Antigen depot is not required for alum adjuvanticity

Alum adjuvants have been in continuous clinical use for more than 80 yr. While the prevailing theory has been that depot formation and the associated slow release of antigen and/or inflammation are responsible for alum enhancement of antigen presentation and subsequent T- and B-cell responses, this has never been formally proven. To examine antigen persistence, we used the chimeric fluorescent protein EαGFP, which allows assessment of antigen presentation in situ, using the Y-Ae antibody. We demonstrate that alum and/or CpG adjuvants induced similar uptake of antigen, and in all cases, GFP signal did not persist beyond 24 h in draining lymph node antigen-presenting cells. Antigen presentation was first detectable on B cells within 6–12 h of antigen administration, followed by conventional dendritic cells (DCs) at 12–24 h, then finally plasmacytoid DCs at 48 h or later. Again, alum and/or CpG adjuvants did not have an effect on the magnitude or sequence of this response; furthermore, they induced similar antigen-specific T-cell activation in vivo. Notably, removal of the injection site and associated alum depot, as early as 2 h after administration, had no appreciable effect on antigen-specific T- and B-cell responses. This study clearly rules out a role for depot formation in alum adjuvant activity

Atomic environments in iron meteorites using EXAFS

Extended x ray absorption fine structure (EXAFS) is observed as a modulation on the high energy side of an x ray absorption edge. It occurs when the photo-ejected electron wave is scattered by neighboring atoms in a solid, and interference occurs between the outgoing and scattered waves. The result is that the absorption spectrum carries a signature that is characteristic of the identity and disposition of scattering atoms around the absorbing atom. Therefore, it may be shown that the Fourier transform of the normalized EXAFS can provide detailed information about the immediate environment of specific atoms in a solid and is ideally suited to the study of cosmic dusts. A study of cosmic dust was initiated using EXAFS and other techniques. The simplest type of cosmic material, namely iron meteorites, was investigated

Non-immune fetal hydrops: etiology and outcome according to gestational age at diagnosis.

OBJECTIVE: Fetal hydrops is associated with increased perinatal morbidity and mortality. The etiology and outcome of fetal hydrops may differ according to the gestational age at diagnosis. The aim of this study was to evaluate the cause, evolution and outcome of non-immune fetal hydrops (NIFH), according to the gestational age at diagnosis. METHODS: This was a retrospective cohort study of all singleton pregnancies complicated by NIFH, at the Fetal Medicine Unit at St George's University Hospital, London, UK, between 2000 and 2018. All fetuses had detailed anomaly and cardiac ultrasound scans, karyotyping and infection screening. Prenatal diagnostic and therapeutic intervention, gestational age at diagnosis and delivery, as well as pregnancy outcome, were recorded. Regression analysis was used to test for potential association between possible risk factors and perinatal mortality. RESULTS: We included 273 fetuses with NIFH. The etiology of the condition varied significantly in the three trimesters. Excluding 30 women who declined invasive testing, the cause of NIFH was defined as unknown in 62 of the remaining 243 cases (25.5%). Chromosomal aneuploidy was the most common cause of NIFH in the first trimester. It continued to be a significant etiologic factor in the second trimester, along with congenital infection. In the third trimester, the most common etiology was cardiovascular abnormality. Among the 152 (55.7%) women continuing the pregnancy, 48 (31.6%) underwent fetal intervention, including the insertion of pleuroamniotic shunts, fetal blood transfusion and thoracentesis. Fetal intervention was associated significantly with lower perinatal mortality (odds ratio (OR), 0.30 (95% CI, 0.14-0.61); P  0.05). CONCLUSIONS: An earlier gestational age at diagnosis of NIFH was associated with an increased risk of aneuploidy and worse pregnancy outcome, including a higher risk of perinatal loss. Fetal therapy was associated significantly with lower perinatal mortality. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology

The Political Economy of Myanmar's Transition

This is an Author's Original Manuscript of an article whose final and definitive form, the Version of Record, has been published in the JOURNAL OF CONTEMPORARY ASIA, 07 Feb 2013, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/00472336.2013.764143.Since holding elections in 2010, Myanmar has transitioned from a direct military dictatorship to a formally democratic system and has embarked on a period of rapid economic reform. After two decades of military rule, the pace of change has startled almost everyone and led to a great deal of cautious optimism. To make sense of the transition and assess the case for optimism, this article explores the political economy of Myanmar's dual transition from state socialism to capitalism and from dictatorship to democracy. It analyses changes within Myanmar society from a critical political economy perspective in order to both situate these developments within broader regional trends and to evaluate the country's current trajectory. In particular, the emergence of state-mediated capitalism and politico-business complexes in Myanmar's borderlands are emphasised. These dynamics, which have empowered a narrow oligarchy, are less likely to be undone by the reform process than to fundamentally shape the contours of reform. Consequently, Myanmar's future may not be unlike those of other Southeast Asian states that have experienced similar developmental trajectories

Leveraging Existing Technology: Developing a Trusted Digital Repository for the U.S. Geological Survey

As Federal Government agencies in the United States pivot to increase access to scientific data (Sheehan, 2016), the U.S. Geological Survey (USGS) has made substantial progress (Kriesberg et al., 2017). USGS authors are required to make federally funded data publicly available in an approved data repository (USGS, 2016b). This type of public data product, known as a USGS data release, serves as a method for publishing reviewed and approved data. In this paper, we present major milestones in the approach the USGS took to transition an existing technology platform to a Trusted Digital Repository. We describe both the technical and the non-technical actions that contributed to a successful outcome.We highlight how initial workflows revealed patterns that were later automated, and the ways in which assessments and user feedback influenced design and implementation. The paper concludes with lessons learned, such as the importance of a community of practice, application programming interface (API)-driven technologies, iterative development, and user-centered design. This paper is intended to offer a potential roadmap for organizations pursuing similar goals. &nbsp

Development and Application of a Needs-based Methodology for Calculating a Capitation Rate for a Comprehensive Health Organization

In this study we develop a methodology for calculating a capitation rate for a Comprehensive Health Organization (CHO). We apply the methodology to the population served by the proposed Fort Frances CHO. The methods of calculating capitation rates used currently by the Ontario Ministry of Health to determine funding levels of Health Service Organizations (HSOs), as well as the methods proposed for calculating CHO capitation rates, are critically reviewed. Both approaches base the calculated capitation rates on the current, or past, levels of health-care utilization, which perpetuate any existing inequalities in access to health care in the province. The methodology developed in this study has the health-care needs of the study population, as distinct from the health-care use of patients, as its focus. We argue that this needs-based approach is consistent with the philosophy of the Canada Health Act (1984) and encompasses aspects of both efficiency and equity in the allocation of health-care resources. Studies on population characteristics which correlate with health status and risks to health are reviewed, as is the literature on population-based planning of health-care resources. The strengths and weaknesses of potential indicators of health-care needs are evaluated. A profile of the study population is constructed, using data from the national census and other sources, which is compared with a corresponding profile of the provincial population. Particular features of the study population are identified as factors giving rise to atypical levels of need for health care. On the basis of the literature review, the standardized mortality ratio (SMR) is used as the best available indicator of need for most programmes.

Genomic analyses of the microsporidian Nosema ceranae, an emergent pathogen of honey bees

Recent steep declines in honey bee health have severely impacted the beekeeping industry, presenting new risks for agricultural commodities that depend on insect pollination. Honey bee declines could reflect increased pressures from parasites and pathogens. The incidence of the microsporidian pathogen Nosema ceranae has increased significantly in the past decade. Here we present a draft assembly (7.86 MB) of the N. ceranae genome derived from pyrosequence data, including initial gene models and genomic comparisons with other members of this highly derived fungal lineage. N. ceranae has a strongly AT-biased genome (74% A+T) and a diversity of repetitive elements, complicating the assembly. Of 2,614 predicted protein-coding sequences, we conservatively estimate that 1,366 have homologs in the microsporidian Encephalitozoon cuniculi, the most closely related published genome sequence. We identify genes conserved among microsporidia that lack clear homology outside this group, which are of special interest as potential virulence factors in this group of obligate parasites. A substantial fraction of the diminutive N. ceranae proteome consists of novel and transposableelement proteins. For a majority of well-supported gene models, a conserved sense-strand motif can be found within 15 bases upstream of the start codon; a previously uncharacterized version of this motif is also present in E. cuniculi. These comparisons provide insight into the architecture, regulation, and evolution of microsporidian genomes, and will drive investigations into honey bee-Nosema interactions

Activation regions in a yeast transposon have homology to mating type control sequences and to mammalian enhancers.

The DNA sequence of the Ty1 activating region from the CYC7-H2 mutant of Saccharomyces cerevisiae is presented. Analysis of the data revealed the presence of four simian virus 40-type enhancer core sequences. Two of the Ty1 enhancer cores are contiguous with sequences also homologous to the diploid control site at MAT alpha. We postulate that these two Ty1 regions of approximately equal to 30 base pairs are regulatory blocks, and we have analyzed deletions to ascertain whether they are necessary for effects of Ty1 on adjacent gene expression. We found that activation is lost when a restriction fragment encompassing both postulated regulatory blocks is deleted. Deletion of restriction fragments that remove only one of the two regulatory blocks has little or no effect on Ty1 activating ability in haploid yeast cells or on repression of this function in diploid yeast cells. Because the most significant internal homologies in the restriction fragments analyzed are the putative regulatory blocks, these observations suggest that enhancer-like sequences are involved in cell-type control of Ty1 effects on gene expression