gebhart/patrepeval huggingface dataset:
In vivo pharmacokinetics of selective mu-opioid peptide agonists. (2001)

Recent evidence suggests that highly selective mu-opioid agonists may provide good analgesia with less development of tolerance and dependence. H-Tyr-D-Arg-Phe-Lys-NH2 (DALDA) and H-Dmt-D-Arg-Phe-Lys-NH2 ([Dmt1]DALDA) were found to display high binding affinity and much greater selectivity for the mu-opioid receptor (K(i)delta/K(i)mu) > 10,000) compared with H-Tyr-D-Ala-Gly-MePhe-Gly-ol (DAMGO). In addition, [Dmt1]DALDA was 3000-fold more potent than morphine when administered intrathecally. A potential problem with peptide analogs as therapeutic agents is their susceptibility to enzymatic degradation in vivo and short elimination half-lives. In this study, we compared the stability of DAMGO, DALDA, and [Dmt1]DALDA after systemic administration in sheep. Peptide concentrations were measured using high performance liquid chromatography-mass spectrometry. When incubated in sheep blood at 37 degrees C, DAMGO, DALDA, and [Dmt1]DALDA were stable over 2 h. When given intravenously to sheep, the apparent volume of distribution was 50 to 80 ml/kg for all three peptides, suggesting that distribution was limited to blood volume. Plasma clearance of DAMGO (223 ml/kg/h) was 10-fold faster than DALDA and [Dmt1]DALDA (24 ml/kg/h), and their elimination half-lives were 0.24, 1.5, and 1.8 h, respectively. The half-lives of DALDA and [Dmt1]DALDA are even longer than morphine or meperidine in sheep. These favorable pharmacokinetic properties of DALDA and [Dmt1]DALDA, together with their mu-selectivity, potency, and long duration of action, make them ideal candidates as opioid analgesics.
An algorithm for matching anonymous hospital discharge records used in occupational disease surveillance: Anonymous record matching algorithm (1991)

The expense of collecting primary data, coupled with limited authority to mandate reporting, requires alternative methods of implementing an occupational disease registry in Illinois. One alternative data source for surveillance of some occupational diseases is hospital discharge records. Because these records lack personal identifiers, it has been impossible historically to match records belonging to the same individual and obtain reliable case estimates. To circumvent this difficulty, an algorithm has been developed to match anonymous hospital discharge records collected from all Illinois hospitals. The algorithm was based on the assumption that specific combinations of occupational disease code, sex, zip code, and date of birth would identify an individual to whom multiple hospitalizations belong. Matching with the algorithm reduced the 1986 case estimates from 597 to 499 for all cases of coal workers' pneumoconiosis, asbestosis, and silicosis.
Crosslinking of surface antigens causes mobilization of intracellular ionized calcium in T lymphocytes. (1987)

Antibodies binding to a large subset of T-cell differentiation antigens, including CD2, CD4, CD5, CD6, CD7, CD8, Tp44, and CDw18, cause an increase in the cytoplasmic calcium concentration [( Ca2+]i) after the antigens are crosslinked on the cell surface. Similar crosslinking-induced signals were seen for a subset of mouse thymocyte differentiation antigens. The various antigens on human T cells differed in the extent of crosslinking required for generating the calcium signal, as evidenced by comparisons with monoclonal versus polyclonal second-step antibody. The [Ca2+]i increase that occurs after crosslinking represents mobilization of cytoplasmic calcium since the initial component of the signal is resistant to depletion of extracellular calcium by chelation with EGTA. The [Ca2+]i increase is completely inhibited by pretreatment of cells with pertussis toxin, indicating that a substrate for pertussis toxin regulates the signal transduction. Crosslinking of antigens other than the CD3/T-cell receptor complex did not result in T-cell proliferation. Crosslinking of CD2 and Tp44, but not other antigens, resulted in expression of functional interleukin 2 receptors. Comparisons of three different anti-CD3 antibodies showed that a second calcium signal was generated by crosslinking, even when the anti-CD3 antibodies were used at optimal concentrations.
Ultrahigh-throughput discovery of promiscuous enzymes by picodroplet functional metagenomics (2015)

Unculturable bacterial communities provide a rich source of biocatalysts, but their experimental discovery by functional metagenomics is difficult, because the odds are stacked against the experimentor. Here we demonstrate functional screening of a million-membered metagenomic library in microfluidic picolitre droplet compartments. Using bait substrates, new hydrolases for sulfate monoesters and phosphotriesters were identified, mostly based on promiscuous activities presumed not to be under selection pressure. Spanning three protein superfamilies, these break new ground in sequence space: promiscuity now connects enzymes with only distantly related sequences. Most hits could not have been predicted by sequence analysis, because the desired activities have never been ascribed to similar sequences, showing how this approach complements bioinformatic harvesting of metagenomic sequencing data. Functional screening of a library of unprecedented size with excellent assay sensitivity has been instrumental in identifying rare genes constituting catalytically versatile hubs in sequence space as potential starting points for the acquisition of new functions.
ChemInform Abstract: A ONE POT SYNTHESIS OF UNSYMMETRICAL SECONDARY ALCOHOLS FROM TWO GRIGNARD REAGENTS (1981)

Abstract Bei der Behandlung mit unterschiedlichen Grignardverbindungen (II) bzw. (IV) erhält man aus N‐Methyl‐N‐formyl‐2‐amino‐pyridin (I) über die Zwischenstufen (III) die unsymmetrischen Carbinole (IV) unter Eliminierung von N‐Methyl‐2‐ amino‐pyridin (V).
Poly(vinyl alcohol) nanoparticles prepared by freezing–thawing process for protein/peptide drug delivery (1998)

Poly(vinyl alcohol) (PVA) hydrogel nanoparticles have been prepared by using a water-in-oil emulsion technology plus cyclic freezing-thawing process. The PVA hydrogel nanoparticles prepared by this method are suitable for protein/peptide drug delivery since formation of the hydrogel does not require crosslinking agents or other adjuvants and does not involve any residual monomer. Particularly, there is no emulsifier involved in this new method. Bovine serum albumin (BSA), as a model protein drug, is incorporated into the PVA hydrogel nanoparticles. The PVA hydrogel nanoparticles possess a skewed or log-normal size distribution. The average diameter of the PVA hydrogel nanoparticles is 675.5+/-42.7 nm. Protein drug loading efficiency in the PVA hydrogel nanoparticles is 96.2+/-3.8%. The PVA hydrogel nanoparticles swell in an aqueous solution and the swelling degree increases with the increase of temperature. In vitro release studies show that the BSA release from the nanoparticles can be prolonged to 30 h. The BSA release follows a diffusion-controlled mechanism. The number of freezing-thawing cycle and release temperature both influence BSA release rate considerably. Less freezing-thawing cycle or higher release temperature leads to faster drug release. The BSA is stable during preparation of the PVA hydrogel nanoparticles.
Removal of Drone Brood From <I>Apis mellifera</I> (Hymenoptera: Apidae) Colonies to Control <I>Varroa destructor</I> (Acari: Varroidae) and Retain Adult Drones (2009)

The parasitic mite Varroa destructor Anderson & Trueman (Acari: Varroidae) has plagued European honey bees, Apis mellifera L. (Hymenoptera: Apidae), in the Americas since its introduction in the 1980s. For many years, these mites were sufficiently controlled using synthetic acaricides. Recently, however, beekeepers have experienced increased resistance by mites to chemical pesticides, which are also known to leave residues in hive products such as wax and honey. Thus there has been increased emphasis on nonchemical integrated pest management control tactics for Varroa. Because mites preferentially reproduce in drone brood (pupal males), we developed a treatment strategy focusing on salvaging parasitized drones while removing mites from them. We removed drone brood from colonies in which there was no acaricidal application and banked them in separate "drone-brood receiving" colonies treated with pesticides to kill mites emerging with drones. We tested 20 colonies divided into three groups: 1) negative control (no mite treatment), 2) positive control (treatment with acaricides), and 3) drone-brood removal and placement into drone-brood receiving colonies. We found that drone-brood trapping significantly lowered mite numbers during the early months of the season, eliminating the need for additional control measures in the spring. However, mite levels in the drone-brood removal group increased later in the summer, suggesting that this benefit does not persist throughout the entire season. Our results suggest that this method of drone-brood trapping can be used as an element of an integrated control strategy to control varroa mites, eliminating a large portion of the Varroa population with limited chemical treatments while retaining the benefits of maintaining adult drones in the population.
One pair must last a lifetime. Case studies of foot care in diabetes. (2002)

Neuropathy is the second most important of the four major 'traffic light' warnings for future foot problems (vascular, neuropathy, structural, self care). Peripheral neuropathy is a significant clinical problem in 20% of patients with diabetes. Painful neuropathy can disrupt patients lives but simple effective interventions are available. Painless neuropathy is often not perceived to be a problem by the patient or their doctor but puts the foot at risk from trauma (physical, chemical and thermal). Patients with neuropathy need systematic reassessment of self and professional diabetes care, and education about footwear and foot care. A podiatrist can be invaluable in prescribing appropriate footwear and orthotics to distribute foot pressure and in educating patients about self care. Patients with the 'double whammy' of neuropathy and vascular disease are at extreme risk of limb threatening problems and should have a regular monitoring program by themselves (or their carers) and their professionals as well as an 'action plan' to detect and deal with problems early.
Purification of biotinylated proteins on streptavidin resin: A protocol for quantitative elution (2004)

The interaction between streptavidin and biotin is one of the most widely used tools in chemistry and biology. However, the release of biotinylated proteins from streptavidin resins remains a major problem, due to the extraordinary stability of this complex. We present a new protocol for the quantitative elution of biotinylated proteins from streptavidin Sepharose, featuring harsh elution conditions and competition with free biotin. The usefulness of the method was demonstrated by the quantitative recovery of biotinylated proteins from organ homogenates, obtained from mice perfused with a reactive ester derivative of biotin.
Rapid Molecular Typing of Methicillin-ResistantStaphylococcus aureusby PCR-RFLP (2001)

This new and rapid PCR-RFLP typing method is an attractive tool in routine epidemiological surveillance. Its impressive characteristics are ease of performance and interpretation, while at the same time guaranteeing good discriminatory power, reproducibility, and typeability.
Sequence and Structure Determinants for the Self-aggregation of Recombinant Polypeptides Modeled after Human Elastin (2003)

Elastin is a polymeric structural protein that imparts the physical properties of extensibility and elastic recoil to tissues. The mechanism of assembly of the tropoelastin monomer into the elastin polymer probably involves extrinsic protein factors but is also related to an intrinsic capacity of elastin for ordered assembly through a process of hydrophobic self-aggregation or coacervation. Using a series of simple recombinant polypeptides based on elastin sequences and mimicking the unusual alternating domain structure of native elastin, we have investigated the influence of sequence motifs and domain structures on the propensity of these polypeptides for coacervation. The number of hydrophobic domains, their context in the alternating domain structure of elastin, and the specific nature of the hydrophobic domains included in the polypeptides all had major effects on self-aggregation. Surprisingly, in polypeptides with the same number of domains, propensity for coacervation was inversely related to the mean Kyte-Doolittle hydropathy of the polypeptide. Point mutations designed to increase the conformational flexibility of hydrophobic domains had the unexpected effect of suppressing coacervation and promoting formation of amyloid-like fibers. Such simple polypeptides provide a useful model system for understanding the relationship between sequence, structure, and mechanism of assembly of polymeric elastin.
Age-Dependent Neurodegeneration and Alzheimer-Amyloid Plaque Formation in TransgenicDrosophila (2004)

Beta-amyloid peptides that are cleaved from the amyloid precursor protein (APP) play a critical role in Alzheimer's disease (AD) pathophysiology. Here, we show that in Drosophila, the targeted expression of the key genes of AD, APP, the beta-site APP-cleaving enzyme BACE, and the presenilins led to the generation of beta-amyloid plaques and age-dependent neurodegeneration as well as to semilethality, a shortened life span, and defects in wing vein development. Genetic manipulations or pharmacological treatments with secretase inhibitors influenced the activity of the APP-processing proteases and modulated the severity of the phenotypes. This invertebrate model of amyloid plaque pathology demonstrates Abeta-induced neurodegeneration as a basic biological principle and may allow additional genetic analyses of the underlying molecular pathways.
Human skeletal growth factor: characterization of the mitogenic effect on bone cells in vitro (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHuman skeletal growth factor: characterization of the mitogenic effect on bone cells in vitroJohn R. Farley, T. Masuda, J. E. Wergedal, and David J. BaylinkCite this: Biochemistry 1982, 21, 14, 3508–3513Publication Date (Print):July 1, 1982Publication History Published online1 May 2002Published inissue 1 July 1982https://pubs.acs.org/doi/10.1021/bi00257a038https://doi.org/10.1021/bi00257a038research-articleACS PublicationsRequest reuse permissionsArticle Views46Altmetric-Citations39LEARN 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
Abuse liability studies of opioid agonist-antagonists in humans (1991)

Prediction of the abuse liability of a drug before it reaches the market is complicated by the fact that there are many factors that influence the actual abuse of a drug. Laboratory methods used in humans to assess the abuse liability of the opioids are reviewed and illustrative studies of morphine and the agonist-antagonist opioids, pentazocine, butorphanol, nalbuphine and buprenorphine, are presented. Three assessment methods, subjective effect measurement, self-administration and drug discrimination, provide information relevant to measuring reinforcing efficacy, a major determinant of the degree to which a drug is sought and self-administered by abusers. Physical dependence capacity, which can contribute to sustained drug use, is evaluated in direct addiction and substitution/suppression studies. Withdrawal precipitation studies measure antagonist activity which might limit abuse. The results of testing the agonist-antagonist opioids are generally consistent across these various methods and consistent with historical experience with these drugs, suggesting that these methods are useful in predicting abuse liability of novel opioids.
Phase III Comparison of Vitespen, an Autologous Tumor-Derived Heat Shock Protein gp96 Peptide Complex Vaccine, With Physician's Choice of Treatment for Stage IV Melanoma: The C-100-21 Study Group (2008)

These results are consistent with the immunologic mechanism of action of vitespen, indicating delayed onset of clinical activity after exposure to the vaccine. The results suggest patients with M1a and M1b disease who are able to receive 10 or more doses of vitespen as the candidate population for a confirmatory study.
Rhesus Monkeys Produced by Nuclear Transfer1 (1997)

Genetically identical nonhuman primates can provide a powerful animal model for gene therapy and research activities where the physiological parameters directly or indirectly under study are heritable. Here we demonstrate that nuclear transfer is a viable technology for the production of identical rhesus macaques. Oocytes recovered from gonadotropin-treated females were enucleated by aspiration of the first polar body and underlying ooplasm, then activated by cycloheximide exposure. Individual diploid blastomeres, recovered from in vitro-fertilization-produced embryos (either fresh or frozen-thawed) and used as nuclear donors, were injected under the zona pellucida of enucleated (chromosome-free) oocytes and fused by electric pulses. The reconstituted embryos were cocultured on buffalo rat liver cells before cryostorage and transfer to synchronized host mothers. Of the 9 females receiving a total of 29 reconstituted embryos, 3 became pregnant, with two live births resulting, one male and one female. The parentage of both infants was established unequivocally by genotype analysis at 7 highly variable short tandem repeat loci.
A Case History: Completion and Stimulation of Horizontal Wells with Multiple Transverse Hydraulic Fractures in the Lost Hills Diatomite (1998)

Abstract The Lost Hills Field Diatomite has traditionally been developed using vertical wells completed with multiple propped hydraulic fracture treatment stages. As the main portion of the field is nearing full development at 2 1/2-acres per producer, the search for additional reserves has moved out to the flanks of the field's anticlinal structure. Due to limited pay thickness, these flank portions of the field will not support economic vertical well development. The use of horizontal wells was determined to have the best chance to economically develop these areas of the field. To evaluate this development concept, three horizontal wells were drilled and completed over the time period from November 1996 to December 1997 To assist with the horizontal well design and evaluation, several vertical data wells were drilled offset and parallel to the intended well path of each horizontal well. Additionally, two vertical core wells were drilled in line with the toe and heel of the horizontal well paths. These data wells were utilized to estimate properties such as in-situ stress profiles, pore pressure gradients, rock properties and fluid saturations, and to determine horizontal well vertical depth placement. The horizontal wells were then drilled in the direction of minimum horizontal stress (transverse to the preferred hydraulic fracture orientation) and completed with multiple-staged propped hydraulic fracture treatments. During the completion of the three horizontal wells, hydraulic fracture growth behavior was characterized using surface tiltmeter fracture mapping and real-time fracture pressure analysis. In the third horizontal well, downhole tiltmeter fracture mapping was also used. This combination of fracture diagnostics provided significant insights into hydraulic fracture behavior, allowing diagnosis of anomalous fracture growth behavior and evaluation of remediation measures. Fracture diagnostics during the first horizontal well revealed an unexpectedly complex near-wellbore fracture geometry, a result of fracture initiation problems. These problems slowed the completion process and severely harmed the effectiveness of the fracture-to-wellbore connection. In the subsequent horizontal wells, a number of design and execution changes were made which resulted in simpler near-wellbore fracture geometry and a greatly improved production response. The paper provides an overview of the completion and stimulation of all three horizontal wells, describes the lessons learned along the way, and discusses the implications for future Lost Hills horizontal well development. P. 335
pEg7, a New Xenopus Protein Required for Mitotic Chromosome Condensation in Egg Extracts (1998)

We have isolated a cDNA, Eg7, corresponding to a Xenopus maternal mRNA, which is polyadenylated in mature oocytes and deadenylated in early embryos. This maternal mRNA encodes a protein, pEg7, whose expression is strongly increased during oocyte maturation. The tissue and cell expression pattern of pEg7 indicates that this protein is only readily detected in cultured cells and germ cells. Immunolocalization in Xenopus cultured cells indicates that pEg7 concentrates onto chromosomes during mitosis. A similar localization of pEg7 is observed when sperm chromatin is allowed to form mitotic chromosomes in cytostatic factor-arrested egg extracts. Incubating these extracts with antibodies directed against two distinct parts of pEg7 provokes a strong inhibition of the condensation and resolution of mitotic chromosomes. Biochemical experiments show that pEg7 associates with Xenopus chromosome-associated polypeptides C and E, two components of the 13S condensin.
IgA antibodies of coeliac disease patients recognise a dominant T cell epitope of Α-gliadin (2004)

IgA antibodies to p57-73 were found in 29/72 (40.2%) endomysial antibody positive patients, all of whom had CD. The peptide antibody appeared to be present when patients were on a diet containing gluten and declined on a gluten free diet. The p57-73 antibody was very specific for CD (98%) and had a sensitivity of 56%. The amino acid at position 65 was not important for IgA binding but was crucial for T cell recognition of p57-73. Pentapeptide PXPQP emerges as a potentially strong candidate for the IgA binding motif in this region of Alpha-gliadin. This study shows that a significant proportion of newly diagnosed CD patients have an antibody response to the immunodominant T cell epitope.