The Early Local and Regional Immune Response to Recall Inoculations of Mycobacterium Leprae in the Skin of Rhesus Macaques (Macaca Mulatta).

Epidemiological studies have failed to show any important impact of human immunodeficiency virus (HIV) infection and disease on leprosy, in contrast to the well documented increase in incidence and morbidity with other mycobacteria in these patients, notably Mycobacterium tuberculosis. The early events following exposure and repeated exposure to Mycobacterium leprae (ML) have not still been studied. Previous studies of first inoculations of ML in the skin of rhesus monkeys have indicated delayed recruitment of CD4+ cells and delayed interleukin (IL) 2 secretion in skin inoculation sites in simian immunodeficiency (SIV) positive animals. The development of the secondary immune response against a challenge of ML was studied over a period of 2 months in the skin of 9 rhesus macaques, all inoculated previously with ML, 3 of which were SIV positive slow progressors. Cell recruitment and types of cytokine response in the skin and draining lymph nodes (LN) were investigated using flow cytometry (FC), immunohistochemistry, and reverse transcription polymerase chain reaction to detect relative levels of messenger ribonucleic acid (mRNA) expression for IL2, IL4, interferon gamma (IFNgamma) and IL10. Results were analyzed according to SIV status and persistence of ML infection. An early vigorous expression of IL2 and IFNgamma mRNA, indicative of a strong T helper (Th) 1 cytokine profile, was seen in the skin of macaques that cleared ML infection. Animals that developed persistent ML infection (ML+) had delayed, weak Th1 response, and no evidence of early Th2 response in the skin. In contrast, early up regulation of IL4 was only observed in the LN of ML+ macaques. Recruitment of CD4+ lymphocytes into the skin was significantly lower and delayed in ML+ animals. CD4:CD8 ratio were significantly lower in the blood in SIV+ monkeys. However, no significant differences in CD4+ lymphocyte recruitment or expression of cytokine mRNA were observed between SIV- and SIV+ monkeys. Despite evidence of systemic immunodepression, the slow progressing SIV+ rhesus macaques are still capable of mounting an adequate response to ML re-inoculation in the skin. A Th2 response is not generated in the skin early after re-infection in animals which developed progressive infection

High performance thin-film optical filters with stress compensation

International audienceWe present a thorough description of high performance thin-film optical filters with high flatness. These components can combine several tens or hundreds of layers and are manufactured using plasma-assisted reactive magnetron sputtering. Stress compensation is achieved using dual side coatings with appropriate spectral function. Examples of highly reflecting mirrors at 515 nm with 15 nm flatness peak-to-valley over up to 75 mm diameter aperture, narrow bandpass filters and filters with broadband controlled transmission are described

Four-component united-atom model of bitumen

We propose a four-component molecular model of bitumen. The model includes realistic chemical constituents and introduces a coarse-graining level that suppresses the highest frequency modes. Molecular dynamics simulations of the model are being carried out using Graphic-Processor-Units based software in time spans in order of microseconds, and this enables the study of slow relaxation processes characterizing bitumen. This paper focuses on the high-temperature dynamics as expressed through the mean-square displacement, the stress autocorrelation function, and rotational relaxation. The diffusivity of the individual molecules changes little as a function of temperature and reveals distinct dynamical time scales as a result of the different constituents in the system. Different time scales are also observed for the rotational relaxation. The stress autocorrelation function features a slow non-exponential decay for all temperatures studied. From the stress autocorrelation function, the shear viscosity and shear modulus are evaluated at the highest temperature, showing a viscous response at frequencies below 100 MHz. The model predictions of viscosity and diffusivities are compared to experimental data, giving reasonable agreement. The model shows that the asphaltene, resin and resinous oil tend to form nano-aggregates. The characteristic dynamical relaxation time of these aggregates is different from the homogeneously distributed parts of the system, leading to strong dynamical heterogeneity.Comment: 10 pages, 12 figure

Impact and Friction Sensitivities of PETN: I. Sensitivities of the Pure and Wetted Material

Pentaerythritol tetranitrate (PETN) is a sensitive and brisant explosive. PETN is transported wetted (25 %) with water to limit its impact and friction sensitivities. Literature on its sensitivities in function of its water content is controversial as the measurements were performed by several operators and laboratories rendering difficult to compare the values. Literature studies of mechanical sensitivity methods show the weaknesses and problems of mechanical measurements. Indeed, it is important to analyze a sample with standardized machines and by a single operator. During this work, pure PETN samples with water contents of 0 to 35 % were prepared and the water content was measured by Karl-Fischer titration. The sensitivities were analyzed by the BAM Fallhammer and the BAM Friction Apparatus. The resulting trends were analyzed and discussed with regard to their meaning for handling safety. The study should help to better assess dangers when working with wet PETN (10-25 %) in order to avoid accidents

Cooee bitumen. II. Stability of linear asphaltene nanoaggregates

Asphaltene and smaller aromatic molecules tend to form linear nanoaggregates in bitumen.Over the years bitumen undergoes chemical aging and during this process, the size of the nanoaggregate increases. This increase is associated with an increase in viscosity and brittleness of the bitumen, eventually leading to road deterioration. This paper focuses on understanding the mechanisms behind nanoaggregate size and stability. We used molecular dynamics simulations to quantify the probability of having a nanoaggregate of a given size in the stationary regime. To model this complicated behavior, we chose first to consider the simple case where only asphaltene molecules are counted in a nanoaggregate. We used a master equation approach and a related statistical mechanics model. The linear asphaltene nanoaggregates behave as a rigid linear chain. The most complicated case where all aromatic molecules are counted in a nanoaggregate is then discussed. The linear aggregates where all aromatic molecules are counted seem to behave as a flexible linear chain.Comment: 31 pages, 9 figure

European Society of Toxicologic Pathology (Pathology 2.0 Molecular Pathology Special Interest Group): Review of In Situ Hybridization Techniques for Drug Research and Development

In situ hybridization (ISH) is used for the localization of specific nucleic acid sequences in cells or tissues by complementary binding of a nucleotide probe to a specific target nucleic acid sequence. In the last years, the specificity and sensitivity of ISH assays were improved by innovative techniques like synthetic nucleic acids and tandem oligonucleotide probes combined with signal amplification methods like branched DNA, hybridization chain reaction and tyramide signal amplification. These improvements increased the application spectrum for ISH on formalin-fixed paraffin-embedded tissues. ISH is a powerful tool to investigate DNA, mRNA transcripts, regulatory noncoding RNA, and therapeutic oligonucleotides. ISH can be used to obtain spatial information of a cell type, subcellular localization, or expression levels of targets. Since immunohistochemistry and ISH share similar workflows, their combination can address simultaneous transcriptomics and proteomics questions. The goal of this review paper is to revisit the current state of the scientific approaches in ISH and its application in drug research and development

Coupled evolution of temperature and carbonate chemistry during the Paleocene–Eocene; new trace element records from the low latitude Indian Ocean

This is the final version. Available on open access from Elsevier via the DOI in this recordThe early Paleogene represents the most recent interval in Earth’s history characterized by global greenhouse warmth on multi-million year timescales, yet our understanding of long-term climate and carbon cycle evolution in the low latitudes, and in particular the Indian Ocean, remains very poorly constrained. Here we present the first long-term sub-eccentricity-resolution stable isotope (δ13 30 C and δ 18 O) and trace element (Mg/Ca and B/Ca) records spanning the late Paleocene–early Eocene (~58– 53 Ma) across a surface–deep hydrographic reconstruction of the northern Indian Ocean, resolving late Paleocene 405-kyr paced cyclicity and a portion of the PETM recovery. Our new records reveal a long-term warming of ~4–5°C at all depths in the water column, with absolute surface ocean temperatures and magnitudes of warming comparable to the low latitude Pacific. As a result of warming, we observe a long-term increase in δ 18 Osw of the mixed layer, implying an increase in net evaporation. We also observe a collapse in the temperature gradient between mixed layer- and thermocline-dwelling species from ~57–54 Ma, potentially due to either the development of a more homogeneous water column with a thicker mixed layer, or depth migration of the Morozovella in response to warming. Synchronous warming at both low and high latitudes, along with decreasing B/Ca ratios in planktic foraminifera indicating a decrease in ocean pH and/or increasing dissolved inorganic carbon, suggest that global climate was forced by rising atmospheric CO2 concentrations during this time.European Consortium for Ocean Research Drilling (ECORD)International Association of Sedimentologists (IAS)NSFNatural Environment Research Council (NERC

Calcium isotope (δ^44/40Ca ) variations of Neogene planktonic foraminifera

Measurements of the calcium isotopic composition (δ44/40Ca) of planktonic foraminifera from the western equatorial Pacific and the Indian sector of the Southern Ocean show variations of about 0.6‰ over the past 24 Myr. The stacked δ44/40Ca record of Globigerinoides trilobus and Globigerina bulloides indicates a minimum in δ44/40Casw (seawater calcium) at 15 to 16 Ma and a subsequent general increase toward the present, interrupted by a second minimum at 3 to 5 Ma. Applying a coupled calcium/carbon cycle model, we find two scenarios that can explain a large portion of the observed δ44/40Casw variations. In both cases, variations in the Ca input flux to the ocean without proportional changes in the carbonate flux are invoked. The first scenario increases the riverine calcium input to the ocean without a proportional increase of the carbonate flux. The second scenario generates an additional calcium flux from the exchange of Ca by Mg during dolomitization. In both cases the calcium flux variations lead to drastic changes in the seawater Ca concentrations on million year timescales. Our δ44/40Casw record therefore indicates that the global calcium cycle may be much more dynamic than previously assumed

Constraining calcium isotope fractionation (δ44/40Ca) in modern and fossil scleractinian coral skeleton

The present study investigates the influence of environmental (temperature, salinity) and biological (growth rate, inter-generic variations) parameters on calcium isotope fractionation (δ44/40Ca) in scleractinian coral skeleton to better constrain this record. Previous studies focused on the δ44/40Ca record in different marine organisms to reconstruct seawater composition or temperature, but only few studies investigated corals. This study presents measurements performed on modern corals from natural environments (from the Maldives for modern and from Tahiti for fossil corals) as well as from laboratory cultures (Centre Scientifique de Monaco). Measurements on Porites sp., Acropora sp., Montipora verrucosa and Stylophora pistillata allow constraining inter-generic variability. Our results show that the fractionation of δ44/40Ca ranges from 0.6 to 0.1‰, independent of the genus or the environmental conditions. No significant relationship between the rate of calcification and δ44/40Ca was found. The weak temperature dependence reported in earlier studies is most probably not the only parameter that is responsible for the fractionation. Indeed, sub-seasonal temperature variations reconstructed by δ18O and Sr/Ca ratio using a multi-proxy approach, are not mirrored in the coral's δ44/40Ca variations. The intergeneric variability and intrageneric variability among the studied samples are weak except for S. pistillata, which shows calcium isotopic values increasing with salinity. The variability between samples cultured at a salinity of 40 is higher than those cultured at a salinity of 36 for this species. The present study reveals a strong biological control of the skeletal calcium isotope composition by the polyp and a weak influence of environmental factors, specifically temperature and salinity (except for S. pistillata). Vital effects have to be investigated in situ to better constrain their influence on the calcium isotopic signal. If vital effects could be extracted from the isotopic signal, the calcium isotopic composition of coral skeletons could provide reliable information on the calcium composition and budget in ocean. Highlights ► Corals cultured in aquaria or from natural environment show the same Ca isotopic composition. ► δ44/40Ca of coral skeleton is independent of depositional setting environment. ► Strong influence of vital effects on coral skeleton δ44/40Ca composition and calcification mechanism