180 research outputs found
P20-14. Co- and superinfection of partners in a cohort of couples previously infected by genotypically different viruses in Kigali
Tunneling-percolation origin of nonuniversality: theory and experiments
A vast class of disordered conducting-insulating compounds close to the
percolation threshold is characterized by nonuniversal values of transport
critical exponent t, in disagreement with the standard theory of percolation
which predicts t = 2.0 for all three dimensional systems. Various models have
been proposed in order to explain the origin of such universality breakdown.
Among them, the tunneling-percolation model calls into play tunneling processes
between conducting particles which, under some general circumstances, could
lead to transport exponents dependent of the mean tunneling distance a. The
validity of such theory could be tested by changing the parameter a by means of
an applied mechanical strain. We have applied this idea to universal and
nonuniversal RuO2-glass composites. We show that when t > 2 the measured
piezoresistive response \Gamma, i. e., the relative change of resistivity under
applied strain, diverges logarithmically at the percolation threshold, while
for t = 2, \Gamma does not show an appreciable dependence upon the RuO2 volume
fraction. These results are consistent with a mean tunneling dependence of the
nonuniversal transport exponent as predicted by the tunneling-percolation
model. The experimental results are compared with analytical and numerical
calculations on a random-resistor network model of tunneling-percolation.Comment: 13 pages, 12 figure
Well dispersed fractal aggregates as filler in polymer-silica nanocomposites: long range effects in rheology
We are presenting a new method of processing polystyrene-silica
nanocomposites, which results in a very well-defined dispersion of small
primary aggregates (assembly of 15 nanoparticles of 10 nm diameter) in the
matrix. The process is based on a high boiling point solvent, in which the
nanoparticles are well dispersed, and controlled evaporation. The filler's fine
network structure is determined over a wide range of sizes, using a combination
of Small Angle Neutron Scattering (SANS) and Transmission Electronic Microscopy
(TEM). The mechanical response of the nanocomposite material is investigated
both for small (ARES oscillatory shear and Dynamical Mechanical Analysis) and
large deformations (uniaxial traction), as a function of the concentration of
the particles. We can investigate the structure-property correlations for the
two main reinforcement effects: the filler network contribution, and a
filler-polymer matrix effect. Above a silica volume fraction threshold, we see
a divergence of the modulus correlated to the build up of a connected network.
Below the threshold, we obtain a new additional elastic contribution of much
longer terminal time than the matrix. Since aggregates are separated by at
least 60 nm, this new filler-matrix contribution cannot be described solely
with the concept of glassy layer (2nm)
Implementation of a mentored professional development programme in laboratory leadership and management in the Middle East and North Africa.
Laboratories need leaders who can effectively utilize the laboratories' resources, maximize the laboratories'capacity to detect disease, and advocate for laboratories in a fluctuating health care environment. To address this need, the University of Washington, USA, created the Certificate Program in Laboratory Leadership and Management in partnership with WHO Regional Office for the Eastern Mediterranean, and implemented it with 17 participants and 11 mentors from clinical and public health laboratories in 10 countries (Egypt, Iraq, Jordan, Lebanon, Morocco, Oman, Pakistan, Qatar, Saudi Arabia, and Yemen) in 2014. Designed to teach leadership and management skills to laboratory supervisors, the programme enabled participants to improve laboratory testing quality and operations. The programme was successful overall, with 80% of participants completing it and making impactful changes in their laboratories. This success is encouraging and could serve as a model to further strengthen laboratory capacity in the Region
Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection
Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model
Modelling percolation in fibre and sphere mixtures: Routes to more efficient network formation
Computer tomographic investigation of subcutaneous adipose tissue as an indicator of body composition
<p>Abstract</p> <p>Background</p> <p>Modern computer tomography (CT) equipment can be used to acquire whole-body data from large animals such as pigs in minutes or less. In some circumstances, computer assisted analysis of the resulting image data can identify and measure anatomical features. The thickness of subcutaneous adipose tissue at a specific site measured by ultrasound, is used in the pig industry to assess adiposity and inform management decisions that have an impact on reproduction, food conversion performance and sow longevity. The measurement site, called "P2", is used throughout the industry. We propose that CT can be used to measure subcutaneous adipose tissue thickness and identify novel measurement sites that can be used as predictors of general adiposity.</p> <p>Methods</p> <p>Growing pigs (<it>N </it>= 12), were each CT scanned on three occasions. From these data the total volume of adipose tissue was determined and expressed as a proportion of total volume (fat-index). A computer algorithm was used to determined 10,201 subcutaneous adipose thickness measurements in each pig for each scan. From these data, sites were selected where correlation with fat-index was optimal.</p> <p>Results</p> <p>Image analysis correctly identified the limits of the relevant tissues and automated measurements were successfully generated. Two sites on the animal were identified where there was optimal correlation with fat-index. The first of these was located 4 intercostal spaces cranial to the caudal extremity of the last rib, the other, a further 5 intercostal spaces cranially.</p> <p>Conclusion</p> <p>The approach to image analysis reported permits the creation of various maps showing adipose thickness or correlation of thickness with other variables by location on the surface of the pig. The method identified novel adipose thickness measurement positions that are superior (as predictors of adiposity) to the site which is in current use. A similar approach could be used in other situations to quantify potential links between subcutaneous adiposity and disease or production traits.</p
Critical Role of IRF-5 in the Development of T helper 1 responses to Leishmania donovani infection
The transcription factor Interferon Regulatory Factor 5 (IRF-5) has been shown to be involved in the induction of proinflammatory cytokines in response to viral infections and TLR activation and to play an essential role in the innate inflammatory response. In this study, we used the experimental model of visceral leishmaniasis to investigate the role of IRF-5 in the generation of Th1 responses and in the formation of Th1-type liver granulomas in Leishmania donovani infected mice. We show that TLR7-mediated activation of IRF-5 is essential for the development of Th1 responses to L. donovani in the spleen during chronic infection. We also demonstrate that IRF-5 deficiency leads to the incapacity to control L. donovani infection in the liver and to the formation of smaller granulomas. Granulomas in Irf5-/- mice are characterized by an increased IL-4 and IL-10 response and concomitant low iNOS expression. Collectively, these results identify IRF-5 as a critical molecular switch for the development of Th1 immune responses following L. donovani infections and reveal an indirect role of IRF-5 in the regulation of iNOS expression
Critical Role of IRF-5 in the Development of T helper 1 responses to Leishmania donovani infection
The transcription factor Interferon Regulatory Factor 5 (IRF-5) has been shown to be involved in the induction of proinflammatory cytokines in response to viral infections and TLR activation and to play an essential role in the innate inflammatory response. In this study, we used the experimental model of visceral leishmaniasis to investigate the role of IRF-5 in the generation of Th1 responses and in the formation of Th1-type liver granulomas in Leishmania donovani infected mice. We show that TLR7-mediated activation of IRF-5 is essential for the development of Th1 responses to L. donovani in the spleen during chronic infection. We also demonstrate that IRF-5 deficiency leads to the incapacity to control L. donovani infection in the liver and to the formation of smaller granulomas. Granulomas in Irf5-/- mice are characterized by an increased IL-4 and IL-10 response and concomitant low iNOS expression. Collectively, these results identify IRF-5 as a critical molecular switch for the development of Th1 immune responses following L. donovani infections and reveal an indirect role of IRF-5 in the regulation of iNOS expression
Leishmania-Induced IRAK-1 Inactivation Is Mediated by SHP-1 Interacting with an Evolutionarily Conserved KTIM Motif
Parasites of the Leishmania genus can rapidly alter several macrophage (MØ) signalling pathways in order to tame down the innate immune response and inflammation, therefore favouring their survival and propagation within their mammalian host. Having recently reported that Leishmania and bacterial LPS generate a significantly stronger inflammatory response in animals and phagocytes functionally deficient for the Src homology 2 domain-containing protein tyrosine phosphatase (SHP-1), we hypothesized that Leishmania could exploit SHP-1 to inactivate key kinases involved in Toll-like receptor (TLR) signalling and innate immunity such as IL-1 receptor-associated kinase 1 (IRAK-1). Here we show that upon infection, SHP-1 rapidly binds to IRAK-1, completely inactivating its intrinsic kinase activity and any further LPS-mediated activation as well as MØ functions. We also demonstrate that the SHP-1/IRAK-1 interaction occurs via an evolutionarily conserved ITIM-like motif found in the kinase domain of IRAK-1, which we named KTIM (Kinase Tyrosyl-based Inhibitory Motif). This regulatory motif appeared in early vertebrates and is not found in any other IRAK family member. Our study additionally reveals that several other kinases (e.g. Erk1/2, IKKα/β) involved in downstream TLR signalling also bear KTIMs in their kinase domains and interact with SHP-1. We thus provide the first demonstration that a pathogen can exploit a host protein tyrosine phosphatase, namely SHP-1, to directly inactivate IRAK-1 through a generally conserved KTIM motif
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