470 research outputs found
VaporāPhase ChargeāTransfer Complexes. Diethyl SulfideāIodine
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71200/2/JCPSA6-43-9-3393-1.pd
Sensitivity Analysis of the Change of Renal Stone Occurrence Rates in Astronauts Using Urine Chemistries
Changes in urine chemistry, during and post-flight, potentially alter the likelihood of renal stones in astronauts. Although much is known about the effects of space flight on urine chemistry, no inflight incidences of renal stones in US astronauts exist and the question How much does this risk change with space flight? remains difficult to accurately quantify. Previous work by our group has illustrated the application of multi-factor deterministic and probabilistic modeling to assess the change in predicted likelihood of renal stone. Utilizing 1517 astronaut urine chemistries to inform the renal stone occurrence rate forecasting model, we performed a sensitivity analysis on urine chemistry components for their influence on predictions of renal stone size and rate of renal stone occurrence
Metabolite Fingerprinting in Transgenic Nicotiana tabacum Altered by the Escherichia coli Glutamate Dehydrogenase Gene
With about 200 000 phytochemicals in existence, identifying those of biomedical significance is a mammoth task. In the postgenomic era, relating metabolite fingerprints, abundances, and profiles to genotype is also a large task. Ion analysis using Fourier transformed ion cyclotron resonance mass spectrometry (FT-ICR-MS) may provide a high-throughput approach to measure genotype dependency of the inferred metabolome if reproducible techniques can be established. Ion profile inferred metabolite fingerprints are coproducts. We used FT-ICR-MS-derived ion analysis to examine gdhA (glutamate dehydrogenase (GDH; EC 1.4.1.1)) transgenic Nicotiana tabacum (tobacco) carrying out altered glutamate, amino acid, and carbon metabolisms, that fundamentally alter plant productivity. Cause and effect between gdhA expression, glutamate metabolism, and plant phenotypes was analyzed by [Formula: see text] labeling of amino acid fractions, and by FT-ICR-MS analysis of metabolites. The gdhA transgenic plants increased (13)N labeling of glutamate and glutamine significantly. FT-ICR-MS detected 2 012 ions reproducible in 2 to 4 ionization protocols. There were 283 ions in roots and 98 ions in leaves that appeared to significantly change abundance due to the measured GDH activity. About 58% percent of ions could not be used to infer a corresponding metabolite. From the 42% of ions that inferred known metabolites we found that certain amino acids, organic acids, and sugars increased and some fatty acids decreased. The transgene caused increased ammonium assimilation and detectable ion variation. Thirty-two compounds with biomedical significance were altered in abundance by GDH including 9 known carcinogens and 14 potential drugs. Therefore, the GDH transgene may lead to new uses for crops like tobacco
High-Resolution Molecular Epidemiology and Evolutionary History of HIV-1 Subtypes in Albania
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
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
Drug-associated changes in amino acid residues in Gag p2, p7NC, and p6Gag/p6Pol in human immunodeficiency virus type 1 (HIV-1) display a dominant effect on replicative fitness and drug response
AbstractRegions 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
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 ā¤ 12 months of age produced ejaculates that would not meet satisfactory levels of a BSE 15% of the time. Ejaculates from bulls 13ā18 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 ā¤ 12 months of age produced the highest amount of ejaculates failing due to primary abnormalities with 24%, while bulls ā„ 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 ā¤ 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
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 Ć 106) compared to artificial vagina (617 Ć 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 Ć 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?
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
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