Structure of the semiquinone form of flavodoxin from Clostridium MP : Extension of 1.8 A resolution and some comparisons with the oxidized state

As part of a series of comparisons of the structures of the three oxidation states of flavodoxin from Clostridium MP, phases for the semiquinono form were determined to 2.0 A resolution by isomorphous replacement (m > = 0.725). Subsequently, the structure was refined at 1.8 A resolution by a combination of difference Fourier, real space and reciprocal space methods. After refining to an R of 0.194, we explored the conformation of the FMN binding site by real space refinement versus maps with Fourier coefficients of the form (2|Fo|- |Fc|) exp (i[alpha]c). To minimize bias in the fitting, groups of atoms were systematically omitted from the structure factors used in computation of the (2|Fo - |Fc|) maps.One-electron reduction of oxidized flavodoxin is accompanied by several changes at the FMN binding site: the conformation of residues in the reverse bend formed by Met56-Gly57-Asp58-Glu59 differs in the crystal structures of the oxidized and semiquinone species; further, backbone atoms in residues 55 and 89 shift by more than 0.5 A and the indole ring of Trp90 undergoes a significant displacement. The orientation of the peptide unit connecting Gly57 and Asp58 is consistent with the presence of a hydrogen bond between the carbonyl oxygen of Gly57 and the flavin N(5) in flavodoxin semiquinone. No equivalent bond is found in oxidized flavodoxin. In both the oxidized and semiquinone species of clostridial flavodoxin, the isoalloxazine ring is essentially planar : the bending angles about N(5)---N(10) are ~2.5 [deg] for the semiquinone structure and ~0 [deg] in oxidized flavodoxin.The intensity changes resulting from the oxidized agsemiquinone conversion (RI = 0.33) arise in part from changes in molecular packing. Intermolecular contacts, including neighbors of the prosthetic group, are altered in the repacking. Maps or models of the two oxidation states can be brought into approximate coincidence by a rigid body motion. The required transformation, determined for the isomorphous replacement maps by the method of Cox (1967), is equivalent to a screw motion with a rotation of 1.18 [deg] and a translation of -0.34 A. The molecular structures of oxidized and semiquinone flavodoxins have been compared after superposition of models with idealized co-ordinates and discrepancy indices Rox = 0.213 and Rsq = 0.200. The root-mean-square distance between 523 backbone atoms (excluding sequences 56 to 59 and 89 to 91) is 0.308 A.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22809/1/0000366.pd

Resource Selection by the California Condor (Gymnogyps californianus) Relative to Terrestrial-Based Habitats and Meteorological Conditions

Condors and vultures are distinct from most other terrestrial birds because they use extensive soaring flight for their daily movements. Therefore, assessing resource selection by these avian scavengers requires quantifying the availability of terrestrial-based habitats, as well as meteorological variables that influence atmospheric conditions necessary for soaring. In this study, we undertook the first quantitative assessment of habitat- and meteorological-based resource selection in the endangered California condor (Gymnogyps californianus) within its California range and across the annual cycle. We found that condor use of terrestrial areas did not change markedly within the annual cycle, and that condor use was greatest for habitats where food resources and potential predators could be detected and where terrain was amenable for taking off from the ground in flight (e.g., sparse habitats, coastal areas). Condors originating from different release sites differed in their use of habitat, but this was likely due in part to variation in habitats surrounding release sites. Meteorological conditions were linked to condor use of ecological subregions, with thermal height, thermal velocity, and wind speed having both positive (selection) and negative (avoidance) effects on condor use in different areas. We found little evidence of systematic effects between individual characteristics (i.e., sex, age, breeding status) or components of the species management program (i.e., release site, rearing method) relative to meteorological conditions. Our findings indicate that habitat type and meteorological conditions can interact in complex ways to influence condor resource selection across landscapes, which is noteworthy given the extent of anthropogenic stressors that may impact condor populations (e.g., lead poisoning, wind energy development). Additional studies will be valuable to assess small-scale condor movements in light of these stressors to help minimize their risk to this critically endangered species

The Parkes Observatory Pulsar Data Archive

The Parkes pulsar data archive currently provides access to 144044 data files obtained from observations carried out at the Parkes observatory since the year 1991. Around 10^5 files are from surveys of the sky, the remainder are observations of 775 individual pulsars and their corresponding calibration signals. Survey observations are included from the Parkes 70cm and the Swinburne Intermediate Latitude surveys. Individual pulsar observations are included from young pulsar timing projects, the Parkes Pulsar Timing Array and from the PULSE@Parkes outreach program. The data files and access methods are compatible with Virtual Observatory protocols. This paper describes the data currently stored in the archive and presents ways in which these data can be searched and downloaded.Comment: Accepted by PAS

The making of an entertainment revolution: How the TV format trade became a global industry

From its humble origins in the 1950s, the TV format industry has become a global trade worth billions of Euros per year. Few viewers are aware that their favourite shows may be local adaptations but formats represent a significant percentage of European broadcasting schedules in access prime time and prime time. Formatted brands exist in all TV genres and reach almost every country in the world. This article defends the thesis that the format business turned into a global industry in the late 1990s. Before this turning point, the few formatted programmes were most likely American game shows that travelled slowly and to a limited number of territories. Following an overview of this early period, this article examines the convergence of factors that created a world format market. These include the emergence of four exceptional formats (Who Wants to Be a Millionaire?, Survivor, Big Brother and Idols), the formation of a programming market, the rise of the independent production sector, and the globalization of information flows within the TV industry

Reviews and bibliographical notices

n/

Comparing the Health Effects of Ambient Particulate Matter Estimated Using Ground-Based versus Remote Sensing Exposure Estimates

BACKGROUND: Remote sensing (RS) is increasingly used for exposure assessment in epidemiological and burden of disease studies, including those investigating whether chronic exposure to ambient fine particulate matter (PM2.5) is associated with mortality. OBJECTIVES: To compare relative risk estimates of mortality from diseases of the circulatory system for PM2.5 modeled from RS with that for PM2.5 modeled using ground-level information. METHODS: We geocoded the baseline residence of 668,629 American Cancer Society Cancer Prevention Study II (CPS-II) cohort participants followed from 1982 to 2004 and assigned PM2.5 levels to all participants using seven different exposure models. Most of the exposure models were averaged for the years 2002-2004, while one RS estimate was for a longer, contemporaneous period. We used Cox proportional hazards regression to estimate relative risks (RR) for the association of PM2.5 with circulatory mortality and ischemic heart disease. RESULTS: Estimates of mortality risk differed among exposure models. The smallest relative risk was observed for the RS estimates that excluded ground-based monitors for circulatory deaths (RR = 1.02 (95% confidence interval (CI): 1.00-1.04 per 10 microg/m3 increment in PM2.5). The largest relative risk was observed for the land use regression model that included traffic information (RR = 1.14, 95% CI: 1.11-1.17 per 10 microg/m3 increment in PM2.5). CONCLUSIONS: We found significant associations between PM2.5 and mortality in every model; however, relative risks estimated from exposure models using ground-based information were generally larger than those estimated with RS alone

COVID-19: Third dose booster vaccine effectiveness against breakthrough coronavirus infection, hospitalisations and death in patients with cancer: A population-based study

Purpose: People living with cancer and haematological malignancies are at increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated. Methods: This study is a population-scale real-world evaluation of the United Kingdom’s third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England’s national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population. Results: The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction (PCR) coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5% respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Lymphoma patients had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01 respectively. p<0.001 for both). Conclusions: Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous, and lower than the general population. Many patients with cancer will remain at increased risk of coronavirus infections, even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic

Global estimates of mortality associated with long-term exposure to outdoor fine particulate matter.

Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5 and nonaccidental mortality using data from 41 cohorts from 16 countries-the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5-10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9-8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3-4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations

In Search of a Trade Mark: Search Practices and Bureaucratic Poetics

Trade marks have been understood as quintessential ‘bureaucratic properties’. This article suggests that the making of trade marks has been historically influenced by bureaucratic practices of search and classification, which in turn were affected by the possibilities and limits of spatial organisation and technological means of access and storage. It shows how the organisation of access and retrieval did not only condition the possibility of conceiving new trade marks, but also served to delineate their intangible proprietary boundaries. Thereby they framed the very meaning of a trade mark. By advancing a historical analysis that is sensitive to shifts, both in actual materiality and in the administrative routines of trade mark law, the article highlights the legal form of trade mark as inherently social and materially shaped. We propose a historical understanding of trade mark law that regards legal practice and bureaucratic routines as being co-constitutive of the very legal object itself