224 research outputs found
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
Investigation of a new promising process for the RDX synthesis via 1,3,5‐triacetyl‐1,3,5‐triazinane (TRAT)
Despite intensive research for possible replacements, RDX (1,3,5-trinitro-1,3,5-triazinane) is still considered to be one of the most important energetic materials because of its versatile application. Due to the high demand for RDX, optimization of synthesis and development of new methods are of great interest to both academia and industry. Therefore, in this work, the synthesis of RDX via the intermediate TRAT (1,3,5-triacetycl-1,3,5-triazinane) was investigated as a possible alternative industrial production method. In addition to the synthesis of TRAT starting from 1,3,5 trioxane, various feasible nitration methods from TRAT to RDX were investigated. Moreover, the suitability for large-scale production, the comparison of already established methods and the feasibility of a new flow process were discussed
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<sup>44/40</sup>Ca ) 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
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