Novel deletions causing pseudoxanthoma elasticum underscore the genomic instability of the ABCC6 region

Mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a heritable disease that affects elastic fibers. Thus far, >200 mutations have been characterized by various PCR-based techniques (primarily direct sequencing), identifying up to 90% of PXE-causing alleles. This study wanted to assess the importance of deletions and insertions in the ABCC6 genomic region, which is known to have a high recombinational potential. To detect ABCC6 deletions/insertions, which can be missed by direct sequencing, multiplex ligation-dependent probe amplification (MLPA) was applied in PXE patients with an incomplete genotype. MLPA was performed in 35 PXE patients with at least one unidentified mutant allele after exonic sequencing and exclusion of the recurrent exon 23-29 deletion. Six multi-exon deletions and four single-exon deletions were detected. Using MLPA in addition to sequencing, we expanded the ABCC6 mutation spectrum with 9 novel deletions and characterized 25% of unidentified disease alleles. Our results further illustrate the instability of the ABCC6 genomic region and stress the importance of screening for deletions in the molecular diagnosis of PXE. Journal of Human Genetics (2010) 55, 112-117; doi: 10.1038/jhg.2009.132; published online 15 January 201

Electrodeposition of In2S3 buffer layer for Cu(In,Ga)Se2 solar cells

AbstractThe electrochemical deposition of In2S3 thin films was carried out from an aqueous solution of InCl3 and Na2S2O3. The effect of the potential of deposition was studied on the cell parameters of CIGSe based solar cells. The obtained films depending on the deposition potential and thickness exhibited complete substrate coverage or nanocolumnar layers. XPS measurements detected the presence of indium sulphide and hydroxide depending on the deposition parameters. Maximum photoelectric conversion efficiency of 10.2% was obtained, limited mainly by a low fill factor (56%). Further process optimization is expected to lead to efficiencies comparable to CdS buffer layers

Genetics of anophthalmia and microphthalmia. Part 1, Non-syndromic anophthalmia/microphthalmia

Eye formation is the result of coordinated induction and differentiation processes during embryogenesis. Disruption of any one of these events has the potential to cause ocular growth and structural defects, such as anophthalmia and microphthalmia (A/M). A/M can be isolated or occur with systemic anomalies, when they may form part of a recognizable syndrome. Their etiology includes genetic and environmental factors; several hundred genes involved in ocular development have been identified in humans or animal models. In humans, around 30 genes have been repeatedly implicated in A/M families, although many other genes have been described in single cases or families, and some genetic syndromes include eye anomalies occasionally as part of a wider phenotype. As a result of this broad genetic heterogeneity, with one or two notable exceptions, each gene explains only a small percentage of cases. Given the overlapping phenotypes, these genes can be most efficiently tested on panels or by whole exome/genome sequencing for the purposes of molecular diagnosis. However, despite whole exome/genome testing more than half of patients currently remain without a molecular diagnosis. The proportion of undiagnosed cases is even higher in those individuals with unilateral or milder phenotypes. Furthermore, even when a strong gene candidate is available for a patient, issues of incomplete penetrance and germinal mosaicism make diagnosis and genetic counselling challenging. In this review, we present the main genes implicated in nonsyndromic human A/M phenotypes and, for practical purposes, classify them according to the most frequent or predominant phenotype each is associated with. Our intention is that this will allow clinicians to rank and prioritize their molecular analyses and interpretations according to the phenotypes of their patients

Coping with citizen demands: a field study of suckling processes in dairy herds

In dairy farms calves and cows are usually separated shortly after birth but this practice raises the question of animal welfare. This social concern may lead to bring back dairy calves to their mother. Even though suckling is quite seldom in dairy production, some farmers are using such a practice for many years. The present study aims to better know farmer’s motivations, practical implementation and farmer’s perception of the impact of suckling on performance and animal behaviour. In January 2018 a semi-quantitative survey was performed on 44 farms where calves suckle at least 24 hours their mother or a nurse cow. The farming systems differed on the size (20 to 140 cows), the type (19 conventional, 25 organic farms), the suckling (28 by the mothers, 16 by nurses), and the breed. Results indicate that main farmers’ motivations are calves’ health (52%), better working conditions (41%) and saving time (34%), with little consideration on animal welfare (7%). Numerous practices were found in terms of allowance of daily cow-calf contact and suckling duration with a difference between male and female calves. According to farmers, these practices were efficient to improved calves’ health (70%), save time (75%) and improved working conditions (52%). Weaning was considered as a stressful situation, especially after long suckling periods. Cow mooing usually stopped 2.5 d after weaning. At least 34 farmers are fully satisfied with this practice. The main challenge appears to be the management of the wildness of future heifers, by investing time to manipulate calves before weaning. The results of this survey could help to propose solutions to farmers who want to cope with the societal demand of keeping calves with dams in dairy herds

Fecal Lipocalin 2, a Sensitive and Broadly Dynamic Non- Invasive Biomarker for Intestinal Inflammation

Inflammation has classically been defined histopathologically, especially by the presence of immune cell infiltrates. However, more recent studies suggest a role for low-grade inflammation in a variety of disorders ranging from metabolic syndrome to cancer, which is defined by modest elevations in pro-inflammatory gene expression. Consequently, there is a need for cost-effective, non-invasive biomarkers that, ideally, would have the sensitivity to detect low-grade inflammation and have a dynamic range broad enough to reflect classic robust intestinal inflammation. Herein, we report that, for assessment of intestinal inflammation, fecal lipocalin 2 (Lcn-2), measured by ELISA, serves this purpose. Specifically, using a well-characterized mouse model of DSS colitis, we observed that fecal Lcn-2 and intestinal expression of pro-inflammatory cytokines (IL-1b, CXCL1, TNFa) are modestly but significantly induced by very low concentrations of DSS (0.25 and 0.5%), and become markedly elevated at higher concentrations of DSS (1.0 and 4.0%). As expected, careful histopathologic analysis noted only modest immune infiltrates at low DSS concentration and robust colitis at higher DSS concentrations. In accordance, increased levels of the neutrophil product myeloperoxidase (MPO) was only detected in mice given 1.0 and 4.0% DSS. In addition, fecal Lcn-2 marks the severity of spontaneous colitis development in IL-10 deficient mice. Unlike histopathology, MPO, and q-RT-PCR, the assay of fecal Lcn-2 requires only a stool sample, permits measurement over time, and can detect inflammation as early as 1 day following DSS administration. Thus, assay of fecal Lcn-2 by ELISA can function as a non-invasive, sensitive, dynamic, stable and cost-effective means to monitor intestinal inflammation in mice

The scaling attractor and ultimate dynamics for Smoluchowski's coagulation equations

We describe a basic framework for studying dynamic scaling that has roots in dynamical systems and probability theory. Within this framework, we study Smoluchowski's coagulation equation for the three simplest rate kernels $K(x,y)=2$, $x+y$ and $xy$. In another work, we classified all self-similar solutions and all universality classes (domains of attraction) for scaling limits under weak convergence (Comm. Pure Appl. Math 57 (2004)1197-1232). Here we add to this a complete description of the set of all limit points of solutions modulo scaling (the scaling attractor) and the dynamics on this limit set (the ultimate dynamics). The main tool is Bertoin's L\'{e}vy-Khintchine representation formula for eternal solutions of Smoluchowski's equation (Adv. Appl. Prob. 12 (2002) 547--64). This representation linearizes the dynamics on the scaling attractor, revealing these dynamics to be conjugate to a continuous dilation, and chaotic in a classical sense. Furthermore, our study of scaling limits explains how Smoluchowski dynamics ``compactifies'' in a natural way that accounts for clusters of zero and infinite size (dust and gel)

Interactions with M cells and macrophages as key steps in the pathogenesis of enterohemorrhagic Escherichia coli infections

Enterohemorrhagic Escherichia coli (EHEC) are food-borne pathogens that can cause serious infections ranging from diarrhea to hemorrhagic colitis (HC) and hemolytic-uremic syndrome (HUS). Translocation of Shiga-toxins (Stx) from the gut lumen to underlying tissues is a decisive step in the development of the infection, but the mechanisms involved remain unclear. Many bacterial pathogens target the follicle-associated epithelium, which overlies Peyer's patches (PPs), cross the intestinal barrier through M cells and are captured by mucosal macrophages. Here, translocation across M cells, as well as survival and proliferation of EHEC strains within THP-1 macrophages were investigated using EHEC O157:H7 reference strains, isogenic mutants, and 15 EHEC strains isolated from HC/HUS patients. We showed for the first time that E. coli O157:H7 strains are able to interact in vivo with murine PPs, to translocate ex vivo through murine ileal mucosa with PPs and across an in vitro human M cell model. EHEC strains are also able to survive and to produce Stx in macrophages, which induce cell apoptosis and Stx release. In conclusion, our results suggest that the uptake of EHEC by M cells and underlying macrophages in the PP may be a critical step in Stx translocation and release in vivo. A new model for EHEC infection in humans is proposed that could help in a fuller understanding of EHEC-associated diseases

Tangling clustering of inertial particles in stably stratified turbulence

We have predicted theoretically and detected in laboratory experiments a new type of particle clustering (tangling clustering of inertial particles) in a stably stratified turbulence with imposed mean vertical temperature gradient. In this stratified turbulence a spatial distribution of the mean particle number density is nonuniform due to the phenomenon of turbulent thermal diffusion, that results in formation of a gradient of the mean particle number density, \nabla N, and generation of fluctuations of the particle number density by tangling of the gradient, \nabla N, by velocity fluctuations. The mean temperature gradient, \nabla T, produces the temperature fluctuations by tangling of the gradient, \nabla T, by velocity fluctuations. These fluctuations increase the rate of formation of the particle clusters in small scales. In the laboratory stratified turbulence this tangling clustering is much more effective than a pure inertial clustering that has been observed in isothermal turbulence. In particular, in our experiments in oscillating grid isothermal turbulence in air without imposed mean temperature gradient, the inertial clustering is very weak for solid particles with the diameter 10 microns and Reynolds numbers Re =250. Our theoretical predictions are in a good agreement with the obtained experimental results.Comment: 16 pages, 4 figures, REVTEX4, revised versio

Back pressure effects on variable geometry turbine performances

Paper presented at the 6th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, South Africa, 30 June - 2 July, 2008.Turbochargers are widely used in applications to increase specific power and decrease fuel consumption. However, recent anti-pollution regulations have became stricter and pressed automotive engineers to find new solutions to reduce Nox emissions. Two of these solutions are the catalytic converter and the intercooler system. All these modifications will change the initial matching of the turbocharger performance characteristics to the engine requirements. In this paper, several compressor wheel sizes are investigated to evaluate the turbine/compressor matching. The intercooler and catalytic converter back pressure induced are respectively modeled by a lower duct section downstream the compressor stage and a variable valve downstream the turbine stage. The influences of the different modifications are identified through the loading and the flow coefficients and also on classical turbine performance maps. First, an analogy between compressor wheel size and back pressure effects is underlined. Second, it is shown that initial control settings of turbine nozzle vanes are no longer appropriate with a catalytic converter.vk201

Turbulent Diffusion and Turbulent Thermal Diffusion of Aerosols in Stratified Atmospheric Flows

The paper analyzes the phenomenon of turbulent thermal diffusion in the Earth atmosphere, its relation to the turbulent diffusion and its potential impact on aerosol distribution. This phenomenon was predicted theoretically more than 10 years ago and detected recently in the laboratory experiments. This effect causes a non-diffusive flux of aerosols in the direction of the heat flux and results in formation of long-living aerosol layers in the vicinity of temperature inversions. We demonstrated that the theory of turbulent thermal diffusion explains the GOMOS aerosol observations near the tropopause (i.e., the observed shape of aerosol vertical profiles with elevated concentrations located almost symmetrically with respect to temperature profile). In combination with the derived expression for the dependence of the turbulent thermal diffusion ratio on the turbulent diffusion, these measurements yield an independent method for determining the coefficient of turbulent diffusion at the tropopause. We evaluated the impact of turbulent thermal diffusion to the lower-troposphere vertical profiles of aerosol concentration by means of numerical dispersion modelling, and found a regular upward forcing of aerosols with coarse particles affected stronger than fine aerosols.Comment: 19 pages, 10 figure