Characterisation of microstructure, defect and high-cycle-fatigue behaviour in a stainless steel joint processed by brazing

We report the characterisation of microstructures and high-cycle-fatigue (HCF) properties of Type 304 stainless steel joints processed by brazing. Pure copper was applied as the filler metal for brazing at 1120 °C. A two-phase microstructure was obtained within the joint region: the star-shaped precipitates and copper matrix. The precipitates with an average size of 0.43 μm were rich in iron and chromium. A fixed orientation relationship was found between the precipitates and copper matrix. The joint exhibited much higher tensile strength and HCF life when compared to pure copper. The strength enhancement can be attributed to the presence of precipitates. Furthermore, the effect of joint interface roughness as well as defects was critically investigated. The joint interface roughness showed little influence on the HCF lives. Post-examinations revealed that fatigue crack initiation and propagation occurred entirely within the joint region, hence being consistent with the similar HCF lives regardless of the pre-defined interface roughness conditions. In addition, it was found that the HCF lives decreased exponentially with the increase of initial defect area. Fractography analysis revealed that fatigue striation spacings near the crack initiation zone increased with the increase of defect area, suggesting that the larger defects result in higher crack growth rate, hence shorten the overall fatigue life.</div

Superlattice properties of carbon nanotubes in a transverse electric field

Electron motion in a (n,1) carbon nanotube is shown to correspond to a de Broglie wave propagating along a helical line on the nanotube wall. This helical motion leads to periodicity of the electron potential energy in the presence of an electric field normal to the nanotube axis. The period of this potential is proportional to the nanotube radius and is greater than the interatomic distance in the nanotube. As a result, the behavior of an electron in a (n,1) nanotube subject to a transverse electric field is similar to that in a semiconductor superlattice. In particular, Bragg scattering of electrons from the long-range periodic potential results in the opening of gaps in the energy spectrum of the nanotube. Modification of the bandstructure is shown to be significant for experimentally attainable electric fields, which raises the possibility of applying this effect to novel nanoelectronic devices.Comment: 7 pages, 3 figure

OATP1B1 and tumour OATP1B3 modulate exposure, toxicity, and survival after irinotecan-based chemotherapy

Background: Treatment of advanced and metastatic colorectal cancer with irinotecan is hampered by severe toxicities. The active metabolite of irinotecan, SN-38, is a known substrate of drug-metabolising enzymes, including UGT1A1, as well as OATP and ABC drug transporters.Methods:Blood samples (n=127) and tumour tissue (n=30) were obtained from advanced cancer patients treated with irinotecan-based regimens for pharmacogenetic and drug level analysis and transporter expression. Clinical variables, toxicity, and outcomes data were collected.Results:SLCO1B1 521C was significantly associated with increased SN-38 exposure (P\u3c0.001), which was additive with UGT1A1∗28. ABCC5 (rs562) carriers had significantly reduced SN-38 glucuronide and APC metabolite levels. Reduced risk of neutropenia and diarrhoea was associated with ABCC2-24C/T (odds ratio (OR)=0.22, 0.06-0.85) and CES1 (rs2244613; OR=0.29, 0.09-0.89), respectively. Progression-free survival (PFS) was significantly longer in SLCO1B1 388G/G patients and reduced in ABCC2-24T/T and UGT1A1∗28 carriers. Notably, higher OATP1B3 tumour expression was associated with reduced PFS.Conclusions:Clarifying the association of host genetic variation in OATP and ABC transporters to SN-38 exposure, toxicity and PFS provides rationale for personalising irinotecan-based chemotherapy. Our findings suggest that OATP polymorphisms and expression in tumour tissue may serve as important new biomarkers

A prospective study of the parent–baby bond in men and women 15 months after birth

Objective: To prospectively examine the impact of parental mental health (PTSD, depression and anxiety), the couple’s relationship quality and the infant temperament on the parent–baby bond in first-time mothers and fathers. Background: Evidence suggests that poor parental mental health, difficult infant temperament and/or lower quality of the couple’s relationship may impede the parent–baby bond. However, little research has included both parents or followed these measures across time. Methods: 75 women and 66 men completed questionnaire measures during pregnancy, 3 and 15 months postpartum, assessing mental health symptoms, the parent–baby bond, the couple’s relationship and infant characteristics. The response rates at different time-points were 90%, 77% and 70%. Results: The parent–baby bond was associated with parental mental health, the couple’s relationship and infant characteristics. The most important predictors of the parent–baby bond three months postpartum for both men and women were the couple’s relationship during pregnancy and their baby’s temperament at three months. At 15 months postpartum, after accounting for the parent–baby bond at 3 months, only concurrent infant temperament remained a significant predictor for women. However, men’s bond with their baby at 15 months was predicted by their relationship with their partner in pregnancy and concurrent affective symptoms. Few significant gender differences were found, apart from women reporting more mental health symptoms than men. Conclusion: This study highlights the significance of the couple’s relationship in pregnancy and the infant’s temperament on the development of the parent–baby bond. Future research is needed to examine this in larger more representative samples

Peace education in a time of war: the Museum of Peace in Rivne, Ukraine as a space of memory making and hope

Peace museums play an important role in peace education by offering visitors informal and non-formal education. As sites of remembrance, peace museums are rich pedagogical spaces for experiential learning and reflection. Educating children in the spirit of peace, tolerance and harmony between nations has been central to the work of the Museum of Peace in Rivne in Ukraine. Whilst peace museums usually engage in peacebuilding and memory making in times of peace, post conflict, this article reports on the work of the Museum in Rivne in a time of war. Wartime brings difficult questions about engaging in peacebuilding in the face of military aggression and about sustaining memory-making work when violent conflict makes memories too immediate and painful. As explained in the article, the reinvigorated peacebuilding effort at the Museum in Rivne demonstrates that, in a time of war, it is even more important to promote peace, in opposition to war. Through the annual event ‘I Vote for Peace’, the Museum has sought to create a network of schools committed to global tolerance and peacekeeping, as well as offer Ukrainian children a space for talking about their experiences and their hope for a peaceful future

AAV-mediated ERdj5 overexpression protects against P23H rhodopsin toxicity

Rhodopsin misfolding caused by the P23H mutation is a major cause of autosomal dominant retinitis pigmentosa (adRP), to date there are no effective treatments for adRP. The BiP co-chaperone and reductase ERdj5 (DNAJC10) is part of the ER quality control machinery and previous studies have shown that overexpression of ERdj5 in vitro enhanced the degradation of P23H rhodopsin; whereas knockdown of ERdj5 increased P23H rhodopsin ER retention and aggregation. Here, we investigated the role of ERdj5 in photoreceptor homeostasis in vivo by using an Erdj5 knock-out mouse crossed with the P23H knock-in mouse, and by adeno associated viral (AAV) vector-mediated gene augmentation of ERdj5 in P23H-3 rats. Electroretinogram (ERG) and optical coherence tomography (OCT) of Erdj5−/− and P23H+/−:Erdj5−/− mice showed no effect of ERdj5 ablation on retinal function or photoreceptor survival. Rhodopsin levels and localisation were similar to those of control animals at a range of time points. By contrast, when AAV2/8-ERdj5-HA was subretinally injected into P23H-3 rats, analysis of the full field ERG suggested that overexpression of ERdj5 reduced visual function loss 10 weeks post-injection. This correlated with a significant preservation of photoreceptor cells at 4 and 10 weeks post-injection. Assessment of the outer nuclear layer (ONL) morphology showed preserved ONL thickness and reduced rhodopsin retention in the ONL in the injected superior retina. Overall, these data suggest that manipulation of the ER quality control and ERAD factors to promote mutant protein degradation could be beneficial for the treatment of adRP caused by mutant rhodopsin

Effects of precompetition state anxiety interventions on performance time and accuracy among amateur soccer players: Revisiting the matching hypothesis

In this study, we tested the matching ypothesis, which contends that administration of a cognitive or somatic anxiety intervention should be matched to a participant's dominant anxiety response. Sixty-one male soccer players (mean age 31.6 years, s=6.3) were assigned to one of four groups based on their responses to the Competitive State Anxiety Inventory-2, which was modified to include a directional scale. Interventions were randomly administered in a counterbalanced order 10 min before each performance trial on a soccer skill test. The dominantly cognitive anxious group (n=17), the dominantly somatic anxious group (n=17), and the non-anxious control intervention group (n=14) completed a baseline performance trial. The second and third trials were completed with random administration of brief cognitive and somatic interventions. The non-anxious control group (n=13) completed three trials with no intervention. A mixed-model, GroupTreatment multivariate analysis of variance indicated significant (P0.05), or performance time or accuracy (P>0.05). The present findings do not provide support for the matching hypothesis for state anxiety intensity and direction, or for performance

REEP6 Deficiency Leads to Retinal Degeneration through Disruption of ER Homeostasis and Protein Trafficking

Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy. We recently identified mutations in REEP6, which encodes the receptor expression enhancing protein 6, in several families with autosomal recessive RP. REEP6 is related to the REEP and Yop1p family of ER shaping proteins and potential receptor accessory proteins, but the role of REEP6 in the retina is unknown. Here we characterise the disease mechanisms associated with loss of REEP6 function using a Reep6 knockout mouse generated by CRISPR/Cas9 gene editing. In control mice REEP6 was localised to the inner segment and outer plexiform layer of rod photoreceptors. The Reep6-/- mice exhibited progressive photoreceptor degeneration from P20 onwards. Ultrastructural analyses at P20 by transmission electron microscopy and 3View serial block face scanning EM revealed an expansion of the distal ER in the Reep6-/- rods and an increase in their number of mitochondria. Electroretinograms revealed photoreceptor dysfunction preceded degeneration, suggesting potential defects in phototransduction. There was no effect on the traffic of rhodopsin, Rom1 or peripherin/rds; however, the retinal guanylate cyclases GC1 and GC2 were severely affected in the Reep6 knockout animals, with almost undetectable expression. These changes correlated with an increase in C/EBP homologous protein (CHOP) expression and the activation of caspase 12, suggesting that ER stress contributes to cell death. Collectively, these data suggest that REEP6 plays an essential role in maintaining cGMP homeostasis though facilitating the stability and/or trafficking of guanylate cyclases and maintaining ER and mitochondrial homeostasis