gebhart/patrepeval huggingface dataset:
Mutations in the gene encoding the alpha subunit of the rod cGMP-gated channel in autosomal recessive retinitis pigmentosa. (1995)

Mutations in the genes encoding two proteins of the retinal rod phototransduction cascade, opsin and the beta subunit of rod cGMP phosphodiesterase, cause retinitis pigmentosa (RP) in some families. Here we report defects in a third member of this biochemical pathway in still other patients with this disease. We screened 94 unrelated patients with autosomal dominant RP and 173 unrelated patients with autosomal recessive RP for mutations in the gene encoding the alpha subunit of the rod cGMP-gated cation channel. Five mutant sequences cosegregated with disease among four unrelated families with autosomal recessive RP. Two of these were nonsense mutations early in the reading frame (Glu76End and Lys139End) and one was a deletion encompassing most if not all of the transcriptional unit; these three alleles would not be expected to encode a functional channel. The remaining two mutations were a missense mutation (Ser316Phe) and a frameshift [Arg654(1-bp del)] mutation truncating the last 32 aa in the C terminus. The latter two mutations were expressed in vitro and found to encode proteins that were predominantly retained inside the cell instead of being targeted to the plasma membrane. We conclude that the absence or paucity of functional cGMP-gated cation channels in the plasma membrane is deleterious to rod photoreceptors and is an uncommon cause of RP.
Aligning and Reorienting Carbon Nanotubes with Nematic Liquid Crystals (2004)

Exploiting the self‐assembling properties of liquid crystals , large‐scale spontaneous alignment of single‐ and multi‐walled carbon nanotubes induced by elastic interactions with the nematic LC matrix is demonstrated (see Figure). Collective reorientation processes of the liquid crystal are further used to reversibly manipulate the alignment direction of the dispersed nanotubes, as evidenced by conductivity measurements.
VEGF as a Therapeutic Target in Cancer (2005)

Tumors require nutrients and oxygen in order to grow, and new blood vessels, formed by the process of angiogenesis, provide these substrates. The key mediator of angiogenesis is vascular endothelial growth factor (VEGF), which is induced by many characteristics of tumors, most importantly hypoxia. Therefore, VEGF is an appealing target for anticancer therapeutics. In addition, VEGF is easy to access as it circulates in the blood and acts directly on endothelial cells. VEGF-mediated angiogenesis is rare in adult humans (except wound healing and female reproductive cycling), and so targeting the molecule should not affect other physiological processes. Tumor blood vessels, formed under the influence of VEGF, are disorganized, tortuous and leaky with high interstitial pressure, reducing access for chemotherapies. Inhibiting VEGF would reduce the vessel abnormality and increase the permeability of the tumor to chemotherapies. Several approaches to targeting VEGF have been investigated. The most common strategies have been receptor-targeted molecules and VEGF-targeting molecules. The disadvantage of receptor-targeted approaches is that the VEGF receptors also bind different members of the VEGF super-family and affect systems other than angiogenesis. The best-studied and most advanced approach to VEGF inhibition is the humanized monoclonal antibody bevacizumab (Avastin), which is the only anti-angiogenic agent approved for treatment of cancer.
Proteomics: A Cold Spring Harbor Laboratory Course Manual (2008)

Preface Introduction Experiments 1. Analysis of Whole-cell Lysates by Two-dimensional Gel Electrophoresis and MALDI Mass Spectrometry 2. Purification of Protein Complexes for Mass Spectrometry Analysis 3. Qualitative and Quantitative Measurement of Peptides with MALDI TOF/TOF Mass Spectrometry 4. Analysis of Protein Complexes: High-sensitivity Liquid Chromatography Coupled with Tandem Mass Spectrometry 5. Phosphopeptide Analysis Using IMAC and Mass Spectrometry 6. Multidimensional Protein Identification Technology (MudPIT) Analysis of Whole-cell Lysates 7. Quantitative Mass Spectrometry Analysis of Whole-cell Extracts (iTRAQ) 8. Analysis and Validation of Tandem Mass Spectra 9. High-throughput Cloning of ORFs: Assembling Large Sets of Expression Constructs 10. Construction of Protein Microarrays Nucleic Acid Programmable Protein Array (NAPPA) 11. Using the Nucleic Acid Programmable Protein Array (NAPPA) for Identifying Protein-Protein Interactions Appendices 1. Setup and Demonstration of a Nanoelectrospray Ionization (nanoESI) Source and Tandem Mass Spectrometry (MS/MS) 2. Solution Protein Digest 3. In-gel Trypsin Digest of Gel Fractionated Proteins 4. Trichloroacetic Acid (TCA) Precipitation of Proteins 5. Monoisotopic and Immonium Ion Masses of Amino Acids 6. Dipeptide Masses of Amino Acids 7. LTQ Instrument Methods 8. Off-line Desalting of Peptide Mixtures 9. Preparing Competent Cells 10. DNA Quantification 11. Cautions Index
Accelerated high‐sensitivity microsequencing of proteins and peptides using a miniature reaction cartridge (1992)

Greatly reduced automated protein sequencing degradation times of less than 25 min with concurrent on-line phenylthiohydantoin (PTH) derivative analysis times of less than 16 min have been achieved by using a miniaturized reaction cartridge with optimized chemical and analytical cycles. Using this method a wide range of standard and novel peptides and proteins have been sequenced with reproducibly high initial and repetitive cycle yields. In these accelerated analyses the recovery of the more labile PTH derivatives was markedly improved by using elevated pressure during cleavage steps and temperature programming throughout the Edman cycle.
Thermal stability of organic electroluminescent devices fabricated using novel charge transporting materials (1998)

Abstract Novel hole and electron transporting materials have been synthesized to improve the thermal stability of organic electroluminescent (EL) devices. Molecular structures of such hole and electron transporting materials were designed based on triphenylamine (TPA) and oxadiazole (OXD) moieties, respectively. It has been found that the resulting materials have high glass transition temperatures (Tg) over 100°C and the vacuum‐deposited thin films are significantly thermally stable. For the two‐layer EL devices using the novel hole transporting materials and the typical emitting material, tris(8‐quinolinolato) aluminum, the thermal stability has been clearly seen to depend on the Tg of the hole transporting material; excellent thermal stability was achieved. For the three‐layer EL device using the novel electron transporting material, good emission efficiency and good stability were achieved. The electron transporting materials have been also applied to the polymeric system with polyvinylcarbazole matrix.
Inheritance of Resistance to Soybean Mosaic Virus in ‘Buffalo’ and HLS Soybean (1992)

Soybean mosaic virus (SMV) is a major disease problem in soybean [ Glycine max (L.) Merr.] production in several regions in the world. The disease is controllable with plant resistance. This study was undertaken to elucidate the genetics of SMV resistance in the cultivar Buffalo and in the breeding line HLS so they can be used effectively in breeding programs. Buffalo and HLS were crossed to the SMV‐susceptible cultivar Jupiter and with each other. Portions of the F 1 , F 2 , and F 2:3 populations from each cross were inoculated with one of seven SMV strains (G1∓G7). Virus inoculations were done in the field or greenhouse using an air‐brush technique. Chi‐square analysis of the segregation ratios of populations from the Buffalo × Jupiter cross show that Buffalo's resistance to SMV strains Gl to G7 is under monogenie control, and exhibited dominance under the conditions of this study. Results of the HLS × Jupiter cross show that resistance in HLS to SMV strains G5, G6, and G7 is also conditioned by a single dominant gene. When inoculated with SMV strain G5, G6, or G7, populations of F 2 plants from the cross Buffalo × HLS segregated in the ratio of 15 resistant to 1 susceptible. This result, supported by the F 2:3 segregation data, suggests that the SMV resistance genes in Buffalo and HLS are located at different loci.
The major chlorophyll a/b binding protein of petunia is composed of several polypeptides encoded by a number of distinct nuclear genes. (1983)

Five distinct cDNA clones for the major chlorophyll a/b binding protein (Cab) of the petunia thylakoid membrane light-harvesting complex have been characterized. The nucleotide sequences of the polypeptide coding regions are similar between clones; however, the 3'-untranslated regions are divergent. Analysis of petunia nuclear DNA through genomic hybridizations and characterization of cloned nuclear fragments indicates there are at least sixteen genes for the major Cab protein. These genes can be classified into at least five small multigene families on the basis of their homology to the different cDNA clones. Two families contain only two genes each and in both cases the genes are closely linked in the genome. In one case, one gene is in an inverted orientation with respect to the other such that the 5' ends are adjacent; in the other case, the two genes are in a tandem array. Both genes from one of these families are transcribed in green leaves. The genes belonging to separate nuclear gene families encode different polypeptide components of the major Cab protein.
Src Family Kinases Mediate Epidermal Growth Factor Receptor Ligand Cleavage, Proliferation, and Invasion of Head and Neck Cancer Cells (2004)

Head and neck squamous cell carcinomas (HNSCCs) are characterized by up-regulation of the epidermal growth factor receptor (EGFR). We previously reported that a gastrin-releasing peptide/gastrin-releasing peptide receptor (GRP/GRPR) autocrine growth pathway is activated early in HNSCC carcinogenesis. GRP can induce rapid phosphorylation of EGFR and p42/44 mitogen-activated protein kinase (MAPK) activation in part via extracellular release of transforming growth factor alpha (TGF-alpha) by matrix metalloproteinases (MMPs). It has been reported that Src family kinases are activated by G-protein-coupled receptors (GPCRs), followed by downstream EGFR and MAPK activation. To further elucidate the mechanism of activation of EGFR by GRP in HNSCC, we investigated the role of Src family kinases. Blockade of Src family kinases using an Src-specific tyrosine kinase inhibitor A-419259 decreased GRP-induced EGFR phosphorylation and MAPK activation. GRP also failed to induce MAPK activation in dominant-negative c-Src-transfected HNSCC cells. Invasion and growth assays showed that c-Src was required for GRP-induced proliferation or invasion of HNSCC cells. In addition to TGF-alpha release, GRP induced amphiregulin, but not EGF, secretion into HNSCC cell culture medium, an effect that was blocked by the MMP inhibitor marimastat. TGF-alpha and amphiregulin secretion by GRP stimulation also was inhibited by blockade of Src family kinases. These results suggest that Src family kinases contribute to GRP-mediated EGFR growth and invasion pathways by facilitating cleavage and release of TGF-alpha and amphiregulin in HNSCC.
Regional Distribution of β-Adrenoceptors in the Human Heart (1986)

We evaluated the amount of beta 1- and beta 2-adrenoceptors in human right and left atrium as well as in right and left ventricular wall obtained from heart transplant recipients who suffered from end-stage congestive cardiomyopathy. The total number of myocardial beta-adrenoceptors was assessed with the nonsubtype selective beta-adrenoceptor radioligand (-)[125I]iodocyanopindolol (ICYP); concomitantly, the number of beta 1-adrenoceptors was determined with the selective beta 1-adrenoceptor radioligand (-)[3H]bisoprolol. The number of beta 2-adrenoceptors was calculated by subtracting (-)[3H]bisoprolol binding sites from ICYP binding sites. With this technique, a beta 1/beta 2-ratio of approximately 65/35% for both atria and of approximately 75/25% for both ventricles was found. Identical results were obtained when the beta 1/beta 2-ratio was calculated indirectly by nonlinear regression analysis of competition curves of the selective beta 1-adrenoceptor antagonist bisoprolol and the selective beta 2-adrenoceptor antagonist ICI 118,551 with ICYP binding. In addition, on atria and on ventricles, adenylate cyclase was activated by norepinephrine (presumably by beta 1- and beta 2-adrenoceptor stimulation) and by procaterol (by beta 2-adrenoceptor stimulation). It is concluded that in the human heart functional beta 1- and beta 2-adrenoceptors coexist on both atria and both ventricles. In end-stage congestive cardiomyopathy, there appears to be a selective down-regulation of cardiac beta 1-adrenoceptors, whereas beta 2-adrenoceptors are obviously not affected. This may explain the beneficial effects of beta 2-adrenoceptor agonists in severe heart failure.
Clinical Use of Anti‐CD25 Antibody Daclizumab to Enhance Immune Responses to Tumor Antigen Vaccination by Targeting Regulatory T cells (2009)

CD4(+) regulatory T cells frustrate productive tumor immune surveillance and represent an obstacle for cancer immunotherapy. In mice, anti-CD25 antibody is an effective method of depleting CD25(+) FOXP3(+) T regulatory cells (Tregs) in vivo and enhancing cancer immunity. Here, we propose the use of the anti-CD25 monoclonal antibody daclizumab for the depletion of Tregs in cancer patients. In early results from an ongoing clinical trial, a single intravenous infusion of daclizumab in patients with metastatic breast cancer is associated with a marked and prolonged elimination of CD25(+) FOXP3(+) Tregs in peripheral blood. When a cancer antigen peptide vaccine is administered during the daclizumab-induced Treg nadir, effective generation of cytotoxic T lymphocytes has been observed, including those specific for neo-antigens, such as cytomegalovirus peptide used as an immunological control. If confirmed in additional patients, these observations suggest that daclizumab may be an effective and available therapeutic agent for Treg modulation in patients with cancer.
Advances in lung adenocarcinoma classification: a summary of the new international multidisciplinary classification system (IASLC/ATS/ERS). (2014)

Due to advances in the understanding of lung adenocarcinoma since the advent of its 2004 World Health System classification, an international multidisciplinary panel [sponsored by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS)] has recently updated the classification system for lung adenocarcinoma, the most common histologic type of lung cancer. Here, we summarize and highlight the new criteria and terminology, certain aspects of its clinical relevance and its potential treatment impact, and future avenues of research related to the new system.
Fiber-Optic Microarray for Simultaneous Detection of Multiple Harmful Algal Bloom Species (2006)

Harmful algal blooms (HABs) are a serious threat to coastal resources, causing a variety of impacts on public health, regional economies, and ecosystems. Plankton analysis is a valuable component of many HAB monitoring and research programs, but the diversity of plankton poses a problem in discriminating toxic from nontoxic species using conventional detection methods. Here we describe a sensitive and specific sandwich hybridization assay that combines fiber-optic microarrays with oligonucleotide probes to detect and enumerate the HAB species Alexandrium fundyense, Alexandrium ostenfeldii, and Pseudo-nitzschia australis. Microarrays were prepared by loading oligonucleotide probe-coupled microspheres (diameter, 3 mum) onto the distal ends of chemically etched imaging fiber bundles. Hybridization of target rRNA from HAB cells to immobilized probes on the microspheres was visualized using Cy3-labeled secondary probes in a sandwich-type assay format. We applied these microarrays to the detection and enumeration of HAB cells in both cultured and field samples. Our study demonstrated a detection limit of approximately 5 cells for all three target organisms within 45 min, without a separate amplification step, in both sample types. We also developed a multiplexed microarray to detect the three HAB species simultaneously, which successfully detected the target organisms, alone and in combination, without cross-reactivity. Our study suggests that fiber-optic microarrays can be used for rapid and sensitive detection and potential enumeration of HAB species in the environment.
Number of adrenergic and Islet‐1 immunoreactive cells is increased in avian trunk neural crest cultures in the presence of human recombinant osteogenic protein‐1 (1995)

OP-1, also known as BMP-7, is a member of the TGF-beta superfamily of proteins and was originally identified on the basis of its ability to induce new bone formation in vivo. OP-1 mRNA is found in the developing kidney and adrenal gland as well as in some brain regions (Ozkaynak et al. [1991] Biochem. Biophys. Res. Commun. 179:116-123). We have tested the effect of recombinant human OP-1 on quail trunk neural crest cultures. The number of catecholamine-positive cells which developed after 7 days in vitro in the presence of OP-1 was increased in a dose-dependent manner, with a greater than 100-fold maximal stimulation observed. The increase in the number of catecholamine-positive cells in the presence of OP-1 was paralleled by an increase in the number of tyrosine hydroxylase (TH)-positive cells. In contrast, total and melanocyte cell number were unaffected by the presence of OP-1. The number of Islet-1-immunoreactive cells was also increased by OP-1, but to only about half the value seen for TH. Double label experiments revealed these Islet-1-positive cells were a subset of the TH-positive cells. Inhibitors of DNA synthesis prevented the OP-1-mediated increase in adrenergic cell number, indicating that OP-1 does not act on a postmitotic cell population. However, labeling studies with bromodeoxyuridine indicated that OP-1 did not increase the proportion of the cell population engaged in DNA synthesis. Thus, the OP-1-mediated increase in adrenergic cell number most likely occurs as a result of the enhanced survival of a subpopulation of adrenergic precursors or an increase in their probability of adrenergic differentiation, but not by increasing the mitotic rate of adrenergic precursors or adrenergic cells themselves. In contrast to OP-1, TGF-beta 1 decreased adrenergic cell number. When OP-1 and TGF-beta 1 were added simultaneously, TGF-beta 1 antagonized the OP-1-mediated increase in adrenergic cell number in a dose-dependent manner.
Regulation of the production of the RANTES chemokine by endothelial cells. Synergistic induction by IFN-gamma plus TNF-alpha and inhibition by IL-4 and IL-13. (1995)

Production by endothelial cells of the regulated on activation normal T expressed and secreted chemokine (RANTES) has recently been evidenced during delayed-type hypersensitivity (DTH) reactions and may contribute to the local accumulation of macrophages and CD4+ memory T lymphocytes. To document the mechanism inducing RANTES production in this condition, we analyzed the effect of cytokines known to influence the formation of DTH granulomas. Little or no RANTES was produced after stimulation of HUVEC with IFN-gamma, IL-1 beta, or TNF-alpha. However, the combination TNF-alpha+IFN-gamma induced a strong RANTES production. In situ hybridization experiments with a RANTES probe showed that this synergy was also observed at the mRNA level and that the effect of the combination was mainly to increase the amount of RANTES mRNA per cell. The expression of the luciferase gene under the control of the RANTES gene regulatory elements was analyzed; TNF-alpha and the combination TNF-alpha+IFN-gamma activated the regulatory elements. Sequential treatment of HUVEC with TNF-alpha and IFN-gamma showed that IFN-gamma sensitized HUVEC to the stimulating effect of TNF-alpha. The production of RANTES induced by TNF-alpha+IFN-gamma was partly but significantly inhibited by the Th2-type cytokines IL-4 and IL-13. In contrast, IL-10 had no effect. These results indicate that the microenvironment of DTH granulomas, containing high levels of both TNF-alpha and IFN-gamma, may be responsible for RANTES production by perigranulomatous endothelial cells. Inhibition of this production by Th2-type cytokines may be a mechanism by which these cytokines interfere with the formation of DTH granulomas.
Time-Varying Meshing Stiffness Calculation and Vibration Analysis for a 16DOF Dynamic Model With Linear Crack Growth in a Pinion (2011)

A modified mathematical model for simulating gear crack from root with linear growth path in a pinion is developed, in which an improved potential energy method is used to calculate the time-varying meshing stiffnesses of the meshing gear pair while we also take the deformation of gear-body into consideration. The formulas for the meshing stiffness are deduced when the crack grows as the linear growth path in the pinion. A 16DOF dynamic model of a one-stage spur gear system is used to study the response from the system considering time-varying meshing stiffnesses and different levels of crack growing in the pinion. As vibration signals induced by the tooth crack are buried in normal vibration signals which are induced by the normal gear pair in meshing at the early stage of crack growth, the algorithm combined autoregressive modeling method and demodulation method is proposed to process the signals to investigate the response characteristics as the crack grows, and the comparison of the relationship between indicators and the crack levels from different simulation methods are given.
Motivational systems of agonistic behavior in muroid rodents: A comparative review and neural model (1980)

The data on agonistic behavior of muroid rodents that have been obtained from field observations and laboratory experiments are reviewed and compared in terms of a hypothetical model of the neural organization of these behaviors. The neural model has been presented elsewhere and is used here only as a way to organize the data. The data are organized in terms of four hypothetical motivational systems: Offense, defense, submission, and patrol/marking. The various behaviors are considered as motor patterns and are compared and analyzed in terms of the proposed motivating, releasing, and directing stimuli of the motivational systems. Interactions and overlaps between the motivational systems are also considered. It is concluded that the organization of agonistic behavior may be similar across all species of muroid rodents. Generalizations are complicated by the profound effects of ontogenetic factors. Four categories of behaviors differ from species to species: Scent-marking, submissive behaviors, threat behaviors, and alarm signals. The possible phylogenetic and ontogenetic factors in these differences are considered.
Shear modulus imaging with 2-D transient elastography (2002)

In previous works, we have shown that time-resolved 2-D transient elastography is a promising technique for characterizing the elasticity of soft tissues. It involves the measurement of the displacements induced by the propagation of low frequency (LF) pulsed shear waves in biological tissues. In this paper, we present a novel apparatus that contains a LF vibrating device surrounding a linear array of 128 ultrasonic transducers that performs ultrafast ultrasonic imaging (up to 10,000 frames/s) and that is able to follow in real time the propagation of a LF shear wave in the human body. The vibrating device is made of two rods, fixed to electromagnetic vibrators, that produce in the ultrasonic image area a large amplitude shear wave. The geometry has been chosen both to enhance the sensitivity and to create a quasi linear shear wave front in the imaging plane. An inversion algorithm is used to recover the shear modulus map from the spatio-temporal data, and the first experimental results obtained from tissue-equivalent materials are presented.