5,458 research outputs found
Diversity and profitability : evidence and future research directions / 1433
Includes bibliographical references (p. 23-24)
Determining the Price-Responsiveness of Demands for Irrigation Water Deliveries versus Consumptive Use
A water-crop simulation/mathematical programming model of irrigation water demand in northeastern Colorado is formulated to develop an original concept of derived demand for consumptive use of water. Conventional demand functions for water deliveries are also developed, and the effect of hypothetical price increases on both consumption and delivery are illustrated. Findings indicate that demand elasticity estimates are quite sensitive to model specification, and consumptive use demand tends to be significantly less price-responsive than delivery demand. Thus price incentives are likely to have only limited impacts on basin-wide water consumption and would not make much additional water available for emerging demands.crop simulation, irrigation, mathematical programming, water conservation, water-demand elasticities, water policy, Demand and Price Analysis, Resource /Energy Economics and Policy,
Zebrafish Model of MLL-Rearranged Acute Myeloid Leukemia
Background: Acute myeloid leukemia (AML) is the second most common type of leukemia. Standard treatment includes chemotherapy as well as stem cell transplantation, but for aging patients and those with impaired immune function these rigorous therapies are not always possible. Furthermore, AML patients harboring a chromosomal rearrangement involving Multiple Lineage Leukemia (MLL) exhibit far worse prognoses than patients without. Given these circumstances new therapies must be developed.
Methods: Danio rerio (zebrafish) has emerged as a powerful model organism for investigating human blood malignancies due to the conservation of hematopoiesis between humans and zebrafish. We developed a transient transgenic model exhibiting AML characteristics by microinjecting single-cell zebrafish embryos with a tissue specific MLL-ENL expression construct.
Results: We found that the expression of MLL-ENL induced a clustered expansion of MLL+ and pu.1+ myeloid cells on the yolk sac at 48 and 72 hours post fertilization (hpf). To characterize our transient AML model, we treated MLL-ENL expressing embryos with either one of or a combination of two drugs that are currently being used in human AML drug trials, Venetoclax and Flavopiridol. We found that treatment with either drug reduced the myeloid expansion induced by the expression of MLL-ENL, and that co-treatment reduced the observed myeloid expansion even further.
Conclusions: Although further analysis is required, these data suggest that we successfully developed a transient transgenic AML model in zebrafish. Furthermore, these data suggest that Venetoclax and Flavopiridol co-treatment could yield better outcomes for AML patients than treatment with either drug individually.https://scholarscompass.vcu.edu/gradposters/1112/thumbnail.jp
Physical structure of northern Colorado River Basin cloud systems
September, 1985.Includes bibliographical references.Sponsored by National Science Foundation ATM-8109490.Sponsored by National Science Foundation ATM-8407543
Microphysical processes in two stably stratified orographic cloud systems
August 1981.Includes bibliographical references (pages [146]-151).Sponsored by National Science Foundation ATM 78-19261
Sentinel surveillance of HIV-1 transmitted drug resistance, acute infection and recent infection.
BackgroundHIV-1 acute infection, recent infection and transmitted drug resistance screening was integrated into voluntary HIV counseling and testing (VCT) services to enhance the existing surveillance program in San Francisco. This study describes newly-diagnosed HIV cases and characterizes correlates associated with infection.Methodology/principal findingsA consecutive sample of persons presenting for HIV VCT at the municipal sexually transmitted infections (STI) clinic from 2004 to 2006 (N = 9,868) were evaluated by standard enzyme-linked immunoassays (EIA). HIV antibody-positive specimens were characterized as recent infections using a less-sensitive EIA. HIV-RNA pooled testing was performed on HIV antibody-negative specimens to identify acute infections. HIV antibody-positive and acute infection specimens were evaluated for drug resistance by sequence analysis. Multivariable logistic regression was performed to evaluate associations. The 380 newly-diagnosed HIV cases included 29 acute infections, 128 recent infections, and 47 drug-resistant cases, with no significant increases or decreases in prevalence over the three years studied. HIV-1 transmitted drug resistance prevalence was 11.0% in 2004, 13.4% in 2005 and 14.9% in 2006 (p = 0.36). Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) was the most common pattern detected, present in 28 cases of resistance (59.6%). Among MSM, recent infection was associated with amphetamine use (AOR = 2.67; p<0.001), unprotected anal intercourse (AOR = 2.27; p<0.001), sex with a known HIV-infected partner (AOR = 1.64; p = 0.02), and history of gonorrhea (AOR = 1.62; p = 0.03).ConclusionsNew HIV diagnoses, recent infections, acute infections and transmitted drug resistance prevalence remained stable between 2004 and 2006. Resistance to NNRTI comprised more than half of the drug-resistant cases, a worrisome finding given its role as the backbone of first-line antiretroviral therapy in San Francisco as well as worldwide. The integration of HIV-1 drug resistance, recent infection, and acute infection testing should be considered for existing HIV/STI surveillance and prevention activities, particularly in an era of enhanced efforts for early diagnosis and treatment
Target Cell APOBEC3C Can Induce Limited G-to-A Mutation in HIV-1
The evolutionary success of primate lentiviruses reflects their high capacity to mutate and adapt to new host species, immune responses within individual hosts, and, in recent years, antiviral drugs. APOBEC3G (A3G) and APOBEC3F (A3F) are host cell DNA-editing enzymes that induce extensive HIV-1 mutation that severely attenuates viral replication. The HIV-1 virion infectivity factor (Vif), expressed in vivo, counteracts the antiviral activity of A3G and A3F by inducing their degradation. Other APOBECs may contribute more to viral diversity by inducing less extensive mutations allowing viral replication to persist. Here we show that in APOBEC3C (A3C)-expressing cells infected with the patient-derived HIV-1 molecular clones 210WW, 210WM, 210MW, and 210MM, and the lab-adapted molecular clone LAI, viral G-to-A mutations were detected in the presence of Vif expression. Mutations occurred primarily in the GA context and were relatively infrequent, thereby allowing for spreading infection. The mutations were absent in cells lacking A3C but were induced after transient expression of A3C in the infected target cell. Inhibiting endogenous A3C by RNA interference in Magi cells prevented the viral mutations. Thus, A3C is necessary and sufficient for G-to-A mutations in some HIV-1 strains. A3C-induced mutations occur at levels that allow replication to persist and may therefore contribute to viral diversity. Developing drugs that inhibit A3C may be a novel strategy for delaying viral escape from immune or antiretroviral inhibition
Phylogenetic Tests of Models of Viral Transmission
The hunt for the immediate non-human host of SARS-CoV-2 has centered on bats of the genus Rhinolophus. We explored the phylogenetic predictions of two models of viral transmission, the SpilloverModel and the CirculationModel and suggest that the Spillover Model can be eliminated. The Circulation Model suggests that viral transmission occurs among susceptible hosts irrespective of their phylogenetic relationships. Susceptibility could be mediated by the ACE2 gene (important for viral docking) and we constructed a phylogeny of this gene for 159 mammal species, finding a phylogenetic pattern consistent with established mammalian relationships. The tree indicates that viral transfer occurs over large evolutionary distances. Although lacking consensus, some studies identify a virus from a particular R. affinis individual (RaTG13) as being most closely related phylogenetically to human SARS-CoV-2. However, other R. affinis harbor viruses that are relatively unrelated to human viruses, and viruses found in this species exhibit sequence differences of up to 20%, suggesting multiple transfers over time. There is little correspondence between viral and host (bat) species limits or phylogenetic relationships. An ACE2 phylogeny for Rhinolophus followed species limits, unlike the pattern in the viral phylogeny indicating that phylogenetic similarity of ACE2 is not a predictor of viral transmission at the bat species level. The Circulation Model could be modified to apply to any individual of any species of Rhinolophus; more individuals and species must be examined
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