Publications by authors named "Shuman R"

Background: Epizootic hemorrhagic disease virus (EHDV) is a pathogen vectored by midges that causes significant economic loss in the cervid farming industry and affects wild deer as well. Despite this, its ecology is poorly understood. Studying movement and space use by ruminant hosts during the transmission season may elucidate EHDV ecology by identifying behaviors that can increase exposure risk.

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The transmission of multiple serotypes of epizootic hemorrhagic disease virus (EHDV) between farmed and free-ranging wildlife is of interest to livestock industries and natural resource agencies. We compared the seroprevalence of EHDV-1, -2, and -6 in wild and farmed white-tailed deer () herds in Florida, US. We compared serological prevalence, circulating serotypes, antibody titers, and viremia with the use of 171 whole-blood samples from 150 unvaccinated white-tailed deer from farm pens, a farm preserve, and wild deer on adjacent public lands between March 2016 and May 2017.

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Background: Vector-borne diseases exert a global economic impact to the livestock industry. Understanding how agriculture practices and acaricide usage affect the ecology of these diseases is important for making informed management decisions. Theileria cervi is a hemoprotozoan parasite infecting white-tailed deer (Odocoileus virginianus) and is transmitted by the lone star tick, Amblyomma americanum.

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Altered metabolism is a hallmark of cancer growth, forming the conceptual basis for development of metabolic therapies as cancer treatments. We performed in vivo metabolic profiling and molecular analysis of lung squamous cell carcinoma (SCC) to identify metabolic nodes for therapeutic targeting. Lung SCCs adapt to chronic mTOR inhibition and suppression of glycolysis through the GSK3α/β signaling pathway, which upregulates glutaminolysis.

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Feral swine (wild hogs) are one of the most widely distributed free-ranging mammals in the world. In the United States, feral swine serve as game animals for the sport of hunting in some areas, while they are nuisance species at other locations. Increasing feral swine populations creates negative impacts to growing crops, native plant communities, and wildlife.

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Background/aim: To assess the impact of drug selection upon the treatment of advanced and metastatic non-small cell lung cancer (NSCLC), we applied a functional platform that measures drug-induced cell death in human tumor primary-culture micro-spheroids isolated from surgical specimens.

Patients And Methods: At diagnosis, microspheroids isolated by mechanical and enzymatic disaggregation were examined for drug-induced cell-death by morphology and staining characteristics. Drugs were administered using standard protocols.

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Most U.S. intimate partner violence (IPV) research to date has been limited to women residing in urban areas, with the small body of research focusing on rural populations being primarily qualitative.

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Background: This study retrospectively compared the effectiveness of vagus nerve stimulation (VNS) therapy among a constant cohort of patients in the patient outcome registry, which systematically monitors outcomes of patients receiving VNS therapy. Patients in the study had pharmacoresistant seizures for 6 years or less (early treatment group) or more than 6 years (late treatment group) before initiation of VNS therapy, and results are provided after both 3 and 12 months.

Review Summary: Of 405 patients, 51 were in the early and 354 in the late treatment groups.

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L-733,725, a new immunosuppressant drug candidate, was prepared by a highly chemoselective alkylation of the macrolide ascomycin at the C32 hydroxy position with the imidazolyl trichloroacetimidate 16. The trichloroacetimidate-activated side chain 16 was prepared by an efficient four-step sequence in 42% overall yield. The high chemoselectivity in the alkylation of the C32 hydroxy group of the unprotected ascomycin was the result of the synergetic effects of the electron-donating protecting group on the imidazole 16, the polar, moderately basic solvent, and the strong acid catalyst.

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An oscillator pore is identified that generates intermittent, large amplitude, ionic current in the plasma membrane. The pore is thought to be composed of 10-12 units of subunit c of ATP synthase. Pore opening and closing is a co-operative process, dependent on the release, or binding, of as many as six calcium ions.

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To enhance the potency of 1,2-dibenzamidobenzene-derived inhibitors of factor Xa (fXa), an amidine substituent was incorporated on one of the benzoyl side chains to interact with Asp189 in the S1 specificity pocket. Lead molecule 1 was docked into the active site of fXa to facilitate inhibitor design. Subsequently, iterative SAR studies and molecular modeling led to a 1000-fold increase in fXa affinity and a refined model of the new inhibitors in the fXa active site.

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Objective: To determine the efficacy of the ketogenic diet in multiple centers.

Design: A prospective study of the change in frequency of seizures in 51 children with intractable seizures who were treated with the ketogenic diet.

Setting: Patients were enrolled from the clinical practices of 7 sites.

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Three new tripeptide arginal thrombin inhibitors were shown to have potent anticoagulant and antithrombotic activity: D-MePhg-Pro-Arg-H (LY287045), D-1-Tiq-Pro-Arg-H (LY294291), and D-MePhe-Pro-Arg-H (Efegatran). Efegatran and the related arginals differ mechanistically from old and from new anticoagulant agents. As illustrated with x-ray diffraction analysis of crystals of the LY294291 complex with human thrombin, the family of arginals binds thrombin with the P3, P2, and P1 residues interacting with the putative S3, S2, and S1 fibrinogen-binding sites.

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In our continuing effort to design novel thrombin inhibitors, a series of conformationally constrained amino acids (e.g. alpha-alkyl, N-alkyl cyclic, etc.

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The Chiari malformations form a group of abnormalities that are pathogenetically interrelated. The most important member of the group is the Chiari type II malformation, known as the Arnold-Chiari malformation. Its cardinal features are the myelomeningocele in the thoraco-lumbar spine, the venting of the intracranial cerebrospinal fluid through the central canal, the hypoplasia of the posterior fossa, the herniation of hindbrain into the cervical spinal canal, and the compressive damage to cranial nerves.

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Direct inhibition of thrombin with agents such as hirudin and argatroban reduces reocclusion rates during experimental coronary thrombolysis. We compared the adjunctive potential of the tripeptide thrombin inhibitor D-methyl-phenylalanyl-prolyl-arginal (LY294468) during thrombolysis with tissue-type plasminogen activator (t-PA) with the less specific tripeptide thrombin inhibitor Boc-D-phenylalanyl-prolyl-arginal (LY178207) and the standard anticoagulant heparin. The left circumflex coronary artery (LCX) was isolated proximal to the first main branch, and coronary blood flow (CBF) was measured in 26 anesthetized dogs.

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Tripeptide aldehydes such as Boc-D-Phe-Pro-Arg-H (51) exhibit potent direct inhibition of thrombin. This distinction offers important insight for the design of more potent and selective serine protease inhibitors which may be useful pharmacological tools and hold promise for development of clinically useful agents. The structure-activity relationships (SAR) on a series of anticoagulant peptides with high selectivity for the enzyme thrombin are discussed.

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Production of transgenic birds.

Experientia

September 1991

The avian embryo presents a tremendous challenge for those interested in accessing and manipulating the avian germ line. By far the most successful method of gene transfer is by retrovirus vector. The efficacy of retrovirus vectors has been demonstrated by germ line insertion of replication-competent retroviruses as well as the insertion of replication-defective retrovirus vectors carrying bacterial marker genes.

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We have evaluated the human leukocyte antigen (HLA) phenotype of six children with parainflammatory leukoencephalomyelitis (PIL). Patients with PIL demonstrate an increased prevalence of the HLA-A1, -A28, -B44, -DR6, and -DR7 antigens. These HLA associations are different from those reported in other inflammatory demyelinating diseases, including multiple sclerosis, optic neuritis, Guillain-Barré syndrome, and chronic relapsing inflammatory polyneuropathy.

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To determine the relative survival of porcine embryos after co-culture with cells producing an avian retrovirus, four-cell stage embryos were obtained from sows following synchronization with altrenogest and superovulation with gonadotropins. These embryos were randomly assigned to the following treatments: no manipulation (zona-intact); zona removed with acidified Tyrode's solution (zona-free); and zona removed followed by co-culture with D-17 canine cells producing an avian retrovirus vector derived from spleen necrosis virus (zona-free + co-culture). The survival rates of four-cell stage embryos to morulae or early blastocysts during a 48-h culture period were 93.

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Two patients with partial (semilobar) holotelencephaly are reported with apparent partial agenesis of the corpora callosa. These patients are of interest because they appear to possess the posterior portion of the corpus callosum but not its anterior component. Because the corpus callosum develops in the commissural plate rostrally and is elaborated in a rostral-caudal gradient, this apparent lack of the rostral component is embryologically puzzling.

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It is very likely that many of the same factors involved in occlusive disease in the adult are operative in the child. The major difference may be in the factors that damage endothelium in these two age groups and thereby initiate this catastrophe (atherosclerosis versus "other" causes of endothelial changes). Our task in this next decade is the rational exploration of the effects of endothelium-mediated kinins, endothelial secretory products, angiospasm, platelet aggregration, prostaglandins, and lipoproteins on pediatric stroke.

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