightly lower than the Snr of DPCM. The penalty is 0.5-0.8 dB if the minimum transmitted bit rate is 2 bits/sample. It is less than 0.3 dB if D is at least 3 bits/sample. Combined with an appropriate adaptive quantizer the embedded DPCM codec produces embedded ADPCM (adaptive DPCM) for variable rate transmission ranging from 2 bits/sample up to any desired maximum. Applications exist in speech interpolation, packet switching, and hardware architecture.
Long-term administration of 13-cis retinoic acid in common variable immunodeficiency: circulating interleukin-6 levels, B-cell surface molecule display, and in vitro and in vivo B-cell antibody production. (1993)

We have previously shown that retinoids can induce differentiation of B cells in vitro as well as in vivo in patients with common variable immunodeficiency (CVI). While changes were observed over 1 week when retinoic acid (RA) was added to CVI hybridoma cells in vitro, maturation of the patients' B-cell compartment in vivo occurred only after 4 months of drug administration. We have now performed a 64-week open trial of oral 13-cis RA in five patients to see if prolonged treatment would result in continued improvement in their humoral immune compartment. In this trial, drug was given for 32 weeks followed by a 32-week wash-out period. During the treatment, the patients showed changes in a variety of parameters indicating an alteration towards normal of their humoral immune systems. This change included a fall in the elevated circulating interleukin-6 (IL-6) levels, a more normal display of B-cell surface markers (L-selectin and CD20), a decrease in B-cell size, and improved in vitro and in vivo B-cell function. In order to determine if VH gene use was affected by the retinoid treatment, VH gene expression in the CVI patients was characterized. Results showed an unusual predominance of non-mutated VH gene sequences, representative of cells that are recent bone marrow emigrants. While no common pattern of change occurred in VH gene segment use in the patients while on retinoid therapy, large-scale (> 10-fold) changes in the expression of these genes were observed in each individual over time. Taken together, these results provide multiple lines of evidence that 13-cis RA promotes maturation of B cells in patients with CVI. However, the effect appears to be partial, such that stimuli in addition to 13-cis RA will be necessary to provide for further B-cell differentiation in order to achieve normalization of humoral immunity.
Identification of Intermediates in the Conversion of Cholesterol to Pregnenolone with a Reconstituted Cytochrome P-450scc System: Accumulation of the Intermediate Modulated by the Adrenodoxin Level (1996)

Dihydroxycholesterol and pregnenolone were clearly detected on HPLC when 22R-hydroxycholesterol was incubated with a reconstituted P450scc system containing equimolar amounts of P450scc and adrenodoxin. The dihydroxycholesterol, which has been accepted to be an intermediate in the conversion of 22R-hydroxycholesterol to pregnenolone, accumulated when adrenodoxin was at a subsaturating level with respect to P450scc. The formation of the intermediate increased with increasing pH in the range of 7.2 to 8.1, and the ratio of the intermediate to the product, pregnenolone, increased with increasing pH. When the binding of P450scc to adrenodoxin was weakened by elevation of the ionic strength, the formation of the intermediate relative to the product increased. The apparent Km for dihydroxycholesterol at a subsaturating level of adrenodoxin was about 7 microM, in contrast to 4 microM at a saturating level of adrenodoxin, implying that the affinity of dihydroxycholesterol is lower at a subsaturating level of adrenodoxin than at a saturating one. These results suggest that a subsaturating level of adrenodoxin weakened the binding of dihydroxycholesterol to P450scc and thus the intermediate, dihydroxycholesterol, was released. An intermediate other than dihydroxycholesterol, obtained when cholesterol was used as the substrate, was identified as 22R-hydroxycholesterol by HPLC and mass spectroscopic analysis. The intermediate obtained when 22R-hydroxycholesterol was used as the substrate was identified as 20R,22R-dihydroxycholesterol by HPLC, mass, and 1H-NMR spectroscopic analyses. These results provide direct evidence that cholesterol is metabolized to pregnenolone by way of 22R-hydroxycholesterol and 20R,22R-dihydroxycholesterol by P45 scc.
Generation of monoclonal antibodies reacting with normal and cancer cells of human breast. (1983)

From the fusion of the murine myeloma P3- X63-Ag8-U1 with spleen cells from a mouse immunized with the human breast cancer cell line MCF-7, 88 hybridomas producing antibodies reacting with the immunizing cells were obtained. After a first screening on human leukocytes, red blood cells, and platelets and on human and fetal calf serum, three monoclonal antibodies, MBr1, MBr2, and MBr3, with specificity for the immunizing cells were isolated and further characterized. The three monoclonals were tested by isotopic antiglobulin assay and immunofluorescence on a panel of normal cells or cell membrane preparations, including milk epithelial and foam cells; on plasma and milk proteins; on cells or cell membrane preparations from fresh surgical specimens of breast, kidney, and ovarian carcinomas; and on various tumor cell lines. MBr1 and MBr2 had a superimposable reactivity and showed specificity for a structure which seems to characterize both normal and neoplastic mammary gland epithelial cells.
Mouse mutagenesis-systematic studies of mammalian gene function (1998)

The mouse will play a pivotal role in mammalian gene function studies as we enter the post-genomics era. The challenge is to develop systematic, genome-wide mutagenesis approaches to the study of gene function. The current mouse mutant resource has been an important source of human genetic disease models. However, despite an apparently large catalogue of mouse mutations, we have access to mutations at only a small fraction of the likely total number of mammalian genes-there is a phenotype gap that needs to be filled by the establishment of new mutagenesis programmes. Two routes, genotype- and phenotype-driven, can be used for the recovery of novel mouse mutations. For the former, gene trap embryonic stem cell libraries appear set to deliver a large number of mutations around the mouse genome. The advantage of genotype-driven approaches is the ease of identification of the mutated locus; the disadvantage that a priori assumptions have to be made concerning the function and likely phenotype of the mutated gene. In contrast, phenotype-driven mutagenesis emphasizes the recovery of novel phenotypes. One phenotype-driven approach that will play an important role in expanding the mouse mutant resource employs the mutagen N-ethyl-N-nitrosourea (ENU). The phenotype-driven route makes no assumptions about the underlying genes involved, and ENU mutagenesis programmes can be expected to play a significant role in uncovering novel pathways and genes; the disadvantage is that the identification of the mutant gene is still not trivial. Together, the complementary routes of genotype- and phenotype-driven mutagenesis will provide a much enlarged catalogue of mouse mutations and phenotypes for future gene function studies.
Science, medicine, and the future: Therapeutic angiogenesis (1999)

Therapeutic angiogenesis is the clinical use of growth factors to enhance or promote the development of collateral blood vessels in ischaemic tissue. Progress in understanding the process of angiogenesis, the isolation of angiogenic growth factors, successful preclinical studies, and promising early results in clinical trials have created great excitement about the potential of therapeutic angiogenesis.1 Although many questions remain, therapeutic angiogenesis may be the next major advance in the treatment of ischaemic heart disease.
Effect of vitamin D analog (1α hydroxy D5) immunoconjugated to Her‐2 antibody on breast cancer (2004)

We previously showed that a new vitamin D analog, 1alpha(OH)D5 (D5), induced differentiation and inhibited the growth of breast cancer cells. In this report, we examined whether D5 specifically delivered to breast cancer cells could have any therapeutic effect. D5 was linked to Her-2 antibody using sulfosuccinimidyl 6-4 azido nitrophenylamido hexanode (SANPAH) as a linker. The Her-2 antibody selected in our study had no significant effect on the in vitro or in vivo growth of breast cancer cells; however, it had cell-differentiating action. In vitro, D5-Her-2 antibody conjugate (IMC) showed the ability to specifically bind to Her-2-expressing cells, to compete with Her-2 antibody for surface receptor and to cause internalization. IMC (equivalent to 5 microg Her-2 antibody given intraperitoneally once weekly for 6 weeks) significantly inhibited the growth of BT-474 cells transplanted into athymic mice. The in vivo growth-inhibitory effect of IMC treatment was similar to that observed in animals receiving D5 continuously as a dietary supplement. These results show that the targeted delivery of D5 by immunoconjugation to cell surface receptor antibodies may be of potential therapeutic value for the treatment of Her-2 positive breast cancer.
IFN-β-1b Inhibits IL-12 Production in Peripheral Blood Mononuclear Cells in an IL-10-Dependent Mechanism: Relevance to IFN-β-1b Therapeutic Effects in Multiple Sclerosis (2000)

IL-12 is a proinflammatory cytokine secreted by dendritic cells in response to microbial Ags and mitogens. IL-12 is thought to contribute to the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). This is based on studies in experimental allergic encephalomyelitis and the demonstration that PBMC IL-12 production correlates with disease progression in MS. IFN-beta-1b is an effective treatment for MS, which is thought to involve in part inhibition of proinflammatory cytokines. In this study we examined the effect of in vitro treatment with IFN-beta-1b, on mitogen-induced IL-12 production in human PBMC and myelin basic protein-specific T cell lines obtained from healthy donors and MS patients. We demonstrate that IFN-beta-1b significantly inhibits inducible IL-12 p40 up to 80% and biologically active IL-12 p70 up to 70% beginning at a dose of 10 IU/ml. This inhibition is IL-10 dependent, as it could be blocked by anti-IL-10 but not anti-IL-4 or control Abs. Thus, endogenously produced IL-10 is a required cofactor for the IFN-beta-1b inhibitory effect on IL-12 to occur. We conclude that IFN-beta-1b has a profound inhibitory effect on PBMC IL-12 production in vitro, and that this effect is IL-10 dependent. These findings are potentially relevant to the therapeutic mechanism of IFN-beta-1b in MS.
Identifying constraints on the higher-order structure of RNA: continued development and application of comparative sequence analysis methods (1992)

Comparative sequence analysis addresses the problem of RNA folding and RNA structural diversity, and is responsible for determining the folding of many RNA molecules, including 5S, 16S, and 23S rRNAs, tRNA, RNAse P RNA, and Group I and II introns. Initially this method was utilized to fold these sequences into their secondary structures. More recently, this method has revealed numerous tertiary correlations, elucidating novel RNA structural motifs, several of which have been experimentally tested and verified, substantiating the general application of this approach. As successful as the comparative methods have been in elucidating higher-order structure, it is clear that additional structure constraints remain to be found. Deciphering such constraints requires more sensitive and rigorous protocols, in addition to RNA sequence datasets that contain additional phylogenetic diversity and an overall increase in the number of sequences. Various RNA databases, including the tRNA and rRNA sequence datasets, continue to grow in number as well as diversity. Described herein is the development of more rigorous comparative analysis protocols. Our initial development and applications on different RNA datasets have been very encouraging. Such analyses on tRNA, 16S and 23S rRNA are substantiating previously proposed associations and are now beginning to reveal additional constraints on these molecules. A subset of these involve several positions that correlate simultaneously with one another, implying units larger than a basepair can be under a phylogenetic constraint.
Citrate treatment reduces endothelial death and inflammation under hyperglycaemic conditions (2011)

Hyperglycaemia and glucose degradation products (GDPs) are closely associated with oxidative stress and inflammation in diabetic patients, a condition that leads to endothelial dysfunction and cardiovascular problems. We evaluated the effect of citrate and gluconate on glucose- and GDP-induced endothelial inflammation by measuring changes in viability, inflammation and function in primary human umbilical vein endothelial cells (HUVECs). The extent of apoptosis/necrosis was measured by flow cytometry and visualised with confocal microscopy by staining with annexin V or propidium iodide, respectively. Protein kinase C-βII (PKC-βII) activation was evaluated with Western blotting. Incubation with glucose (30 mM) and GDP (50 µM) significantly increased PKC-βII expression, endothelial cell death and inflammation. The addition of citrate decreased hyperglycaemia-induced apoptosis (p = 0.021), necrosis (p = 0.04) and reduced PKC-βII expression (p = 0.021) down to background levels. Citrate improved endothelial function by reducing the inflammatory markers (p = 0.01) and by decreasing neutrophil diapedesis (p = 0.012). These results suggest that citrate may have therapeutic potential by reducing hyperglycaemia-induced endothelial inflammation and abolishing endothelial dysfunction.
TRPM7 channels in hippocampal neurons detect levels of extracellular divalent cations (2007)

Exposure to low Ca(2+) and/or Mg(2+) is tolerated by cardiac myocytes, astrocytes, and neurons, but restoration to normal divalent cation levels paradoxically causes Ca(2+) overload and cell death. This phenomenon has been called the "Ca(2+) paradox" of ischemia-reperfusion. The mechanism by which a decrease in extracellular Ca(2+) and Mg(2+) is "detected" and triggers subsequent cell death is unknown. Transient periods of brain ischemia are characterized by substantial decreases in extracellular Ca(2+) and Mg(2+) that mimic the initial condition of the Ca(2+) paradox. In CA1 hippocampal neurons, lowering extracellular divalents stimulates a nonselective cation current. We show that this current resembles TRPM7 currents in several ways. Both (i) respond to transient decreases in extracellular divalents with inward currents and cell excitation, (ii) demonstrate outward rectification that depends on the presence of extracellular divalents, (iii) are inhibited by physiological concentrations of intracellular Mg(2+), (iv) are enhanced by intracellular phosphatidylinositol 4,5-bisphosphate (PIP(2)), and (v) can be inhibited by Galphaq-linked G protein-coupled receptors linked to phospholipase C beta1-induced hydrolysis of PIP(2). Furthermore, suppression of TRPM7 expression in hippocampal neurons strongly depressed the inward currents evoked by lowering extracellular divalents. Finally, we show that activation of TRPM7 channels by lowering divalents significantly contributes to cell death. Together, the results demonstrate that TRPM7 contributes to the mechanism by which hippocampal neurons "detect" reductions in extracellular divalents and provide a means by which TRPM7 contributes to neuronal death during transient brain ischemia.
Rational Design of α-Helical Antimicrobial Peptides with Enhanced Activities and Specificity/Therapeutic Index (2005)

In the present study, the 26-residue peptide sequence Ac-KWKSFLKTFKSAVKTVLHTALKAISS-amide (V681) was utilized as the framework to study the effects of peptide hydrophobicity/hydrophilicity, amphipathicity, and helicity (induced by single amino acid substitutions in the center of the polar and nonpolar faces of the amphipathic helix) on biological activities. The peptide analogs were also studied by temperature profiling in reversed-phase high performance liquid chromatography, from 5 to 80 degrees C, to evaluate the self-associating ability of the molecules in solution, another important parameter in understanding peptide antimicrobial and hemolytic activities. A higher ability to self-associate in solution was correlated with weaker antimicrobial activity and stronger hemolytic activity of the peptides. Biological studies showed that strong hemolytic activity of the peptides generally correlated with high hydrophobicity, high amphipathicity, and high helicity. In most cases, the D-amino acid substituted peptides possessed an enhanced average antimicrobial activity compared with L-diastereomers. The therapeutic index of V681 was improved 90- and 23-fold against Gram-negative and Gram-positive bacteria, respectively. By simply replacing the central hydrophobic or hydrophilic amino acid residue on the nonpolar or the polar face of these amphipathic derivatives of V681 with a series of selected D-/L-amino acids, we demonstrated that this method has excellent potential for the rational design of antimicrobial peptides with enhanced activities.
The effect of phospholipids, calcium ions and protein S on rate constants of human factor Va inactivation by activated human protein C (1992)

Rate constants for human factor Va inactivation by activated human protein C (APC) were determined in the absence and presence of Ca2+ ions, protein S and varying concentrations of phospholipid vesicles of different lipid composition. APC-catalyzed factor Va inactivation in free solution (in the presence of 2 mM Ca2+) was studied under first-order reaction conditions with respect to both APC and factor Va and was characterized by an apparent second-order rate constant of 6.1 x 10(5) M-1 s-1. Stimulation of APC-catalyzed factor Va inactivation by phospholipids was dependent on the concentration and composition of the phospholipid vesicles. Optimal acceleration (230-fold) of factor Va inactivation was observed with 10 microM phospholipid vesicles composed of 20 mol% dioleoylglycerophosphoserine (Ole2GroPSer) and 80 mol% dioleoylglycerophosphocholine (Ole2GroPCho). At higher vesicle concentrations and at higher molar fractions of Ole2GroPSer some inhibition of APC-catalyzed factor Va inactivation was observed. Membranes that contained anionic phospholipids other than phosphatidylserine also promoted factor Va inactivation. The ability of different anionic lipids to enhance factor Va inactivation increased in the order phosphatidylethanolamine less than oleic acid less than phosphatidic acid less than phosphatidylglycerol less than phosphatidylmethanol less than phosphatidylserine. APC-catalyzed factor Va inactivation in the presence of phospholipid vesicles could be saturated with respect to factor Va and the reaction obeyed Michaelis-Menten kinetics. Both the Km for factor Va and the Vmax of factor Va inactivation were a function of the phospholipid concentration. The Km increased from 1 nM at 2.5 microM phospholipid (Ole2GroPSer/Ole2GroPCho 20:80, mol/mol) to 65 nM at 250 microM phospholipid. The Vmax increased from 20 mol factor Va inactivated.min-1.mol APC-1 at 2.5 microM phospholipid to 62 mol factor Va inactivated.min-1.mol APC-1 at 10 microM phospholipid and remained constant at higher phospholipid concentrations. Protein S appeared to be a rather poor stimulator of APC-catalyzed factor Va inactivation. Protein-S-dependent rate enhancements were only observed in reaction mixtures that contained negatively charged phospholipid vesicles. Independent of the concentration and the lipid composition of the vesicles, protein S caused a twofold stimulation of APC-catalyzed factor Va inactivation. This suggests that, in the human system, enhancement of APC binding to phospholipid vesicles by protein S is of minor importance. Considering that protein S is a physiologically essential antithrombotic agent, it is likely that other factors or phenomena contribute to the in vivo antithrombotic action of protein S.