gebhart/patrepeval huggingface dataset:
Experimental reproduction of swine infertility and respiratory syndrome in pregnant sows (1992)

The purpose of this study was to experimentally reproduce swine infertility and respiratory syndrome (SIRS). Six multiparous sows were intranasally inoculated at 93 days of gestation with lung homogenates from clinically affected pigs, and 3 additional sows were similarly inoculated with a virus isolated in cell culture from the lung homogenate (SIRS virus, isolate ATCC VR-2332). Inoculated sows developed transient anorexia, farrowed up to 7 days prematurely, and delivered a mean of 5.8 live pigs and 6.0 dead fetuses/litter. Clinical signs of disease were not observed in 3 sham-inoculated control sows that delivered a mean of 12.7 live pigs and 0.3 stillborn fetuses/litter. The SIRS virus was isolated from 50 of 76 live-born and stillborn fetuses from the 9 infected litters. Virus was not isolated from 26 autolyzed fetuses or 15 control pigs. Six of 9 inoculated sows developed neutralizing antibodies to SIRS virus. The reproductive effects found in these experiments were identical to those found in field cases. On the basis of our findings, virus isolate ATCC VR-2332 causes the reproductive failure associated with SIRS.
A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis (2010)

The 0-10 NRS and responder PP analyses demonstrated that Sativex treatment resulted in a significant reduction in treatment-resistant spasticity, in subjects with advanced MS and severe spasticity. The response observed within the first 4 weeks of treatment appears to be a useful aid to prediction of responder/non-responder status.
Random-clone strategy for genomic restriction mapping in yeast. (1986)

An approach to global restriction mapping is described that is applicable to any complex source DNA. By analyzing a single restriction digest for each member of a redundant set of lambda clones, a data base is constructed that contains fragment-size lists for all the clones. The clones are then grouped into subsets, each member of which is related to at least one other member by a significant overlap. Finally, a tree-searching algorithm seeks restriction maps that are consistent with the fragment-size lists for all the clones in each subset. The feasibility of the approach has been demonstrated by collecting data on 5000 lambda clones containing random 15-kilobase inserts of yeast DNA. It is shown that these data can be analyzed to produce regional maps of the yeast genome, extending in some cases for over 100 kilobases. In combination with hybridization probes to previously cloned genes, these local maps are already useful for defining the physical arrangement of closely linked genes. They may in the future serve as building blocks for the construction of a continuous global map.
Identification of a carbohydrate-based endothelial ligand for a lymphocyte homing receptor. (1991)

Lymphocyte attachment to high endothelial venules within lymph nodes is mediated by the peripheral lymph node homing receptor (pnHR), originally defined on mouse lymphocytes by the MEL-14 mAb. The pnHR is a calcium-dependent lectin-like receptor, a member of the LEC-CAM family of adhesion proteins. Here, using a soluble recombinant form of the homing receptor, we have identified an endothelial ligand for the pnHR as an approximately 50-kD sulfated, fucosylated, and sialylated glycoprotein, which we designate Sgp50 (sulfated glycoprotein of 50 kD). Recombinant receptor binding to this lymph node-specific glycoprotein requires calcium and is inhibitable by specific carbohydrates and by MEL-14 mAb. Sialylation of the component is required for binding. Additionally, the glycoprotein is precipitated by MECA-79, an adhesion-blocking mAb reactive with lymph node HEV. A related glycoprotein of approximately 90 kD (designated as Sgp90) is also identified.
The Effect of Propranolol on Posttraumatic Stress Disorder in Burned Service Members (2009)

Posttraumatic stress disorder (PTSD) is reported to affect almost one third of the civilian burn patient population. Predisposing factors for PTSD include experiencing a traumatic event. Of Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) soldiers returning home after deployment without injury, 17% reported cognitive symptoms of PTSD. The authors recent study of soldiers burned in OIF/OEF showed a PTSD prevalence of approximately 30%, which is similar to civilian studies. Burns are characterized by hypermetabolism and increased catecholamine levels. beta-Adrenergic receptor blocking agents, like propranolol, decrease catecholamine levels. Propranolol may reduce consolidation of memory and a prophylaxis for PTSD. This retrospective study examines the relationship between PTSD prevalence and propranolol administration. After institutional review board approval, propranolol received, number of surgeries, anesthetic/analgesic regimen, TBSA burned, and injury severity score were collected from patients charts. The military burn center received 603 soldiers injured in OIF/OEF, of which 226 completed the PTSD Checklist-Military. Thirty-one soldiers received propranolol and 34 matched soldiers did not. In propranolol patients, the prevalence of PTSD was 32.3% vs 26.5% in those not receiving propranolol (P = .785). These data suggest propranolol does not decrease PTSD development in burned soldiers. The prevalence of PTSD in patients receiving propranolol is the same as those not receiving propranolol. More research is needed to determine the relationship between PTSD and propranolol.
Pharmacological Profile of the 5‐HT2C Receptor Agonist WAY‐163909; Therapeutic Potential in Multiple Indications (2006)

The 5-HT(2C) receptor subtype has been implicated in a wide variety of conditions including obesity, anxiety, depression, obsessive compulsive disorder, schizophrenia, migraine and erectile dysfunction and as a consequence has received considerable attention as a target for drug discovery. Here we review the pharmacological, pharmacokinetic and toxicological profile of WAY-163909 {(7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole}, a novel 5-HT(2C) receptor selective agonist. Consistent with a potential therapeutic utility in obesity, schizophrenia and depression WAY-163909 was found to have robust dose-dependent effects in animal models of obesity, psychotic-like behavior or depression.
Exo‐Dig Radical Cascades of Skipped Enediynes: Building a Naphthalene Moiety within a Polycyclic Framework (2013)

Cascade radical transformations of acyclic precursors open efficient, convenient and atom-economical access to functionalized compounds of increased structural complexity. This report describes a selective sequence of 5-exo-dig and 6-exo-dig cyclizations followed by attack at a pendant aromatic moiety and rearomatization.
Multivalent Effects of RGD Peptides Obtained by Nanoparticle Display (2006)

The binding of RGD peptides to integrins offers an excellent system to study the multivalent mediated changes in affinity that arise when peptides, displayed on the surface of a nanoparticle carrier, bind to integrins displayed on the cell membrane. The IC50 of an RGD nanoparticle for endothelial adhesion was 1.0 nM nanoparticle or 20 nM peptide (20 peptide/nanoparticle) and was associated with strong multivalent effects, defined as a multivalent enhancement factor (MVE) of 38 (MVE=IC50 (peptide)/IC50 (peptide when displayed by nanoparticle)). The attachment of RGD peptides to nanoparticles resulted in an extension of the peptide blood half-life from 13 to 180 min. Based on the multivalent enhancement of affinity and extension of blood half-life, multivalent RGD nanoparticle-sized materials should be potent inhibitors of the alpha(V)beta(3) function on endothelial cells in vivo.
Manipulating the Crystalline State of Pharmaceuticals by Nanoconfinement (2007)

We show that nanoconfinement is a handle to rationally produce and stabilize otherwise metastable or transient polymorphs of pharmaceuticals, as required for controllable and efficient drug delivery. The systematic investigation of crystallization under confinement unveils thermodynamic properties of metastable polymorphs not accessible otherwise and may enhance the understanding of the crystallization behavior of pharmaceuticals in general. As an example in this case, we studied acetaminophen confined to inexpensive and biocompatible nanoporous host systems. Calorimetric and X-ray scattering data clearly evidence that either the stable polymorph form I or the metastable polymorph form III can be stabilized in high yields. Thermodynamic parameters for form III of acetaminophen are reported, and strategies to manipulate the crystalline state in pores by thermal treatments are presented.
The effects of ageing on cutaneous wound healing in mammals. (1995)

The dogma that cutaneous wound healing is impaired as a function of age is largely unsubstantiated. This can be attributed to poor experimental design of human studies, the lack of subject characterisation with the exclusion of disease processes, and the study of inappropriate animal models. Structural and functional changes in skin with age have been reported, such as a decrease in dermal thickness, decline in collagen content, a subtle alteration in the glycosaminoglycan profile, and a loss of elasticity, but these reports are subject to the above criticisms in addition to the often-neglected requirement for site specificity. Wound repair can be thought of as a culmination of three major overlapping phases: inflammation, proliferation and remodelling. The inflammatory process has not been studied systematically with respect to age, and despite a reported decline in cellular function and number, there is a confounding increase in the production of specific cytokines involved in the process of repair. The proliferative phase is associated with a loss of cellular responsiveness to specific cytokines with a decline in motility and proliferation; however caution in interpreting these findings is important as, for example, the definition of 'ageing' is used rather loosely with the result that neonatal versus young adult cells are compared instead of young versus old adults. During remodelling, fibronectin and collagen production may increase with age, as may wound contraction; the deposition of elastin has not been assessed and the resulting mechanical properties of the scar are controversial, not least because human in vivo studies have been ignored. The absence of a critical review on the effects of advancing age on wound healing has conspired to permit the perpetuation of the belief that well defined tenets exist. This review aims to redress this imbalance and to highlight the need for well designed research into an increasingly important field.
Effective bactericidal activity of tobramycin and vancomycin eluted from acrylic bone cement (2001)

We studied the bioactivity of vancomycin and tobramycin eluted from methylmethacrylate bone cement. Aliquots of the drainage were obtained at 1, 6, 12 and 24 hours following total hip prosthetic implantation with vancomycin-tobramycin-loaded cement in 3 patients. The samples were analyzed with fluorescence polarization immunoassay and bioassay, using group B streptococcus for vancomycin and Escherichia coli for tobramycin. These bacteria were selected due to the effectiveness of vancomycin and poor effectiveness of tobramycin against group B streptococcus and conversely with E. coli. The immunodetection of vancomycin averaged 14 (1 hour), 9 (6 hours), 10 (12 hours) and 11 microg/mL (24 hours). The bioassay averaged 47, 36, 79 and 41 microg/mL (p = 0.03). The immunodetection of tobramycin averaged 43, 21, 18 and 14 microg/mL; and bioassay 30, 15, 15 and 12 microg/mL (p = 0.1). Both antibiotics eluted with a highly effective bactericidal activity. Our findings indicate that the presence of tobramycin has a synergistic-like effect on the bactericidal activity of vancomycin, which has not been previously reported. We recommend a combination of vancomycin and tobramycin with cement for the treatment of orthopedic infections caused by gram-positive organisms.
Selective Activation of the Rat Hepatic Endosomal Insulin Receptor Kinase (1995)

Insulin administration activates the insulin receptor kinase (IRK) in both plasma membrane (PM) and endosomes (ENs) raising the possibility of transmembrane signaling occurring in the endosomal compartment. Peroxovanadium compounds activate the IRK by inhibiting IR-associated phosphotyrosine phosphatase(s). Following the administration of the phosphotyrosine phosphatase inhibitor bisperoxo(1,10-phenanthroline)-oxovanadate (V) anion (bpV(phen)) activation of the hepatic IRK in ENs preceded that in PM by 5 min. When colchicine treatment preceded bpV(phen) administration IRK activation in ENs was unaffected but was totally abrogated in PM. Insulin receptor substrate-1 tyrosine phosphorylation followed the kinetics of IRK activation in ENs not PM and a hypoglycemic response similar to that achieved with a pharmacological dose of insulin ensued. These studies demonstrate that ENs constitute a site for IR-mediated signal transduction.
A Novel ATP-dependent Inward Rectifier Potassium Channel Expressed Predominantly in Glial Cells (1995)

We have isolated a novel inward rectifier K+ channel predominantly expressed in glial cells of the central nervous system. Its amino acid sequence exhibited 53% identity with ROMK1 and approximately 40% identity with other inward rectifier K+ channels. Xenopus oocytes injected with cRNA derived from this clone expressed a K+ current, which showed classical inward rectifier K+ channel characteristics. Intracellular Mg.ATP was required to sustain channel activity in excised membrane patches, which is consistent with a Walker type-A ATP-binding domain on this clone. We designate this new clone as KAB-2 (the second type of inward rectifying K+ channel with an ATP-binding domain). In situ hybridization showed KAB-2 mRNA to be expressed predominantly in glial cells of the cerebellum and forebrain. This is the first description of the cloning of a glial cell inward rectifier potassium channel, which may be responsible for K+ buffering action of glial cells in the brain.
Low‐Temperature Solid‐Oxide Fuel Cells Utilizing Thin Bilayer Electrolytes (1997)

Solid‐oxide fuel cells (SOFCs) with electrolytes that provide high open‐circuit voltage (OCV) and low ohmic loss down to 550°C are described. The electrolytes were bilayers consisting of a 4 to 8 μm thick Y‐doped ceria (YDC) layer with a 1 to 1.5 μm thick Y‐doped zirconia (YSZ) layer on the fuel side. The cathode/supports were . The anodes consisted of thin YDC and Ni‐YSZ layers. The YDC/YSZ electrolyte SOFCs yielded 85 to 98% of the theoretical OCV, compared with ≈50% for YDC electrolyte SOFCs. The cathode overpotential, which was a main factor limiting SOFC power density, was lower for YDC/YSZ than YSZ electrolytes. The maximum power density at 600°C, 210 mW/cm2, is higher than for previously reported SOFCs.
Design of Three-Dimensional, Path Length Matched Optical Waveguides (2012)

A method for designing physically path length matched, three-dimensional photonic circuits is described. These waveguides, with arbitrary endpoints, were fabricated via the femtosecond laser direct-write technique. The focus is specifically on the case where all waveguides are uniquely routed from the input to output; a problem which has not been addressed to date and allows for the waveguides to be used in interferometric measurements. Two iterative design methods were created for path length matched waveguides with adequate separation in three dimensions and minimized curvature. These algorithms could be used to calculate predicted radius of curvature, bend and transition loss in the waveguides, with results confirmed by computer simulation methods. Demonstrations via interferometric methods show that the fabricated circuits were indeed optically path length matched to within 45 μm which is well within the coherence length required for typical applications, includi ng astronomical measurements.
Interferon therapy of relapsed and refractory Hodgkin's disease: Cancer and Leukemia Group B Study 8652. (1990)

A phase II trial of alpha 2b-interferon in patients with relapsed or refractory Hodgkin's disease was conducted by the Cancer and Leukemia Group B. Nineteen patients were eligible for study. These patients had received at least two (median of four) previous chemotherapeutic programs and 79% had received prior radiation therapy. Three patients had undergone intensive chemotherapy and autologous bone marrow transplantation. The treatment regimen consisted of interferon-alpha 2b 10 X 10(6) IU/m2 subcutaneously three times per week. Only limited antineoplastic activity was seen in this heavily pretreated group of patients. There was one partial response and four patients had reduction in measurable disease not meeting the criteria for partial response. The drug was well tolerated. Toxicity was predominantly myelosuppression. Thrombocytopenia was particularly severe in patients with bone marrow involvement. The observed antineoplastic activity, albeit limited, in this heavily pretreated group of patients suggests a potential role for this agent in combination regimens in patients with earlier disease.
Resistance Mutations in Protease and Reverse Transcriptase Genes of Human Immunodeficiency Virus Type 1 Isolates from Patients with Combination Antiretroviral Therapy Failure (1998)

High-density oligonucleotide arrays were used to determine the sequence of the protease (PR) and reverse transcriptase (RT) genes of human immunodeficiency virus type 1 isolates from 35 patients in whom combination therapy that included a protease inhibitor had failed. Isolates had a median of three PR mutations (range, none to six). Three isolates had no known resistance mutations in PR. Twelve isolates (34%) had two or fewer resistance mutations in PR. The most commonly observed PR mutations were L10I, V82A/T/F, and L90M. No mutations were observed at codons 30 or 48. Mutations at RT codons 215 and 184 were observed in the majority of isolates. These data suggest that therapy can fail in some patients with relatively few PR resistance mutations. Clinical failure in the absence of resistance mutations implies inadequate drug exposure due to pharmacologic factors or suboptimal patient adherence to drug therapy.
Physical and Biological Interface Dose Effects in Tissue due to X-Ray-Induced Release of Secondary Radiation from Metallic Gold Surfaces (1998)

Dose enhancement up to more than a factor of 100 was found in an environment of tissue-equivalent polymethylmethacrylate (PMMA) close to the surface of a thin metallic gold foil. The enhancement factors were determined for heavily filtered X rays (40 to 120 kV tube potential) under backscatter conditions, using thin-film radiation detectors with sub-micrometer resolution. The secondary electrons were found to range up to some 10 microm in tissue-equivalent material. Correspondingly, enhanced biological effects could be shown in vitro, using monolayers of C3H 10T1/2 mouse embryo fibroblasts exposed in intimate contact with the gold surface. The decay of the survival curves of cells irradiated on gold was significantly steeper than for those obtained from irradiation between PMMA disks with the same dose, also giving biological evidence for significantly enhanced doses at the gold interface. The shape of the inactivation curves resembled those for high-LET radiation, lacking a pronounced shoulder at the lower doses. Quantitatively, doses of e.g. 50 mGy (80 kV X rays) in homogeneous PMMA caused about 35% cell killing and 200 mGy about 80% when the cells were irradiated at the gold surface. From a comparison of these inactivation numbers with those found for irradiation between PMMA disks, biological dose enhancement factors for the cell system considered ranged up to about a factor of 50. In addition to cell inactivation, the in vitro irradiations of C3H 10T1/2 cells adjacent to the gold surface resulted in increased rates of oncogenic transformation. A dose of 100 mGy 80 kV X rays (measured in homogeneous PMMA) caused a frequency at an inserted gold surface comparable to that obtained with a dose of about 4.5 Gy of 60Co gamma rays in homogeneous PMMA.
An improved linker for single-chain Fv with reduced aggregation and enhanced proteolytic stability (1993)

The effects of linker length on binding affinity and degree of aggregation have been examined in the antifluorescein 4-4-20 and anticarcinoma CC49 single-chain Fvs. Longer linkers in the antifluorescein sFvs have higher affinities for fluorescein and aggregate less. A proteolytically susceptible site between Lys8 and Ser9, in the previously reported 212 linker has been identified. A new linker sequence, 218 (GSTSGSGKPGSGEGSTKG) was designed in which a proline was placed at the C-terminal side of the proteolytic clip site in the 212 linker. The CC49 sFv containing the 218 linker showed reduced aggregation and was found to be more stable to proteolysis in vitro, when compared to the CC49/212 sFv. The CC49 sFv with the longer 218 linker had higher affinity than CC49/212 sFv. An aggregated CC49/212 sFv sample had higher affinity than CC49/218 sFv. The CC49/218 and CC49/212 sFvs had similar blood clearances in mice, while the aggregated CC49/212 sFv remained in circulation significantly longer. In mice bearing LS-174T human colon carcinoma xenografts, the CC49/218 sFv showed higher tumor uptake than the CC49/212 sFv and lower tumor uptake than the aggregated CC49/212 sFv. The higher tumor uptake of the CC49/218 is most likely a result of its higher resistance to proteolysis. The higher affinity and higher tumor uptake of the aggregated CC49/212 sFv are most likely due to the repetitive nature of the TAG-72 antigen and the higher avidity of multivalent aggregates. When the sFvs were radiolabeled with a lutetium-chelate the CC49/218 sFv showed a lower accumulation in the liver and spleen compared to the aggregated CC49/212 sFv.
Further Characterization of Reproductive Abnormalities in mCd59b Knockout Mice: A Potential New Function of mCd59 in Male Reproduction (2005)

CD59 is a GPI-linked membrane protein that inhibits formation of the membrane attack complex of complement. We reported recently that mice have two CD59 genes (termed mCd59a and mCd59b), and that the targeted deletion of mCd59b (mCd59b-/-) results in spontaneous hemolytic anemia and progressive loss of male fertility. Further studies of the reproductive abnormalities in mCd59b-/- mice reported in this study revealed the presence of abnormal multinucleated cells and increased apoptotic cells within the walls of the seminiferous tubules, and a decrease in the number, motility, and viability of sperm associated with a significant increase in abnormal sperm morphologies. Both the capacitation-associated tyrosine phosphorylation and the ionophore-induced acrosome reaction as well as luteinizing hormone, follicle-stimulating hormone, and testosterone serum levels were similar in mCd59b-/- and mCd59b+/+. Surprisingly, the functional deficiency of the complement protein C3 did not rescue the abnormal reproductive phenotype of mCd59b-/-, although it was efficient in rescuing their hemolytic anemia. These results indicate that the male reproductive abnormalities in mCd59b-/- are complement-independent, and that mCd59 may have a novel function in spermatogenesis that is most likely unrelated to its function as an inhibitor of membrane attack complex formation.