Discrete dislocation plasticity analysis of the high-temperature cyclic response of composites

Discrete dislocation plasticity (DDP) analysis of the high-temperature cyclic deformation of two- phase composites comprising a plastic matrix and elastic precipitates is presented. Deformation of the matrix is by climb-assisted glide of dislocations while the precipitates deform by a combination of bulk elasticity and stress-driven interfacial diffusion. The DDP calculations predict a cyclically softening response due to the formation of dislocation cell structures within the matrix. The dislocation cell sizes decrease with decreasing size of the unit cell (or equivalently matrix channels) and this results in an increased cyclic softening rate in composites with smaller unit cells. Interfacial diffusion also enhances the formation of dislocation cell structures and thereby promotes cyclic softening. These results are consistent with predictions of the creep behaviour that indicate that the increase in the creep rate (i.e. tertiary creep) is also associated with the formation of dislocation cell structures within the matrix

Discrete dislocation plasticity analysis of the effect of interfacial diffusion on the creep response of Ni single-crystal superalloys

© 2017 Acta Materialia Inc. Discrete dislocation plasticity (DDP) analysis of the high temperature creep deformation of a single crystal Ni superalloy comprising Ni3Al precipitates (γ′) in a Ni matrix (γ) is presented. The γ′ precipitates remain elastic but can also deform due to the stress-driven inter-diffusion of the Al within the Ni on the γ/γ′ interface while plastic deformation of the γ phase occurs by a combination of dislocation glide and dislocation climb coupled to the diffusion of vacancies. At relatively low applied uniaxial tensile stresses, the creep strain rates are very low in the absence of interfacial diffusion. This is due to the stress-induced pile up of dislocations at γ/γ′ interfaces that serves to inhibit further nucleation and suppresses continued plastic flow in the γ phase. When interfacial diffusion is permitted, the creep rates not only increase but the superalloy also exhibits distinct secondary and tertiary creep regimes. While this change in behaviour is a result of interfacial diffusion, the contribution of the average γ′ strain to the deformation of the superalloy is small. Rather, the diffusional deformation at the interface results in the development of a wavy interface which relaxes the back-stresses of dislocations piled-up at the γ/γ′ interfaces. This permits continued dislocation activity within the γ phase with dislocations arranging themselves into low energy cell-structures in the γ phase via dislocation climb. The formation of these structures results in an increase in the creep strain rate and the onset of the tertiary creep regime. At high applied stresses, the high initial dislocation density within the γ phase results in the continued climb motion of dislocations and an evolving spatial distribution of vacancies within the superalloy. Thus, creep deformation occurs even in the absence of interfacial diffusion although the creep rates are significantly increased when interfacial diffusion is present. The DDP analysis presented here demonstrates the critical role of interfacial diffusion in controlling the creep rates of Ni superalloys and suggests that interface engineering to reduce interfacial diffusion rates will aid in improving the creep performance of these alloys

Outcomes of Cardiac Transplantation in Highly Sensitized Pediatric Patients

Despite aggressive immunosuppressive therapy, pediatric orthotopic heart transplant (OHT) candidates with elevated pre-transplant panel reactive antibody (PRA) carry an increased risk of rejection and early graft failure following transplantation. This study has aimed to more specifically evaluate the outcomes of transplant candidates stratified by PRA values. Records of pediatric patients listed for OHT between April 2004 and July 2008 were reviewed (n = 101). Survival analysis was performed comparing patients with PRA < 25 to those with PRA > 25, as well as patients with PRA < 80 and PRA > 80. Patients with PRA > 25 had decreased survival compared with those with PRA < 25 after listing (P = 0.004). There was an even greater difference in survival between patients with PRA > 80 and those with PRA < 80 (P = 0.002). Similar analyses for the patients who underwent successful transplantation showed no significant difference in post-transplant survival between patients with a pre-transplant PRA > 25 and those with PRA < 25 (P = 0.23). A difference approaching significance was noted for patients with PRA > 80 compared with PRA < 80 (P = 0.066). Patients with significantly elevated pre-transplant PRAs at the time of listing have a significantly worse outcome compared to those with moderately increased PRA values or non-sensitized patients. Further study is necessary to guide physician and family treatment decisions at the time of listing

Evaluation of Indirect Fluorescent Antibody Assays Compared to Rapid Influenza Diagnostic Tests for the Detection of Pandemic Influenza A (H1N1) pdm09

Performance of indirect fluorescent antibody (IFA) assays and rapid influenza diagnostic tests (RIDT) during the 2009 H1N1 pandemic was evaluated, along with the relative effects of age and illness severity on test accuracy. Clinicians and laboratories submitted specimens on patients with respiratory illness to public health from April to mid October 2009 for polymerase chain reaction (PCR) testing as part of pandemic H1N1 surveillance efforts in Orange County, CA; IFA and RIDT were performed in clinical settings. Sensitivity and specificity for detection of the 2009 pandemic H1N1 strain, now officially named influenza A(H1N1)pdm09, were calculated for 638 specimens. Overall, approximately 30% of IFA tests and RIDTs tested by PCR were falsely negative (sensitivity 71% and 69%, respectively). Sensitivity of RIDT ranged from 45% to 84% depending on severity and age of patients. In hospitalized children, sensitivity of IFA (75%) was similar to RIDT (84%). Specificity of tests performed on hospitalized children was 94% for IFA and 80% for RIDT. Overall sensitivity of RIDT in this study was comparable to previously published studies on pandemic H1N1 influenza and sensitivity of IFA was similar to what has been reported in children for seasonal influenza. Both diagnostic tests produced a high number of false negatives and should not be used to rule out influenza infection

Transmission patterns of smallpox: systematic review of natural outbreaks in Europe and North America since World War II

BACKGROUND: Because smallpox (variola major) may be used as a biological weapon, we reviewed outbreaks in post-World War II Europe and North America in order to understand smallpox transmission patterns. METHODS: A systematic review was used to identify papers from the National Library of Medicine, Embase, Biosis, Cochrane Library, Defense Technical Information Center, WorldCat, and reference lists of included publications. Two authors reviewed selected papers for smallpox outbreaks. RESULTS: 51 relevant outbreaks were identified from 1,389 publications. The median for the effective first generation reproduction rate (initial R) was 2 (range 0–38). The majority outbreaks were small (less than 5 cases) and contained within one generation. Outbreaks with few hospitalized patients had low initial R values (median of 1) and were prolonged if not initially recognized (median of 3 generations); outbreaks with mostly hospitalized patients had higher initial R values (median 12) and were shorter (median of 3 generations). Index cases with an atypical presentation of smallpox were less likely to have been diagnosed with smallpox; outbreaks in which the index case was not correctly diagnosed were larger (median of 27.5 cases) and longer (median of 3 generations) compared to outbreaks in which the index case was correctly diagnosed (median of 3 cases and 1 generation). CONCLUSION: Patterns of spread during Smallpox outbreaks varied with circumstances, but early detection and implementation of control measures is a most important influence on the magnitude of outbreaks. The majority of outbreaks studied in Europe and North America were controlled within a few generations if detected early

The effect of stress and anxiety associated with maternal prenatal diagnosis on feto-maternal attachment

<p>Abstract</p> <p>Background</p> <p>A couple's decision to undergo an invasive test based on a screening test result is a process associated with anxiety. The aim of this study was to determine whether anxiety and prenatal attachment were affected by undergoing an invasive test compared to women in early pregnancy and after a reassuring anomaly scan.</p> <p>Methods</p> <p>200 women were recruited at booking, 14 women and 20 partners after an invasive test and 81 women following an anomaly scan. A questionnaire was completed using the Beck Anxiety Inventory and Maternal or Paternal Antenatal Attachment Scales.</p> <p>Results</p> <p>Women who have had an invasive test have higher levels of anxiety compared to women at booking (P < 0.01) and after an anomaly scan (P = 0.002). Anxiety declines from booking to the time of an anomaly scan (P = 0.025), whilst attachment increases (P < 0.001). There is a positive correlation between anxiety and attachment in women who have had an invasive test (r = 0.479). Partners of women undergoing an invasive test experience lower levels of anxiety (P < 0.05).</p> <p>Conclusions</p> <p>Women undergoing prenatal diagnostic procedures experience more psychological distress, which may be currently underestimated. Establishment of interdisciplinary treatment settings where access to psychological support is facilitated may be beneficial.</p

Assessing the cost of global biodiversity and conservation knowledge

Knowledge products comprise assessments of authoritative information supported by standards, governance, quality control, data, tools, and capacity building mechanisms. Considerable resources are dedicated to developing and maintaining knowledge products for biodiversity conservation, and they are widely used to inform policy and advise decision makers and practitioners. However, the financial cost of delivering this information is largely undocumented. We evaluated the costs and funding sources for developing and maintaining four global biodiversity and conservation knowledge products: The IUCN Red List of Threatened Species, the IUCN Red List of Ecosystems, Protected Planet, and the World Database of Key Biodiversity Areas. These are secondary data sets, built on primary data collected by extensive networks of expert contributors worldwide. We estimate that US$160 million (range: US$116-204 million), plus 293 person-years of volunteer time (range: 278-308 person-years) valued at US$14 million (range US$12-16 million), were invested in these four knowledge products between 1979 and 2013. More than half of this financing was provided through philanthropy, and nearly three-quarters was spent on personnel costs. The estimated annual cost of maintaining data and platforms for three of these knowledge products (excluding the IUCN Red List of Ecosystems for which annual costs were not possible to estimate for 2013 ) is US$6.5 million in total (range: US$6.2-6.7 million). We estimated that an additional US$114 million will be needed to reach pre-defined baselines of data coverage for all the four knowledge products, and that once achieved, annual maintenance costs will be approximately US$12 million. These costs are much lower than those to maintain many other, similarly important, global knowledge products. Ensuring that biodiversity and conservation knowledge products are sufficiently up to date, comprehensive and accurate is fundamental to inform decision-making for biodiversity conservation and sustainable development. Thus, the development and implementation of plans for sustainable long-term financing for them is critical

Disentangling Direct from Indirect Co-Evolution of Residues in Protein Alignments

Predicting protein structure from primary sequence is one of the ultimate challenges in computational biology. Given the large amount of available sequence data, the analysis of co-evolution, i.e., statistical dependency, between columns in multiple alignments of protein domain sequences remains one of the most promising avenues for predicting residues that are contacting in the structure. A key impediment to this approach is that strong statistical dependencies are also observed for many residue pairs that are distal in the structure. Using a comprehensive analysis of protein domains with available three-dimensional structures we show that co-evolving contacts very commonly form chains that percolate through the protein structure, inducing indirect statistical dependencies between many distal pairs of residues. We characterize the distributions of length and spatial distance traveled by these co-evolving contact chains and show that they explain a large fraction of observed statistical dependencies between structurally distal pairs. We adapt a recently developed Bayesian network model into a rigorous procedure for disentangling direct from indirect statistical dependencies, and we demonstrate that this method not only successfully accomplishes this task, but also allows contacts with weak statistical dependency to be detected. To illustrate how additional information can be incorporated into our method, we incorporate a phylogenetic correction, and we develop an informative prior that takes into account that the probability for a pair of residues to contact depends strongly on their primary-sequence distance and the amount of conservation that the corresponding columns in the multiple alignment exhibit. We show that our model including these extensions dramatically improves the accuracy of contact prediction from multiple sequence alignments

Multiple receptor tyrosine kinases are expressed in adult rat retinal ganglion cells as revealed by single-cell degenerate primer polymerase chain reaction

BACKGROUND: To achieve a better understanding of the repertoire of receptor tyrosine kinases (RTKs) in adult retinal ganglion cells (RGCs) we performed polymerase chain reaction (PCR), using degenerate primers directed towards conserved sequences in the tyrosine kinase domain, on cDNA from isolated single RGCs univocally identified by retrograde tracing from the superior colliculi.RESULTS: All the PCR-amplified fragments of the expected sizes were sequenced, and 25% of them contained a tyrosine kinase domain. These were: Axl, Csf-1R, Eph A4, Pdgfrbeta, Ptk7, Ret, Ros, Sky, TrkB, TrkC, Vegfr-2, and Vegfr-3. Non-RTK sequences were Jak1 and 2. Retinal expression of Axl, Csf-1R, Pdgfrbeta, Ret, Sky, TrkB, TrkC, Vegfr-2, and Vegfr-3, as well as Jak1 and 2, was confirmed by PCR on total retina cDNA. Immunodetection of Csf-1R, Pdgfralpha/beta, Ret, Sky, TrkB, and Vegfr-2 on retrogradely traced retinas demonstrated that they were expressed by RGCs. Co-localization of Vegfr-2 and Csf-1R, of Vegfr-2 and TrkB, and of Csf-1R and Ret in retrogradely labelled RGCs was shown. The effect of optic nerve transection on the mRNA level of Pdgfrbeta, Csf-1R, Vegfr-2, Sky, and Axl, and of the Axl ligands Gas6 and ProteinS, was analysed. These analyses show transection-induced changes in Axl and ProteinS mRNA levels.CONCLUSIONS: The repertoire of RTKs expressed by RGCs is more extensive than previously anticipated. Several of the receptors found in this study, including Pdgfrbeta, Csf-1R, Vegfr-2, Sky, and Axl, and their ligands, have not previously been primarily associated with retinal ganglion cells

Activation of TRPC6 channels is essential for lung ischaemia–reperfusion induced oedema in mice

Lung ischaemia–reperfusion-induced oedema (LIRE) is a life-threatening condition that causes pulmonary oedema induced by endothelial dysfunction. Here we show that lungs from mice lacking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox2y/−) or the classical transient receptor potential channel 6 (TRPC6−/−) are protected from LIR-induced oedema (LIRE). Generation of chimeric mice by bone marrow cell transplantation and endothelial-specific Nox2 deletion showed that endothelial Nox2, but not leukocytic Nox2 or TRPC6, are responsible for LIRE. Lung endothelial cells from Nox2- or TRPC6-deficient mice showed attenuated ischaemia-induced Ca2+ influx, cellular shape changes and impaired barrier function. Production of reactive oxygen species was completely abolished in Nox2y/− cells. A novel mechanistic model comprising endothelial Nox2-derived production of superoxide, activation of phospholipase C-γ, inhibition of diacylglycerol (DAG) kinase, DAG-mediated activation of TRPC6 and ensuing LIRE is supported by pharmacological and molecular evidence. This mechanism highlights novel pharmacological targets for the treatment of LIRE