gebhart/patrepeval huggingface dataset:
B(OCH2CF3)3-mediated direct amidation of pharmaceutically relevant building blocks in cyclopentyl methyl ether (2015)

The use of B(OCH2CF3)3 for mediating direct amidation reactions of a wide range of pharmaceutically relevant carboxylic acids and amines is described, including numerous heterocycle-containing examples. An initial screen of solvents for the direct amidation reaction suggested that cyclopentyl methyl ether, a solvent with a very good safety profile suitable for use over a wide temperature range, was an excellent replacement for the previously used solvent acetonitrile. Under these conditions amides could be prepared from 18 of the 21 carboxylic acids and 18 of the 21 amines examined. Further optimisation of one of the low yielding amidation reactions (36% yield) via a design of experiments approach enabled an 84% yield of the amide to be obtained.
Progress towards cloning the cystic fibrosis gene (1988)

Genetic linkage analysis with polymorphic DNA markers (restriction fragment length polymorphisms: RFLPS) has allowed the assignment of the cystic fibrosis (CF) locus to the long arm of chromosome 7, within the region of band q31. Two of these markers, MET and D7S8, are tightly linked to the disease locus. Although recent data suggest that they are located on opposite sides of CF, the two can be separated by as much as 5 centimorgans. To obtain a better description of the CF locus and, eventually, to identify the affected gene, additional DNA markers are required to connect MET and D7S8, physically. We have screened the flow-sorted chromosome-7-specific library and thus far isolated 28 new probes from the 7q31 region by DNA hybridization analysis that uses a series of somatic cell hybrids containing various portions of human chromosome 7. Together with the previously identified markers, MET, D7S8, D7S13 and D7S16, these new markers should provide a fine genetic and physical map for the chromosomal region surrounding CF. DNA segments can then be sequentially cloned by chromosome walking from points closest to the CF locus and examined for genes that are preferentially expressed in tissues known to be affected in the disease.
Physical properties of undoped and doped hydrogenated amorphous silicon carbide (1991)

A systematic study on the basic characteristics of p-type a-SiC:H films doped with B2H6 and n-type doped with PH3 is presented. The effect of doping on the optical and electrical properties of the films has been examined. The results obtained on energy gap, spin density, Urbach energy and integral of excess absorption suggest that the phosphorus dopant atoms introduce fewer additional defects than does boron. The difference in the behaviour of the two types of doping has been attributed to the chemistry of boron and phosphorus.
Spoken language understanding (2005)

This article is intended to serve as an introduction to the field of statistical SLU, based on the mainstream statistical modeling approach that shares a similar mathematical framework with many other statistical pattern recognition applications such as speech recognition. In particular, we formulated a number of statistical models for SLU in the literature as extensions to HMMs as segment models, where a multiple-word block (segment) with word dependency is generated from each underlying Markov state corresponding to each individual semantic slot defined from the application domain. In the past, due partly to its nature of symbolic rather than numeric processing, the important field of SLU in human language technology has not been widely exposed to the signal processing research community. However, many key techniques in SLU originated from statistical signal processing. And because SLU is becoming increasingly important, as one major target application area of ASR that has been dear to many signal processing researchers, we contribute this article to provide a natural bridge between ASR and SLU in methodological and mathematical foundation. It is our hope that when the mathematical basis of SLU becomes well known through this introductory article, more powerful techniques established by signal processing researchers may further advance SLU to form a solid application area, making speech technology a successful component for intelligent human-machine communication.
CD40 Signaling Replaces CD4+ Lymphocytes and Its Blocking Prevents Chronic Rejection of Heart Transplants (2000)

Chronic rejection remains the major obstacle to long term survival in heart transplant recipients. The cellular and molecular mechanisms that underlie chronic rejection are not known, and their discovery can form the basis of clinical intervention. Several investigators have suggested that the development of chronic rejection in solid organ transplants is dependent on help mediated by CD4(+) lymphocytes. Importantly, the mechanism through which help is provided has not been fully delineated in transplant rejection. Using a murine heterotopic heart transplant model without immunosuppression, this study defines the functional role of CD4(+) lymphocytes in chronic rejection. In an MHC class II-mismatched model, we demonstrate that chronic rejection was absolutely contingent on the presence of CD4(+) lymphocytes. Importantly, here we report that signaling through CD40 can replace the requirement of CD4(+) lymphocytes, demonstrated by the development of chronic rejection in CD4 knockout recipients treated with a CD40-activating mAb (FGK45). The return of rejection appears to be a CD8(+) lymphocyte-dependent process, noted by the absence of rejection in FGK45-treated recombinase-activated gene knockout (CD4(+) and CD8(+) lymphocyte-deficient) recipients. The CD40 signaling pathway works independently of B7-CD28 costimulation, as indicated by the development of severe chronic rejection in CD28 knockout recipients. Importantly, this study provides evidence that CD40 ligand-targeted therapies may prevent chronic rejection only in strain combinations where CD4(+) lymphocyte help is absolutely required.
Isolation and characterization of a DNA sequence complementary to an androgen-inducible messenger RNA from mouse kidney. (1981)

Clones containing sequences corresponding to testosterone-inducible RNAs of mouse kidney have been identified within a cDNA clone bank prepared from size-fractionated poly(A)-containing kidney RNA. A novel screening method was employed to specifically detect such sequences. One of these, pMK908, containing a 1.2 kilobase pair insert, was studied in detail. RNA blotting experiments show that the inserted DNA of pMK908 hybridizes to two kidney-specific RNA sequences, 2500 and 1500 nucleotides in length, both of which are rapidly induced by testosterone treatment of female mice in vivo. RNA excess hybridization studies reveal that these RNAs constitute approximately 0.004% of th total RNA population in female kidneys and are induced approximately 7-8-fold by testosterone. The RNA has been isolated and translated in a cell-free system and encodes a 43,000-dalton polypeptide chain. The induction of these RNAs by testosterone is independent of the pituitary gland, but does depend upon the testosterone receptor protein. The existence of pMK908, and other chimeric plasmids containing testosterone-inducible sequences, should be valuable in understanding the response of the mouse kidney to androgens.
Noninvasive imaging of in vivo blood flow velocity using optical Doppler tomography (1997)

We report the development of an optical technique for noninvasive imaging of in vivo blood flow dynamics and tissue structures with high spatial resolution (2-10 microm) in biological systems. The technique is based on optical Doppler tomography (ODT), which combines Doppler velocimetry with optical coherence tomography to measure blood flow velocity at discrete spatial locations. The exceptionally high resolution of ODT permits noninvasive in vivo imaging of both blood microcirculation and tissue structures surrounding the vessel, which has significance for biomedical research and clinical applications. Tomographic imaging of in vivo blood flow velocity in the chick chorioallantoic membrane and in rodent skin is demonstrated.
Tumor necrosis factor inhibits the terminal events in mesenchymal stem cell differentiation (1988)

Control of the terminal event in cellular differentiation is an important normal regulatory process, and the expression of defects in the control of this process has been implicated in the pathogenesis of cancer. To determine if tumor necrosis factor (TNF), which is an important biological response modifier, can inhibit terminal differentiation, we have studied 3T3 T mesenchymal stem cells. This experimental cell system was employed because a well-defined series of steps in differentiation has been defined and cells at each stage of differentiation can be isolated. For example, nonterminal differentiated cells can be isolated, and their transition to a terminal differentiation state can be evaluated. The most interesting results in the current studies show that TNF blocks the terminal event in mesenchymal stem cell differentiation. Inhibition of the terminal event of differentiation by TNF is reversible and is not associated with inhibition of selective or general protein synthesis. Evidence is also presented that cell clones that are defective in their ability to undergo the terminal event in differentiation secrete factor(s) that inhibit the terminal event in differentiation. These observations suggest that the inhibition of the terminal event in differentiation may be mediated via autocrine or paracrine regulatory molecules such as tumor necrosis factor.
Magnesium Treatment for Sudden Hearing Loss (2004)

Magnesium treatment has been repeatedly shown to reduce the incidence of both temporary and permanent noise-induced hearing loss. We hypothesized that it might also improve the permanent threshold shift in patients with acute-onset hearing loss. In a prospective, randomized, double-blind, placebo-controlled trial, 28 patients with idiopathic sudden sensorineural hearing loss were treated with either steroids and oral magnesium (study group) or steroids and a placebo (control group). Compared to the controls, the magnesium-treated group had a significantly higher proportion of patients with improved hearing (>10 dB hearing level) across all frequencies tested, and a significantly greater mean improvement in all frequencies. Analysis of the individual data confirmed that more patients treated with magnesium experienced hearing improvement, and at a larger magnitude, than control subjects. Magnesium is a relatively safe and convenient adjunct to steroid treatment for enhancing the improvement in hearing, especially in the low-tone range, in patients with sudden sensorineural hearing loss.
A protein–protein interaction map of yeast RNA polymerase III (1999)

The structure of the yeast RNA polymerase (pol) III was investigated by exhaustive two-hybrid screening using a library of random genomic fragments fused to the Gal4 activation domain. This procedure allowed us to identify contacts between individual polypeptides, localize the contact domains, and deduce a protein-protein interaction map of the multisubunit enzyme. In all but one case, pol III subunits were able to interact in vivo with one or sometimes two partner subunits of the enzyme or with subunits of TFIIIC. Four subunits that are common to pol I, II, and III (ABC27, ABC14.5, ABC10alpha, and ABC10beta), two that are common to pol I and III (AC40 and AC19), and one pol III-specific subunit (C11) can associate with defined regions of the two large subunits. These regions overlapped with highly conserved domains. C53, a pol III-specific subunit, interacted with a 37-kDa polypeptide that copurifies with the enzyme and therefore appears to be a unique pol III subunit (C37). Together with parallel interaction studies based on dosage-dependent suppression of conditional mutants, our data suggest a model of the pol III preinitiation complex.
[Development of anti cancer drugs targeted on Fas-mediated apoptosis signal]. (1997)

The elimination of tumor cells by cytotoxic T lymphocytes (CTLs) is, in part, executed by inducing apoptosis through the cell surface antigen Fas on the target cells. There are many cancer cells that resist Fas-mediated apoptosis. To elucidate the mechanism of this resistance is very important to understand the process of tumor development. We focused on FAP-1 (Fas-associated phos phatase-1), a negative regulator of Fas-mediated apoptosis. The expression of FAP-1 was detected in many colon cancer cell lines. On the other hand no FAP-1 expression was detected in the normal colon tissue. We have found that the tri-peptide of Fas C-terminus inhibited the binding of Fas and FAP-1 in vitro. Microinjection of the tri peptide (Ac SLV) could induce Fas-mediated apoptosis in the DLD 1 human colon cancer cell line that was resistant to anti-Fas-antibody. These findings suggest that the interaction of Fas and FAP-1 has a very important role in Fas-mediated apoptosis signal transduction. The inhibition of the Fas/ FAP-1 binding will provide a good target to develop anti-cancer drugs.
Mitochondrial loss, dysfunction and altered dynamics in Huntington's disease (2010)

Although a direct causative pathway from the gene mutation to the selective neostriatal neurodegeneration remains unclear in Huntington's disease (HD), one putative pathological mechanism reported to play a prominent role in the pathogenesis of this neurological disorder is mitochondrial dysfunction. We examined mitochondria in preferentially vulnerable striatal calbindin-positive neurons in moderate-to-severe grade HD patients, using antisera against mitochondrial markers of COX2, SOD2 and cytochrome c. Combined calbindin and mitochondrial marker immunofluorescence showed a significant and progressive grade-dependent reduction in the number of mitochondria in spiny striatal neurons, with marked alteration in size. Consistent with mitochondrial loss, there was a reduction in COX2 protein levels using western analysis that corresponded with disease severity. In addition, both mitochondrial transcription factor A, a regulator of mtDNA, and peroxisome proliferator-activated receptor-co-activator gamma-1 alpha, a key transcriptional regulator of energy metabolism and mitochondrial biogenesis, were also significantly reduced with increasing disease severity. Abnormalities in mitochondrial dynamics were observed, showing a significant increase in the fission protein Drp1 and a reduction in the expression of the fusion protein mitofusin 1. Lastly, mitochondrial PCR array profiling in HD caudate nucleus specimens showed increased mRNA expression of proteins involved in mitochondrial localization, membrane translocation and polarization and transport that paralleled mitochondrial derangement. These findings reveal that there are both mitochondrial loss and altered mitochondrial morphogenesis with increased mitochondrial fission and reduced fusion in HD. These findings provide further evidence that mitochondrial dysfunction plays a critical role in the pathogenesis of HD.
Defect Engineering in π-Conjugated Polymers (2009)

The optoelectronic properties of thin films of poly(3-hexylthiophene) (P3HT) are markedly improved by treating the polymer in solution with either electrophiles or nucleophiles. The work function is strongly decreased by treatment with lithium aluminum hydride, consistent with hydride ion addition and the observed ∼400-fold decrease in p-type defect density. The exciton diffusion length (Lex) doubled to 14 nm, while the bulk carrier mobility (μ) improved by more than an order of magnitude to 2.4 × 10−3 cm2/(V s). The work function is increased after treatment with dimethylsulfate, which is consistent with methyl cation addition and, again, both Lex and μ are increased substantially. Both treatments greatly improve the polymer’s stability against photo-oxidation. We discuss these results in the framework of defect engineering in organic semiconductors, in analogy to defect engineering studies of inorganic semiconductors.
Developing Fluency in the Disabled Reader (1983)

As a reading teacher, do you know of a third grader or older student exhibiting the following reading difficulties? (1) The student is unsure of high frequency words such as the Dolch words. (2) The student is a word-by-word reader. (3) The student reads connected discourse in a disjointed manner- ignoring punctuation, making abnormal pausal units, etc. (4) The student frequently repeats words and phrases. In general, this type of student has difficulties comprehending text, and lacks the desire and motivation to pursue reading. These reading difficulties describe students who have trouble with fluency. If you are teaching students with fluency problems, the suggested strategies that follow can aid you in helping students overcome these problematic behaviors.
Therapy with oral clotrimazole induces inhibition of the Gardos channel and reduction of erythrocyte dehydration in patients with sickle cell disease. (1996)

Pathologic water loss from sickle erythrocytes concentrates the abnormal hemoglobin and promotes sickling. The Ca2+-activated K+ channel (Gardos channel) contributes to this deleterious dehydration in vitro, and blockade of K+ and water loss via this channel could be a potential therapy in vivo. We treated five subjects who have sickle cell anemia with oral clotrimazole, a specific Gardos channel inhibitor. Patients were started on a dose of 10 mg clotrimazole/kg/d for one week. Protocol design allowed the daily dose to be escalated by 10 mg/kg each week until significant changes in erythrocyte density and K+ transport were achieved. Blood was sampled three times a week for hematological and chemical assays, erythrocyte density, cation content, and K+ transport. At dosages of 20 mg clotrimazole/kg/d, all subjects showed Gardos channel inhibition, reduced erythrocyte dehydration, increased cell K+ content, and somewhat increased hemoglobin levels. Adverse effects were limited to mild/moderate dysuria in all subjects, and a reversible increase in plasma alanine transaminase and aspartic transaminase levels in two subjects treated with 30 mg clotrimazole/kg/d. This is the first in vivo evidence that the Gardos channel causes dehydration of sickle erythrocytes, and that its pharmacologic inhibition provides a realistic antisickling strategy.
The phosphatidylinositol 3-kinase alpha is required for DNA synthesis induced by some, but not all, growth factors. (1994)

The phosphatidylinositol 3-kinase (PI 3-K) becomes activated when quiescent cells are stimulated with a variety of growth factors. We have microinjected antibodies specific for the p110 alpha subunit of the PI 3-K into quiescent fibroblasts and tested their effect on the ability of growth factors to stimulate exit from quiescence and entry into S phase. The antibodies inhibited platelet-derived growth factor-induced DNA synthesis, a result in keeping with previous studies using mutant platelet-derived growth factor receptors. Interestingly, functional PI 3-K was required for the first 6 hr of G1--i.e., until approximately 4 hr before the point at which the cells were committed to make DNA. A second tyrosine kinase receptor, the epidermal growth factor receptor, also required the PI 3-K for efficient signaling. However, colony-stimulating factor 1 (whose receptor is highly related to the platelet-derived growth factor receptor) could induce DNA synthesis in the absence of active PI 3-K, as could two growth factors (bombesin and lysophosphatidic acid) whose receptors are functionally coupled to G proteins. These data, therefore, demonstrate that some, but not all, growth factors require functional PI 3-K.
Peroxisome Proliferator-activated Receptor γ (PPARγ) as a Molecular Target for the Soy Phytoestrogen Genistein (2003)

The principal soy phytoestrogen genistein has an array of biological actions. It binds to estrogen receptor (ER) alpha and beta and has ER-mediated estrogenic effects. In addition, it has antiestrogenic effects as well as non-ER-mediated effects such as inhibition of tyrosine kinase. Because of its complex biological actions, the molecular mechanisms of action of genistein are poorly understood. Here we show that genistein dose-dependently increases estrogenic transcriptional activity in mesenchymal progenitor cells, but its biological effects on osteogenesis and adipogenesis are different. At low concentrations (< or =1 microm), genistein acts as estrogen, stimulating osteogenesis and inhibiting adipogenesis. At high concentrations (>1 microm), however, genistein acts as a ligand of PPARgamma, leading to up-regulation of adipogenesis and down-regulation of osteogenesis. Transfection experiments show that activation of PPARgamma by genistein at the micromolar concentrations down-regulates its estrogenic transcriptional activity, while activation of ERalpha or ERbeta by genistein down-regulates PPARgamma transcriptional activity. Genistein concurrently activates two different transcriptional factors, ERs and PPARgamma, which have opposite effects on osteogenesis or adipogenesis. As a result, the balance between activated ERs and PPARgamma determines the biological effects of genistein on osteogenesis and adipogenesis. Our findings may explain distinct effects of genistein in different tissues.
A Decade of Development in Immunoassay Methodology (1990)

Immunoassays are now very widely used in the clinical laboratory, either because no other type of assay system is feasible or because they are often the most effective and suitable of the possible analytical methods. The last decade has seen the development and refinement of many new immunoassay reagents and systems. The major trend has been away from liquid-phase assays involving radioisotopic labels, towards fast homogeneous or solid-phase assays capable of operation anywhere; and towards precise and reliable nonisotopic, automated or semi-automated laboratory assays, often with detection limits measured in pico- or attomoles. The use of monoclonal antibodies is now widespread, and the methodologies of labels and of solid-phase components are much more sophisticated. New assay formulations, novel homogeneous systems, immunosensors, free-analyte assays, the importance of thorough validation and of interfering substances, and future trends are discussed.
Real-time drawing assistance through crowdsourcing (2013)

We propose a new method for the large-scale collection and analysis of drawings by using a mobile game specifically designed to collect such data. Analyzing this crowdsourced drawing database, we build a spatially varying model of artistic consensus at the stroke level. We then present a surprisingly simple stroke-correction method which uses our artistic consensus model to improve strokes in real-time. Importantly, our auto-corrections run interactively and appear nearly invisible to the user while seamlessly preserving artistic intent. Closing the loop, the game itself serves as a platform for large-scale evaluation of the effectiveness of our stroke correction algorithm.
Analysis of endogenous peptides bound by soluble MHC class I molecules: a novel approach for identifying tumor-specific antigens (2002)

The Human MHC Project aims at comprehensive cataloging of peptides presented within the context of different human leukocyte antigens (HLA) expressed by cells of various tissue origins, both in health and in disease. Of major interest are peptides presented on cancer cells, which include peptides derived from tumor antigens that are of interest for immunotherapy. Here, HLA-restricted tumor-specific antigens were identified by transfecting human breast, ovarian and prostate tumor cell lines with truncated genes of HLA-A2 and HLA-B7. Soluble HLA secreted by these cell lines were purified by affinity chromatography and analyzed by nano-capillary electrospray ionization-tandem mass spectrometry. Typically, a large peptide pool was recovered and sequenced including peptides derived from MAGE-B2 and mucin and other new tumor-derived antigens that may serve as potential candidates for immunotherapy.