gebhart/patrepeval huggingface dataset:
ODM-201, a new generation androgen receptor inhibitor for castration-resistant prostate cancer: Preclinical and phase I data. (2013)

65^ Background: Castration resistant prostate cancer (CRPC) is characterized by persistent, high level androgen receptor (AR) expression and resistance to conventional AR inhibitors. ODM-201 is a novel AR inhibitor with unique pharmacologic properties that has shown promising results in preclinical and clinical studies. Methods: AR binding affinity of ODM-201 to wild type AR was determined in cytosolic lysates obtained from ventral prostates of castrated rats using a competition binding assay. Additionally, effects of ODM-201 on the growth of castration resistant VCaP tumors was evaluated. Tumors were established by subcutaneous injection of VCaP prostate cancer cells into male nude mice. After initial tumor growth, mice were castrated. ODM-201 (50 mg/kg QD or BID orally) was initiated upon tumor regrowth. Since the risk of seizures has been reported for some second generation AR inhibitors, ODM-201 concentrations in mouse brain homogenates were studied after repeated oral administration to assess the risk. The clinical effects of ODM-201 (100, 200, 300, 500, 700, 900 mg BID) was examined in a Phase I/II dose-escalation trial in patients (N=24) with progressive metastatic CRPC. Results: ODM-201 binds to wild type AR with superior affinity compared to enzalutamide (Ki of 9 and 39 nM, respectively). In the VCaP CRPC model, ODM-201 significantly (p&lt;0.001 compared to castrated control), and more efficiently than enzalutamide, inhibited tumor growth. After oral administration, tissue/plasma ratio of ODM-201 in mouse brain homogenates was negligible in all studied doses. In the Phase I/II clinical study, ODM-201 (100 to 700 mg results available) was well tolerated, and most commonly reported adverse events were asthenia, diarrhea and nausea. A PSA response (defined as ≥ 50% decrease) was obtained in 13/15 patients evaluable at 12 weeks with all patients achieving partial response or stable disease by RECIST/PCWG2 criteria. Conclusions: ODM-201 is a new generation AR inhibitor with superior preclinical efficacy compared to enzalutamide and bicalutamide, it does not enter the brain in preclinical studies, and it shows very promising activity and no significant toxicity in patients with CRPC. Clinical trial information: NCT01317641.
Purification of human seminal plasma no. 7 antigen by immunoaffinity chromatography on bound monoclonal antibody. (1982)

Human seminal plasma (HSP) No. 7 antigen was purified by immunoaffinity chromatography on bound 1C4 monoclonal antibody (Moab) (Shigeta et al., 1980b). The pooled HSP protein was applied to a CNBr-activated Sepharose 4B column of bound 1C4 Moab gamma globulin and the antibody bound fraction (fr) eluted was further purified by rechromatography in the same way. The purified antigen in the antibody bound fr obtained by rechromatography gave a single band on SDS-PAGE in a position corresponding to a molecular weight of 15,000 daltons. This preparation was 196.2 times more effective than the original HSP protein in neutralizing the sperm immobilizing activity of 1C4 Moab. The purified HSP No. 7 antigen contained iron, but was different from lactoferrin and transferrin. It did not show any enzymatic activities, such as those of acid phosphatase, LDH or trypsin inhibitor, and shared antigenicity with human milk protein. It was present in seminal plasma as a molecule with a higher molecular weight but seemed to be cleaved to a monomer of 15,000 daltons during purification procedures. This antigen is present on spermatozoa as sperm-coating antigen and the corresponding antibody can immobilize spermatozoa with complement.
Immunoreactivity in mammals of two typical plant glyco-epitopes, core alpha(1,3)-fucose and core xylose (2002)

The presence of nonmammalian core alpha(1,3)-fucose and core xylose glyco-epitopes on glycans N-linked to therapeutic glycoproteins produced in plants has raised the question of their immunogenicity in human therapy. We address this question by studying the distribution of these N-glycans in pea, rice, and maize (which are the crops intended for the production of therapeutic proteins) and by reinvestigating their immunogenicity in rodents. We found that immunization with a model glycoprotein, horseradish peroxidase, elicits in C57BL/6 mice and rats the production of antibodies (Abs) specific for core alpha(1,3)-fucose and core xylose epitopes. Furthermore, we demonstrated that about 50% of nonallergic blood donors contains in their sera Abs specific for core xylose, whereas 25% have Abs against core alpha(1,3)-fucose. These Abs probably result from sensitization to environmental antigens. Although the immunological significance of these data is too speculative at the moment, the presence of such Abs might introduce some limitations to the use of plant-derived biopharmaceutical glycoproteins, such as an accelerated clearance during human therapy.
Adhesive and Elastic Properties of Thin Gel Layers (1999)

We employ linear elastic fracture mechanics to describe the adhesive and frictional properties of thin, elastic gel layers against a glass, hemispherical indenter. A triblock copolymer with poly (methyl methacrylate) endblocks and a poly (n-butyl acrylate) midblock is diluted with a selective solvent for the center block in order to form a low modulus, thermally reversible gel that behaves as an elastic solid at room temperature. Through simultaneous measurements of the circular contact area, normal displacement, and applied load, we show that the fracture mechanics expressions provide an accurate means to describe the adhesive behavior of the highly compliant polymer gels. By modifying the surface properties of the indenter, we show that the relationship between load and displacement is sensitive to the response of shear forces at the gel/indenter interface, whereas the relationship between the contact area and displacement is unaffected by this response. In addition, we demonstrate the utility of our methodology for quantifying adhesion in situations where the applied load cannot be measured directly.
The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator (2009)

The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na+) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor.
Ethyl-eicosapentaenoic acid reduces liver lipids and lowers plasma levels of lipids in mice fed a high-fat diet. (2009)

Fatty liver disease is characterized by a wide spectrum of liver damage, i.e. simple steatosis may progress to advanced fibrosis and to cryptogenic cirrhosis via steatohepatitis, and ultimately to hepatocellular carcinoma. Eicosapentaenoic acid (EPA), a marine-derived n-3 fatty acid like docosahexaenoic acid (DHA), is an anti-thrombotic and hypolipidemic agent, and is an antagonist of platelet aggregation and an inhibitor of cholesterol and lipoprotein. In an attempt to confirm the hypolipidemic action of this agent, the effects of EPA on liver and plasma levels of lipids in mice fed a high-fat diet were investigated. EPA markedly reduced the fatty droplets in the liver cells and the liver weight, also lowering plasma levels of total cholesterol, free total cholesterol, phospholipids and triglyceride. It is suggested that n-3 fatty acid intake and fish consumption may be able to prevent the occurrence not only of metabolic syndrome, but also of fatty liver and non-alcohlic steatohepatitis.
Alternative inclusion of fibroblast growth factor receptor 2 exon IIIc in Dunning prostate tumors reveals unexpected epithelial mesenchymal plasticity (2006)

In epithelial cells, alternative splicing of fibroblast growth factor receptor 2 (FGFR2) transcripts leads to the expression of the FGFR2(IIIb) isoform, whereas in mesenchymal cells, the same process results in the synthesis of FGFR2(IIIc). Expression of the FGFR2(IIIc) isoform during prostate tumor progression suggests a disruption of the epithelial character of these tumors. To visualize the use of FGFR2 exon IIIc in prostate AT3 tumors in syngeneic rats, we constructed minigene constructs that report on alternative splicing. Imaging these alternative splicing decisions revealed unexpected mesenchymal-epithelial transitions in these primary tumors. These transitions were observed more frequently where tumor cells were in contact with stroma. Indeed, these transitions were frequently observed among lung micrometastases in the organ parenchyma and immediately adjacent to blood vessels. Our data suggest an unforeseen relationship between epithelial mesenchymal plasticity and malignant fitness.
Frequent Inactivation of PTEN by Promoter Hypermethylation in Microsatellite Instability-High Sporadic Colorectal Cancers (2004)

Loss of PTEN tumor suppressor function is observed in tumors of breast, prostate, thyroid, and endometrial origin. Allelic losses in the proximity of the PTEN locus (10q23) also occur in sporadic colorectal cancers (CRCs), but biallelic inactivation of this site has not been frequently demonstrated. We hypothesized that alternative mechanisms of PTEN allelic inactivation, such as promoter hypermethylation, might be operative in CRC and that PTEN inactivation may be related to recognized forms of genomic instability. We characterized a cohort of 273 sporadic CRCs by determining their microsatellite instability (MSI) status. Of these, 146 cancers were examined for PTEN promoter methylation by methylation-specific PCR. Mutations at the poly(A)6 repeat sequences in PTEN exons 7 and 8 and deletions at the 10q23 locus were also identified using microsatellite analysis. The presence of PTEN protein was determined by immunostaining, and the results were correlated with the promoter methylation status. We observed that PTEN promoter hypermethylation was a frequent occurrence in MSI-high (MSI-H) tumors (19.1% of MSI-H versus 2.2% of MSI-low/microsatellite stable tumors; P = 0.002). A PTEN mutation or a deletion event was present in 60% of the tumors with promoter region hypermethylation. Hypermethylation of the PTEN promoter correlated significantly with either decreased or complete loss of PTEN protein expression (P = 0.004). This is the first demonstration of PTEN inactivation as a result of promoter hypermethylation in MSI-H sporadic CRCs. These data suggest that this silencing mechanism plays a major role in PTEN inactivation and, in colon cancer, may be more important than either allelic losses or inactivating mutations. The significant correlation of PTEN hypermethylation with MSI-H tumors further suggests that PTEN is an additional important "target" of methylation along with the hMLH1 gene in the evolution of MSI-H CRCs and also confers the "second hit" in the biallelic inactivation mechanism for some proportion of tumors.
Production of moth sex pheromones for pest control by yeast fermentation (2020)

The use of insect sex pheromones is an alternative technology for pest control in agriculture and forestry, which, in contrast to insecticides, does not have adverse effects on human health or environment and is efficient also against insecticide-resistant insect populations. Due to the high cost of chemically synthesized pheromones, mating disruption applications are currently primarily targeting higher value crops, such as fruits. Here we demonstrate a biotechnological method for the production of (Z)-hexadec-11-en-1-ol and (Z)-tetradec-9-en-1-ol, using engineered yeast cell factories. These unsaturated fatty alcohols are pheromone components or the immediate precursors of pheromone components of several economically important moth pests. Biosynthetic pathways towards several pheromones or their precursors were reconstructed in the oleaginous yeast Yarrowia lipolytica, which was further metabolically engineered for improved pheromone biosynthesis by decreasing fatty alcohol degradation and downregulating storage lipid accumulation. The sex pheromone of the cotton bollworm Helicoverpa armigera was produced by oxidation of fermented fatty alcohols into corresponding aldehydes. The resulting yeast-derived pheromone was just as efficient and specific for trapping of H. armigera male moths in cotton fields in Greece as a conventionally produced synthetic pheromone mixture. We further demonstrated the production of (Z)-tetradec-9-en-1-yl acetate, the main pheromone component of the fall armyworm Spodoptera frugiperda. Taken together our work describes a biotech platform for the production of commercially relevant titres of moth pheromones for pest control via yeast fermentation.
Amplicon Melting Analysis with Labeled Primers: A Closed-Tube Method for Differentiating Homozygotes and Heterozygotes (2003)

High-resolution melting analysis of PCR products amplified with labeled primers can identify both heterozygous and homozygous sequence variants.
Thermal protection materials: Thermophysical property data (1992)

This publication presents a thermophysical property survey on materials that could potentially be used for future spacecraft thermal protection systems (TPS). This includes data that was reported in the 1960's as well as more current information reported through the 1980's. An attempt was made to cite the manufacturers as well as the data source in the bibliography. This volume represents an attempt to provide in a single source a complete set of thermophysical data on a large variety of materials used in spacecraft TPS analysis. The property data is divided into two categories: ablative and reusable. The ablative materials have been compiled into twelve categories that are descriptive of the material composition. An attempt was made to define the Arrhenius equation for each material although this data may not be available for some materials. In a similar manner, char data may not be available for some of the ablative materials. The reusable materials have been divided into three basic categories: thermal protection materials (such as insulators), adhesives, and structural materials.
Abstract 3062: Minimally Invasive Epicardial Injection Using a Miniature Crawling Robotic Device Through a Subxiphoid Approach (2007)

Itroduction: We have developed a miniature crawling robot (HeartLander) that navigates on the surface of a heart to dedicate minimally invasive intrapericardial interventions. We performed a series of epicardial injections with the HeartLander using a beating porcine heart through a closed chest subxiphoid approach. Hypothesis: The HeartLander can provide precise and safe epicardial injections under the minimally invasive approach. Methods: HeartLander consists of two articulated modules that adhere to the epicardium using suction. The modules are each 6.5 mm tall and 8 mm wide, and include two working channels for instrumentation. Vacuum pressure and wire actuation for inchworm-like locomotion are provided through the tether of the robot. The device uses 3-D magnetic tracking for navigation, and a joystick for control input. The control software also enables semi-automated navigation to a selected target location, as well as pre-planning of injection locations after the target is reached. In 8 porcine preparations, the device was inserted into the pericardial space through a subxiphoid approach. Epicardial injection on the ventricular wall was performed with a dedicated injection needle device through the working port. Results: The HeartLander could precisely be maneuvered to designated targets. Injections into left ventricles (i.e. anterior, lateral, posterior walls) were successfully accomplished in all cases. Mean depth of injection was 3.1 ± 0.34 mm. Mean path length was 48 ± 10 mm. Mean speed was 22 ± 7 mm/min. Mean suction pressure and force on wires during trials was 562 ± 26 mmHg and 4.1 ± 0.9 Newton, respectively. The magnetic tracking system provided adequate visualization. Mean deviation from the target path was 0.2 ± 1.0 mm. Target acquisition was within 2.1 ± 1.4 mm. No fatal arrhythmia and bleeding were noted during the trials. There were no injuries to the heart and surrounding structures due to the robot locomotion. A histological study verified no epicardial damage. Conclusions: The HeartLander demonstrated successful epicardial injection on a beating porcine heart through a closed chest subxiphoid approach. This approach may facilitate the cardiac cell transplantation therapy in the field of minimally invasive surgery.
Investigating the pathogenesis of posttraumatic stress disorder with neuroimaging. (2001)

Rapidly evolving brain neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) are proving fruitful in exploring the pathogenesis and pathophysiology of posttraumatic stress disorder (PTSD). Structural abnormalities in PTSD found with MRI include nonspecific white matter lesions and decreased hippocampal volume. These abnormalities may reflect pretrauma vulnerability to develop PTSD, or they may be a consequence of traumatic exposure, PTSD, and/or PTSD sequelae. Functional neuroimaging symptom provocation and cognitive activation paradigms using PET measurement of regional cerebral blood flow have revealed greater activation of the amygdala and anterior paralimbic structures (which are known to be involved in processing negative emotions such as fear), greater deactivation of Broca's region (motor speech) and other nonlimbic cortical regions, and failure of activation of the cingulate cortex (which possibly plays an inhibitory role) in response to trauma-related stimuli in individuals with PTSD. Functional MRI research has shown the amygdala to be hyperresponsive to fear-related stimuli in this disorder. Research with PET suggests that cortical, notably hippocampal, metabolism is suppressed to a greater extent by pharmacologic stimulation of the noradrenergic system in persons with PTSD. The growth of knowledge concerning the anatomical and neurochemical basis of this important mental disorder will hopefully eventually lead to rational psychological and pharmacologic treatments.
Managing evaporation for more robust microscale assays : Part 2. Characterization of convection and diffusion for cell biology (2008)

Cell based microassays allow the screening of a multitude of culture conditions in parallel, which can be used for various applications from drug screening to fundamental cell biology research. Tubeless microfluidic devices based on passive pumping are a step towards accessible high throughput microassays, however they are vulnerable to evaporation. In addition to volume loss, evaporation can lead to the generation of small flows. Here, we focus on issues of convection and diffusion for cell culture in microchannels and particularly the transport of soluble factors secreted by cells. We find that even for humidity levels as high as 95%, convection in a passive pumping channel can significantly alter distributions of these factors and that appropriate system design can prevent convection.
CTCF: insights into insulator function during development (2012)

The genome of higher eukaryotes exhibits a patchwork of inactive and active genes. The nuclear protein CCCTC-binding factor (CTCF) when bound to insulator sequences can prevent undesirable crosstalk between active and inactive genomic regions, and it can also shield particular genes from enhancer function, a role that has many applications in development. Exciting recent work has demonstrated roles for CTCF in, for example, embryonic, neuronal and haematopoietic development. Here, we discuss the underlying mechanisms of developmentally regulated CTCF-dependent transcription in relation to model genes, and highlight genome-wide results indicating that CTCF might play a master role in regulating both activating and repressive transcription events at sites throughout the genome.
Accelerated Reendothelialization With Suppressed Thrombogenic Property and Neointimal Hyperplasia of Rabbit Jugular Vein Grafts by Adenovirus-Mediated Gene Transfer of C-Type Natriuretic Peptide (2002)

Infected Ad.CNP accelerated reendothelialization and suppressed thrombosis and neointimal hyperplasia. The method may potentially prevent vein graft disease in patients undergoing coronary artery revascularization.
Indigenous bacteria that influence the number of Salmonella typhimurium in the spleen of intravenously challenged mice (1980)

Intravenous inoculation of conventional mice with 6 out of 13 bacterial strains indigenous to the mouse gastrointestinal tract led to reduced numbers of Salmonella typhimurium in the spleen following intravenous challenge with the pathogen. Gnotobiotic mice harbouring an Enterococcus in their gastrointestinal tract did not have Salmonella in the spleen following intravenous challenge. Some germfree mice or gnotobiotic mice associated with a Lactobacillus strain, in contrast, had Salmonella in the spleen following challenge.
Running Microsoft Excel 4 (1991)

This book offers comprehensive coverage of Excel for Windows, taking users from the basics of using worksheets through creating macro applications. This book covers all the main features of the program (worksheets, databases, charts, macros) as well as how to use Excel with other applications. This edition, packed with examples and tutorials, will give beginner to advanced users an understanding of the latest version of Excel for Windows.
Distribution of Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) in Human Tissues: Cellular Surface Localization of HAI-1 in Simple Columnar Epithelium and Its Modulated Expression in Injured and Regenerative Tissues (1999)

We used a specific monoclonal antibody to human hepatocyte growth factor activator inhibitor type 1 (HAI-1) in immunohistochemical procedures to determine the distribution and localization of HAI-1 in human tissues. In normal adult tissues, HAI-1 was predominantly expressed in the simple columnar epithelium of the ducts, tubules, and mucosal surface of various organs. In all cases, HAI-1 was localized predominantly on the cellular lateral (or basolateral) surface. By contrast, hepatocytes, acinar cells, endocrine cells, stromal mesenchymal cells, and inflammatory cells were hardly stainable with the antibody, and stratified squamous epithelium showed only faint immunoreactivity on the surface of cells of the basal layer. In the gastrointestinal tract, the surface epithelium was strongly stained. RNA blot analysis confirmed the presence of specific mRNA transcript in the gastrointestinal mucosa, and in situ hybridization revealed that HAI-1 mRNA showed a similar cellular distribution pattern. Although HAI-1 was not expressed in normal hepatocytes, strong immunoreactivity was observed on the epithelium of pseudo-bile ducts and on the surface of scattered hepatocytes in fulminant hepatitis. The enhanced expression was also noted in regenerating tubule epithelial cells of the kidney after infarction. We conclude that HAI-1 is preferentially expressed in the simple columnar epithelium of the mucosal surface and duct, that the predominant localization of HAI-1 is the cell surface, and that the expression of HAI-1 can be modulated by tissue injury and regeneration.
Cyclic GMP phosphodiesterase from cattle retina (1986)

The primary structure of the gamma-subunit of cyclic GMP phosphodiesterase was determined by parallel analysis of the amino acid sequence of the protein and nucleotide sequence of the corresponding cDNA. The enzyme gamma-subunit contains 87 amino acid residues, its N-terminal amino group being acetylated.