Optical Lattices for Atom Based Quantum Microscopy

We describe new techniques in the construction of optical lattices to realize a coherent atom-based microscope, comprised of two atomic species used as target and probe atoms, each in an independently controlled optical lattice. Precise and dynamic translation of the lattices allows atoms to be brought into spatial overlap to induce atomic interactions. For this purpose, we have fabricated two highly stable, hexagonal optical lattices, with widely separted wavelengths but identical lattice constants using diffractive optics. The relative translational stability of 12nm permits controlled interactions and even entanglement operations with high fidelity. Translation of the lattices is realized through a monolithic electro-optic modulator array, capable of moving the lattice smoothly over one lattice site in 11 microseconds, or rapidly on the order of 100 nanoseconds.Comment: 7 pages, 9 figure

Identification and HLA-Tetramer-Validation of Human CD4(+) and CD8(+) T Cell Responses against HCMV Proteins IE1 and IE2

Human cytomegalovirus (HCMV) is an important human pathogen. It is a leading cause of congenital infection and a leading infectious threat to recipients of solid organ transplants as well as of allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both CD4+ and CD8+ T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on CD8+ T cell responses against the pp65 phosphoprotein. In this study, we have focused on CD4+ and CD8+ T cell responses against the immediate early 1 and 2 proteins (IE1 and IE2). Using overlapping peptides spanning the entire IE1 and IE2 sequences, peripheral blood mononuclear cells from 16 healthy, HLA-typed, donors were screened by ex vivo IFN-γ ELISpot and in vitro intracellular cytokine secretion assays. The specificities of CD4+ and CD8+ T cell responses were identified and validated by HLA class II and I tetramers, respectively. Eighty-one CD4+ and 44 CD8+ T cell responses were identified representing at least seven different CD4 epitopes and 14 CD8 epitopes restricted by seven and 11 different HLA class II and I molecules, respectively, in total covering 91 and 98% of the Caucasian population, respectively. Presented in the context of several different HLA class II molecules, two epitope areas in IE1 and IE2 were recognized in about half of the analyzed donors. These data may be used to design a versatile anti-HCMV vaccine and/or immunotherapy strategy

A MISSING-LINK IN THE SUPERNOVA-GRB CONNECTION: THE CASE OF SN 2012ap

Gamma Ray Bursts (GRBs) are characterized by ultra-relativistic outflows, while supernovae are generally characterized by non-relativistic ejecta. GRB afterglows decelerate rapidly usually within days, because their low-mass ejecta rapidly sweep up a comparatively larger mass of circumstellar material. However supernovae, with heavy ejecta, can be in nearly free expansion for centuries. Supernovae were thought to have non-relativistic outflows except for few relativistic ones accompanied by GRBs. This clear division was blurred by SN 2009bb, the first supernova with a relativistic outflow without an observed GRB. Yet the ejecta from SN 2009bb was baryon loaded, and in nearly-free expansion for a year, unlike GRBs. We report the first supernova discovered without a GRB, but with rapidly decelerating mildly relativistic ejecta, SN 2012ap. We discovered a bright and rapidly evolving radio counterpart driven by the circumstellar interaction of the relativistic ejecta. However, we did not find any coincident GRB with an isotropic fluence of more than a sixth of the fluence from GRB 980425. This shows for the first time that central engines in type Ic supernovae, even without an observed GRB, can produce both relativistic and rapidly decelerating outflows like GRBs.Comment: 8 pages, 5 figures, 1 table, accepted for publication in Ap

Worldwide trends in diabetes prevalence and treatment from 1990 to 2022: a pooled analysis of 1108 population-representative studies with 141 million participants

Background: Diabetes can be detected at the primary health-care level, and effective treatments lower the risk of complications. There are insufficient data on the coverage of treatment for diabetes and how it has changed. We estimated trends from 1990 to 2022 in diabetes prevalence and treatment for 200 countries and territories. Methods: We used data from 1108 population-representative studies with 141 million participants aged 18 years and older with measurements of fasting glucose and glycated haemoglobin (HbA1c), and information on diabetes treatment. We defined diabetes as having a fasting plasma glucose (FPG) of 7·0 mmol/L or higher, having an HbA1c of 6·5% or higher, or taking medication for diabetes. We defined diabetes treatment as the proportion of people with diabetes who were taking medication for diabetes. We analysed the data in a Bayesian hierarchical meta-regression model to estimate diabetes prevalence and treatment. Findings: In 2022, an estimated 828 million (95% credible interval [CrI] 757-908) adults (those aged 18 years and older) had diabetes, an increase of 630 million (554-713) from 1990. From 1990 to 2022, the age-standardised prevalence of diabetes increased in 131 countries for women and in 155 countries for men with a posterior probability of more than 0·80. The largest increases were in low-income and middle-income countries in southeast Asia (eg, Malaysia), south Asia (eg, Pakistan), the Middle East and north Africa (eg, Egypt), and Latin America and the Caribbean (eg, Jamaica, Trinidad and Tobago, and Costa Rica). Age-standardised prevalence neither increased nor decreased with a posterior probability of more than 0·80 in some countries in western and central Europe, sub-Saharan Africa, east Asia and the Pacific, Canada, and some Pacific island nations where prevalence was already high in 1990; it decreased with a posterior probability of more than 0·80 in women in Japan, Spain, and France, and in men in Nauru. The lowest prevalence in the world in 2022 was in western Europe and east Africa for both sexes, and in Japan and Canada for women, and the highest prevalence in the world in 2022 was in countries in Polynesia and Micronesia, some countries in the Caribbean and the Middle East and north Africa, as well as Pakistan and Malaysia. In 2022, 445 million (95% CrI 401-496) adults aged 30 years or older with diabetes did not receive treatment (59% of adults aged 30 years or older with diabetes), 3·5 times the number in 1990. From 1990 to 2022, diabetes treatment coverage increased in 118 countries for women and 98 countries for men with a posterior probability of more than 0·80. The largest improvement in treatment coverage was in some countries from central and western Europe and Latin America (Mexico, Colombia, Chile, and Costa Rica), Canada, South Korea, Russia, Seychelles, and Jordan. There was no increase in treatment coverage in most countries in sub-Saharan Africa; the Caribbean; Pacific island nations; and south, southeast, and central Asia. In 2022, age-standardised treatment coverage was lowest in countries in sub-Saharan Africa and south Asia, and treatment coverage was less than 10% in some African countries. Treatment coverage was 55% or higher in South Korea, many high-income western countries, and some countries in central and eastern Europe (eg, Poland, Czechia, and Russia), Latin America (eg, Costa Rica, Chile, and Mexico), and the Middle East and north Africa (eg, Jordan, Qatar, and Kuwait). Interpretation: In most countries, especially in low-income and middle-income countries, diabetes treatment has not increased at all or has not increased sufficiently in comparison with the rise in prevalence. The burden of diabetes and untreated diabetes is increasingly borne by low-income and middle-income countries. The expansion of health insurance and primary health care should be accompanied with diabetes programmes that realign and resource health services to enhance the early detection and effective treatment of diabetes

HPLC and mass spectrometry analysis of dolichol-phosphates at the cell culture scale

Dolichols (Dol) are polyprenol lipids that are essential structural components of eukaryotic membranes. In addition, the phosphorylated derivatives of Dol function as lipid anchors of mono- and oligosaccharide precursors involved in protein glycosylation. The biological importance of Dol phosphates (Dol-P) is illustrated by the severe outcome of human disorders linked to Dol biosynthetic defects, such as Dol-kinase deficiency. For characterization of inherited human diseases and evaluation of therapeutic trials, cultured cells often serve as a sole possible source for experimentation. Limited amounts of cell culture material render the quantitative analysis of Dol a challenging task. Here, we present HPLC- and mass spectrometry-based approaches to analyze and quantitate Dol-P from cultured human cells. The composition of naturally occurring Dol-P and the saturation state of the alpha-isoprene units was identified by negative-ion electrospray ionization mass spectrometry. Furthermore, fluorescently labeled Dol-P were separated by HPLC and quantified by comparison to known amounts of the internal standard polyprenol-P. The effect of pravastatin, a 3-hydroxy-3-methyl-glutaryl coenzyme-A reductase inhibitor, on the formation of Dol-P in HeLa cells was investigated. As expected, this treatment led to a decrease of Dol-P down to 35% of normal levels

The importance of sample size with regard to the robustness of postmortem reference values

Evaluating postmortem toxicological results is a challenging task due to multiple factors affecting blood concentrations after death. In order to improve the diagnostic accuracy in cases of suspected fatal intoxication different compilations of postmortem reference drug concentrations are often used. However, it is not clear what constitutes a reliable postmortem reference value. The current study presents reference concentrations for 13 substances from seven substance groups according to a standardized protocol. The reference concentrations were gathered from 3767 autopsy cases and subdivided into intoxications by one substance only (Group A, n= 611), multi-substance intoxications (Group B, n = 1355) and postmortem controls, in which incapacitation by drugs were excluded (Group C, n = 1801). In particular, this study presents statistical information about the precision and conformity change with various sample sizes. Based on the present data &amp;gt;10 detections are usually needed, for the substances examined, to differentiate between intoxication cases and controls. Repeated samplings show that the median of small samples (N= &amp;lt;= 5) has a high variation (normalized interquartile range 138-75%) and that a high number of detections (N = &amp;gt;20) in each group are needed to reduce the variation. (C) 2020 The Author(s). Published by Elsevier B.V.Funding Agencies|Swedish National Board of Forensic Medicine</p