The Interstellar Medium In Galaxies Seen A Billion Years After The Big Bang

Evolution in the measured rest frame ultraviolet spectral slope and ultraviolet to optical flux ratios indicate a rapid evolution in the dust obscuration of galaxies during the first 3 billion years of cosmic time (z>4). This evolution implies a change in the average interstellar medium properties, but the measurements are systematically uncertain due to untested assumptions, and the inability to measure heavily obscured regions of the galaxies. Previous attempts to directly measure the interstellar medium in normal galaxies at these redshifts have failed for a number of reasons with one notable exception. Here we report measurements of the [CII] gas and dust emission in 9 typical (~1-4L*) star-forming galaxies ~1 billon years after the big bang (z~5-6). We find these galaxies have >12x less thermal emission compared with similar systems ~2 billion years later, and enhanced [CII] emission relative to the far-infrared continuum, confirming a strong evolution in the interstellar medium properties in the early universe. The gas is distributed over scales of 1-8 kpc, and shows diverse dynamics within the sample. These results are consistent with early galaxies having significantly less dust than typical galaxies seen at z<3 and being comparable to local low-metallicity systems.Comment: Submitted to Nature, under review after referee report. 22 pages, 4 figures, 4 Extended Data Figures, 5 Extended Data table

Using small molecules to facilitate exchange of bicarbonate and chloride anions across liposomal membranes

Bicarbonate is involved in a wide range of biological processes, which include respiration, regulation of intracellular pH and fertilization. In this study we use a combination of NMR spectroscopy and ion-selective electrode techniques to show that the natural product prodigiosin, a tripyrrolic molecule produced by microorganisms such as Streptomyces and Serratia, facilitates chloride/bicarbonate exchange (antiport) across liposomal membranes. Higher concentrations of simple synthetic molecules based on a 4,6-dihydroxyisophthalamide core are also shown to facilitate this antiport process. Although it is well known that proteins regulate Cl-/HCO3- exchange in cells, these results suggest that small molecules may also be able to regulate the concentration of these anions in biological systems

A self-organized model for cell-differentiation based on variations of molecular decay rates

Systemic properties of living cells are the result of molecular dynamics governed by so-called genetic regulatory networks (GRN). These networks capture all possible features of cells and are responsible for the immense levels of adaptation characteristic to living systems. At any point in time only small subsets of these networks are active. Any active subset of the GRN leads to the expression of particular sets of molecules (expression modes). The subsets of active networks change over time, leading to the observed complex dynamics of expression patterns. Understanding of this dynamics becomes increasingly important in systems biology and medicine. While the importance of transcription rates and catalytic interactions has been widely recognized in modeling genetic regulatory systems, the understanding of the role of degradation of biochemical agents (mRNA, protein) in regulatory dynamics remains limited. Recent experimental data suggests that there exists a functional relation between mRNA and protein decay rates and expression modes. In this paper we propose a model for the dynamics of successions of sequences of active subnetworks of the GRN. The model is able to reproduce key characteristics of molecular dynamics, including homeostasis, multi-stability, periodic dynamics, alternating activity, differentiability, and self-organized critical dynamics. Moreover the model allows to naturally understand the mechanism behind the relation between decay rates and expression modes. The model explains recent experimental observations that decay-rates (or turnovers) vary between differentiated tissue-classes at a general systemic level and highlights the role of intracellular decay rate control mechanisms in cell differentiation.Comment: 16 pages, 5 figure

Neutron scattering effects on fusion ion temperature measurements.

To support the nuclear fusion program at Sandia National Laboratories (SNL), a consistent and verifiable method to determine fusion ion temperatures needs to be developed. Since the fusion temperature directly affects the width in the spread of neutron energies produced, a measurement of the neutron energy width can yield the fusion temperature. Traditionally, the spread in neutron energies is measured by using time-of-flight to convert a spread in neutron energies at the source to a spread in time at detector. One potential obstacle to using this technique at the Z facility at SNL is the need to shield the neutron detectors from the intense bremsstrahlung produced. The shielding consists of eight inches of lead and the concern is that neutrons will scatter in the lead, artificially broaden the neutron pulse width and lead to an erroneous measurement. To address this issue, experiments were performed at the University of Rochester's Laboratory for Laser Energetics, which demonstrated that a reliable ion temperature measurement can be achieved behind eight inches of lead shielding. To further expand upon this finding, Monte Carlo N-Particle eXtended (MCNPX) was used to simulate the experimental geometric conditions and perform the neutron transport. MCNPX was able to confidently estimate results observed at the University of Rochester

Study of Zγ events and limits on anomalous ZZγ and Zγγ couplings in pp̄ collisions at s=1.96TeV

We present a measurement of the Zγ production cross section and limits on anomalous ZZγ and Zγγ couplings for form-factor scales of Λ=750 and 1000 GeV. The measurement is based on 138 (152) candidates in the eeγ (μμγ) final state using 320(290)pb-1 of pp̄ collisions at s=1.96TeV. The 95% C.L. limits on real and imaginary parts of individual anomalous couplings are |h10,30Z|<0.23, |h20,40Z|<0.020, |h10,30γ|<0.23, and |h20,40γ|<0.019 for Λ=1000GeV. © 2005 The American Physical Society

The Bicarbonate Transporter Is Essential for Bacillus anthracis Lethality

In the pathogenic bacterium Bacillus anthracis, virulence requires induced expression of the anthrax toxin and capsule genes. Elevated CO2/bicarbonate levels, an indicator of the host environment, provide a signal ex vivo to increase expression of virulence factors, but the mechanism underlying induction and its relevance in vivo are unknown. We identified a previously uncharacterized ABC transporter (BAS2714-12) similar to bicarbonate transporters in photosynthetic cyanobacteria, which is essential to the bicarbonate induction of virulence gene expression. Deletion of the genes for the transporter abolished induction of toxin gene expression and strongly decreased the rate of bicarbonate uptake ex vivo, demonstrating that the BAS2714-12 locus encodes a bicarbonate ABC transporter. The bicarbonate transporter deletion strain was avirulent in the A/J mouse model of infection. Carbonic anhydrase inhibitors, which prevent the interconversion of CO2 and bicarbonate, significantly affected toxin expression only in the absence of bicarbonate or the bicarbonate transporter, suggesting that carbonic anhydrase activity is not essential to virulence factor induction and that bicarbonate, and not CO2, is the signal essential for virulence induction. The identification of this novel bicarbonate transporter essential to virulence of B. anthracis may be of relevance to other pathogens, such as Streptococcus pyogenes, Escherichia coli, Borrelia burgdorferi, and Vibrio cholera that regulate virulence factor expression in response to CO2/bicarbonate, and suggests it may be a target for antibacterial intervention

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Evidence of Dopaminergic Processing of Executive Inhibition

Inhibition of unwanted response is an important function of the executive system. Since the inhibitory system is impaired in patients with dysregulated dopamine system, we examined dopamine neurotransmission in the human brain during processing of a task of executive inhibition. The experiment used a recently developed dynamic molecular imaging technique to detect and map dopamine released during performance of a modified Eriksen's flanker task. In this study, young healthy volunteers received an intravenous injection of a dopamine receptor ligand (11C-raclopride) after they were positioned in the PET camera. After the injection, volunteers performed the flanker task under Congruent and Incongruent conditions in a single scan session. They were required to inhibit competing options to select an appropriate response in the Incongruent but not in the Congruent condition. The PET data were dynamically acquired during the experiment and analyzed using two variants of the simplified reference region model. The analysis included estimation of a number of receptor kinetic parameters before and after initiation of the Incongruent condition. We found increase in the rate of ligand displacement (from receptor sites) and decrease in the ligand binding potential in the Incongruent condition, suggesting dopamine release during task performance. These changes were observed in small areas of the putamen and caudate bilaterally but were most significant on the dorsal aspect of the body of left caudate. The results provide evidence of dopaminergic processing of executive inhibition and demonstrate that neurochemical changes associated with cognitive processing can be detected and mapped in a single scan session using dynamic molecular imaging

Prevalence and changes in chronic diseases among South Korean farmers: 1998 to 2005

<p>Abstract</p> <p>Background</p> <p>Epidemiologic studies have suggested a unique pattern of disease among farmers in Western countries, but limited information is available about the magnitude of disease prevalence and their changes over time in Asian farmers. The aim of this study was to compare the prevalence and changes in chronic diseases among farmers with those of other occupational groups in South Korea.</p> <p>Methods</p> <p>Using data from three consecutive cross-sectional national surveys: the Korean National Health and Nutrition Examination Survey 1998 (n = 39,060), 2001 (n = 37,769), and 2005 (n = 34,145), we calculated age and gender-standardized prevalence of chronic diseases by the direct method and compared the prevalence changes from 1998 to 2005.</p> <p>Results</p> <p>Female farmers had significantly higher chronic disease prevalence than other occupational groups in all three surveys. Arthritis was the most prevalent chronic disease among farmers for both men and women. Compared with other populations, farmers demonstrated a higher prevalence of arthritis and intervertebral disc disorders. Farmers showed higher prevalence changes for intervertebral disc disorders than other occupational workers.</p> <p>Conclusion</p> <p>Our findings support that South Korean farmers have a distinct pattern of diseases prevalence from other populations. More detailed studies investigating the risk of musculoskeletal diseases and intensive intervention efforts to reduce the prevalence these diseases, particularly among female farmers, are required.</p

Prognostic significance of fascin expression in advanced colorectal cancer: an immunohistochemical study of colorectal adenomas and adenocarcinomas

BACKGROUND: Fascin is an actin bundling protein with roles in the formation of cell protrusions and motility of mesenchymal and neuronal cells. Fascin is normally low or absent from epithelia, but is upregulated in several epithelial neoplasms where it may contribute to an invasive phenotype. Here, we report on the prevalence and potential clinical significance of fascin expression in relation to the progression of colorectal adenocarcinoma and to tumor cell proliferation as measured by Ki67 index. METHODS: Conventional tissue sections of 107 colorectal adenomas and 35 adenocarcinomas were analyzed by immunohistochemistry for fascin and Ki67 expression. Fascin expression and Ki67 proliferation index were also investigated by use of a tissue microarray containing cores from a further 158 colorectal adenocarcinomas and 15 adenomas linked to a CCF, IRB-approved database with a mean of 38 months of clinical follow-up. Survival analysis was carried out by the Kaplan-Meier and Cox regression methods. RESULTS: Fascin was not expressed by the normal colonic epithelium. In conventional sections, 16% of adenomas and 26% of adenocarcinomas showed fascin expression in greater than 10% of the tumor cells. In the clinically-annotated tumors, fascin immunoreactivity was more common in tumors located in the proximal colon (p = 0.009), but was not associated with age, gender, or TNM stage. Patients with stage III/IV adenocarcinomas (n = 62) with strong fascin immunoreactivity had a worse prognosis than patients with low or absent fascin, (3-year overall survival of 11% versus 43% for fascin-negative patients; p = 0.023). In adenomas, fascin and Ki67 tended to be inversely correlated at the cellular level; this trend was less apparent in adenocarcinomas. CONCLUSION: Fascin is upregulated in a proportion of adenomas, where its expression is often focal. Strong and diffuse expression was seen in a subset of advanced colorectal adenocarcinomas that correlated with shorter survival in stage III and IV patients. Fascin may have prognostic value as an early biomarker for more aggressive colorectal adenocarcinomas