Heterogeneous nucleation near a metastable vapour-liquid transition: the effect of wetting transitions

Phase transformations such as freezing typically start with heterogeneous nucleation. Heterogeneous nucleation near a wetting transition, of a crystalline phase is studied. The wetting transition occurs at or near a vapour-liquid transition which occurs in a metastable fluid. The fluid is metastable with respect to crystallisation, and it is the crystallisation of this fluid phase that we are interested in. At a wetting transition a thick layer of a liquid phase forms at a surface in contact with the vapour phase. The crystalline nucleus is then immersed in this liquid layer, which reduces the free energy barrier to nucleation and so dramatically increases the nucleation rate. The variation in the rate of heterogeneous nucleation close to wetting transitions is calculated for systems in which the longest-range forces are dispersion forces.Comment: 11 pages including 3 figure

Structural and functional conservation of the human homolog of the Schizosaccharomyces pombe rad2 gene, which is required for chromosome segregation and recovery from DNA damage

The rad2 mutant of Schizosaccharomyces pombe is sensitive to UV irradiation and deficient in the repair of UV damage. In addition, it has a very high degree of chromosome loss and/or nondisjunction. We have cloned the rad2 gene and have shown it to be a member of the Saccharomyces cerevisiae RAD2/S. pombe rad13/human XPG family. Using degenerate PCR, we have cloned the human homolog of the rad2 gene. Human cDNA has 55% amino acid sequence identity to the rad2 gene and is able to complement the UV sensitivity of the rad2 null mutant. We have thus isolated a novel human gene which is likely to be involved both in controlling the fidelity of chromosome segregation and in the repair of UV-induced DNA damage. Its involvement in two fundamental processes for maintaining chromosomal integrity suggests that it is likely to be an important component of cancer avoidance mechanisms

Practical 3-splitting beyond Strang

Operator splitting is a popular divide-and-conquer strategy for solving differential equations. Typically, the right-hand side of the differential equation is split into a number of parts that can then be integrated separately. Many methods are known that split the right-hand side into two parts. This approach is limiting, however, and there are situations when 3-splitting is more natural and ultimately more advantageous. The second-order Strang operator-splitting method readily generalizes to a right-hand side splitting into any number of operators. It is arguably the most popular method for 3-splitting because of its efficiency, ease of implementation, and intuitive nature. Other 3-splitting methods exist, but they are less well-known, and evaluations of their performance in practice are scarce. We demonstrate the effectiveness of some alternative 3-split, second-order methods to Strang splitting on two problems: the reaction-diffusion Brusselator, which can be split into three parts that each have closed-form solutions, and the kinetic Vlasov--Poisson equations that is used in semi-Lagrangian plasma simulations. We find alternative second-order 3-operator-splitting methods that realize efficiency gains of 10\%--20\% over traditional Strang splitting

Effect of catalyst layer defects on local membrane degradation in polymer electrolyte fuel cells

© 2016 Elsevier B.V. All rights reserved. Aiming at durability issues of fuel cells, this research is dedicated to a novel experimental approach in the analysis of local membrane degradation phenomena in polymer electrolyte fuel cells, shedding light on the potential effects of manufacturing imperfections on this process. With a comprehensive review on historical failure analysis data from field operated fuel cells, local sources of iron oxide contaminants, catalyst layer cracks, and catalyst layer delamination are considered as potential candidates for initiating or accelerating the local membrane degradation phenomena. Customized membrane electrode assemblies with artificial defects are designed, fabricated, and subjected to membrane accelerated stress tests followed by extensive post-mortem analysis. The results reveal a significant accelerating effect of iron oxide contamination on the global chemical degradation of the membrane, but dismiss local traces of iron oxide as a potential stressor for local membrane degradation. Anode and cathode catalyst layer cracks are observed to have negligible impact on the membrane degradation phenomena. Notably however, distinct evidence is found that anode catalyst layer delamination can accelerate local membrane thinning, while cathode delamination has no apparent effect. Moreover, a substantial mitigating effect for platinum residuals on the site of delamination is observed

Discrepancies in the diagnosis of intraductal proliferative lesions of the breast and its management implications: results of a multinational survey

To measure discrepancies in diagnoses and recommendations impacting management of proliferative lesions of the breast, a questionnaire of five problem scenarios was distributed among over 300 practicing pathologists. Of the 230 respondents, 56.5% considered a partial cribriform proliferation within a duct adjacent to unequivocal ductal carcinoma in situ (DCIS) as atypical ductal hyperplasia (ADH), 37.7% of whom recommended reexcision if it were at a resection margin. Of the 43.5% who diagnosed the partially involved duct as DCIS, 28.0% would not recommend reexcision if the lesion were at a margin. When only five ducts had a partial cribriform proliferation, 35.7% considered it as DCIS, while if ≥20 ducts were so involved, this figure rose to 60.4%. When one duct with a complete cribriform pattern measured 0.5, 1.5, or 4 mm, a diagnosis of DCIS was made by 22.6, 31.3, and 94.8%, respectively. When multiple ducts with flat epithelial atypia were at a margin, 20.9% recommended reexcision. Much of these discrepancies arise from the artificial separation of ADH and low-grade DCIS and emphasize the need for combining these two under the umbrella designation of ductal intraepithelial neoplasia grade 1 (DIN 1) to diminish the impact of different terminologies applied to biologically similar lesions

Design and Synthesis of Neuroprotective Methylthiazoles and Modification as NO-Chimeras for Neurodegenerative Therapy

Learning and memory deficits in Alzheimer’s disease (AD) result from synaptic failure and neuronal loss, the latter caused in part by excitotoxicity and oxidative stress. A therapeutic approach is described that uses NO-chimeras directed at restoration of both synaptic function and neuroprotection. 4-Methylthiazole (MZ) derivatives were synthesized, based upon a lead neuroprotective pharmacophore acting in part by GABAA receptor potentiation. MZ derivatives were assayed for protection of primary neurons against oxygen−glucose deprivation and excitotoxicity. Selected neuroprotective derivatives were incorporated into NO-chimera prodrugs, coined nomethiazoles. To provide proof of concept for the nomethiazole drug class, selected examples were assayed for restoration of synaptic function in hippocampal slices from AD-transgenic mice, reversal of cognitive deficits, and brain bioavailability of the prodrug and its neuroprotective MZ metabolite. Taken together, the assay data suggest that these chimeric nomethiazoles may be of use in treatment of multiple components of neurodegenerative disorders, such as AD

The relationship between sensory reactivity differences and mental health symptoms in children with neurodevelopmental conditions and their neurotypical peers

Children with neurodevelopmental conditions (NDC) often have sensory reactivity differences, such as being overwhelmed by sounds, which can elicit distress in their everyday life. Furthermore, children with an NDC often present with a greater frequency of mental health symptoms compared to their typically developing peers. However little research has examined the relationship of these sensory reactivity differences on broader mental health. This study set out to explore the relationship between sensory reactivity and mental health symptoms. Data from parent-reported measures of sensory reactivity and mental health symptoms were collected for 49 children presenting with a neurodevelopmental condition and 42 typically developing (TD) controls. Partial correlational analyses, controlling for IQ, were used to elucidate the relationship between sensory reactivity and mental health symptoms. Children with an NDC were significantly more likely to present with a sensory reactivity difference or mental health symptom. Sensory seeking was found to be the sensory subtype most related to mental health symptoms, especially in externalising conditions. There was evidence also found for a relationship between depression, sensory seeking and sensory hypo-reactivity, and GAD and hyper-reactivity. Findings suggest a relationship between sensory reactivity and mental health symptoms in children with a neurodevelopmental condition. There is also preliminary evidence of unique sensory-based profiles of mental health. Assessment of sensory difficulties as part of more rigorous mental health assessments within mental health services will support more accurate diagnoses and intervention

De novo SCN2A splice site mutation in a boy with autism spectrum disorder

BACKGROUND: SCN2A is a gene that codes for the alpha subunit of voltage-gated, type II sodium channels, and is highly expressed in the brain. Sodium channel disruptions, such as mutations in SCN2A, may play an important role in psychiatric disorders. Recently, de novo SCN2A mutations in autism spectrum disorder (ASD) have been identified. The current study characterizes a de novo splice site mutation in SCN2A that alters mRNA and protein products. CASE PRESENTATION: We describe results from clinical and genetic characterizations of a seven-year-old boy with ASD. Psychiatric interview and gold standard autism diagnostic instruments (ADOS and ADI-R) were used to confirm ASD diagnosis, in addition to performing standardized cognitive and adaptive functioning assessments (Leiter-R and Vineland Adaptive Behavior Scale), and sensory reactivity assessments (Sensory Profile and Sensory Processing Scales). Genetic testing by whole exome sequencing revealed four de novo events, including a splice site mutation c.476 + 1G > A in SCN2A, a missense mutation (c.2263G > A) causing a p.V755I change in the TLE1 gene, and two synonymous mutations (c.2943A > G in the BUB1 gene, and c.1254 T > A in C10orf68 gene). The de novo SCN2A splice site mutation produced a stop codon 10 amino acids downstream, possibly resulting in a truncated protein and/or a nonsense-mediated mRNA decay. The participant met new DSM-5 criteria for ASD, presenting with social and communication impairment, repetitive behaviors, and sensory reactivity issues. The participant's adaptive and cognitive skills fell in the low range of functioning. CONCLUSION: This report indicates that a splice site mutation in SCN2A might be contributing to the risk of ASD. Describing the specific phenotype associated with SCN2A mutations might help to reduce heterogeneity seen in ASD