Carter County - Carter Caves

A history of the founding of Carter Caves Park by Hubert V. Crawford written sometime in the 1990s

Carter County - Railroads & Industry

A 1992 manuscript written by Hubert V. Crawford titled The Role of Railroads and Heavy Industry in Carter County, Kentucky

Carter County - Schools

A 1993 manuscript written by Hubert V. Crawford titled Carter County Public School System: Then and Now

Genetic Crossovers Are Predicted Accurately by the Computed Human Recombination Map

Hotspots of meiotic recombination can change rapidly over time. This instability and the reported high level of inter-individual variation in meiotic recombination puts in question the accuracy of the calculated hotspot map, which is based on the summation of past genetic crossovers. To estimate the accuracy of the computed recombination rate map, we have mapped genetic crossovers to a median resolution of 70 Kb in 10 CEPH pedigrees. We then compared the positions of crossovers with the hotspots computed from HapMap data and performed extensive computer simulations to compare the observed distributions of crossovers with the distributions expected from the calculated recombination rate maps. Here we show that a population-averaged hotspot map computed from linkage disequilibrium data predicts well present-day genetic crossovers. We find that computed hotspot maps accurately estimate both the strength and the position of meiotic hotspots. An in-depth examination of not-predicted crossovers shows that they are preferentially located in regions where hotspots are found in other populations. In summary, we find that by combining several computed population-specific maps we can capture the variation in individual hotspots to generate a hotspot map that can predict almost all present-day genetic crossovers

Amyloid-β Inhibits No-cGMP Signaling in a CD36- and CD47-Dependent Manner

Amyloid-β interacts with two cell surface receptors, CD36 and CD47, through which the matricellular protein thrombospondin-1 inhibits soluble guanylate cyclase activation. Here we examine whether amyloid-β shares this inhibitory activity. Amyloid-β inhibited both drug and nitric oxide-mediated activation of soluble guanylate cyclase in several cell types. Known cGMP-dependent functional responses to nitric oxide in platelets and vascular smooth muscle cells were correspondingly inhibited by amyloid-β. Functional interaction of amyloid-β with the scavenger receptor CD36 was indicated by inhibition of free fatty acid uptake via this receptor. Both soluble oligomer and fibrillar forms of amyloid-β were active. In contrast, amyloid-β did not compete with the known ligand SIRPα for binding to CD47. However, both receptors were necessary for amyloid-β to inhibit cGMP accumulation. These data suggest that amyloid-β interaction with CD36 induces a CD47-dependent signal that inhibits soluble guanylate cyclase activation. Combined with the pleiotropic effects of inhibiting free fatty acid transport via CD36, these data provides a molecular mechanism through which amyloid-β can contribute to the nitric oxide signaling deficiencies associated with Alzheimer's disease

Fundamental Neutron Physics: a White Paper on Progress and Prospects in the US

Fundamental neutron physics, combining precision measurements and theory, probes particle physics at short range with reach well beyond the highest energies probed by the LHC. Significant US efforts are underway that will probe BSM CP violation with orders of magnitude more sensitivity, provide new data on the Cabibbo anomaly, more precisely measure the neutron lifetime and decay, and explore hadronic parity violation. World-leading results from the US Fundamental Neutron Physics community since the last Long Range Plan, include the world's most precise measurement of the neutron lifetime from UCN$\tau$, the final results on the beta-asymmetry from UCNA and new results on hadronic parity violation from the NPDGamma and n-${^3}$He runs at the FNPB (Fundamental Neutron Physics Beamline), precision measurement of the radiative neutron decay mode and n-${}^4$He at NIST. US leadership and discovery potential are ensured by the development of new high-impact experiments including BL3, Nab, LANL nEDM and nEDM@SNS. On the theory side, the last few years have seen results for the neutron EDM from the QCD $\theta$ term, a factor of two reduction in the uncertainty for inner radiative corrections in beta-decay which impacts CKM unitarity, and progress on {\it ab initio} calculations of nuclear structure for medium-mass and heavy nuclei which can eventually improve the connection between nuclear and nucleon EDMs. In order to maintain this exciting program and capitalize on past investments while also pursuing new ideas and building US leadership in new areas, the Fundamental Neutron Physics community has identified a number of priorities and opportunities for our sub-field covering the time-frame of the last Long Range Plan (LRP) under development. This white paper elaborates on these priorities.Comment: arXiv admin note: text overlap with arXiv:2304.0345

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder