There are two major forms of long-term depression (LTD) of synaptic transmission in the central nervous system, which require activation of either N-methyl-D-aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). In synapses in the perirhinal cortex we have directly compared the Ca2+ signalling mechanisms involved in NMDAR-LTD and mGluR-LTD. Whilst both forms of LTD involve Ca2+ release from intracellular stores the Ca2+ sensors involved are different; NMDAR-LTD involves calmodulin, whilst mGluR-LTD involves the neuronal Ca2+ sensor (NCS) protein NCS-1. In addition, there is a specific requirement for IP3 and PKC as well as protein interacting with C-kinase (PICK-1) in mGluR-LTD. NCS-1 binds directly to PICK1, via its BAR domain, in a Ca2+-dependent manner. Furthermore, the NCS-1-PICK1 association is stimulated by activation of mGluRs, but not NMDARs, and introduction of a PICK1 BAR domain fusion protein specifically blocks mGluR-LTD. Thus, NCS-1 is a component of a novel mechanism involved in mGluR-LTD.

The goal of this randomly-assigned placebo-controlled double-blind study was to determine if the addition of buspirone, a widely available 5-HT1A partial agonist, would enhance cognitive function, in subjects with schizophrenia treated with atypical antipsychotic drugs (AAPDs). Seventy-three patients with schizophrenia, who had been treated with an AAPD for at least three months, were randomly assigned to receive either buspirone, 30 mg/day, or matching placebo. All other medications remained unchanged. Attention, verbal fluency, verbal learning and memory, verbal working memory, and executive function, as well as psychopathology, were assessed at baseline, and 6 weeks, and 3 and 6 months after baseline. A significant Time x Group interaction effect was noted on the Digit Symbol Substitution Test, a measure of attention/speeded motor performance, due to better performance of the buspirone group compared to the placebo group at 3 months. No significant interaction effects were noted for other domains of cognition. Scores on the Brief Psychiatric Rating Scale (Total, Positive) were improved during treatment with buspirone but not placebo, but the effects did not reach statistical significance.

The results of this study showed a possible benefit of buspirone augmentation of AAPDs to enhance attention. However, we did not replicate the results of the previous study with tandospirone that improved executive function and verbal learning and memory, which may be due to the differences between tandospirone and buspirone, between typical antipsychotics and AAPDs, or a combination of the above. Further study to determine the usefulness of 5-HT1A agonist treatment in schizophrenia is indicated.

Stigma and social exclusion related to mental health are of substantial public health importance for Europe. As part of ROAMER (ROAdmap for MEntal health Research in Europe), we used systematic mapping techniques to describe the current state of research on stigma and social exclusion across Europe. Findings demonstrate growing interest in this field between 2007 and 2012. Most studies were descriptive (60%), focused on adults of working age (60%) and were performed in Northwest Europe—primarily in the UK (32%), Finland (8%), Sweden (8%) and Germany (7%). In terms of mental health characteristics, the largest proportion of studies investigated general mental health (20%), common mental disorders (16%), schizophrenia (16%) or depression (14%). There is a paucity of research looking at mechanisms to reduce stigma and promote social inclusion, or at factors that might promote resilience or protect against stigma/social exclusion across the life course. Evidence is also limited in relation to evaluations of interventions. Increasing incentives for cross-country research collaborations, especially with new EU Member States and collaboration across European professional organizations and disciplines, could improve understanding of the range of underpinning social and cultural factors which promote inclusion or contribute toward lower levels of stigma, especially during times of hardship.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

We present a broad study of linear, clustered, noble gas puffs irradiated with the frequency doubled (527 nm) Titan laser at Lawrence Livermore National Laboratory. Pure Ar, Kr, and Xe clustered gas puffs, as well as two mixed-gas puffs consisting of KrAr and XeKrAr gases, make up the targets. Characterization experiments to determine gas-puff density show that varying the experimental parameter gas-delay timing (the delay between gas puff initialization and laser-gas-puff interaction) provides a simple control over the gas-puff density. X-ray emission (>1.4 keV) is studied as a function of gas composition, density, and delay timing. Xe gas puffs produce the strongest peak radiation in the several keV spectral region. The emitted radiation was found to be anisotropic, with smaller X-ray flux observed in the direction perpendicular to both laser beam propagation and polarization directions. The degree of anisotropy is independent of gas target type but increases with photon energy. X-ray spectroscopic measurements estimate plasma parameters and highlight their difference with previous studies. Electron beams with energy in excess of 72 keV are present in the noble gas-puff plasmas and results indicate that Ar plays a key role in their production. A drastic increase in harder X-ray emissions (X-ray flash effect) and multi-MeV electron-beam generation from Xe gas-puff plasma occurred when the laser beam was focused on the front edge of the linear gas puff.

In this paper, we presented design specifications and operational test results of large-sized high temperature superconducting (HTS) magnets for Superconducting Induction Heater (SIH). HTS magnets were designed and fabricated with the metal insulation method. Critical currents of the HTS magnets were estimated by considering the angular dependency on the magnetic flux density of HTS tape. The characteristic resistance, the charging and discharging time were calculated and measured in the liquid nitrogen and the conduction cooling condition achieved with the 2nd stage GM cryo-cooler. The saturated temperature of the HTS magnet reached at 5.6 K. The performances of the large-sized HTS magnet including cooling and magnetic field characteristics were tested under the conduction cooling. These results were evaluated with those of finite element method analysis results. The characteristic analysis results of the large-sized HTS magnets will be applied for development of the commercial 300 kW SIH.

Fluid–structure interactions are ubiquitous in nature and technology. However, the systems are often so complex that numerical simulations or ad hoc assumptions must be used to gain insight into the details of the complex interactions between the fluid and solid mechanics. In this paper, we present experiments and theory on viscous flow in a simple bioinspired soft valve which illustrate essential features of interactions between hydrodynamic and elastic forces at low Reynolds numbers. The set-up comprises a sphere connected to a spring located inside a tapering cylindrical channel. The spring is aligned with the central axis of the channel and a pressure drop is applied across the sphere, thus forcing the liquid through the narrow gap between the sphere and the channel walls. The sphere’s equilibrium position is determined by a balance between spring and hydrodynamic forces. Since the gap thickness changes with the sphere’s position, the system has a pressure-dependent hydraulic resistance. This leads to a nonlinear relation between applied pressure and flow rate: flow initially increases with pressure, but decreases when the pressure exceeds a certain critical value as the gap closes. To rationalize these observations, we propose a mathematical model that reduced the complexity of the flow to a two-dimensional lubrication approximation. A closed-form expression for the pressure drop/flow rate is obtained which reveals that the flow rate $Q$ depends on the pressure drop $\unicode[STIX]{x0394}p$ , sphere radius $a$ , gap thickness $h_{0}$ , and viscosity $\unicode[STIX]{x1D702}$ as $Q\sim \unicode[STIX]{x1D702}^{-1}a^{1/2}h_{0}^{5/2}(1-\unicode[STIX]{x0394}p/\unicode[STIX]{x0394}p_{c})^{5/2}\unicode[STIX]{x0394}p$ , where the critical pressure $\unicode[STIX]{x0394}p_{c}$ scales with the spring constant $k$ as $\unicode[STIX]{x0394}p_{c}\sim kh_{0}a^{-2}$ . These predictions compared favourably to the results of our experiments with no free parameters.

Respiratory syncytial virus (RSV) can cause serious respiratory infections, second only to influenza virus. In order to know RSV's genetic changes we examined 4028 respiratory specimens from local hospital outpatients in Gyeonggi Province, South Korea over six consecutive years by real-time one-step RT–PCR; 183 patients were positive for RSV infection. To investigate the specific distribution of RSV genotypes, we performed partial sequencing of the glycoprotein gene. Of the 131 RSV-A specimens sequenced, 61 (43·3%) belonged to the ON1 genotype, 66 (46·8%) were NA1 genotype, 3 (2·1%) were GA5 genotype, and 1 (0·7%) belonged to the GA1 genotype. Of the 31 RSV-B specimens sequenced, 29 were BA9 genotype (87·9%) and 2 were BA10 genotype (6·1%). The most common clinical symptoms were fever, cough, nasal discharge, and phlegm; multiple logistic regression analysis showed that RSV-positive infection on pediatric patients was strongly associated with cough (OR = 2·8, 95% CI 1·6–5·1) and wheezing (OR = 2·8, 95% CI 1·7–4·4). The ON1 genotype was significantly associated with phlegm (OR = 11·8, 95% CI 3·8–46·7), while the NA1 genotype was associated with the pediatric patients’ gender (males, OR = 2·4, 95% CI 1·1–5·4) and presence of chills (OR = 5·1, 95% CI 1·1–27·2). RSV subgroup B was showed association with nasal obstruction (OR = 4·6, 95% CI 1·2–20·0). The majority of respiratory virus coinfections with RSV were human rhinovirus (47·2%). This study contributes to our understanding of the molecular epidemiological characteristics of RSV, which promotes the potential for improving RSV vaccines.

Bhutan is a small country in the Himalayan mountains where subsistence agriculture is practiced due to small land holdings and undulating mountainous terrains. Due to diverse altitudinal and agro-ecological environments, many food crops are cultivated. Wheat is currently a secondary cereal, grown over an area of 1,964 ha with a total production of 3,465 Mg. While there are enormous opportunities to increase wheat production in Bhutan, it is challenged by numerous biotic and socio-economic factors such as labour shortage and low economic return. Among the biotic constraints, stripe rust and leaf rust are the most important diseases. Stem rust has not yet been reported. Poor crop nutrition, both through low soil fertility and inadequate external supply, also results in low productivity. In addition, better remunerative crops and affordable-imported products discourage wheat production. However, the availability and accessibility to higher yielding disease-resistant varieties, fertilization (both organic and inorganic), appropriate seed rate, optimum planting time, mechanization, rotation with legumes and expansion of wheat area are some measures that will play a crucial role in managing sustainable wheat production in Bhutan. In this paper, we provide a brief overview of the current scenario of wheat production, discuss the constraints and provide strategic guidance to improve wheat production in Bhutan.

This study aimed to examine the association between vitamin B6, folate and vitamin B12 biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43 % males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) and n-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found with n-6:n-3 ratio, trans-fatty acids and oleic:stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15·85 µmol/l of EPA (P value <0·01), whereas an increase of 10 nmol/l of tHcy in males produces a decrease of 2·06 µmol/l of DHA (P value <0·05). Positive associations between B-vitamins and specific fatty acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies.

Extended-spectrum β-lactamase (ESBL) production has been very rare in serotype K1 Klebsiella pneumoniae ST23 strains, which are well-known invasive community strains. Among 92 ESBL-producing strains identified in 218 isolates from nine Asian countries, serotype K1 K. pneumoniae strains were screened. Two ESBL-producing K. pneumoniae isolates from Singapore and Indonesia were determined to be serotype K1 and ST23. Their plasmids, which contain CTX-M-15 genes, are transferable rendering the effective transfer of ESBL resistance plasmids to other organisms.

We present recent observation results of Sgr A* at millimeter obtained with VLBI arrays in Korea and Japan.

7 mm monitoring of Sgr A* is part of our AGN large project. The results at 7 epochs during 2013-2014, including high resolution maps, flux density and two-dimensional size measurements are presented. The source shows no significant variation in flux and structure related to the G2 encounter in 2014. According to recent MHD simulations by kawashima et al., flux and magnetic field energy can be expected to increase several years after the encounter; We will keep our monitoring in order to test this prediction.

Astrometric observations of Sgr A* were performed in 2015 at 7 and 3.5 millimeter simultaneously. Source-frequency phase referencing was applied and a combined ”core-shift” of Sgr A* and a nearby calibrator was measured. Future observations and analysis are necessary to determine the core-shift in each source.