CUTANEOUS ANGIITIS (VASCULITIS)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66185/1/j.1365-4362.1978.tb06119.x.pd

Cutaneous effects of exposure to polybrominated biphenyls (PBBs): The Michigan PBB incident

In 1973 an environmental accident occurred in northern Michigan in which 1000-2000 pounds of the toxic fire retardant polybrominated biphenyl (PBB) was added to the livestock food supply of much of northern Michigan. PBB is highly lipophilic, poorly metabolized, and biocumulative. It subsequently entered the human food chain of the entire state of Michigan. Health effects were noted in contaminated animals and among exposed farmers some months after the contamination; these often included cutaneous problems. Three years later a multidisciplinary study of the farming population was undertaken. Detected cutaneous abnormalities included halogen acne, hair loss, skin redness, skin peeling, and scaling, itching, increased sweating, and increased growth of fingernails and toenails. The mechanisms underlying these effects are unknown. PBBs appear to be etiologically implicated for significant cutaneous toxicity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23843/1/0000082.pd

SARS-CoV-2 Mac1 is an essential virulence factor

Several coronavirus (CoV) encoded proteins are being evaluated as targets for antiviral therapies for COVID-19. Included in this set of proteins is the conserved macrodomain, or Mac1, an ADP-ribosylhydrolase and ADP-ribose binding protein. Utilizing point mutant recombinant viruses, Mac1 was shown to be critical for both murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV virulence. However, as a potential drug target, it is imperative to understand how a complete Mac1 deletion impacts the replication and pathogenesis of different CoVs. To this end, we created recombinant bacterial artificial chromosomes (BACs) containing complete Mac1 deletions (ΔMac1) in MHV, MERS-CoV, and SARS-CoV-2. While we were unable to recover infectious virus from MHV or MERS-CoV ΔMac1 BACs, SARS-CoV-2 ΔMac1 was readily recovered from BAC transfection, indicating a stark difference in the requirement for Mac1 between different CoVs. Furthermore, SARS-CoV-2 ΔMac1 replicated at or near wild-type levels in multiple cell lines susceptible to infection. However, in a mouse model of severe infection, ΔMac1 was quickly cleared causing minimal pathology without any morbidity. ΔMac1 SARS-CoV-2 induced increased levels of interferon (IFN) and interferon-stimulated gene (ISG) expression in cell culture and mice, indicating that Mac1 blocks IFN responses which may contribute to its attenuation. ΔMac1 infection also led to a stark reduction in inflammatory monocytes and neutrophils. These results demonstrate that Mac1 only minimally impacts SARS-CoV-2 replication, unlike MHV and MERS-CoV, but is required for SARS-CoV-2 pathogenesis and is a unique antiviral drug target.National Institutes of Health (NIH) grant P20GM103648 (RC) National Institutes of Health (NIH) grant 2P01AI060699 (LE) National Institutes of Health (NIH) grant P20GM113117 (ARF) National Institutes of Health (NIH) grant K22AI134993 (ARF) National Institutes of Health (NIH) grant R35GM138029 (ARF) National Science Foundation (NSF) grant 2135167 (RLU) University of Kansas General Research Fund (GRF) and Start-up funds (ARF) NIH Graduate Training at the Biology-Chemistry Interface grant T32GM132061 (CMK) University of Kansas College of Liberal Arts and Sciences Graduate Research Fellowship (CMK) Government of Spain (PID2019-107001RB-I00 AEI/FEDER, UE) LE European Commission (H2020-SC1-2019, ISOLDA Project nº 848166-2) LEN

Jute/polypropylene composites: Effect of enzymatic modification on thermo-mechanical and dynamic mechanical properties

In this study, a high-performance composite was prepared from jute fabrics and polypropylene (PP). In order to improve the compatibility of the polar fibers and the non-polar matrix, alkyl gallates with different hydrophobic groups were enzymatically grafted onto jute fabric by laccase to increase the surface hydrophobicity of the fiber. The grafting products were characterized by FTIR. The results of contact angle and wetting time showed that the hydrophobicity of the jute fabrics was improved after the surface modification. The effect of the enzymatic graft modification on the properties of the jute/PP composites was evaluated. Results showed that after the modification, tensile and dynamic mechanical properties of composites improved, and water absorption and thickness swelling clearly decreased. However, tensile properties drastically decreased after a long period of water immersion. The thermal behavior of the composites was evaluated by TGA/DTG. The fiber-matrix morphology in the modified jute/PP composites was confirmed by SEM analysis of the tensile fractured specimens.This work was financially supported by the National Natural Science Foundation of China (51173071), the Program for New Century Excellent Talents in University (NCET-12-0883), the Program for Changjiang Scholars and Innovative Research Team in University (IRT1135) and the Fundamental Research Funds for the Central Universities (JUSRP51312B, JUSRP51505)

Integrated vector management for malaria control

Integrated vector management (IVM) is defined as "a rational decision-making process for the optimal use of resources for vector control" and includes five key elements: 1) evidence-based decision-making, 2) integrated approaches 3), collaboration within the health sector and with other sectors, 4) advocacy, social mobilization, and legislation, and 5) capacity-building. In 2004, the WHO adopted IVM globally for the control of all vector-borne diseases. Important recent progress has been made in developing and promoting IVM for national malaria control programmes in Africa at a time when successful malaria control programmes are scaling-up with insecticide-treated nets (ITN) and/or indoor residual spraying (IRS) coverage. While interventions using only ITNs and/or IRS successfully reduce transmission intensity and the burden of malaria in many situations, it is not clear if these interventions alone will achieve those critical low levels that result in malaria elimination. Despite the successful employment of comprehensive integrated malaria control programmes, further strengthening of vector control components through IVM is relevant, especially during the "end-game" where control is successful and further efforts are required to go from low transmission situations to sustained local and country-wide malaria elimination. To meet this need and to ensure sustainability of control efforts, malaria control programmes should strengthen their capacity to use data for decision-making with respect to evaluation of current vector control programmes, employment of additional vector control tools in conjunction with ITN/IRS tactics, case-detection and treatment strategies, and determine how much and what types of vector control and interdisciplinary input are required to achieve malaria elimination. Similarly, on a global scale, there is a need for continued research to identify and evaluate new tools for vector control that can be integrated with existing biomedical strategies within national malaria control programmes. This review provides an overview of how IVM programmes are being implemented, and provides recommendations for further development of IVM to meet the goals of national malaria control programmes in Africa

Science with the Daksha High Energy Transients Mission

We present the science case for the proposed Daksha high energy transients mission. Daksha will comprise of two satellites covering the entire sky from 1~keV to $>1$~MeV. The primary objectives of the mission are to discover and characterize electromagnetic counterparts to gravitational wave source; and to study Gamma Ray Bursts (GRBs). Daksha is a versatile all-sky monitor that can address a wide variety of science cases. With its broadband spectral response, high sensitivity, and continuous all-sky coverage, it will discover fainter and rarer sources than any other existing or proposed mission. Daksha can make key strides in GRB research with polarization studies, prompt soft spectroscopy, and fine time-resolved spectral studies. Daksha will provide continuous monitoring of X-ray pulsars. It will detect magnetar outbursts and high energy counterparts to Fast Radio Bursts. Using Earth occultation to measure source fluxes, the two satellites together will obtain daily flux measurements of bright hard X-ray sources including active galactic nuclei, X-ray binaries, and slow transients like Novae. Correlation studies between the two satellites can be used to probe primordial black holes through lensing. Daksha will have a set of detectors continuously pointing towards the Sun, providing excellent hard X-ray monitoring data. Closer to home, the high sensitivity and time resolution of Daksha can be leveraged for the characterization of Terrestrial Gamma-ray Flashes.Comment: 19 pages, 7 figures. Submitted to ApJ. More details about the mission at https://www.dakshasat.in

The James Webb Space Telescope Mission: Optical Telescope Element Design, Development, and Performance

The James Webb Space Telescope (JWST) is a large, infrared space telescope that has recently started its science program which will enable breakthroughs in astrophysics and planetary science. Notably, JWST will provide the very first observations of the earliest luminous objects in the Universe and start a new era of exoplanet atmospheric characterization. This transformative science is enabled by a 6.6 m telescope that is passively cooled with a 5-layer sunshield. The primary mirror is comprised of 18 controllable, low areal density hexagonal segments, that were aligned and phased relative to each other in orbit using innovative image-based wavefront sensing and control algorithms. This revolutionary telescope took more than two decades to develop with a widely distributed team across engineering disciplines. We present an overview of the telescope requirements, architecture, development, superb on-orbit performance, and lessons learned. JWST successfully demonstrates a segmented aperture space telescope and establishes a path to building even larger space telescopes.Comment: accepted by PASP for JWST Overview Special Issue; 34 pages, 25 figure

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. FUNDING: Bill & Melinda Gates Foundation