FY 2005 Quantum Cascade Laser Alignment System Final Report

The Alignment Lasers Task of Pacific Northwest National Laboratory's (PNNL's) Remote Spectroscopy Project (Project PL211I) is a co-funded project between DOE NA-22 and a Classified Client. This project, which began in the second half of FY03, involved building and delivering a Quantum Cascade (QC) Laser Alignment System to be used for testing the pupil alignment of an infrared sensor by measuring the response from four pairs of diametrically opposed QC lasers. PNNL delivered the system in FY04 and provided technical assistance in FY05 culminating into a successful demonstration of the system. This project evolved from the Laser Development Task of PL211I, which is involved in developing novel laser technology to support development of advanced chemical sensors for detecting the proliferation of nuclear weapons. The laser systems are based on quantum cascade (QC) lasers, a new semiconductor source in the infrared. QC lasers can be tailored to emit light throughout the infrared region (3.5 ? 17 ?m) and have high output power and stability. Thus, these lasers provide an infrared source with superb power and spectral stability enabling them to be used for applications such as alignment and calibration in addition to chemical sensing

Halo globular clusters observed with AAOmega: dark matter content, metallicity and tidal heating

Globular clusters have proven to be essential to our understanding of many important astrophysical phenomena. Here we analyse spectroscopic observations of ten Halo globular clusters to determine their dark matter content, their tidal heating by the Galactic disc and halo, describe their metallicities and the likelihood that Newtonian dynamics explain their kinematics. We analyse a large number of members in all clusters, allowing us to address all these issues together, and we have included NGC 288 and M30 to overlap with previous studies. We find that any flattening of the velocity dispersion profiles in the outer regions of our clusters can be explained by tidal heating. We also find that all our GCs have M/L_V < 5, therefore, we infer the observed dynamics do not require dark matter, or a modification of gravity. We suggest that the lack of tidal heating signatures in distant clusters indicates the Halo is not triaxial. The isothermal rotations of each cluster are measured, with M4 and NGC 288 exhibiting rotation at a level of 0.9 +/- 0.1 km/s and 0.25 +/- 0.15 km/s, respectively. We also indirectly measure the tidal radius of NGC 6752, determining a more realistic figure for this cluster than current literature values. Lastly, an unresolved and intriguing puzzle is uncovered with regard to the cooling of the outer regions of all ten clusters.Comment: 12 pages, 8 figures, 1 table. Accepted for publication in MNRAS

The Toxicology Investigators Consortium Case Registry-the 2016 Experience.

The Toxicology Investigators Consortium (ToxIC) Case Registry was established by the American College of Medical Toxicology in 2010. The Registry contains data from participating sites with the agreement that all bedside medical toxicology consultations will be entered. Currently, 83% of accredited medical toxicology fellowship programs in the USA participate. The Registry continues to grow each year, and as of 31 December 2016, a new milestone was reached, with more than 50,000 cases reported since its inception. The objective of this seventh annual report is to summarize the Registry\u27s 2016 data and activity with its additional 8529 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2016. Detailed data was collected from these cases and aggregated to provide information which includes the following: demographics (age, gender, race, ethnicity, HIV status), reason for medical toxicology evaluation (intentional pharmaceutical exposure, envenomation, withdrawal from a substance), agent and agent class, clinical signs and symptoms (vital sign abnormalities, organ system dysfunction), treatments and antidotes administered, fatality and life support withdrawal data. Fifty percent of cases involved females, and adults aged 19-65 were the most commonly reported. There were 86 patients (1.0%) with HIV-positive status known. Non-opioid analgesics were the most commonly reported agent class, with acetaminophen the most common agent reported. There were 126 fatalities reported in 2016 (1.5% of cases). Major trends in demographics and exposure characteristics remained similar overall with past years\u27 reports. While treatment interventions were commonly required, fatalities were rare

MLH1-methylated endometrial cancer under 60 years of age as the “sentinel” cancer in female carriers of high-risk constitutional MLH1 epimutation

Objective. Universal screening of endometrial carcinoma (EC) for mismatch repair deficiency (MMRd) and Lynch syndrome uses presence of MLH1 methylation to omit common sporadic cases from follow-up germline testing. However, this overlooks rare cases with high-risk constitutional MLH1 methylation (epimutation), a poorly-recognized mechanism that predisposes to Lynch-type cancers with MLH1 methylation. We aimed to de-termine the role and frequency of constitutional MLH1 methylation among EC cases with MMRd, MLH1- methylated tumors.Methods. We screened blood for constitutional MLH1 methylation using pyrosequencing and real-time methylation-specific PCR in patients with MMRd, MLH1-methylated EC ascertained from (i) cancer clinics (n = 4, <60 years), and (ii) two population-based cohorts; Columbus-area (n = 68, all ages) and Ohio Colo-rectal Cancer Prevention Initiative (OCCPI) (n = 24, <60 years).Results. Constitutional MLH1 methylation was identified in three out of four patients diagnosed between 36 and 59 years from cancer clinics. Two had mono-/hemiallelic epimutation (similar to 50% alleles methylated). One with multiple primaries had low-level mosaicism in normal tissues and somatic second-hits affecting the unmethylated allele in all tumors, demonstrating causation. In the population-based cohorts, all 68 cases from the Columbus-area cohort were negative and low-level mosaic constitutional MLH1 methylation was identified in one patient aged 36 years out of 24 from the OCCPI cohort, representing one of six (similar to 17%) patients <50 years and one of 45 patients (similar to 2%) <60 years in the combined cohorts. EC was the first/dual-first cancer in three pa-tients with underlying constitutional MLH1 methylation.Conclusions. A correct diagnosis at first presentation of cancer is important as it will significantly alter clinical management. Screening for constitutional MLH1 methylation is warranted in patients with early-onset EC or syn-chronous/metachronous tumors (any age) displaying MLH1 methylation.(c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/)

Correction to: The Toxicology Investigators Consortium Case Registry-The 2017 Annual Report.

Please note the Collaborators for this article listed in the Acknowledgements

Preserving the Chesapeake: Law, Ecology, and the Bay

This event was co-sponsored by the Merhige Center for Environmental Studies, the Allen Chair of Law, the Virginia State Bar, and the Miller Center of Public Affairs. The “Historical Background” session, held from 9:30 - 10:30 a.m., was presented by the Hon. Governor Gerald L. Baliles, Director of the Miller Center of Public Affairs and 65th Governor of the Commonwealth of Virginia; Gerald McCarthy, Executive Director of the Virginia Environmental Endowment; and Russell W. Baxter, Deputy Director of the Virginia Department of Conservation and Recreation. Rodney A. Smolla, Dean of the University of Richmond School of Law, served as moderator. The “Current State of the Bay” session, held on Friday, October 20, 2006 from 10:45 - 11:45 a.m., was presented by Jonathan Z. Cannon, Director of the Center for Environmental and Land Use Law at the University of Virginia School of Law; Erin Ryan, of the Marshall-Wythe School of Law at the College of William and Mary; and Richard Batiuk, Associate Director for Science of the Chesapeake Bay Program Office, United States Environmental Protection Agency. Joel Eisen, University of Richmond School of Law, served as moderator. The Keynote was given from 11:45 a.m. - 1:15 p.m. by L. Preston Bryant, Secretary of Natural Resources of the Commonwealth of Virginia. The “Regulatory Efforts” session, held 1:15-2:15 p.m., was presented by Kathy R. Frahm, Director of the Division of Policy at the Virginia Department of Environmental Quality; Joseph J. Tannery, Virginia Staff Attorney for the Chesapeake Bay Foundation; David E. Evans, Partner at McGuireWoods LLP; and Mark Smith, Environmental Scientist with the Water Protection Division, U.S. Environmental Protection Agency. The “Future and Solutions” session, held from 2:30-3:45 p.m., was presented by Nikki Rovner, Deputy Secretary of Natural Resources for the Commonwealth of Virginia; Timothy G. Hayes, Partner at Hunton & Williams LLP; Clyde Wilbur, Principal of Greeley & Hanson; and Alexandra Dunn, General Counsel for the National Association of Clean Water Agencies. Carl W. Tobias, Williams Professor of Law University of Richmond School of Law, served as moderator

Functional Evolution of Leptin of Ochotona curzoniae in Adaptive Thermogenesis Driven by Cold Environmental Stress

BACKGROUND: Environmental stress can accelerate the directional selection and evolutionary rate of specific stress-response proteins to bring about new or altered functions, enhancing an organism's fitness to challenging environments. Plateau pika (Ochotona curzoniae), an endemic and keystone species on Qinghai-Tibetan Plateau, is a high hypoxia and low temperature tolerant mammal with high resting metabolic rate and non-shivering thermogenesis to cope in this harsh plateau environment. Leptin is a key hormone related to how these animals regulate energy homeostasis. Previous molecular evolutionary analysis helped to generate the hypothesis that adaptive evolution of plateau pika leptin may be driven by cold stress. METHODOLOGY/PRINCIPAL FINDINGS: To test the hypothesis, recombinant pika leptin was first purified. The thermogenic characteristics of C57BL/6J mice injected with pika leptin under warm (23±1°C) and cold (5±1°C) acclimation is investigated. Expression levels of genes regulating adaptive thermogenesis in brown adipose tissue and the hypothalamus are compared between pika leptin and human leptin treatment, suggesting that pika leptin has adaptively and functionally evolved. Our results show that pika leptin regulates energy homeostasis via reduced food intake and increased energy expenditure under both warm and cold conditions. Compared with human leptin, pika leptin demonstrates a superior induced capacity for adaptive thermogenesis, which is reflected in a more enhanced β-oxidation, mitochondrial biogenesis and heat production. Moreover, leptin treatment combined with cold stimulation has a significant synergistic effect on adaptive thermogenesis, more so than is observed with a single cold exposure or single leptin treatment. CONCLUSIONS/SIGNIFICANCE: These findings support the hypothesis that cold stress has driven the functional evolution of plateau pika leptin as an ecological adaptation to the Qinghai-Tibetan Plateau

Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci.

BACKGROUND: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. METHODS: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history. RESULTS: The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). CONCLUSIONS: Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. IMPACT: We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs.D F. Easton was recipient of the CR-UK grant C1287/A10118. R A. Eeles was recipient of the CR-UK grant C5047/A10692 and B E. Henderson was recipient of the NIH grant 1U19CA148537-01This is the author accepted manuscript. The final version is available via AACR at http://cebp.aacrjournals.org/content/early/2015/04/02/1055-9965.EPI-14-0317.long

Science Opportunities offered by Mercury's Ice-Bearing Polar Deposits

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Seasonal pulses of Marburg virus circulation in juvenile Rousettus aegyptiacus bats coincide with periods of increased risk of human infection

Marburg virus (family Filoviridae) causes sporadic outbreaks of severe hemorrhagic disease in sub-Saharan Africa. Bats have been implicated as likely natural reservoir hosts based most recently on an investigation of cases among miners infected in 2007 at the Kitaka mine, Uganda, which contained a large population of Marburg virus-infected Rousettus aegyptiacus fruit bats. Described here is an ecologic investigation of Python Cave, Uganda, where an American and a Dutch tourist acquired Marburg virus infection in December 2007 and July 2008. More than 40,000 R. aegyptiacus were found in the cave and were the sole bat species present. Between August 2008 and November 2009, 1,622 bats were captured and tested for Marburg virus. Q-RT-PCR analysis of bat liver/spleen tissues indicated ,2.5% of the bats were actively infected, seven of which yielded Marburg virus isolates. Moreover, Q-RT-PCR-positive lung, kidney, colon and reproductive tissues were found, consistent with potential for oral, urine, fecal or sexual transmission. The combined data for R. aegyptiacus tested from Python Cave and Kitaka mine indicate low level horizontal transmission throughout the year. However, Q-RT-PCR data show distinct pulses of virus infection in older juvenile bats (,six months of age) that temporarily coincide with the peak twiceyearly birthing seasons. Retrospective analysis of historical human infections suspected to have been the result of discrete spillover events directly from nature found 83% (54/65) events occurred during these seasonal pulses in virus circulation, perhaps demonstrating periods of increased risk of human infection. The discovery of two tags at Python Cave from bats marked at Kitaka mine, together with the close genetic linkages evident between viruses detected in geographically distant locations, are consistent with R. aegyptiacus bats existing as a large meta-population with associated virus circulation over broad geographic ranges. These findings provide a basis for developing Marburg hemorrhagic fever risk reduction strategies.The Department of Health and Human Serviceshttp://www.plospathogens.or