Nature of Cu Interstitials in Al2O3 and the Implications for Filament Formation in Conductive Bridge Random Access Memory Devices

Resistive random access memory (RRAM) is a prime candidate to replace Flash memory. Of the two classes of RRAM, conductive bridge RAM (CBRAM) is favoured over that based on filaments of oxygen vacancies because of its larger on/off resistance ratio. The nature of the filament in Cu/Al₂O₃-based CBRAM is analysed using density functional theory. The defect and binding energies of Cu interstitials and clusters in Al₂O₃ are calculated. The binding energy per Cu interstitial is shown to significantly increase with increasing Cu coordination, whereas the binding per oxygen vacancy only slightly increases with vacancy concentration. This explains why metal filaments in CBRAM devices tend to be denser than oxygen vacancy filaments. Using three different filament models, we discover that the strong binding between Cu interstitials drives filament formation, resulting in Al ions being driven out of the Cu-rich environment. This leads to the formation of densely packed metallic Cu filaments with bonding similar to Cu metal, as confirmed by electronic structure calculations

Energetics of intrinsic defects in NiO and the consequences for its resistive random access memory performance

Energetics for a variety of intrinsic defects in NiO are calculated using state-of-the-art ab initio hybrid density functional theory calculations. At the O-rich limit, Ni vacancies are the lowest cost defect for all Fermi energies within the gap, in agreement with the well-known p-type behaviour of NiO. However, the ability of the metal electrode in a resistive random access memory metal-oxide-metal setup to shift the oxygen chemical potential towards the O-poor limit results in unusual NiO behaviour and O vacancies dominating at lower Fermi energy levels. Calculated band diagrams show that O vacancies in NiO are positively charged at the operating Fermi energy giving it the advantage of not requiring a scavenger metal layer to maximise drift. Ni and O interstitials are generally found to be higher in energy than the respective vacancies suggesting that significant recombination of O vacancies and interstitials does not take place as proposed in some models of switching behaviour.The authors thank the Engineering and Physical Sciences Research Council for funding from EPSRC Grant No. EP/M009297.This is the accepted manuscript. The final version is available at http://scitation.aip.org/content/aip/journal/apl/107/12/10.1063/1.4931751

Do maternal and child health promote economic development? A case study of six sub-Saharan African countries

Economic development leads to improved health for both women and children through advances in the field of medicine, reduction in mortality rates, and increase in life expectancy. Similarly, optimum maternal and child health are instrumental in human capital formation and productivity, with the potential for economic development. However, the majority of previously published research has focused on the impact of economic development on maternal and child health and rarely examines the reverse relationship (that is, the impact of child and maternal health on economic development), especially in sub-Saharan Africa (SSA). Therefore, the objective of this study was to determine the magnitude of the impact of maternal and child health on economic development (Gross Domestic Product (GDP) per capita), and vice versa, using a 10- year horizon and variance decompositions, for six countries in SSA. These countries, Burkina Faso, Togo, Ghana, Ivory Coast, Botswana and South Africa were grouped according to income brackets. Analyses were all based on Vector Auto Regression models and conducted on annual time-series data from the World Development Indicator data set, 1960-2012. The proxies for child health and maternal health were infant mortality rate and life expectancy at birth for females (in years), respectively. The magnitude of the contribution of child health to GDP per capita was generally higher than vice versa across countries in all income groups: Burkina Faso (41.7% vs 11.6%), Togo (12.2% vs 27.1%), Ghana (17.3% vs 7.8%), Ivory Coast (16.4% vs 9.7%), Botswana (33.4% vs 0.6%) and South Africa (29.3% vs 2.7%). The magnitude of the contribution of maternal health to GDP per capita was higher than the impact of the reverse relationship for the lower middle-income countries of Ghana (10.6% vs 2.4%) and Ivory Coast (82.3% vs 0.1%) and the upper middle-income countries of Botswana (2.3% vs 1.5%) and South Africa (25.6% vs 0.1%). However, the magnitude of the effect of GDP per capita on maternal health was higher than the other way around only for the lower income countries of Burkina Faso (27.9% vs 1.1%) and Togo (30.0% vs 3.8%). This study adds further policy support for improving maternal and child health to achieve substantial benefits on long-term economic growth in SSA.Key words: Maternal health, child health, economic development, sub-Saharan Africa, GDP per capit

Walking as a meaningful leisure occupation: the implications for occupational therapy

Introduction: In response to growing interest in leisure in occupational therapy and the importance of understanding how occupations maintain, enhance and promote health and wellbeing, a qualitative phenomenological study was conducted to explore the experiences of walking for leisure. Method: Six healthy student participants, identified as regular walkers, were interviewed using a semi-structured format. Data were analysed following interpretative phenomenological analysis methodology. Findings: Participants expressed how and why walking was meaningful to them; the four main themes were social connectedness, wellbeing, connection to nature and achievement from a challenge. Findings suggest that occupational therapists could use walking and leisure occupations in intervention, and that there is scope for an occupational therapy perspective in health promotion. Conclusion: Determining the subjective meaning of engaging in walking as a leisure occupation has implications for occupational science and health promotion in helping to explain why people do what they do

Improved Calculation of Li and Na Intercalation Properties in Anatase, Rutile, and TiO2(B)

In recent years, TiO2, as a potential electrode material in Li and Na batteries, has been the subject of considerable experimental and computational research. However, the typical density functional theory (DFT) functionals used (e.g., the generalized gradient (GGA)) for such calculations are not without their shortcomings. To avoid these well-known issues, we report the first use of hybrid DFT calculations to calculate the Li and Na intercalation properties for anatase, rutile, and TiO2(B). The magnitude of GGA intercalation voltage underestimation is shown to vary depending on the polymorphs. We find that Li intercalation is most energetically preferred in anatase, while Na intercalation is most feasible for TiO2(B). Using the screened exchange hybrid functional, all intercalation processes are shown to be thermodynamically favorable, with the exception of Na in rutile. The electronic structures of these intercalated materials are also calculated, and significant improvements, in terms of band gap prediction and charge localization, are presented in comparison with GGA. We hope that our results will encourage more use of hybrid density functionals in the modeling of fundamental battery material properties.We thank the Engineering and Physical Sciences Research Council for funding from EPSRC grant EP/M009297

Evidence of distinct RELN and TGFB1 genetic associations in familial and non-familial otosclerosis in a British population

Otosclerosis is a common form of hearing loss which typically presents in young adults. The disease has a familial, monogenic form and a non-familial form with a more complex aetiology. A previous genome wide association study identified evidence that variants within RELN are associated with the condition. Other genes in which an association has been reported include BMP2, COL1A1, FGF2, PPP2R5B and TGFB1. However, follow up studies have often failed to replicate initial positive results. The aim of this study was to establish if an association exists between eight single nucleotide polymorphisms (SNPs) in these six previously implicated genes and otosclerosis in a British case-control cohort (n = 748). Evidence of an association between rs1800472 in TGFB1 and otosclerosis was found (p = 0.034), this association was strongest amongst non-familial cases (p = 0.011). No evidence of an association was detected with variants in COL1A1, FGF2, BMP2, and PPP2R5B. No association between variation in RELN and otosclerosis was observed in the whole cohort. However, a significant association (p = 0.0057) was detected between one RELN SNP (rs39399) and otosclerosis in familial patients. Additionally, we identify expression of one RELN transcript in 51 of 81 human stapes tested, clarifying previous conflicting data as to whether RELN is expressed in the affected tissue. Our findings strengthen the association of TGFB1 (rs1800472) with otosclerosis and support a relationship between RELN and familial otosclerosis only, which may explain previous variable replications

Mutations and altered expression of SERPINF1 in patients with familial otosclerosis

Otosclerosis is a relatively common heterogenous condition, characterized by abnormal bone remodelling in the otic capsule leading to fixation of the stapedial footplate and an associated conductive hearing loss. Although familial linkage and candidate gene association studies have been performed in recent years, little progress has been made in identifying disease-causing genes. Here, we used whole-exome sequencing in four families exhibiting dominantly inherited otosclerosis to identify 23 candidate variants (reduced to 9 after segregation analysis) for further investigation in a secondary cohort of 84 familial cases. Multiple mutations were found in the SERPINF1 (Serpin Peptidase Inhibitor, Clade F) gene which encodes PEDF (pigment epithelium-derived factor), a potent inhibitor of angiogenesis and known regulator of bone density. Six rare heterozygous SERPINF1 variants were found in seven patients in our familial otosclerosis cohort; three are missense mutations predicted to be deleterious to protein function. The other three variants are all located in the 5'-untranslated region (UTR) of an alternative spliced transcript SERPINF1-012 RNA-seq analysis demonstrated that this is the major SERPINF1 transcript in human stapes bone. Analysis of stapes from two patients with the 5'-UTR mutations showed that they had reduced expression of SERPINF1-012 All three 5'-UTR mutations are predicted to occur within transcription factor binding sites and reporter gene assays confirmed that they affect gene expression levels. Furthermore, RT-qPCR analysis of stapes bone cDNA showed that SERPINF1-012 expression is reduced in otosclerosis patients with and without SERPINF1 mutations, suggesting that it may be a common pathogenic pathway in the disease

Methods to Assess the Direct Interaction of C. Jejuni With Mucins

Studies of the interaction of bacteria with mucus secreting cells can be complemented at a more mechanistic level by exploring the interaction of bacteria with purified mucins. Here we describe a far western blotting approach to show how C. jejuni proteins separated by SDS PAGE and transferred to a membrane or slot blotted directly onto a membrane can be probed biotinylated mucin. In addition we describe the use of novel mucin microarrays to assess bacterial interactions with mucins in a high throughput manner

Common activation of canonical Wnt signaling in pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is an extremely aggressive malignancy, which carries a dismal prognosis. Activating mutations of the Kras gene are common to the vast majority of human PDA. In addition, recent studies have demonstrated that embryonic signaling pathway such as Hedgehog and Notch are inappropriately upregulated in this disease. The role of another embryonic signaling pathway, namely the canonical Wnt cascade, is still controversial. Here, we use gene array analysis as a platform to demonstrate general activation of the canonical arm of the Wnt pathway in human PDA. Furthermore, we provide evidence for Wnt activation in mouse models of pancreatic cancer. Our results also indicate that Wnt signaling might be activated downstream of Hedgehog signaling, which is an early event in PDA evolution. Wnt inhibition blocked proliferation and induced apoptosis of cultured adenocarcinoma cells, thereby providing evidence to support the development of novel therapeutical strategies for Wnt inhibition in pancreatic adenocarcinoma