Multiscale correlative tomography: an investigation of creep cavitation in 316 stainless steel

Creep cavitation in an ex-service nuclear steam header Type 316 stainless steel sample is investigated through a multiscale tomography workflow spanning eight orders of magnitude, combining X-ray computed tomography (CT), plasma focused ion beam (FIB) scanning electron microscope (SEM) imaging and scanning transmission electron microscope (STEM) tomography. Guided by microscale X-ray CT, nanoscale X-ray CT is used to investigate the size and morphology of cavities at a triple point of grain boundaries. In order to understand the factors affecting the extent of cavitation, the orientation and crystallographic misorientation of each boundary is characterised using electron backscatter diffraction (EBSD). Additionally, in order to better understand boundary phase growth, the chemistry of a single boundary and its associated secondary phase precipitates is probed through STEM energy dispersive X-ray (EDX) tomography. The difference in cavitation of the three grain boundaries investigated suggests that the orientation of grain boundaries with respect to the direction of principal stress is important in the promotion of cavity formation

Reemergence of anthropogenic carbon into the ocean's mixed layer strongly amplifies transient climate sensitivity

A positive marine chemistry‐climate feedback was originally proposed by Revelle and Suess (1957, https://doi.org/10.3402/tellusa.v9i1.9075), whereby the invasion flux of anthropogenic carbon into the ocean serves to inhibit future marine CO2 uptake through reductions to the buffering capacity of surface seawater. Here we use an ocean circulation‐carbon cycle model to identify an upper limit on the impact of reemergence of anthropogenic carbon into the ocean's mixed layer on the cumulative airborne fraction of CO2 in the atmosphere. We find under an RCP8.5 emissions pathway (with steady circulation) that the cumulative airborne fraction of CO2 has a sevenfold reduction by 2100 when the CO2 buffering capacity of surface seawater is maintained at preindustrial levels. Our results indicate that the effect of reemergence of anthropogenic carbon into the mixed layer on the buffering capacity of CO2 amplifies the transient climate sensitivity of the Earth system

Talk to the Virtual Hands: Self-Animated Avatars Improve Communication in Head-Mounted Display Virtual Environments

Background When we talk to one another face-to-face, body gestures accompany our speech. Motion tracking technology enables us to include body gestures in avatar-mediated communication, by mapping one's movements onto one's own 3D avatar in real time, so the avatar is self-animated. We conducted two experiments to investigate (a) whether head-mounted display virtual reality is useful for researching the influence of body gestures in communication; and (b) whether body gestures are used to help in communicating the meaning of a word. Participants worked in pairs and played a communication game, where one person had to describe the meanings of words to the other. Principal Findings In experiment 1, participants used significantly more hand gestures and successfully described significantly more words when nonverbal communication was available to both participants (i.e. both describing and guessing avatars were self-animated, compared with both avatars in a static neutral pose). Participants ‘passed’ (gave up describing) significantly more words when they were talking to a static avatar (no nonverbal feedback available). In experiment 2, participants' performance was significantly worse when they were talking to an avatar with a prerecorded listening animation, compared with an avatar animated by their partners' real movements. In both experiments participants used significantly more hand gestures when they played the game in the real world. Conclusions Taken together, the studies show how (a) virtual reality can be used to systematically study the influence of body gestures; (b) it is important that nonverbal communication is bidirectional (real nonverbal feedback in addition to nonverbal communication from the describing participant); and (c) there are differences in the amount of body gestures that participants use with and without the head-mounted display, and we discuss possible explanations for this and ideas for future investigation

Inhibition of the tyrosine phosphatase SHP-2 suppresses angiogenesis in vitro and in vivo

Endothelial cell survival is indispensable to maintain endothelial integrity and initiate new vessel formation. We investigated the role of SHP-2 in endothelial cell survival and angiogenesis in vitro as well as in vivo. SHP-2 function in cultured human umbilical vein and human dermal microvascular endothelial cells was inhibited by either silencing the protein expression with antisense-oligodesoxynucleotides or treatment with a pharmacological inhibitor (PtpI IV). SHP-2 inhibition impaired capillary-like structure formation (p < 0.01; n = 8) in vitro as well as new vessel growth ex vivo (p < 0.05; n = 10) and in vivo in the chicken chorioallantoic membrane (p < 0.01, n = 4). Additionally, SHP-2 knock-down abrogated fibroblast growth factor 2 (FGF-2)-dependent endothelial proliferation measured by MTT reduction ( p ! 0.01; n = 12). The inhibitory effect of SHP-2 knock-down on vessel growth was mediated by increased endothelial apoptosis ( annexin V staining, p ! 0.05, n = 9), which was associated with reduced FGF-2-induced phosphorylation of phosphatidylinositol 3-kinase (PI3-K), Akt and extracellular regulated kinase 1/2 (ERK1/2) and involved diminished ERK1/2 phosphorylation after PI3-K inhibition (n=3). These results suggest that SHP-2 regulates endothelial cell survival through PI3-K-Akt and mitogen-activated protein kinase pathways thereby strongly affecting new vessel formation. Thus, SHP-2 exhibits a pivotal role in angiogenesis and may represent an interesting target for therapeutic approaches controlling vessel growth. Copyright (C) 2007 S. Karger AG, Basel

Modulation of Bacterial Type III Secretion System by a Spermidine Transporter Dependent Signaling Pathway

10.1371/journal.pone.0001291PLoS ONE212

Performance of Genotype Imputation for Rare Variants Identified in Exons and Flanking Regions of Genes

Genotype imputation has the potential to assess human genetic variation at a lower cost than assaying the variants using laboratory techniques. The performance of imputation for rare variants has not been comprehensively studied. We utilized 8865 human samples with high depth resequencing data for the exons and flanking regions of 202 genes and Genome-Wide Association Study (GWAS) data to characterize the performance of genotype imputation for rare variants. We evaluated reference sets ranging from 100 to 3713 subjects for imputing into samples typed for the Affymetrix (500K and 6.0) and Illumina 550K GWAS panels. The proportion of variants that could be well imputed (true r2>0.7) with a reference panel of 3713 individuals was: 31% (Illumina 550K) or 25% (Affymetrix 500K) with MAF (Minor Allele Frequency) less than or equal 0.001, 48% or 35% with 0.001<MAF< = 0.005, 54% or 38% with 0.005<MAF< = 0.01, 78% or 57% with 0.01<MAF< = 0.05, and 97% or 86% with MAF>0.05. The performance for common SNPs (MAF>0.05) within exons and flanking regions is comparable to imputation of more uniformly distributed SNPs. The performance for rare SNPs (0.01<MAF< = 0.05) was much more dependent on the GWAS panel and the number of reference samples. These results suggest routine use of genotype imputation for extending the assessment of common variants identified in humans via targeted exon resequencing into additional samples with GWAS data, but imputation of very rare variants (MAF< = 0.005) will require reference panels with thousands of subjects

Microbial Communication, Cooperation and Cheating: Quorum Sensing Drives the Evolution of Cooperation in Bacteria

An increasing body of empirical evidence suggests that cooperation among clone-mates is common in bacteria. Bacterial cooperation may take the form of the excretion of “public goods”: exoproducts such as virulence factors, exoenzymes or components of the matrix in biofilms, to yield significant benefit for individuals joining in the common effort of producing them. Supposedly in order to spare unnecessary costs when the population is too sparse to supply the sufficient exoproduct level, many bacteria have evolved a simple chemical communication system called quorum sensing (QS), to “measure” the population density of clone-mates in their close neighborhood. Cooperation genes are expressed only above a threshold rate of QS signal molecule re-capture, i.e., above the local quorum of cooperators. The cooperative population is exposed to exploitation by cheaters, i.e., mutants who contribute less or nil to the effort but fully enjoy the benefits of cooperation. The communication system is also vulnerable to a different type of cheaters (“Liars”) who may produce the QS signal but not the exoproduct, thus ruining the reliability of the signal. Since there is no reason to assume that such cheaters cannot evolve and invade the populations of honestly signaling cooperators, the empirical fact of the existence of both bacterial cooperation and the associated QS communication system seems puzzling. Using a stochastic cellular automaton approach and allowing mutations in an initially non-cooperating, non-communicating strain we show that both cooperation and the associated communication system can evolve, spread and remain persistent. The QS genes help cooperative behavior to invade the population, and vice versa; cooperation and communication might have evolved synergistically in bacteria. Moreover, in good agreement with the empirical data recently available, this synergism opens up a remarkably rich repertoire of social interactions in which cheating and exploitation are commonplace

Phosphoinositide-3 kinase inhibition modulates responses to rhinovirus by mechanisms that are predominantly independent of autophagy

Human rhinoviruses (HRV) are a major cause of exacerbations of airways disease. Aspects of cell signalling responses to HRV infection remain unclear, particularly with regard to signalling via PI3K, and the PI3K-dependent pathway, autophagy. We investigated the roles of PI3K and autophagy in the responses of epithelial cells to major and minor group HRV infection. The PI3K inhibitor 3-MA, commonly used to inhibit autophagy, markedly reduced HRV-induced cytokine induction. Further investigation of potential targets of 3-MA and comparison of results using this inhibitor to a panel of general and class I-selective PI3K inhibitors showed that several PI3Ks cooperatively regulate responses to HRV. Targeting by siRNA of the autophagy proteins Beclin-1, Atg7, LC3, alone or in combination, or targeting of the autophagy-specific class III PI3K had at most only modest effects on HRV-induced cell signalling as judged by induction of proinflammatory cytokine production. Our data indicate that PI3K and mTOR are involved in induction of proinflammatory cytokines after HRV infection, and that autophagy has little role in the cytokine response to HRV or control of HRV replication

Sendai five years on: reflections on the role of international law in the creation and reduction of disaster risk

This article offers a critical examination of the position of the Sendai Framework for Disaster Risk Reduction 2015-2030 within international law. It is argued that any interrogation into the role of international law must begin not with existing disaster risk reduction (DRR) laws and policies, but rather with an enquiry into the nature of disaster risk and the role of international law in its creation and reduction. It is demonstrated how, while areas such as international human rights law can be utilized to enforce obligations in support of DRR, other areas – in particular international investment law – actively work to undermine DRR efforts. In order for international law to be a productive tool in the reduction of disaster risk international lawyers must engage with critical work in disaster studies in order to explore the role that the former has played – and can play – in creating and addressing hazards, vulnerabilities and capacities

Low back pain beliefs are associated to age, location of work, education and pain-related disability in Chinese healthcare, professionals working in China: a cross sectinal survey

Background: Low back pain (LBP) is the leading cause of disability worldwide. Evidence pointing towards a more efficacious model of care using a biopsychosocial approach for LBP management highlights the need to understand the pain-related beliefs of patients and those who treat them. The beliefs held by healthcare professionals (HCPs) are known to influence the treatment advice given to patients and consequently management outcomes. Back pain beliefs are known to be influenced by factors such as culture, education, health literacy, place of work, personal experience of LBP and the sequelae of LBP such as disability. There is currently a knowledge gap among these relationships in non-western countries. The aim of this study was to examine the associations between LBP-related beliefs among Chinese HCPs and characteristics of these HCPs. Methods: A convenience sample of 432 HCPs working in various health settings in Shanghai, China, completed a series of questionnaires assessing their demographic characteristics, LBP status, pain-related disability and their beliefs about their own LBP experience, using the Back beliefs Questionnaire (BBQ) and the Fear Avoidance Beliefs Questionnaire (FABQ).Results: Younger Chinese HCPs (20–29 years) held more negative beliefs and attitudes related to LBP compared to older HCPs (>40years; BBQ mean difference [95% CI]: 2.4 [0.9 - 3.9], p = 0.001). HCPs working outside tertiary hospitals had poorer beliefs concerning the inevitable consequences of LBP (BBQ mean difference [95% CI]: -2.4 [-3.8 - -1.0], p = 0.001). HCPs who experienced LBP had higher level of fear avoidance beliefs when experiencing high LBP-related disability (FABQ-physical mean difference [95% CI]: 2.8 [1.5 - 4.1], p < 0.001; FABQ-work mean difference [95% CI]: 6.2 [4.0 - 8.4], p < 0.001)) and had lower level of fear avoidance beliefs if they had completed postgraduate study(FABQ-physical mean difference [95% CI]: 2.9 [-5.8 - 0.0], p = 0.049).Conclusion: This study suggests that LBP-related beliefs and attitudes among Chinese HCPs are influenced by age, location of work, level of LBP-related disability and education level. Understanding back pain beliefs of Chinese HCPs forms an important foundation for future studies into the condition and its management in China