gebhart/patrepeval huggingface dataset:
Dihydrotestosterone Concentration of Beagle Prostatic Tissue: Effect of Age and Hyperplasia* (1983)

Dihydrotestosterone (DHT) concentration was measured in prostatic tissue obtained from castrate or intact beagles treated with androgens and/or estradiol-17 beta. Also DHT concentration was measured in prostatic tissue of beagles ranging from 0.7-9.2 yr; some with and others without spontaneously occurring benign prostatic hyperplasia (BPH). Three major results were forthcoming. First, a linear, positive correlation was observed between prostatic weight and DHT concentration in castrated or intact beagles treated with 11 of 15 steroid hormone regimens. Four additional treatments including intact or castrated beagles treated with either DHT or 5 alpha-androstan-3 alpha,17 beta-diol alone resulted in high concentrations of prostatic DHT but not equally high prostatic weight. Thus, prostatic DHT concentration is not always tightly coupled with prostate weight in the beagle. Second, there was no significant (P greater than 0.25) difference in prostatic DHT concentration between dogs with histologically normal prostates and those with spontaneous BPH. Thus, contrary to earlier reports, the tissue concentration of DHT in dog prostatic hyperplasia is not supranormal. Third, there was a dramatic change in prostatic DHT concentration which peaked at 3.8 yr. We conclude that steroid hormone treatment regimens which caused elevated prostatic DHT concentrations did not always result in equally high prostatic weight in the beagle. Also, if androgens like DHT are related causally to BPH in the dog, they probably play a permissive rather than an inductive role in the disease process.
Surface Properties of Bottlebrush Polymer Thin Films (2012)

Bottlebrush polymer thin films may be attractive for the preparation of antifouling and/or stimuli-responsive surface coatings due to the high grafting density and conformational flexibility of polymeric side chains, but bottlebrush polymer thin films have not been previously reported and their surface properties are unknown. Herein, we report a study of the surface properties of mixed bottlebrush polymer (MBBPs) films. MBBPs with hydrophobic polystyrene (PS) and hydrophilic poly(ethylene glycol) (PEG) side chains are synthesized using a “grafting-through” ring-opening metathesis polymerization (ROMP) approach. Stimuli-responsive MBBPs films are prepared by spin-casting a solution of MBBPs onto a solid surface, and the resulting film morphology and surface properties are characterized using atomic force microscopy (AFM), grazing-incidence small-angle X-ray scattering (GISAXS), water contact angle measurements, and X-ray photoelectron spectroscopy (XPS). The water contact angles of MBBPs films decrease or increase upon exposure of the MBBPs films to selective solvents methanol or cyclohexane, respectively. This contact angle change is dependent on the length of the PEG side chain; longer PEG side chains result in greater contact angle changes with solvent exposure. Consistent with water-contact angle measurements, XPS indicates enrichment of PEG or PS chains at the film surface after exposure of the MBBPs film to methanol or cyclohexane solvent vapors, respectively. Finally, it is demonstrated that bottlebrush polymer films can be stabilized by the addition of a radical cross-linker and irradiation with UV light. This work demonstrates that bottlebrush polymers enable the preparation of stimuli-responsive, “brush-like” polymeric coatings using simple solution processing methods.
Safety and immunogenicity in humans of an attenuated Salmonella typhi vaccine vector strain expressing plasmid-encoded hepatitis B antigens stabilized by the Asd-balanced lethal vector system (1997)

Attenuated Salmonella typhi organisms which express genes encoding protective antigens of other pathogens have been developed for use as experimental oral vaccines. A delta asd S. typhi strain attenuated by deletions in cya, crp, and cdt which contains hepatitis B core (HBc) and pre-S genes encoded on an Asd+ pBR-based plasmid vector was constructed. Healthy adult volunteers ingested a single dose of 5 x 10(5) to 5 x 10(8) CFU of strain chi4073 (delta cya delta crp delta cdt S. typhi Ty2), 6 x 10(7) or 1 x 10(9) CFU of strain chi4632(pYA3149), a further derivative of chi4073 deleted in asd and containing the Asd+ vector without the HBc-pre-S fusion, or 3 x 10(7) or 7 x 10(8) CFU of strain X4632(pYA3167), a derivative containing the vector with the HBc-pre-S fusion. Chi4073 was generally well tolerated by 22 volunteers. No volunteer had fever or positive blood cultures; 4 of 22 volunteers shed vaccine organisms in the stool in the first 48 h only. Two of 18 volunteers who received one of the plasmid-containing derivatives of chi4073 developed low-grade fevers on day 10 or 12 after ingestion. One of these volunteers had positive blood cultures on days 7 and 8. Seven of these 18 volunteers had vaccine organisms detected in their stools in the first 48 h only. Most volunteers developed S. typhi-specific serum responses and developed S. typhi-specific antibody-secreting cells. However, no volunteer developed serum antibody to hepatitis pre-S or pre-S-specific antibody-secreting cells. Although the parent strain chi4073 was well tolerated, induced immunoglobulin G seroconversion to S. typhi lipopolysaccharide in 80 to 100% of vaccinees and stimulated specific IgA-secreting lymphocytes in 80 to 100% of vaccinees given a single oral dose of 2 x 10(7) and 5 x 10(8) CFU, chi4073 derivatives containing the Asd+ vector with and without sequences encoding the HBc-pre-S fusion caused occasional febrile reactions at high doses and did not stimulate detectable immune responses to hepatitis B antigens.
Using standardised patients to measure physicians' practice: validation study using audio recordings (2002)

Standardised patients' assessments seem to be a valid measure of the quality of physicians' care for a variety of common medical conditions in actual outpatient settings. Properly trained standardised patients compare well with independent assessment of recordings of the consultations and may justify their use as a "gold standard" in comparing the quality of care across sites or evaluating data obtained from other sources, such as medical records and clinical vignettes.
Granulocyte‐macrophage–colony‐stimulating factor added to a multipeptide vaccine for resected Stage II melanoma (2002)

These data suggest a significant number of patients with resected melanoma mount an antigen-specific immune response against a peptide vaccine. There is a trend for GM-CSF to modestly increase the immune response and support further development of GM-CSF as a vaccine adjuvant.
Terminal ion pairs stabilize the second β‐hairpin of the B1 domain of protein G (2006)

The effects of terminal ion pairs on the stability of a beta-hairpin peptide corresponding to the C-terminal residues of the B1 domain of protein G were determined using thermal unfolding as monitored by nuclear magnetic resonance and circular dichroism spectroscopy. Molecular dynamics (MD) simulations were also performed to examine the effect of ion pairs on the structures. Eight peptides were studied including the wild type (G41) and the N-terminal modified sequences that had the first residue deleted (E42), replaced with a Lys (K41), or extended by an additional Gly (G40). Acetylated variants were made to examine the effect of removing the positive N-terminal charge on beta-hairpin stability. The rank in stability determined experimentally is K41 > E42 approximately G41 approximately G40 > Ac-K41 > Ac-E42 approximately Ac-G41 > Ac-G40. The Tm of the K41 peptide is 12 degrees C higher than G41, while the Tm values for the acetylated peptides are less than their unacetylated forms by more than 15 degrees C. NOE cross-peaks between side-chain methylene groups at the N- and C-termini and larger CalphaH shifts compared to random values are seen for K41. The addition of 20% methanol increases the stability in K41 and G41. The MD studies complement these results by showing that the charged N-terminus is important to stability. The type of ion pair observed varies with peptide, and when formed the simulations show that the ion pair can prevent fraying of the beta-strands through electrostatic and hydrophobic contacts. Therefore, introducing favorable electrostatic interactions at the N- and C-termini can substantially enhance beta-hairpin stability and help define the structure.
Induction of the Mammalian GRP78/BiP Gene by Ca 2+ Depletion and Formation of Aberrant Proteins: Activation of the Conserved Stress-Inducible grp Core Promoter Element by the Human Nuclear Factor YY1 (1997)

Previously, we have identified a constitutive nuclear factor, p70CORE, from HeLa cell nuclear extract which interacts specifically with the stress-inducible change region (SICR) of the grp78 promoter. Here we report that p70CORE is identical to YY1, a member of the GLI zinc finger family, by criteria of biochemical properties including apparent molecular weight, binding site homology, immunoreactivity, and affinity purification. Recombinant YY1 binds the double-stranded SICR with high specificity but has no affinity for its single-stranded form. In cotransfection studies, YY1 specifically enhanced the transcriptional activation of the grp78 promoter under a variety of stress conditions: depletion of the endoplasmic reticulum calcium stores, protein glycosylation block, and formation of aberrant proteins by azetidine treatment. In contrast, YY1 has minimal effect on the stress induction of the hsp70 promoter. YY1 enhancement of the grp78 stress response is dependent on its DNA-binding domain, with little effect on the basal expression of the promoter. The effect of YY1 transactivation may be mediated by the highly conserved grp78 core element. This is the first example of the ubiquitous factor YY1 involved in regulating inducible gene expression and its involvement in mediating stress signals generated from the endoplasmic reticulum to the nucleus.
Protection against myocardial dysfunction induced by global ischemia-reperfusion by antisense-oligodeoxynucleotides directed at beta(1)-adrenoceptor mRNA. (2000)

Plasma catecholamine levels rise, and myocardial beta(1)-adrenoceptor (beta(1)-AR) sensitivity increases during ischemia. These factors enhance myocardial injury and cardiac dysfunction. beta(1)-AR blockers are clinically used to protect heart against ischemia and to improve cardiac dysfunction in patients with ischemic heart disease, but these agents often cause intolerable side effects. To examine the potential cardioprotective effect of therapy with antisense-oligodeoxynucleotides directed at beta(1)-AR mRNA (beta(1)-AS-ODNs) during myocardial ischemia-reperfusion, Sprague-Dawley rats were treated with beta(1)-AS-ODNs or inverted-oligodeoxynucleotides (IN-ODNs), each 200 microg/rat. Hearts were excised, perfused, and subjected to global ischemia (30 min) followed by reperfusion (30 min). Other rats were given selective beta(1)-AR blocker atenolol (2 mg/kg) or saline before excising the hearts. Ischemia-reperfusion resulted in cardiac dysfunction, indicated by an increase in coronary perfusion pressure and left ventricular end-diastolic pressure and a decrease in developed left ventricular pressure, as well as evidence of lipid peroxidation in saline-treated rats (all P <.05 versus control values). Administration of AS-ODNs or atenolol, but not IN-ODNs, protected hearts against functional deterioration and lipid peroxidation (P <.05 versus saline or IN-ODNs treatment). AS-ODNs therapy appeared to be equivalent to atenolol in these effects. Expression of beta(1)-AR protein as well as mRNA in the myocardium were markedly up-regulated after ischemia-reperfusion, and treatment with beta(1)-AS-ODNs, but not atenolol, decreased the rise in enhanced expression of beta(1)-AR. These observations imply that beta(1)-AS-ODNs can ameliorate cardiac dysfunction after ischemia-reperfusion by reducing the expression of beta(1)-AR in the ischemic-reperfused myocardium.
Toxic phytoplankton blooms in the sea : proceedings of the Fifth International Conference on Toxic Marine Phytoplankton, Newport, Rhode Island, U.S.A., 28 October-1 November 1991 (1993)

Dedicatory (1 paper). Blooms: Status, Trends and Patterns (9 papers). Organisms: Speciation, Taxonomy, Life Cycle, Dispersal (19 papers). Regional Blooms, Toxic Outbreaks, Management (29 papers). PSP and Shellfish (1 4 papers). Ciguatoxicity, DSP, Dinophysis, Okadaic Acid (23 papers). Domoic Acid, Nitzschia, Harmful Diatoms (10 papers). Brown Tide Blooms Harmful and Toxic Phytoflagellates (9 papers). Autecology and Bloom Ecology (23 papers). Biochemistry, Toxigenesis, Analytical Techniques (12 papers).
Hematologic Malignancies (2001)

This article reviews highlights in the field of hematologic malignancies presented at the 2001 annual meeting of the American Society of Clinical Oncology. Targeted therapies continue to proceed from the laboratory to the clinic. Monoclonal antibody-based therapies predominate, and further data on radioimmunoconjugates (RICs) (tositumomab and Iodine 131 tositumomab [Bexxar] and ibritumomab tiuxetan [Zevalin]) are presented. Both agents have high response rates in relapsed B-cell non-Hodgkin's lymphoma (NHL). Results from the first trial directly comparing an RIC (Zevalin) to an unconjugated antibody (rituximab) are presented. A novel application of RIC therapy as part of high-dose therapy for mantle cell NHL is described. A new fusion toxin, BL22, targets the CD22 antigen and shows marked activity in the treatment of hairy cell leukemia. Similarly, the Hu1D10 monoclonal antibody has activity in B-cell NHL and might have a relatively unique mechanism of action. Finally, advances in the treatment of mucositis are described. These abstracts all describe therapies derived from our enhanced understanding of tumor immunology and molecular biology.
Large‐scale genomic analysis of ovarian carcinomas (2008)

Epithelial ovarian cancers are typified by frequent genomic aberrations that have been difficult to unravel. Recently, high-resolution array technologies have provided the first glimpse of the remarkable complexity of these aberrations with some ovarian cancers containing hundreds of copy number breakpoints, micro-deletions and amplifications. Many of these alterations contain cancer-related genes suggesting that the majority is disease-associated and not just the product of random genomic instability. Future developments such as next-generation sequencing and integrated analysis of data from multiple array platforms on large numbers of samples are poised to revolutionize our understanding of this complex disease.
The Role of the Cannabinoid CB2 Receptor in Pain Transmission and Therapeutic Potential of Small Molecule CB2 Receptor Agonists (2007)

This review gives a brief overview of the expression patterns, molecular pharmacology and physiological role of the cannabinoid 2 receptor (CB2) in pain. Particular emphasis is given to the therapeutic utility of CB2 receptor agonists. Through studies utilizing selective CB2 receptor agonists, non-selective cannabinoid agonists in conjunction with selective CB1 and CB2 receptor antagonists, or CB2 receptor knockout mice, it is now clear that this receptor plays a critical role in nociception. To this end, CB2 receptors have been shown to modulate acute pain, chronic inflammatory pain, post-surgical pain, cancer pain and pain associated with nerve injury. Here we review these studies and the compounds that were utilized. We hypothesize the mechanism of action by which the CB2 receptor could be involved in these processes. Finally we summarize the most recent novel chemical scaffolds that are being investigated towards advancing selective CB2 receptor agonists into the clinic. Many new pharmacological agents have been identified by high throughput screening and small molecule lead discovery and optimization in the past 10 years. It is anticipated that at least some of these agents may ultimately constitute effective new pain therapeutics that lack the side effects associated with traditional cannabinoid ligands.
Genotyping SNPs With Molecular Beacons (2003)

Single-nucleotide substitutions represent the largest source of diversity in the human genome. Some of these variations have been directly linked to human disease, though the vast majority are neutral. Even neutral variations are important because they provide guideposts in the preparation of detailed maps of the human genome, serving as essential elements in linkage analyses that identify genes responsible for complex disorders (). Although sequencing is adequate for the initial discovery of single-nucleotide variations, simpler, faster, and more automated genotyping methods are needed for routine clinical diagnostics and population studies. High-throughput methods are essential for understanding the distribution of genetic variations in populations, as well as for identifying the genes responsible for genetic disorders. Current alternatives to sequence analysis either miss some single-nucleotide substitutions or are too complex to enable high-throughput assays ().
In vitro fibroblast seeding of prosthetic anterior cruciate ligaments (1988)

To evaluate the effect of in vitro seeding of fibroblasts on the connective tissue encapsulation of implanted ligament prostheses, canine skin fibroblasts were grown in tissue culture and seeded onto knitted Dacron prostheses. When the cells on the prostheses reached contact growth inhibition, as determined by growth curves, the prostheses were implanted into the dogs' knees as ACL replacements. Gross and histologic evaluation at 4 and 8 weeks revealed that the seeded prostheses consistently showed more uniform and abundant encapsulation with connective tissue than did the control (unseeded) prostheses. The giant cell response observed in the tissue surrounding the unseeded prostheses was not noted in the seeded prostheses. This may be because seeding a prosthesis with fibroblasts prior to implantation "walls off" the prosthesis from the environment of the joint, and therefore the prosthesis may not elicit as great a foreign body response as does an unseeded prosthesis. The results of this preliminary study suggest that the in vitro seeding of a ligament prosthesis with fibroblasts accelerates the connective tissue encapsulation of the implanted prosthesis.
Cloning, nucleotide sequence, and regulatory analysis of the Lactococcus lactis dnaJ gene (1993)

The dnaJ gene of Lactococcus lactis was isolated from a genomic library of L. lactis NIZO R5 and cloned into pUC19. Nucleotide sequencing revealed an open reading frame of 1,137 bp in length, encoding a protein of 379 amino acids. The deduced amino acid sequence showed homology to the DnaJ proteins of Escherichia coli, Mycobacterium tuberculosis, Bacillus subtilis, and Clostridium acetobutylicum. The level of the dnaJ monocistronic mRNA increased approximately threefold after heat shock. The transcription initiation site of the dnaJ gene was determined and appeared to be preceded by a typical gram-positive vegetative promoter sequence (TTGCCA-17 bp-TAAAAT). Upstream of the promoter region, an inverted repeat is located that is identical to those detected upstream of heat shock genes of other gram-positive organisms. A transcriptional fusion between the dnaJ expression signals and a usp45-amyS secretion cassette caused a significant increase in alpha-amylase activity after heat shock induction. Deletion mutagenesis showed that the inverted repeat is involved in heat shock regulation of the dnaJ gene. The conservation of this palindromic sequence in gram-positive heat shock genes suggests a common regulatory pathway distinct from the system used in gram-negative bacteria.
Metabolism of 3-(p-bromophenyl)-1-methoxy-1-methylurea (metobromuron) by selected soil microorganisms (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMetabolism of 3-(p-bromophenyl)-1-methoxy-1-methylurea (metobromuron) by selected soil microorganismsBilly G. Tweedy, Carol. Loeppky, and James A. RossCite this: J. Agric. Food Chem. 1970, 18, 5, 851–853Publication Date (Print):May 1, 1970Publication History Published online1 May 2002Published inissue 1 May 1970https://pubs.acs.org/doi/10.1021/jf60171a031https://doi.org/10.1021/jf60171a031research-articleACS PublicationsRequest reuse permissionsArticle Views98Altmetric-Citations32LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Diagnostic workup and management of patients with suspected Niemann-Pick type C disease (2016)

Niemann-Pick type C (NP-C) disease is a neurovisceral disorder caused by mutations in the NPC1 and NPC2 genes. It is characterized by lysosomal storage of a broad range of lipids as a result of abnormal intracellular lipid trafficking. Typically patients develop neurodegeneration; however, the speed of disease progression is variable. The exact functions of NPC1 and NPC2 proteins have not been determined and therefore the molecular pathophysiology of NP-C is still not clearly understood. Due to the disease's rarity and clinical heterogeneity, delays from symptom onset to diagnosis and treatment initiation are common. Current therapeutic approaches focus on multidisciplinary symptom control and deceleration (rather than reversal) of disease progression. Thus identification of cases at early stages of disease is particularly important. Recent advances in genetic and biochemical testing have resulted in the generation of relatively non-invasive, quick and cost-effective laboratory assays that are highly sensitive and specific and have the capacity to enhance the clinicians' ability to reach a diagnosis earlier. Miglustat is a compound recently licensed in many countries for the treatment of NP-C that has been shown to decelerate neurological regression, whereas many other promising drugs are currently being trialled in preclinical models or human studies. This review summarizes key clinical, genetic and biochemical features of NP-C, suggests a simple diagnostic investigation strategy and gives an overview of available therapeutic options as well as potential novel treatments currently under development.
A Model for the Interaction of the GM-CSF, IL-3 and IL-5 Receptors with their Ligands (1993)

The high affinity receptors for GM-CSF, IL-3 and IL-5 are heterodimers consisting of a ligand-specific alpha chain and a common beta chain. These proteins are members of a family of proteins known as the "cytokine receptor family" which is characterized by the presence of a 200-residue ligand-binding module. The GM-CSF, IL-3 and IL-5 receptor alpha chains constitute a distinct subgroup and share features not found in other members of the cytokine receptor family, features which we propose to be important for their interaction with the common beta chain and for their binding of the structurally-related ligands. The growth hormone receptor is a well-characterized member of the cytokine receptor family. Based on the structure of the complex between growth hormone and its receptor, we have proposed sites of contact between the GM-CSF, IL-3 and IL-5 receptors and their cognate ligands.