Silicon based oxidation-resistant coatings on Ti6242 alloy by dynamic ion mixing

The influence of SixCy and SixNy amorphous coatings on the oxidation resistance of a Ti6242 (Ti–6Al–2Sn–4Zr–2Mo) alloy was investigated. They were produced at room temperature by the dynamic ion mixing technique combining physical vapour deposition with simultaneous bombardment with 120 keV Ar+ ions. Isothermal oxidation tests were carried out at 600 °C in 1 atm flowing synthetic air (80% N2, 20% O2) demonstrating a considerable reduction (not, vert, similartwo orders of magnitude) of the oxidation rate for at least 100 h. The structural modifications after oxidation were investigated by XPS, XRD, SEM, SIMS. The formation of SiO2 is detected as the main oxidation product in the coating and the formation of Ti–Si compounds is also observed in the coating/substrate interface region. The crystallisation of SixNy is not detected and for SixCy only some traces of β-SiC could exist. The improvement of oxidation resistance of Ti6242 is discussed in relation with the intrinsic properties of the coatings and with the interface mixing and ion beam densification

Temperature influence on water transport in hardened cement pastes

International audienceDescribing water transport in concrete is an important issue for the durability assessment of radioactive wastemanagement reinforced concrete structures. Due to the waste thermal output such structures would besubmitted to moderate temperatures (up to 80 °C). We have then studied the influence of temperature onwater transport within hardened cement pastes of four different formulations. Using a simplified approach(describing only the permeation of liquid water) we characterized the properties needed to describe watertransport (up to 80 °C) using dedicated experiments. For each hardened cement paste the results are presentedand discussed

Which place for stem cell therapy in the treatment of acute radiation syndrome?

Radiation-induced (RI) tissue injuries can be caused by radiation therapy, nuclear accidents or radiological terrorism. Notwithstanding the complexity of RI pathophysiology, there are some effective approaches to treatment of both acute and chronic radiation damages. Cytokine therapy is the main strategy capable of preventing or reducing the acute radiation syndrome (ARS), and hematopoietic growth factors (GF) are particularly effective in mitigating bone marrow (BM) aplasia and stimulating hematopoietic recovery. However, first, as a consequence of RI stem and progenitor cell death, use of cytokines should be restricted to a range of intermediate radiation doses (3 to 7 Gy total body irradiation). Second, ARS is a global illness that requires treatment of damages to other tissues (epithelial, endothelial, glial, etc.), which could be achieved using pleiotropic or tissue-specific cytokines. Stem cell therapy (SCT) is a promising approach developed in the laboratory that could expand the ability to treat severe radiation injuries. Allogeneic hematopoietic stem cell transplantation (BM, mobilized peripheral blood and cord blood) transplantation has been used in radiation casualties with variable success due to limiting toxicity related to the degree of graft histocompatibility and combined injuries. Ex vivo expansion should be used to augment cord blood graft size and/or promote very immature stem cells. Autologous SCT might also be applied to radiation casualties from residual hematopoietic stem and progenitor cells (HSPC). Stem cell plasticity of different tissues such as liver or skeletal muscle, may also be used as a source of hematopoietic stem cells. Finally, other types of stem cells such as mesenchymal, endothelial stem cells or other tissue committed stem cells (TCSC), could be used for treating damages to nonhematopoietic organs

Rural populations of the red fox Vulpes vulpes show little evidence of reproductive senescence

International audienceThe ageing theory predicts fast and early senescence for fast-living species. We investigated whether the pattern of senescence of a medium-sized, fast-living and heavily-culled mammal, the red fox (Vulpes vulpes), fits this theoretical prediction. We used cross-sectional data from a large-scale culling experiment of red fox conducted over six years in five study sites located in two regions of France to explore the age-related variation in reproductive output. We used both placental scars and embryos counts from 755 vixens’ carcasses aged by the tooth cementum method (age range : 1-10) , as proxies for litter size. Mean litter size per vixen was 4.7 ± 1.4. Results from Generalized Additive Mixed Models revealed a significant variation of litter size with age. Litter size peaked at age 4 with 5. 0 ± 0.2 placental scars and decreased there after by 0.5 cubs per year. Interestingly, we found a different age-specific variation when counting embryos which reached a plateau at age 5-6 (5.5 ± 0.2)and decreased slower than placent al scars across older ages, pointing out embryo resorption as a potential physiological mechanism of reproductive senescence in the red fox. Contrary to our expectation, reproductive senescence is weak, occurs late in life and takes place at an age reached by less than 11.7% of the population such that very few females exhibit senescence in these heavily culled populations

Alleles of the α1 immunoglobulin gene 3′ enhancer control evolution of IgA nephropathy toward renal failure

Alleles of the α1 immunoglobulin gene 3′ enhancer control evolution of IgA nephropathy toward renal failure.BackgroundIgA nephropathy is the most common glomerular disease. Mechanisms leading to its occurrence and controlling the evolution of the disease remain largely unknown. Various genetic factors have been found, mostly implicating immunologically relevant genes (IgH, TCR, human lymphocyte antigen, and complement loci). A regulatory region recently identified downstream, the α1 gene of the IgH locus, was a likely candidate for the control of IgA1 production in patients. Alleles of this region, differing by size, sequence, and orientation of the α1 hs1,2 transcriptional enhancer, were first identified through Southern blot hybridization.MethodsWe established a polymerase chain reaction (PCR) method suitable for routine testing that amplifies minisatellites within the α1 hs1,2 enhancer, with variable numbers of tandem repeats (VNTR) defining the two alleles. This assay allowed the typing of 104 patients with IgAN and 83 healthy volunteers. Results from typing of α1 hs1,2 alleles were compared with long-term clinical outcome in patients. Enhancer alleles were compared in a luciferase reporter gene assay.ResultsThe α1 hs1,2 alleles do not constitute a predictive factor for IgA nephropathy, since similar allelic frequencies were observed in healthy individuals and in unrelated European patients. In contrast, among patients, homozygosity for the weakest enhancer allele (AA genotype) was significantly correlated with a milder form of the disease, whereas the allele B was associated with severe evolution. The minisatellite region within the α1 hs1,2 enhancer carried potential transcription factor-binding sites, and its duplication increased the transcriptional strength of the α1 hs1,2 allele B over that of allele A.ConclusionAltogether, these alleles may constitute a risk factor for the prognosis of IgA nephropathy

Autologous Adipocyte Derived Stem Cells Favour Healing in a Minipig Model of Cutaneous Radiation Syndrome

Cutaneous radiation syndrome (CRS) is the delayed consequence of localized skin exposure to high doses of ionizing radiation. Here we examined for the first time in a large animal model the therapeutic potential of autologous adipose tissue-derived stroma cells (ASCs). For experiments, Göttingen minipigs were locally gamma irradiated using a 60Co source at the dose of 50 Gy and grafted (n = 5) or not (n = 8). ASCs were cultured in MEM-alpha with 10% fetal calf serum and basic fibroblast growth factor (2 ng.mL−1) and post irradiation were intradermally injected on days 25, 46, 67 and finally between days 95 and 115 (50×106 ASCs each time) into the exposed area. All controls exhibited a clinical evolution with final necrosis (day 91). In grafted pigs an ultimate wound healing was observed in four out of five grafted animals (day 130 +/− 28). Immunohistological analysis of cytokeratin expression showed a complete epidermis recovery. Grafted ASCs accumulated at the dermis/subcutis barrier in which they attracted numerous immune cells, and even an increased vasculature in one pig. Globally this study suggests that local injection of ASCs may represent a useful strategy to mitigate CRS

A Randomized Comparison of High Clopidogrel Loading Doses in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes The ALBION (Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and Ongoing Necrosis) Trial

ObjectivesWe sought to compare the antiplatelet effects of three clopidogrel loading doses (LDs).BackgroundAdministration of a 300-mg clopidogrel LD is beneficial in situations requiring rapid platelet inhibition. Whether higher LDs can provide further benefits remains unknown.MethodsPatients (n = 103) with non–ST-segment elevation acute coronary syndromes were randomized to receive a 300-mg, 600-mg, or 900-mg clopidogrel LD, given on top of other standard therapy (including acetylsalicylic acid). The main outcome measure was inhibition of adenosine diphosphate-induced inhibition of platelet aggregation (IPA); inhibition of platelet activation, inflammatory markers, troponin I release, and major adverse cardiac events also were evaluated; all measures were blindly evaluated.ResultsCompared with the 300-mg LD, greater doses were associated with significantly greater platelet inhibition, with dose-effect relationships observed for onset of action, maximal plateau, 24-h areas under the curves of IPA, and rates of low IPA (<10% at 6 h), using 20 μmol/l major adverse cardiac events. A significant dose-response was also observed for the vasodilator-stimulated phosphoprotein index, a measure of P2Y12receptor inhibition. Similar but nonsignificant trends were observed for troponin release and major adverse cardiac events. Bleeding rates were similar in each group.ConclusionsIn low-to-moderate risk patients with non–ST-elevation acute coronary syndromes, clopidogrel LDs >300 mg provide a faster onset of action, a higher IPA plateau, and greater reductions in platelet activation during the first 24 h. A 900-mg LD may induce a greater antiplatelet effect than 600 mg, when compared with the standard 300-mg regimen. These findings require further clinical confirmation

Taking stock of national climate policies to evaluate implementation of the Paris Agreement

Many countries have implemented national climate policies to accomplish pledged Nationally Determined Contributions and to contribute to the temperature objectives of the Paris Agreement on climate change. In 2023, the global stocktake will assess the combined effort of countries. Here, based on a public policy database and a multi-model scenario analysis, we show that implementation of current policies leaves a median emission gap of 22.4 to 28.2 GtCO2eq by 2030 with the optimal pathways to implement the well below 2 °C and 1.5 °C Paris goals. If Nationally Determined Contributions would be fully implemented, this gap would be reduced by a third. Interestingly, the countries evaluated were found to not achieve their pledged contributions with implemented policies (implementation gap), or to have an ambition gap with optimal pathways towards well below 2 °C. This shows that all countries would need to accelerate the implementation of policies for renewable technologies, while efficiency improvements are especially important in emerging countries and fossil-fuel-dependent countries

Function of von Willebrand factor after crossed bone marrow transplantation between normal and von Willebrand disease pigs: effect on arterial thrombosis in chimeras.

von Willebrand factor (vWF) is essential for the induction of occlusive thrombosis in stenosed and injured pig arteries and for normal hemostasis. To separate the relative contribution of plasma and platelet vWF to arterial thrombosis, we produced chimeric normal and von Willebrand disease pigs by crossed bone marrow transplantation; von Willebrand disease (vWD) pigs were engrafted with normal pig bone marrow and normal pigs were engrafted with vWD bone marrow. Thrombosis developed in the chimeric normal pigs that showed normal levels of plasma vWF and an absence of platelet vWF; but no thrombosis occurred in the chimeric vWD pigs that demonstrated normal platelet vWF and an absence of plasma vWF. The ear bleeding times of the chimeric pigs were partially corrected by endogenous plasma vWF but not by platelet vWF. Our animal model demonstrated that vWF in the plasma compartment is essential for the development of arterial thrombosis and that it also contributes to the maintenance of bleeding time and hemostasis