Oil and Gas Maps of the Pikeville 30 x 60 Minute Quadrangle, Kentucky

The purpose of these oil and gas maps is to portray the distribution of types of wells in a manner useful to the oil and gas industry and geologists interested in subsurface research. The maps are designed to help geologists better evaluate acreage holdings and exploratory/development potential

Highly Sideophile Element Abundance Constraints on the Nature of the Late Accretionary Histories of Earth, Moon and Mars

The highly siderophile elements (HSE) include Re, Os, Ir, Ru, Pt and Pd. These elements are initially nearly-quantitatively stripped from planetary silicate mantles during core segregation. They then may be re-enriched in mantles via continued accretion sans continued core segregation. This suite of elements and its included long-lived radiogenic isotopes systems (Re-187 (right arrow) Os-187; Pt-190 (right arrow) Os-186) can potentially be used to fingerprint the characteristics of late accreted materials. The fingerprints may ultimately be useful to constrain the prior nebular history of the dominant late accreted materials, and to compare the proportion and genesis of late accretionary materials added to the inner planets. The past ten years have seen considerable accumulation of isotopic and compositional data for HSE present in the Earth's mantle, lunar mantle and impact melt breccias, and Martian meteorites. Here we review some of these data and consider the broader implications of the compiled data

The Role of Galactic Winds on Molecular Gas Emission from Galaxy Mergers

We assess the impact of starburst and AGN feedback-driven winds on the CO emission from galaxy mergers, and, in particular, search for signatures of these winds in the simulated CO morphologies and emission line profiles. We do so by combining a 3D non-LTE molecular line radiative transfer code with smoothed particle hydrodynamics (SPH) simulations of galaxy mergers that include prescriptions for star formation, black hole growth, a multiphase interstellar medium (ISM), and the winds associated with star formation and black hole growth. Our main results are: (1) Galactic winds can drive outflows of masses ~10^8-10^9 Msun which may be imaged via CO emission line mapping. (2) AGN feedback-driven winds are able to drive imageable CO outflows for longer periods of time than starburst-driven winds owing to the greater amount of energy imparted to the ISM by AGN feedback compared to star formation. (3) Galactic winds can control the spatial extent of the CO emission in post-merger galaxies, and may serve as a physical motivation for the sub-kiloparsec scale CO emission radii observed in local advanced mergers. (4) Secondary emission peaks at velocities greater than the circular velocity are seen in the CO emission lines in all models. In models with winds, these high velocity peaks are seen to preferentially correspond to outflowing gas entrained in winds, which is not the case in the model without winds. The high velocity peaks seen in models without winds are typically confined to velocity offsets (from the systemic) < 1.7 times the circular velocity, whereas the models with AGN feedback-driven winds can drive high velocity peaks to ~2.5 times the circular velocity.Comment: Accepted by ApJ; Minor revisions; Resolution tests include

The Impact of Beef Cattle Projects on Youth Leadership Life Skills Development

Highlights of a study designed to determine the leadership life skills development (YLLSD) of youth beef cattle exhibitors and to determine if there is a relationship between YLLSD and participation in the beef project are discussed in this paper. The study was conducted using a correlational, ex post facto design. A sample of 374 individuals was randomly selected from a population of 4,229 national junior cattle exhibitors of the National Junior Angus Association. The population frame consisted of junior members ages 18 to 21. Participants’ YLLSD scores ranged from 40 to 90 with a composite mean of 73.02. Significant relationships existed between YLLSD scores and shows per year, hours working with projects per week, and years of beef project exhibition

An Evolutionary Reduction Principle for Mutation Rates at Multiple Loci

A model of mutation rate evolution for multiple loci under arbitrary selection is analyzed. Results are obtained using techniques from Karlin (1982) that overcome the weak selection constraints needed for tractability in prior studies of multilocus event models. A multivariate form of the reduction principle is found: reduction results at individual loci combine topologically to produce a surface of mutation rate alterations that are neutral for a new modifier allele. New mutation rates survive if and only if they fall below this surface - a generalization of the hyperplane found by Zhivotovsky et al. (1994) for a multilocus recombination modifier. Increases in mutation rates at some loci may evolve if compensated for by decreases at other loci. The strength of selection on the modifier scales in proportion to the number of germline cell divisions, and increases with the number of loci affected. Loci that do not make a difference to marginal fitnesses at equilibrium are not subject to the reduction principle, and under fine tuning of mutation rates would be expected to have higher mutation rates than loci in mutation-selection balance. Other results include the nonexistence of 'viability analogous, Hardy-Weinberg' modifier polymorphisms under multiplicative mutation, and the sufficiency of average transmission rates to encapsulate the effect of modifier polymorphisms on the transmission of loci under selection. A conjecture is offered regarding situations, like recombination in the presence of mutation, that exhibit departures from the reduction principle. Constraints for tractability are: tight linkage of all loci, initial fixation at the modifier locus, and mutation distributions comprising transition probabilities of reversible Markov chains.Comment: v3: Final corrections. v2: Revised title, reworked and expanded introductory and discussion sections, added corollaries, new results on modifier polymorphisms, minor corrections. 49 pages, 64 reference

Probing Cellular Dynamics with a Chemical Signal Generator

Observations of material and cellular systems in response to time-varying chemical stimuli can aid the analysis of dynamic processes. We describe a microfluidic “chemical signal generator,” a technique to apply continuously varying chemical concentration waveforms to arbitrary locations in a microfluidic channel through feedback control of the interface between parallel laminar (co-flowing) streams. As the flow rates of the streams are adjusted, the channel walls are exposed to a chemical environment that shifts between the individual streams. This approach can be used to probe the dynamic behavior of objects or substances adherent to the interior of the channel. To demonstrate the technique, we exposed live fibroblast cells to ionomycin, a membrane-permeable calcium ionophore, while assaying cytosolic calcium concentration. Through the manipulation of the laminar flow interface, we exposed the cells' endogenous calcium handling machinery to spatially-contained discrete and oscillatory intracellular disturbances, which were observed to elicit a regulatory response. The spatiotemporal precision of the generated signals opens avenues to previously unapproachable areas for potential investigation of cell signaling and material behavior

Efficacious Intermittent Dosing of a Novel JAK2 Inhibitor in Mouse Models of Polycythemia Vera

A high percentage of patients with the myeloproliferative disorder polycythemia vera (PV) harbor a Val617→Phe activating mutation in the Janus kinase 2 (JAK2) gene, and both cell culture and mouse models have established a functional role for this mutation in the development of this disease. We describe the properties of MRLB-11055, a highly potent inhibitor of both the WT and V617F forms of JAK2, that has therapeutic efficacy in erythropoietin (EPO)-driven and JAK2V617F-driven mouse models of PV. In cultured cells, MRLB-11055 blocked proliferation and induced apoptosis in a manner consistent with JAK2 pathway inhibition. MRLB-11055 effectively prevented EPO-induced STAT5 activation in the peripheral blood of acutely dosed mice, and could prevent EPO-induced splenomegaly and erythrocytosis in chronically dosed mice. In a bone marrow reconstituted JAK2V617F-luciferase murine PV model, MRLB-11055 rapidly reduced the burden of JAK2V617F-expressing cells from both the spleen and the bone marrow. Using real-time in vivo imaging, we examined the kinetics of disease regression and resurgence, enabling the development of an intermittent dosing schedule that achieved significant reductions in both erythroid and myeloid populations with minimal impact on lymphoid cells. Our studies provide a rationale for the use of non-continuous treatment to provide optimal therapy for PV patients

Patterns of Polymorphism and Demographic History in Natural Populations of Arabidopsis lyrata

Many of the processes affecting genetic diversity act on local populations. However, studies of plant nucleotide diversity have largely ignored local sampling, making it difficult to infer the demographic history of populations and to assess the importance of local adaptation. Arabidopsis lyrata, a self-incompatible, perennial species with a circumpolar distribution, is an excellent model system in which to study the roles of demographic history and local adaptation in patterning genetic variation.We studied nucleotide diversity in six natural populations of Arabidopsis lyrata, using 77 loci sampled from 140 chromosomes. The six populations were highly differentiated, with a median FST of 0.52, and structure analysis revealed no evidence of admixed individuals. Average within-population diversity varied among populations, with the highest diversity found in a German population; this population harbors 3-fold higher levels of silent diversity than worldwide samples of A. thaliana. All A. lyrata populations also yielded positive values of Tajima's D. We estimated a demographic model for these populations, finding evidence of population divergence over the past 19,000 to 47,000 years involving non-equilibrium demographic events that reduced the effective size of most populations. Finally, we used the inferred demographic model to perform an initial test for local adaptation and identified several genes, including the flowering time gene FCA and a disease resistance locus, as candidates for local adaptation events.Our results underscore the importance of population-specific, non-equilibrium demographic processes in patterning diversity within A. lyrata. Moreover, our extensive dataset provides an important resource for future molecular population genetic studies of local adaptation in A. lyrata

DISC1 genetics, biology and psychiatric illness

Psychiatric disorders are highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points towards DISC1 being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain

Early Low-Titer Neutralizing Antibodies Impede HIV-1 Replication and Select for Virus Escape

Single genome sequencing of early HIV-1 genomes provides a sensitive, dynamic assessment of virus evolution and insight into the earliest anti-viral immune responses in vivo. By using this approach, together with deep sequencing, site-directed mutagenesis, antibody adsorptions and virus-entry assays, we found evidence in three subjects of neutralizing antibody (Nab) responses as early as 2 weeks post-seroconversion, with Nab titers as low as 1∶20 to 1∶50 (IC50) selecting for virus escape. In each of the subjects, Nabs targeted different regions of the HIV-1 envelope (Env) in a strain-specific, conformationally sensitive manner. In subject CH40, virus escape was first mediated by mutations in the V1 region of the Env, followed by V3. HIV-1 specific monoclonal antibodies from this subject mapped to an immunodominant region at the base of V3 and exhibited neutralizing patterns indistinguishable from polyclonal antibody responses, indicating V1–V3 interactions within the Env trimer. In subject CH77, escape mutations mapped to the V2 region of Env, several of which selected for alterations of glycosylation. And in subject CH58, escape mutations mapped to the Env outer domain. In all three subjects, initial Nab recognition was followed by sequential rounds of virus escape and Nab elicitation, with Nab escape variants exhibiting variable costs to replication fitness. Although delayed in comparison with autologous CD8 T-cell responses, our findings show that Nabs appear earlier in HIV-1 infection than previously recognized, target diverse sites on HIV-1 Env, and impede virus replication at surprisingly low titers. The unexpected in vivo sensitivity of early transmitted/founder virus to Nabs raises the possibility that similarly low concentrations of vaccine-induced Nabs could impair virus acquisition in natural HIV-1 transmission, where the risk of infection is low and the number of viruses responsible for transmission and productive clinical infection is typically one