A model of defect cluster creation in fragmented cascades in metals based on morphological analysis

The impacts of ions and neutrons in metals cause cascades of atomic collisions that expand and shrink, leaving microstructure defect debris, i.e. interstitial or vacancy clusters or loops of different sizes. In De Backer et al (2016 Europhys. Lett. 115 26001), we described a method to detect the first morphological transition, i.e. the cascade fragmentation in subcascades, and a model of primary damage combining the binary collision approximation and molecular dynamics (MD). In this paper including W, Fe, Be, Zr and 20 other metals, we demonstrate that the fragmentation energy increases with the atomic number and decreases with the atomic density following a unique power law. Above the fragmentation energy, the cascade morphology can be characterized by the cross pair correlation functions of the multitype point pattern formed by the subcascades. We derive the numbers of pairs of subcascades and observed that they follow broken power laws. The energy where the power law breaks indicates the second morphological transition when cascades are formed by branches decorated by chaplets of small subcascades. The subcascade interaction is introduced in our model of primary damage by adding pairwise terms. Using statistics obtained on hundreds of MD cascades in Fe, we demonstrate that the interaction of subcascades increases the proportion of large clusters in the damage created by high energy cascades. Finally, we predict the primary damage of 500 keV Fe ion in Fe and obtain cluster size distributions when large statistics of MD cascades arc not feasible.Peer reviewe

Physical mechanisms and parameters for models of microstructure evolution under irradiation in Fe alloys – Part I: Pure Fe

This paper is the first of three that overview the main mechanisms that drive the microstructure evolution in Fe alloys under irradiation. It focuses on pure α-Fe and compiles the parameters that describe quantitatively the mobility and stability of point-defects and especially their clusters, including possible reactions and criteria to decide when they should react. These parameters are the result of several years of calculations and application in microstructure evolution models. They are mainly collected from the literature and the parameter choice tries to reconcile different sets of values that, while being in general qualitatively similar, are often quantitatively not coincident. A few calculation results are presented here for the first time to support specific approximations concerning defect properties or features. Since calculations cannot cover all possible defect configurations, the definition of these parameters often requires educated guesses to fill knowledge gaps. These guesses are here listed and discussed whenever relevant. This is therefore a “hands-on” paper that: (i) collects in a single report most microstructure evolution parameters that are found in the literature for irradiated α-Fe, including a discussion of the most important mechanisms at play based on current knowledge; (ii) selects a ready-to-use set that can be employed in microstructure evolution models, such as those based on object kinetic Monte Carlo (OKMC) methods. This work also identifies parameters that are needed, but not known, hopefully prompting corresponding calculations in the future.This work has received funding from the Euratom research and training programme 2014-2018 under grant agreement No. 755039 (M4F project). This research also contributes to the Joint Programme on Nuclear Materials of the European Energy Research Alliance (EERA-JPNM)

Association of KIR2DS1 and KIR2DS3 with fatal outcome in Ebola virus infection

Zaïre ebolavirus (ZEBOV) infection rapidly outruns the host's immunity and leads to death within a week. Fatal cases have been associated with an aberrant innate, proinflammatory immune response followed by a suppressed adaptive response leading to the rapid depletion of peripheral NK cells and lymphocytes. A critical role for NK cells has been suggested but not elucidated. In this genetic study, we investigated the association of KIR genotype with disease outcome by comparing genotypes of a Gabonese control population, IgG+ contacts, survivors, and fatalities of ZEBOV infection. We showed that the activating KIR2DS1 and KIR2DS3 genes associate with fatal outcome in Ebola virus infection. In addition, this study brings supplemental evidence in favor of the specificity of the IgG+ contact population. The outcome of fulminating Ebola virus infection could depend in part on the host's inherited KIR gene repertoire. This supports a key role for KIRs in disease susceptibility to infections

Genital warts and infection with human immunodeficiency virus in high-risk women in Burkina Faso: a longitudinal study

BACKGROUND: Human papillomaviruses are the most common sexually transmitted infections, and genital warts, caused by HPV-6 and 11, entail considerable morbidity and cost. The natural history of genital warts in relation to HIV-1 infection has not been described in African women. We examined risk factors for genital warts in a cohort of high-risk women in Burkina Faso, in order to further describe their epidemiology. METHODS: A prospective study of 765 high-risk women who were followed at 4-monthly intervals for 27 months in Burkina Faso. Logistic and Cox regression were used to identify factors associated with prevalent, incident and persistent genital warts, including HIV-1 serostatus, CD4+ count, and concurrent sexually transmitted infections. In a subset of 306 women, cervical HPV DNA was tested at enrollment. RESULTS: Genital wart prevalence at baseline was 1.6% (8/492) among HIV-uninfected and 7.0% (19/273) among HIV-1 seropositive women. Forty women (5.2%) experienced at least one incident GW episode. Incidence was 1.1 per 100 person-years among HIV-uninfected women, 7.4 per 100 person-years among HIV-1 seropositive women with a nadir CD4+ count >200 cells/μL and 14.6 per 100 person-years among HIV-1 seropositive women with a nadir CD4+ count ≤ 200 cells/μL. Incident genital warts were also associated with concurrent bacterial vaginosis, and genital ulceration. Antiretroviral therapy was not protective against incident or persistent genital warts. Detection of HPV-6 DNA and abnormal cervical cytology were strongly associated with incident genital warts. CONCLUSIONS: Genital warts occur much more frequently among HIV-1 infected women in Africa, particularly among those with low CD4+ counts. Antiretroviral therapy did not reduce the incidence or persistence of genital warts in this population

Cell-free (RNA) and cell-associated (DNA) HIV-1 and postnatal transmission through breastfeeding

<p>Introduction - Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum.</p> <p>Materials and Methods - Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission.</p> <p>Results - There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33–4.59) vs. aHR 1.52 (95% CI, 1.17–1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64–3.92) vs. 1.73 (95% CI 0.94–3.19), respectively].</p> <p>Conclusions - The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.</p&gt

Disorder-Driven Pretransitional Tweed in Martensitic Transformations

Defying the conventional wisdom regarding first--order transitions, {\it solid--solid displacive transformations} are often accompanied by pronounced pretransitional phenomena. Generally, these phenomena are indicative of some mesoscopic lattice deformation that ``anticipates'' the upcoming phase transition. Among these precursive effects is the observation of the so-called ``tweed'' pattern in transmission electron microscopy in a wide variety of materials. We have investigated the tweed deformation in a two dimensional model system, and found that it arises because the compositional disorder intrinsic to any alloy conspires with the natural geometric constraints of the lattice to produce a frustrated, glassy phase. The predicted phase diagram and glassy behavior have been verified by numerical simulations, and diffraction patterns of simulated systems are found to compare well with experimental data. Analytically comparing to alternative models of strain-disorder coupling, we show that the present model best accounts for experimental observations.Comment: 43 pages in TeX, plus figures. Most figures supplied separately in uuencoded format. Three other figures available via anonymous ftp

Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR

Erratum in : Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR. [Cell. 2019]International audienceInnate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-likereceptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatorysignals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect theimmune response is unknown. We demonstrate that TLR-dependent responses of dendritic cells (DC)are exacerbated by a high fatty acid (FA) metabolic environment. FA suppress the TLR-inducedhexokinase activity and perturb tricarboxylic acid cycle metabolism. These metabolic changesenhance mitochondrial reactive oxygen species (mtROS) production and, in turn, the unfolded proteinresponse (UPR) leading to a distinct transcriptomic signature, with IL-23 as hallmark. Interestingly,chemical or genetic suppression of glycolysis was sufficient to induce this specific immune response.Conversely, reducing mtROS production or DC-specific deficiency in XBP1 attenuated IL-23expression and skin inflammation in an IL-23-dependent model of psoriasis. Thus, fine-tuning of innateimmunity depends on optimization of metabolic demands and minimization of mtROS-induced UPR

All-oral combination of oral vinorelbine and capecitabine as first-line chemotherapy in HER2-negative metastatic breast cancer: an International Phase II Trial

BACKGROUND: This multicentre, international phase II trial evaluated the efficacy and safety profile of a first-line combination of oral vinorelbine plus capecitabine for women with metastatic breast cancer (MBC). METHODS: Patients with measurable, HER2-negative disease received, as a first line in metastatic setting, 3-weekly cycles of oral vinorelbine 80 mg m(-2) (after a first cycle at 60) on day 1 and day 8, plus capecitabine 1000 mg m(-2) (750 if >or=65 years of age) twice daily, on days 1-14. Treatment was continued until progression or unacceptable toxicity. RESULTS: A total of 55 patients were enrolled and 54 were treated (median age: 58.5 years). Most (78%) had visceral involvement and 63% had received earlier (neo)adjuvant chemotherapy. The objective response rate (RECIST) in 49 evaluable patients was 51% (95% confidence interval (CI), 36-66), including complete response in 4%. The clinical benefit rate (response or stable disease for >or=6 months) was 63% (95% CI, 48-77). The median duration of response was 7.2 months (95% CI, 6.4-10.2). After a median follow-up of 41 months, median progression-free survival was 8.4 months (95% CI, 5.8-9.7) and median overall survival was 29.2 months (95% CI, 18.2-40.1). Treatment-related adverse events were manageable, the main grade 3-4 toxicity was neutropaenia (49%); two patients experienced febrile neutropaenia and three patients had a neutropaenic infection (including one septic death). A particularly low rate of alopaecia was observed. CONCLUSION: These results show that the all-oral combination of oral vinorelbine and capecitabine is an effective and well-tolerated first-line regimen for MB