380 research outputs found

    Vapor‐Phase Charge—Transfer Complexes. Diethyl Sulfide—Iodine

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71200/2/JCPSA6-43-9-3393-1.pd

    High-Resolution Molecular Epidemiology and Evolutionary History of HIV-1 Subtypes in Albania

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    HIV-1 epidemic in Western Europe is largely due to subtype B. Little is known about the HIV-1 in Eastern Europe, but a few studies have shown that non-B subtypes are quite common. In Albania, where a recent study estimated a ten-fold increase of AIDS incidence during the last six years, subtype A and B account for 90% of the know infections.We investigated the demographic history of HIV-1 subtype A and B in Albania by using a statistical framework based on coalescent theory and phylogeography. High-resolution phylogenetic and molecular clock analysis showed a limited introduction to the Balkan country of subtype A during the late 1980s followed by an epidemic outburst in the early 1990 s. In contrast, subtype B was apparently introduced multiple times between the mid-1970s and mid-1980s. Both subtypes are growing exponentially, although the HIV-1A epidemic displays a faster growth rate, and a significantly higher basic reproductive number R(0). HIV-1A gene flow occurs primarily from the capital Tirane, in the center of the country, to the periphery, while HIV-1B flow is characterized by a balanced exchange between center and periphery. Finally, we calculated that the actual number of infections in Albania is at least two orders of magnitude higher than previously thought.Our analysis demonstrates the power of recently developed computational tools to investigate molecular epidemiology of pathogens, and emphasize the complex factors involved in the establishment of HIV-1 epidemics. We suggest that a significant correlation exists between HIV-1 exponential spread and the socio-political changes occurred during the Balkan wars. The fast growth of a relatively new non-B epidemic in the Balkans may have significant consequences for the evolution of HIV-1 epidemiology in neighboring countries in Eastern and Western Europe

    Drug-Associated Changes in Amino Acid Residues in Gag p2, p7\u3csup\u3eNC\u3c/sup\u3e, and p6\u3csup\u3eGag\u3c/sup\u3e/p6\u3csup\u3ePol\u3c/sup\u3e in Human Immunodeficiency Virus Type 1 (HIV-1) Display a Dominant Effect on Replicative Fitness and Drug Response

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    Regions of HIV-1 gag between p2 and p6Gag/p6Pol, in addition to protease (PR), develop genetic diversity in HIV-1 infected individuals who fail to suppress virus replication by combination protease inhibitor (PI) therapy. To elucidate functional consequences for viral replication and PI susceptibility by changes in Gag that evolve in vivo during PI therapy, a panel of recombinant viruses was constructed. Residues in Gag p2/p7NC cleavage site and p7NC, combined with residues in the flap of PR, defined novel fitness determinants that restored replicative capacity to the posttherapy virus. Multiple determinants in Gag have a dominant effect on PR phenotype and increase susceptibility to inhibitors of drug-resistant or drug-sensitive PR genes. Gag determinants of drug sensitivity and replication alter the fitness landscape of the virus, and viral replicative capacity can be independent of drug sensitivity. The functional linkage between Gag and PR provides targets for novel therapeutics to inhibit drug-resistant viruses

    Challenges Associated with Semen Quality While Collecting Beef Bulls for Semen Freezing

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    Objective: The objective of this study was to evaluate the frequency of failure to freeze semen due to semen quality. Study Description: Semen collection data from 2008 to 2018 were obtained from the Kansas Artificial Breeding Services Unit and consisted of 14,750 ejaculates from bulls. Bulls were collected twice weekly on Mondays and Thursdays with an artificial vagina. Bulls not receptive to the artificial vagina were subject to electro-ejaculation. A single technician was responsible for all pre-freeze and post-thaw semen analysis. Ejaculates were required to meet quality standards for both progressive motility and morphology. Results: Over the ten years, 21% of ejaculates met all freezing quality standards, 11% of all ejaculates collected did not have a high enough motility to be considered satisfactory for a breeding soundness exam (BSE), and 63% of all ejaculates did not reach the motility quality threshold for freezing. Ejaculates from bulls ≤ 12 months of age produced ejaculates that would not meet satisfactory levels of a BSE 15% of the time. Ejaculates from bulls 13–18 months of age produced unsatisfactory ejaculates for motility for a BSE 6% of the time. When evaluating primary sperm abnormalities, 87% of ejaculates had less than 20% primary sperm abnormalities. Ejaculates from bulls ≤ 12 months of age produced the highest amount of ejaculates failing due to primary abnormalities with 24%, while bulls ≥ 31 months of age produced the least amount of ejaculates failing due to primary abnormalities at 10% of ejaculates. When evaluating total sperm abnormalities per ejaculate, 77% of ejaculates met the threshold of less than 30% total abnormalities. Ejaculates from bulls ≤ 12 months of age failed to meet the total sperm abnormality threshold 28% of the time. These results highlight one of the main difficulties of collecting freezing quality semen, in which semen meets the standards of normal spermatozoa but where most samples do not meet needs for progressive motility. The Bottom Line: Of over 14,000 collections, only 21% met all requirements for freezing semen, approximately 63% did not meet progressive motility freezing standards, and 11% did not meet the satisfactory level of a BSE

    The Effect of Method of Collection and Number of Sequential Ejaculates on Semen Characteristics of Beef Bulls

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    Objective: The objective of this study was to determine the effect of collection method and number of sequential ejaculates on beef bull ejaculate characteristics. Study Description: Semen collection data from 2008 to 2018 was obtained from the Kansas Artificial Breeding Services Unit and consisted of 11,642 ejaculates from 906 bulls. Bulls were collected twice weekly on Mondays and Thursdays with an artificial vagina. Bulls not receptive to the artificial vagina were subject to electro-ejaculation. A single technician was responsible for all pre-freeze and post-thaw semen analysis. Ejaculates were required to meet quality standards. Results: Progressive motility before freezing was greater (P \u3c 0.0001) for bulls collected with electro-ejaculate compared to artificial vagina. Ejaculate volume for electro-ejaculate collections was greater (P \u3c 0.0001) than those collected with artificial vagina. Percent spermatozoa with secondary abnormalities was greater (P \u3c 0.05) for bulls collected with electro-ejaculate compared to artificial vagina. Concentration of spermatozoa/mL was less (P \u3c 0.0001) for bulls collected with an electro-ejaculate (514 × 106) compared to artificial vagina (617 × 106). Total number of straws frozen/ejaculate was less (P \u3c 0.001) for bulls collected with electro ejaculate (94) compared to artificial vagina (108). The number of ejaculates collected/day was significant for the percent of spermatozoa with secondary abnormalities (P \u3c 0.001). As ejaculate number/day increased, the concentration of spermatozoa decreased (713, 580, 535, and 434 × 106/mL, respectively; P \u3c 0.0001) and the number of straws frozen/ejaculate decreased (123, 107, 93, and 82, respectively; P \u3c 0.0001). The Bottom Line: Producers and collection facilities should work together to balance collection method and number of ejaculates collected/day to maximize production while maintaining semen quality

    Can Simulation Credibility Be Improved Using Sensitivity Analysis to Understand Input Data Effects on Model Outcome?

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    Model and simulation (MS) credibility is defined as, the quality to elicit belief or trust in MS results. NASA-STD-7009 [1] delineates eight components (Verification, Validation, Input Pedigree, Results Uncertainty, Results Robustness, Use History, MS Management, People Qualifications) that address quantifying model credibility, and provides guidance to the model developers, analysts, and end users for assessing the MS credibility. Of the eight characteristics, input pedigree, or the quality of the data used to develop model input parameters, governing functions, or initial conditions, can vary significantly. These data quality differences have varying consequences across the range of MS application. NASA-STD-7009 requires that the lowest input data quality be used to represent the entire set of input data when scoring the input pedigree credibility of the model. This requirement provides a conservative assessment of model inputs, and maximizes the communication of the potential level of risk of using model outputs. Unfortunately, in practice, this may result in overly pessimistic communication of the MS output, undermining the credibility of simulation predictions to decision makers. This presentation proposes an alternative assessment mechanism, utilizing results parameter robustness, also known as model input sensitivity, to improve the credibility scoring process for specific simulations

    Genetic diversity of Brazilian isolates of feline immunodeficiency virus

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    We isolated Feline immunodeficiency virus (FIV) from three adult domestic cats, originating from two open shelters in Brazil. Viruses were isolated from PBMC following co-cultivation with the feline T-lymphoblastoid cell line MYA-1. All amplified env gene products were cloned directly into pGL8MYA. The nucleic acid sequences of seven clones were determined and then compared with those of previously described isolates. The sequences of all of the Brazilian virus clones were distinct and phylogenetic analysis revealed that all belong to subtype B. Three variants isolated from one cat and two variants were isolated from each of the two other cats, indicating that intrahost diversity has the potential to pose problems for the treatment and diagnosis of FIV infection

    Δ9-Tetrahydrocannabinol (THC) enhances lipopolysaccharide-stimulated tissue factor in human monocytes and monocyte-derived microvesicles

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    Abstract Background Immunomodulatory effects in humans of Δ9−Tetrahydrocannabinol (THC), the psychoactive component of marijuana are controversial. Tissue factor (TF), the activator of the extrinsic coagulation cascade, is increased on circulating activated monocytes and is expressed on microvesicles released from activated monocytes during inflammatory conditions, which perpetuate coagulopathies in a number of diseases. In view of the increased medicinal use of marijuana, effects of THC on human monocytes and monocyte-derived microvesicles activated by lipopolysaccharide (LPS) were investigated. Findings Peak levels of TF procoagulant activity developed in monocytes or microvesicles 6 h following LPS treatment and were unaltered by THC. After 24 h of LPS stimulation, TF activity declined in control-treated or untreated cells and microvesicles, but persisted with THC treatment. Peak TF protein occurred within 6 h of LPS treatment independent of THC; by 24 h, TF protein declined to almost undetectable levels without THC, but was about 4-fold greater with THC. Steady-state TF mRNA levels were similar up to 2 h in the presence of LPS with or without THC, while 10-fold greater TF mRNA levels persisted over 3–24 h with THC treatment. Activation of MAPK or NF-κB pathways was unaltered by THC treatment and inflammatory cytokine IL-6 levels were unchanged. In contrast, TNF and IL-8 levels were enhanced by 20–50 %. Conclusions THC enhances TF expression in activated monocytes resulting in elevated procoagulant activity. Marijuana use could potentiate coagulopathies in individuals with chronic immune activation such as HIV-1 infection or inflammatory bowel disease
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