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Depression and dementia are highly prevalent in older adults and often co-occur. This Phase IV study investigated the effectiveness and tolerability of vortioxetine in improving depressive symptoms, cognitive performance, daily and global functioning and health-related quality of life (HRQoL) in patients with major depressive disorder (MDD) and comorbid early-stage dementia. Patients (n = 82) aged 55–85 years with a primary diagnosis of MDD (onset before age 55 years) and comorbid early-stage dementia (diagnosed ≥6 months before screening and after onset of MDD; Mini-Mental State Examination-2 total score, 20–24) received vortioxetine for 12 weeks (initiated at 5 mg/day and up-titrated to 10 mg/day at day 8, with flexible dosing thereafter [5–20 mg/day]). The primary endpoint was change from baseline in Montgomery–Åsberg Depression Rating Scale (MADRS) total score at week 12. Significant improvement in depressive symptom severity was seen from week 1 onwards (P < 0.0001). At week 12, the least-square mean (standard error) change in MADRS total score from baseline was −12.4 (0.78). Significant improvements in cognitive performance were observed (from week 1 for the Digit Symbol Substitution Test and week 4 for the Rey Auditory Verbal Learning Test). Patients also experienced significant improvements in daily and global functioning, and HRQoL. Vortioxetine was well tolerated. From week 4 onwards, more than 50 % of patients were receiving 20 mg/day. Open-label study. Vortioxetine demonstrated effectiveness in clinically significantly improving depressive symptoms, cognitive performance, daily and global functioning, and HRQoL in patients with MDD and comorbid early-stage dementia treated for 12 weeks. ClinicalTrials.gov/ct2/show/NCT04294654. • Depression and dementia are highly prevalent in older adults and often co-occur. • Effectiveness of vortioxetine was assessed in patients with MDD and early-stage dementia. • Significant improvement in depressive symptom severity after vortioxetine initiation. • Cognitive performance significantly improved as assessed by the DSST and RAVLT. • Daily and global functioning and quality of life also improved with vortioxetine. [ABSTRACT FROM AUTHOR]

In 2019, Aterias et al. constructed pairs of quantum isomorphic, non‐isomorphic graphs from linear constraint systems. This article deals with quantum automorphisms and quantum isomorphisms of colored versions of those graphs. We show that the quantum automorphism group of such a colored graph is the dual of the homogeneous solution group of the underlying linear constraint system. Given a vertex‐ and edge‐colored graph with certain properties, we construct an uncolored graph that has the same quantum automorphism group as the colored graph we started with. Using those results, we obtain the first‐known example of a graph that has quantum symmetry and finite quantum automorphism group. Furthermore, we construct a pair of quantum isomorphic, non‐isomorphic graphs that both have no quantum symmetry. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are frequently comorbid. Aims: To assess the effectiveness of vortioxetine in patients with MDD and comorbid GAD. Methods: Open-label, 8-week study (NCT04220996) in 100 adult outpatients with severe MDD and severe comorbid GAD receiving vortioxetine as first treatment for the current depressive episode or switching to vortioxetine due to inadequate response to another drug for depression. Vortioxetine starting dosage was 10 mg/day, with forced up-titration to 20 mg/day after 1 week. Response was defined as ⩾50% decrease in Montgomery–Åsberg Depression Rating Scale (MADRS) and/or Hamilton Anxiety Rating Scale (HAM-A) total score from baseline; remission defined as MADRS and/or HAM-A total score ⩽10. Results: Clinically meaningful and statistically significant improvements from baseline in symptoms of depression and anxiety, and overall functioning and health-related quality of life, were observed after 8 weeks' vortioxetine treatment (all changes p < 0.0001 vs baseline). At week 8, rates of MADRS response and remission were 61% and 35%, respectively. Corresponding rates of HAM-A response and remission were 55% and 42%. Response on both the MADRS and HAM-A scales was achieved by 52% of patients; 31% achieved remission on both scales. Vortioxetine dose up-titration was well tolerated; no unexpected adverse events were reported. Conclusion: Vortioxetine demonstrates effectiveness in significantly reducing symptoms of both depression and anxiety in patients with severe MDD comorbid with severe GAD. Findings support increasing vortioxetine dosage to 20 mg/day early in the course of therapy, and show that this may be achieved without compromising tolerability. [ABSTRACT FROM AUTHOR]

Iron and steels are allotropes, meaning they exhibit different crystal configurations. The martensitic transformation is crucial for a variety of processes, such as hardening. It is induced by a combination of undercooling and mechanical deformation. Due to the changing material properties within the phases, and due to topological changes that might occur during the transformation, a phase field approach was chosen that incorporates both the mechanical and the chemical aspect of this problem. A comparison of the Voigt/Taylor approach to the Khachaturyan approach within a multi-variant phase field modeling of the martensitic transformation including a chemical and a mechanical energy contribution is presented in this paper. The model was implemented in the finite element codes FEAP and Z-set independently. Numerical examples are given in order to highlight the features of this model. [ABSTRACT FROM AUTHOR]

Research was and still is involved in the controversial issue about innate talent or extensive practice as the determinants of excellent performance in a range of domains. This study aims to contribute by presenting an analysis of practice activities in a domain that appears to be particularly suitable—orchestral conducting. Most conductors usually attain expertise in instrument playing prior to commencing conducting studies. Twenty-seven students of German study programs of orchestral conducting (approximately 18.7% of the population) responded to a questionnaire about their practice activities in conducting programs and their instrumental experiences. Descriptive results show the wealth of prestudy experiences conducting students have. A clear influence on practice activities cannot be stated. During study, students rated conducting-specific practice activities as more demanding and devoted more time to them than to general music practice activities. Therefore, conducting-specific practice activities might have been practiced more deliberately than general music practice activities. [ABSTRACT FROM AUTHOR]

Open Hardware-based microcontrollers, especially the Arduino platform, have become a comparably easy-to-use tool for rapid prototyping and implementing creative solutions. Such devices in combination with dedicated front-end electronics can offer low-cost alternatives for student projects, slow control and independently operating small-scale instrumentation. The capabilities can be extended to data taking and signal analysis at mid-level rates. Two detector realizations are presented, which cover the readouts of proportional counter tubes and of scintillators or wavelength-shifting fibers with silicon photomultipliers (SiPMs). The SiPMTrigger realizes a small-scale design for coincidence readout of SiPMs as a trigger or veto detector. It consists of a custom mixed signal front-end board featuring signal amplification, discrimination and a coincidence unit for rates of up to 200 kHz. The nCatcher transforms an Arduino Nano to a proportional counter readout with pulse shape analysis: time over threshold measurement and a 10-bit analog-to-digital converter for pulse heights. The device is suitable for low-to-medium-rate environments up to 5 kHz, where a good signal-to-noise ratio is crucial. We showcase the monitoring of thermal neutrons. For data taking and slow control, a logger board is presented that features an SD card and GSM/LoRa interface. [ABSTRACT FROM AUTHOR]

This study presents magnetic resonance velocimetry (MRV) Reynolds Stress measurements in a periodic hill channel with a hill Reynolds number of Re = 29,500. The velocity encoding scheme is based on the ICOSA6 method with six icosahedral encoding directions and multiple encoding values are measured to increase the dynamic range. The full Reynolds stress tensor is obtained from a voxel-wise three-dimensional Gaussian fit using the magnitude data of all acquisitions. The MRV results are compared to a wall-resolved large eddy simulation and laser Doppler velocimetry measurements conducted in the same channel. It is shown that the MRV Reynolds stress data have excellent precision and agree qualitatively with the reference data. However, there are apparent systematic deviations. One of the most prominent error contributions is the signal attenuation caused by higher orders of motion, which leads to an overestimation of the turbulence level. Another fundamental error is identified in the assumption that the turbulence is Gaussian distributed. With the presented reconstruction technique, the MRV data are fitted to a statistical model, and depending on the examined flow setup, the Gaussian model can lead to considerable errors. Possible ways of how to reduce all identified errors are presented. In summary, this technique enables Reynolds stress tensor measurements in complex internal flows with high dynamic range and excellent precision. However, several issues need to be resolved to make the turbulence quantification more accurate. [ABSTRACT FROM AUTHOR]

The purpose of this study is to provide a PRF-shift method for fluid temperature measurements in convective heat transfer systems, which contain functional parts made of metal. Such measurements are extremely useful to examine and design convective cooling systems for industrial devices. Metals like copper seem inevitable for such applications because no commonly available non-metallic material reaches the same level of thermal conductivity as for example copper. In MRI, electrically conductive parts embedded in the measured sample are known to produce various kinds of errors including errors in the image phase caused by eddy currents. Two methods are compared that can be used to remove the eddy currents induced phase: via the phase difference of two readouts at different echo times and via the sum of the phase of two acquisitions with reverse gradient polarity and same echo time. The latter method, termed Rot-Echo, provides a better measurement efficiency because of higher temperature sensitivity. Also, this technique is able to directly measure the eddy currents induced phase map. After verification in a stationary water experiment, the Rot-Echo method was applied to time-averaged temperature measurements in a Pin Fin heat exchanger, comprised of water flow that is heated by an array of copper pins. The temperature fields acquired in the Pin Fin heat exchanger under stable thermal-hydraulic conditions agreed well with data from temperature sensors. No eddy currents effects were visible in any of the data sets in the vicinity of the copper rods. In conclusion, this study shows that unbiased PRF-shift temperature measurements are feasible in complex flow systems even if metallic material is used for the functional parts. Unlabelled Image • PRF-shift temperature measurement technique for convective heat transfer systems. • Simultaneous measurement of fluid temperature and fluid velocity. • MRI flow models often require functional parts made of metal to achieve sufficient heat transfer. • Method to measure and suppress the eddy currents induced phase near the metallic structures is presented. • Experimental verification in a pin fin heat exchanger comprised of an array of copper pins. [ABSTRACT FROM AUTHOR]

Aureobasidium pullulans is the most abundant and ubiquitous species within the genus and is also considered a core component of the grape juice microflora. So far, a small number of other Aureobasidium species have been reported, that in contrast to A. pullulans , appear far more constrained to specific habitats. It is unknown whether grape juice is a reservoir of novel Aureobasidium species, overlooked in the course of conventional morphological and meta-barcoding analyses. In this study, eight isolates from grape juice taxonomically classified as Aureobasidium through ITS sequencing were subjected to whole-genome phylogenetic, synteny and nucleotide identity analyses, which revealed three isolates to likely represent newly discovered Aureobasidium species. Analyses of ITS and metagenomic sequencing datasets show that these species can be present in grape juice samples from different locations and vintages. Functional annotation revealed the Aureobasidium isolates possess the genetic potential to support growth on the surface of plants and grapes. However, the loss of several genes associated with tolerance to diverse environmental stresses suggest a more constrained ecological range than A. pullulans. [ABSTRACT FROM AUTHOR]

To investigate velocity encoded and velocity compensated variants of multi-spoke RF pulses that can be used for flip-angle homogenization at ultra-high fields (UHF). Attention is paid to the velocity encoding for each individual spoke pulse and to displacement artifacts that arise in Fourier transform imaging in the presence of flow. A gradient waveform design for multi-spoke excitation providing an algorithm for minimal TE was proposed that allows two different encodings. Such schemes were compared to an encoding approach that applies an established scheme to multi-spoke excitations. The impact on image quality and quantitative velocity maps was evaluated in phantoms using single- and two-spoke excitations. Additional validation measurements were obtained in-vivo at 7 T. Phantom experiments showed that keeping the first gradient moment constant for all k-space lines eliminates any displacements in phase-encoding and slice-selection direction for all spoke pulses but leads to artifacts for non-zero velocity components along readout direction. Introducing variable but well-defined first gradient moments in the phase-encoding direction creates displacements along the velocity vector and thus minimizes velocity-induced geometrical distortions. Phase-resolved mean volume flow in the ascending and descending aorta obtained from two-spoke excitation showed excellent agreement with single-spoke excitation over the cardiac cycle (mean difference 0.8 ± 16.2 ml/s). The use of single- and multi-spoke RF pulses for flow quantification at 7 T with controlled displacement artifacts has been successfully demonstrated. The presented techniques form the basis for correct velocity quantification and compensation not only for conventional but also for multi-spoke RF pulses allowing in-plane B 1 + homogenization using parallel transmission at UHF. [ABSTRACT FROM AUTHOR]

When a wine yeast is inoculated into grape juice the potential variation in juice composition that confronts it is huge. Assessing the performance characteristics of the many commercially available wine yeasts in the many possible grape juice compositions is a daunting task. To this end we have developed a barcoded Saccharomyces cerevisiae wine yeast collection to facilitate the task of performance assessment that will contribute to a broader understanding of genotype-phenotype relations. Barcode sequencing of mixed populations is used to monitor strain abundance in different grape juices and grape juice-like environments. Choice of DNA extraction method is shown to affect strain-specific barcode count in this highly related set of S. cerevisiae strains; however, the analytical approach is shown to be robust toward strain dependent variation in DNA extraction efficiency. Of the 38 unique compositional variables assessed, resistance to copper and SO2 are found to be dominant discriminatory factors in wine yeast performance. Finally, a comparison of competitive fitness profile with performance in single inoculum fermentations reveal strain dependent correspondence of yeast performance using these two different approaches. [ABSTRACT FROM AUTHOR]

This study presents the first mapping of soil erosion risk modelling based on the Revised Universal Soil Loss Equation (RUSLE) at a sub-annual (monthly) temporal resolution and national scale (100 m spatial resolution). The monthly maps show highest water erosion rates on Swiss grasslands in August (1.25 t ha–1 month–1). In summer, the mean monthly soil loss by water erosion is 48 times higher than the mean soil loss in winter. Considering the annual average fraction of green vegetation cover of 54%, the predicted soil erosion rate for the Swiss national grassland area would add up to a total eroded soil mass of 5.26 Mt yr–1. The RUSLE application with an intact 100% vegetation cover would largely reduce the soil loss to an average annual rate of 0.14 t ha–1 year–1. These findings clearly highlight the importance to consider and maintain the current status of the vegetation cover for soil erosion prediction and soil conservation, respectively. [ABSTRACT FROM AUTHOR]

Aromatic amino acid metabolism in yeast is an important source of secondary compounds that influence the aroma and flavour of alcoholic beverages and foods. Examples are the higher alcohol 2-phenylethanol, and its acetate ester, 2-phenylethyl acetate, which impart desirable floral aromas in wine, beer and baker's products. Beyond this well-known influence on the organoleptic properties of alcoholic beverages and foods, there is a growing interest in understanding and modulating yeast aromatic amino acid metabolism. The tryptophan derivatives melatonin and serotonin have bioactive properties and exert positive effects on human health, and aromatic amino acids are also the precursors of products of industrial interest, such as nutraceuticals, fragrances, and opium-derived drugs. This mini-review presents current knowledge on the formation of compounds from aromatic amino acids by Saccharomyces cerevisiae, from genetic and environmental influences on their flavour impacts in alcoholic beverages to their potential as bioactive compounds, and the use of yeast as microbial factories for the production of commercially relevant aromatic compounds. [ABSTRACT FROM AUTHOR]

Background: Recent developments in third-gen long read sequencing and diploid-aware assemblers have resulted in the rapid release of numerous reference-quality assemblies for diploid genomes. However, assembly of highly heterozygous genomes is still problematic when regional heterogeneity is so high that haplotype homology is not recognised during assembly. This results in regional duplication rather than consolidation into allelic variants and can cause issues with downstream analysis, for example variant discovery, or haplotype reconstruction using the diploid assembly with unpaired allelic contigs. Results: A new pipeline—Purge Haplotigs—was developed specifically for third-gen sequencing-based assemblies to automate the reassignment of allelic contigs, and to assist in the manual curation of genome assemblies. The pipeline uses a draft haplotype-fused assembly or a diploid assembly, read alignments, and repeat annotations to identify allelic variants in the primary assembly. The pipeline was tested on a simulated dataset and on four recent diploid (phased) de novo assemblies from third-generation long-read sequencing, and compared with a similar tool. After processing with Purge Haplotigs, haploid assemblies were less duplicated with minimal impact on genome completeness, and diploid assemblies had more pairings of allelic contigs. Conclusions: Purge Haplotigs improves the haploid and diploid representations of third-gen sequencing based genome assemblies by identifying and reassigning allelic contigs. The implementation is fast and scales well with large genomes, and it is less likely to over-purge repetitive or paralogous elements compared to alignment-only based methods. [ABSTRACT FROM AUTHOR]

Abstract: Soil erodibility, commonly expressed as the K‐factor in USLE‐type erosion models, is a crucial parameter for determining soil loss rates. However, a national soil erodibility map based on measured soil properties did so far not exist for Switzerland. As an EU non‐member state, Switzerland was not included in previous soil mapping programs such as the Land Use/Cover Area frame Survey (LUCAS). However, in 2015 Switzerland joined the LUCAS soil sampling program and extended the topsoil sampling to mountainous regions higher 1500 m asl for the first time in Europe. Based on this soil property dataset we developed a K‐factor map for Switzerland to close the gap in soil erodibility mapping in Central Europe. The K‐factor calculation is based on a nomograph that relates soil erodibility to data of soil texture, organic matter content, soil structure, and permeability. We used 160 Swiss LUCAS topsoil samples below 1500 m asl and added in an additional campaign 39 samples above 1500 m asl. In order to allow for a smooth interpolation in context of the neighboring regions, additional 1638 LUCAS samples of adjacent countries were considered. Point calculations of K‐factors were spatially interpolated by Cubist Regression and Multilevel B‐Splines. Environmental features (vegetation index, reflectance data, terrain, and location features) that explain the spatial distribution of soil erodibility were included as covariates. The Cubist Regression approach performed well with an RMSE of 0.0048 t ha h ha−1 MJ−1 mm−1. Mean soil erodibility for Switzerland was calculated as 0.0327 t ha h ha−1 MJ−1 mm−1 with a standard deviation of 0.0044 t ha h ha−1 MJ−1 mm−1. The incorporation of stone cover reduces soil erodibility by 8.2%. The proposed Swiss erodibility map based on measured soil data including mountain soils was compared to an extrapolated map without measured soil data, the latter overestimating erodibility in mountain regions (by 6.3%) and underestimating in valleys (by 2.5%). The K‐factor map is of high relevance not only for the soil erosion risk of Switzerland with a particular emphasis on the mountainous regions but also has an intrinsic value of its own for specific land use decisions, soil and land suitability and soil protection. [ABSTRACT FROM AUTHOR]

Abstract Metabolic engineering has been vital to the development of industrial microbes such as the yeast Saccharomyces cerevisiae. However, sequential rounds of modification are often needed to achieve particular industrial design targets. Systems biology approaches can aid in identifying genetic targets for modification through providing an integrated view of cellular physiology. Recently, research into the generation of commercial yeasts that can produce reduced-ethanol wines has resulted in metabolically-engineered strains of S. cerevisiae that are less efficient at producing ethanol from sugar. However, these modifications led to the concomitant production of off-flavour by-products. A combination of transcriptomics, proteomics and metabolomics was therefore used to investigate the physiological changes occurring in an engineered low-ethanol yeast strain during alcoholic fermentation. Integration of 'omics data identified several metabolic reactions, including those related to the pyruvate node and redox homeostasis, as being significantly affected by the low-ethanol engineering methodology, and highlighted acetaldehyde and 2,4,5-trimethyl-1,3-dioxolane as the main off-flavour compounds. Gene remediation strategies were then successfully applied to decrease the formation of these by-products, while maintaining the 'low-alcohol' phenotype. The data generated from this comprehensive systems-based study will inform wine yeast strain development programmes, which, in turn, could potentially play an important role in assisting winemakers in their endeavour to produce low-alcohol wines with desirable flavour profiles. Highlights • A systems-level wine fermentation data set was established for wine strain AWRI1631. • A systems-based comparison between wild-type and low-alcohol strains was performed. • Off-flavour metabolites produced by the low-ethanol strain AWRI2531 were determined. • Gene remediation strategies decreased the formation of off-flavour metabolites. [ABSTRACT FROM AUTHOR]

Several central problems in quantum information theory (such as measurement compatibility and quantum steering) can be rephrased as membership in the minimal matrix convex set corresponding to special polytopes (such as the hypercube or its dual). In this article, we generalize this idea and introduce the notion of polytope compatibility, by considering arbitrary polytopes. We find that semiclassical magic squares correspond to Birkhoff polytope compatibility. In general, we prove that polytope compatibility is in one-to-one correspondence with measurement compatibility, when the measurements have some elements in common and the post-processing of the joint measurement is restricted. Finally, we consider how much tuples of operators with appropriate joint numerical range have to be scaled in the worst case in order to become polytope compatible and give both analytical sufficient conditions and numerical ones based on linear programming. [ABSTRACT FROM AUTHOR]

The decrease in vegetation cover is one of the main triggering factors for soil erosion of grasslands. Within the Revised Universal Soil Loss Equation (RUSLE), a model commonly used to describe soil erosion, the vegetation cover for grassland is expressed in the cover and management factor (C-factor). The site-specific C-factor is a combination of the relative erosion susceptibility of a particular plant development stage (here expressed as soil loss ratio SLR) and the corresponding rainfall pattern (here expressed as R-factor ratio). Thus, for grasslands the fraction of green vegetation cover (FGVC) determines the SLRs. Although Switzerland is a country dominated by grassland with high percentages of mountainous regions and evidence for high erosion rates of grassland exists, soil erosion risk modeling of grasslands and especially of mountainous grasslands in Switzerland is restricted to a few studies. Here, we present a spatio-temporal approach to assess the dynamics of the C-factor for Swiss grasslands and to identify erosion prone regions and seasons simultaneously. We combine different satellite data, aerial data, and derivative products like Climate Change Initiative (CCI) Land Cover, Swissimage false-color infrared (Swissimage FCIR), PROBA-V Fraction of green Vegetation Cover (FCover300m), and MODIS Vegetation Indices 16-Day L3 Global (MOD13Q1) for the FGVC mapping of grasslands. In the spatial mapping, the FGVC is extracted from Swissimage FCIR (spat. res. 2 m) by linear spectral unmixing (LSU). The spatially derived results are then fused with the 10-day deviations of temporal FGVC derived by FCover300m. Following the original RUSLE approach, the combined FGVC are transformed to SLRs and weighted with high spatio-temporal resolved ratios of R-factors to result in spatio-temporal C-factors for Swiss grasslands. The annual average C-factor of all Swiss grasslands is 0.012. Seasonal and regional patterns (low C in winter, high C in summer, dependency on elevation) are recognizable in the spatio-temporal mapping approach. They are mainly explicable by the R-factor distribution within a year. Knowledge about the spatio-temporal dynamic of erosion triggering factors is of high interest for agronomists who can introduce areal and time specific selective erosion control measures and thereby reduce the direct costs of mitigation as well as erosion measures. [ABSTRACT FROM AUTHOR]

Abstract: In 2007, Banica and Bichon asked whether the well‐known Petersen graph has quantum symmetry. In this article, we show that the Petersen graph has no quantum symmetry, that is, the quantum automorphism group of the Petersen graph is its usual automorphism group, the symmetric group S 5. [ABSTRACT FROM AUTHOR]

In order to consider temperature dependency in a phase field model for martensitic transformations a temperature dependent phase separation potential is introduced. The kinematics and the energetic setup underlying the phase transformation are briefly explained. Parameters are identified using molecular dynamics (MD) simulations. The kinetics of the phase field model are in good agreement with those of the MD simulations. Further, the effect of temperature on the microstructure evolution is studied for varying initial austenite contents. [ABSTRACT FROM AUTHOR]

The 3 / 5 -conjecture for the domination game states that the game domination numbers of an isolate-free graph G on n vertices are bounded as follows: γ g ( G ) ≤ 3 n 5 and γ g ′ ( G ) ≤ 3 n + 2 5 . Recent progresses have been made on the subject and the conjecture is now proved for graphs with minimum degree at least 2 . One powerful tool, introduced by Bujtás, is the so-called greedy-like strategy for Dominator. In particular, using this strategy, she has proved the conjecture for isolate-free forests without leaves at distance exactly 4 . In this paper, we improve this strategy to extend the result to the larger class of weakly S ( K 1 , 3 ) -free forests, where a weakly S ( K 1 , 3 ) -free forest F is an isolate-free forest without induced S ( K 1 , 3 ) , whose leaves are leaves of F as well. [ABSTRACT FROM AUTHOR]

Evaluate the long-term safety and efficacy of vortioxetine in the management of major depressive disorder (MDD) in two open-label one-year studies, including a post-hoc analysis of its effects on symptoms related to anhedonia. Both studies were 52-week, open-label, flexible-dose extension studies to evaluate the safety and efficacy of vortioxetine in adult patients with MDD following prior double-blind studies. Patients in the first study (NCT00761306) were flexibly treated with vortioxetine 5 or 10 mg/day (N = 74), and patients in the second study (NCT01323478) received vortioxetine 15 or 20 mg/day (N = 71). The safety and tolerability profile of vortioxetine was similar between the two studies; treatment-emergent adverse events with the highest incidence were nausea, dizziness, headache, and nasopharyngitis. Across both studies, improvements achieved during the preceding double-blind studies period were maintained, and additional improvements were observed with open-label treatment. Patients showed a mean ± SD reduction (improvement) in Montgomery and Åsberg Depression Rating Scale (MADRS) total score from open-label baseline to Week 52 of 4.3 ± 9.2 points in the 5–10 mg study, and 10.9 ± 10.0 in the 15–20 mg study. Post-hoc MMRM analyses of MADRS anhedonia factor scores also showed continued improvements over long-term treatment; patients showed a mean ± SE reduction from an open-label baseline to Week 52 of 3.10 ± 0.57 points in the 5–10 mg study, and 5.62 ± 0.60 in the 15–20 mg study. Data from both studies confirm the safety and efficacy of flexibly dosed vortioxetine over 52 weeks of treatment and demonstrate that MADRS anhedonia factor scores continue to improve with long-term maintenance treatment. [ABSTRACT FROM AUTHOR]

We investigate the complexity of finding a winning strategy for the misère version of three games played on graphs: two variants of the game NimG , introduced by Stockmann in 2004 and the game Vertex Geography on both directed and undirected graphs. We show that on general graphs those three games are pspace -Hard or Complete. For one pspace -Hard variant of NimG , we find an algorithm to compute an effective winning strategy in time O ( | V ( G ) | . | E ( G ) | ) when G is a bipartite graph. [ABSTRACT FROM AUTHOR]

DC-DC converters are widely used in a large number of power conversion applications. As in many other systems, they are designed to automatically prevent dangerous failures or control them when they arise; this is called functional safety. Therefore, random hardware failures such as sensor faults have to be detected and handled properly. This proper handling means achieving or maintaining a safe state according to ISO 26262. However, to achieve or maintain a safe state, a fault has to be detected first. Sensor faults within DC-DC converters are generally detected with hardware-redundant sensors, despite all their drawbacks. Within this article, this redundancy is addressed using observer-based techniques utilizing Extended Kalman Filters (EKFs). Moreover, the paper proposes a fault detection and isolation scheme to guarantee functional safety. For this, a cross-EKF structure is implemented to work in cross-parallel to the real sensors and to replace the sensors in case of a fault. This ensures the continuity of the service in case of sensor faults. This idea is based on the concept of the virtual sensor which replaces the sensor in case of fault. Moreover, the concept of the virtual sensor is broader. In fact, if a system is observable, the observer offers a better performance than the sensor. In this context, this paper gives a contribution in this area. The effectiveness of this approach is tested with measurements on a buck converter prototype. [ABSTRACT FROM AUTHOR]

Wine is arguably the oldest biotechnological endeavor, with humans having been involved in wine production for at least 7000 years. Despite the artisan nature of its production, work by pioneering scientists such as Antoine-Laurent de Lavoisier and Louis Pasteur placed wine research in a prominent position for the application of cutting-edge biological and chemical sciences, a position it still holds to this day. Technologies such as whole-genome sequencing and systems biology are now revolutionizing winemaking by combining the ability to engineer phenotypes rationally, with a precise understanding of the genetic makeup and key phenotypic drivers of the key organisms that contribute to this age-old industry. [Copyright &y& Elsevier]

Experimental samples are valuable and can represent a significant investment in time and resources. It is highly desirable at times to obtain as much information as possible from a single sample. This is especially relevant for systems biology approaches in which several 'omics platforms are studied simultaneously. Unfortunately, each platform has a particular extraction methodology which increases sample number and sample volume requirements when multiple 'omics are analyzed. We evaluated the integration of a yeast extraction method; specifically we explored whether fractions from a single metabolite extraction could be apportioned to multiple downstream 'omics analytical platforms. In addition, we examined how variations to a chloroform/methanol yeast metabolite extraction regime influence metabolite recoveries. We show that protein suitable for proteomic analysis can be recovered from a metabolite extraction and that recovery of lipids, while reproducible, are not wholly quantitative. Higher quenching solution temperatures (−30 °C) can be used without significant leakage of intracellular metabolites when lower fermentation temperatures (20 °C) are employed. However, extended residence time in quenching solution, in combination with vigorous washing of quenched cell pellets, leads to extensive leakage of intracellular metabolites. Finally, there is minimal difference in metabolite amounts obtained when metabolite extractions are performed at 4 °C compared to extractions at −20 °C. The evaluated extraction method delivers material suitable for metabolomic and proteomic analyses from the same sample preparation. [ABSTRACT FROM AUTHOR]

Chardonnay, being the predominant white wine-grape cultivar in the Australian wine sector, is subject to widely varying winemaking processes with the aim of producing a variety of wine styles. Therefore, juice composition might not always be ideal for optimal fermentation outcomes. Our aim was to better understand the composition of Chardonnay juice and how compositional parameters impact on fermentation outcomes. This was achieved through a survey of 96 commercially prepared Chardonnay juices during the 2009 vintage. Common juice variables were estimated using near infrared spectroscopy, and elemental composition was determined using radial view inductively coupled plasma optical emission spectrometry. The influence of elemental composition on fermentation outcomes was assessed by fermentation of a defined medium formulated to reflect the composition and range of concentrations as determined by the juice survey. Yeast ( Saccharomyces cerevisiae) strain effects were also assessed. Key parameters influencing fermentation outcomes were verified by laboratory scale fermentation of Chardonnay juice. This exploration of Chardonnay juice identified interactions between juice pH and potassium concentration as key factors impacting on fermentation performance and wine quality. Outcomes differed depending on yeast strain. [ABSTRACT FROM AUTHOR]

Sensor models provide the required environmental perception information for the development and testing of automated driving systems in virtual vehicle environments. In this article, a configurable sensor model architecture is introduced. Based on methods of model-based systems engineering (MBSE) and functional decomposition, this approach supports a flexible and continuous way to use sensor models in automotive development. Modeled sensor effects, representing single-sensor properties, are combined to an overall sensor behavior. This improves reusability and enables adaptation to specific requirements of the development. Finally, a first practical application of the configurable sensor model architecture is demonstrated, using two exemplary sensor effects: the geometric field of view (FoV) and the object-dependent FoV. [ABSTRACT FROM AUTHOR]

Alternative splicing is an important step in controlling gene expression and has been shown to occur for a number of plant disease resistance (R) genes. The specific biological role of alternatively spliced transcripts from most R genes is unknown, yet in two cases it is clear that functional disease resistance cannot be activated without them. We report 12 splice isoforms of the M flax rust resistance gene, a TIR–NBS–LRR class of R gene. Collectively, these isoforms are predicted to encode at least nine different polypeptide products, only one of which is a full length peptide believed to confer functional M gene-specific disease resistance. An additional intron to that previously described was found in the 5′ untranslated region. Splicing of this leader intron removes an upstream ORF (μORF) sequence. In some transcripts the leader intron is retained and in this case we predict negligible translation initiation of the full length M gene-encoding ORF. The majority of the alternatively spliced isoforms of M would encode truncated TIR and TIR–NBS containing proteins. Although the role of alternative splicing and the existence and function of the products they encode is still unclear, the complexities of the splicing profile, and the 5′ UTR of the M gene, are likely to serve in mechanisms to regulate R protein levels. [ABSTRACT FROM AUTHOR]

Background: The multimodal antidepressant vortioxetine is effective in reducing somatic symptoms in patients with major depressive disorder (MDD), but little is known about its effects in reducing depressive symptoms in patients with common comorbid physical illnesses.Methods: This was a pooled analysis of 13 randomized, placebo-controlled trials which evaluated the efficacy (using the Montgomery-Åsberg Depression Rating Scale [MADRS]) and safety of vortioxetine (5-20 mg/day) in adult patients with MDD. We evaluated stable somatic comorbid conditions that were verified by a diagnosis and had sufficient database representation.Results: Of the 5982 patients included in the database, 963 (16.1%) patients had a diagnosis of cardiovascular disease, 152 (2.5%) had diabetes mellitus and 26 (0.4%) had chronic obstructive pulmonary disorder (COPD). At Week 8, adjusted mean[95%CI] treatment differences (vortioxetine vs. placebo) on MADRS total scores were -2.7[-4.2, -1.3] (p = 0.0002) points for the cardiovascular disease, -4.0[-7.7, -0.4] (p = 0.03) for the diabetes, and -6.2[-21.3, 8.9] (p = 0.36) for the COPD groups. The rate and pattern of adverse events were similar across the sub-groups with comorbidities and was consistent with that expected for vortioxetine treatment.Limitations: The primary studies were not designed to investigate the relationship between vortioxetine and comorbidities, nor were the post hoc analyses powered to detect group differences.Conclusions: Patients with MDD and comorbid cardiovascular disease or diabetes respond to vortioxetine in a similar way to the broader MDD population. Vortioxetine was generally safe and well tolerated and without unexpected adverse events in these subpopulations, most of whom are taking multiple concomitant medications. [ABSTRACT FROM AUTHOR]

Sparkling wine made by the traditional method (Méthode Traditionelle) develops a distinct and desirable flavour and aroma profile attributed to proteolytic processes during prolonged ageing on lees. Microwave, ultrasound and addition of β-glucanase enzymes were applied to accelerate the disruption of Saccharomyces cerevisiae, and added to the tirage solution for secondary fermentation in traditional sparkling winemaking. Scanning electron microscopy and flow cytometry analyses were used to observe and describe yeast whole-cell anatomy, and cell integrity and structure via propidium iodide (PI) permeability after 6-, 12- and 18-months post-tirage. Treatments applied produced features on lees that were distinct from that of the untreated control yeast. Whilst control yeast displayed budding cells (growth features) with smooth, cavitated and flat external cell appearances; microwave treated yeast cells exhibited modifications like 'doughnut' shapes immediately after treatment (time 0). Similar 'doughnut'-shaped and 'pitted/porous' cell features were observed on progressively older lees from the control. Flow cytometry was used to discriminate yeast populations; features consistent with cell disruption were observed in the microwave, ultrasound and enzyme treatments, as evidenced by up to 4-fold increase in PI signal in the microwave treatment. Forward and side scatter signals reflected changes in size and structure of yeast cells, in all treatments applied. When flow cytometry was interpreted alongside the scanning electron microscopy images, bimodal populations of yeast cells with low and high PI intensities were revealed and distinctive 'doughnut'-shaped cell features observed in association with the microwave treatment only at tirage, that were not observed until 12 months wine ageing in older lees from the control. This work offers both a rapid approach to visualise alterations to yeast cell surfaces and a better understanding of the mechanisms of yeast lysis. Microwave, ultrasound or β-glucanase enzymes are tools that could potentially initiate the release of yeast cell compounds into wine. Further investigation into the impact of such treatments on the flavour and aroma profiles of the wines through sensory evaluation is warranted. [ABSTRACT FROM AUTHOR]

Austenitic TRansformation Induced Plasticity (TRIP) steels offer an outstanding combination of formability and strength. Using Electron Backscatter Diffraction (EBSD) technique, the grain orientation and morphology of f.c.c. and b.c.c. phases can be clearly detected in initial state and at definite strains [2]. In order to qualify the driving mechanisms of phase transformations occuring during deformation of metastable austenites, e.g. TRIP steels, a phase field model is used. For the modelling, we follow [6]. The field equations are solved using the finite element method with bi‐linear shape functions and 4‐node elements. Features of this model are demonstrated by illustrative numerical examples. [ABSTRACT FROM AUTHOR]

In this article, we study quantum automorphism groups of distance-transitive graphs. We show that the odd graphs, the Hamming graphs H (n , 3) , the Johnson graphs J (n , 2) and the Kneser graphs K (n , 2) do not have quantum symmetry. We also give a table with the quantum automorphism groups of all cubic distance-transitive graphs. Furthermore, with one graph missing, we can now decide whether or not a distance-regular graph of order ≤20 has quantum symmetry. Moreover, we prove that the Hoffman-Singleton graph has no quantum symmetry. On a final note, we present an example of a pair of graphs with the same intersection array (the Shrikhande graph and the 4 × 4 rook's graph), where one of them has quantum symmetry and the other one does not. [ABSTRACT FROM AUTHOR]

Swirled flows often feature global modes that become manifest as skew-symmetric helical vortices, also known as precessing vortex cores, which dominate the flow dynamics. This study uses linear stability analysis (LSA) and bispectral mode decomposition (BMD) to elucidate the interactions of such modes in the turbulent, nonreacting, swirled flow of an industrial, three-passage, aeroengine fuel injector obtained via large-eddy simulation. A discrete Fourier transform in time retrieves the modes as narrow-banded, evenly spaced peaks in the spectral amplitude of the turbulent signal, where the second mode is dominant. Similar arrangements are known to appear as a consequence of a saturated global mode, which amplifies its higher harmonic frequencies due to nonlinear effects. We show that each mode appears in the spectrum of LSA eigenvalues, indicating that the subdominant peaks are caused not only due to nonlinear interactions but that they have an underlying linear mechanism. A structural sensitivity analysis based on the adjoint LSA shows that the observed helical modes originate close to the exit plane of the fuel injector. Finally, the BMD reveals significant nonlinear interaction between the individual modes. It is hypothesized that this interaction amplifies the modes, which are linearly stable, leading to the strong dynamics in the flow. [ABSTRACT FROM AUTHOR]

Metastable austenitic steels can undergo phase transformation. As an allotrope two crystal configurations are of interest: the softer austenitic parent phase and the martensitic phases. Here, the bain orientation relationship leads to distinct orientations for the martensitic variants with a different transformation strain [7]. A phase field approach is used to model the transformation, where a multi‐valued order parameter ϕ̲ identifies the austenitic parent phase and the martensitic variants. This allows to define bulk and surface energies as regularized functions in terms of the order parameter and its gradient. The kinetics of the martensitic transformation are temperature dependent. Temperatures below an equilibrium temperature favour the growth of the martensitic phase, whereas temperatures above the equilibrium favour the austenitic phase. Approaching the equilibrium temperature slows down the transformation [5]. In this work we consider a static crack under mode I and mode II loading. [ABSTRACT FROM AUTHOR]

Abstract: We study the martensitic transformation with a phase field model, where we consider the Bain transformation path in a small strain setting. For the order parameter, interpolating between an austenitic parent phase and martensitic phases, we use a Ginzburg‐Landau evolution equation, assuming a constant mobility. In [1], a temperature dependent separation potential is introduced. We use this potential to extend the model in [2], by considering a transient temperature field, where the temperature is introduced as an additional degree of freedom. This leads to a coupling of both the evolution equation of the order parameter and the mechanical field equations (in terms of thermal expansion) with the heat equation. The model is implemented in FEAP as a 4‐node element with bi‐linear shape functions. Numerical examples are given to illustrate the influence of the temperature on the evolution of the martensitic phase. (© 2017 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Metallic materials often exhibit a complex microstructure with varying material properties in the different phases. Of major importance in mechanical engineering is the evolution of the austenitic and martensitic phases in steel. The martensitic transformation can be induced by heat treatment or by plastic surface deformation at low temperatures. A two dimensional elastic phase field model for martensitic transformations considering several martensitic orientation variants to simulate the phase change at the surface is introduced in [1]. However here, only one martensitic orientation variant is considered for the sake of simplicity. The separation potential is temperature dependent. Therefore, the coefficients of the Landau polynomial are identified by results of molecular dynamics (MD) simulations for pure iron [1]. The resulting separation potential is applied to analyse the mean interface velocity with respect to temperature and load. The interface velocity is computed by use of the dissipative part to the configurational forces balance as suggested in [3]. The model is implemented in the finite element code FEAP using standard 4-node elements with bi-linear shape functions. (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Temperate bacteriophages are known for their bistability, which in TP901‐1 is controlled by two proteins, CI and MOR. Clear 1 repressor (CI) is hexameric and binds three palindromic operator sites via an N‐terminal helix‐turn‐helix domain (NTD). A dimeric form, such as the truncated CI∆58 investigated here, is necessary for high‐affinity binding to DNA. The crystal structure of the dimerization region (CTD1) is determined here, showing that it forms a pair of helical hooks. This newly determined structure is used together with the known crystal structure of the CI‐NTD and small angle X‐ray scattering data, to determine the solution structure of CI∆58 in complex with a palindromic operator site, showing that the two NTDs bind on opposing sides of the DNA helix. [ABSTRACT FROM AUTHOR]

Copper tolerance and SO2 tolerance are two well-studied phenotypic traits of Saccharomyces cerevisiae. The genetic bases of these traits are the allelic expansion at the CUP1 locus and reciprocal translocation at the SSU1 locus, respectively. Previous work identified a negative association between SO2 and copper tolerance in S. cerevisiae wine yeasts. Here we probe the relationship between SO2 and copper tolerance and show that an increase in CUP1 copy number does not always impart copper tolerance in S. cerevisiae wine yeast. Bulk-segregant QTL analysis was used to identify variance at SSU1 as a causative factor in copper sensitivity, which was verified by reciprocal hemizygosity analysis in a strain carrying 20 copies of CUP1. Transcriptional and proteomic analysis demonstrated that SSU1 over-expression did not suppress CUP1 transcription or constrain protein production and provided evidence that SSU1 over-expression induced sulfur limitation during exposure to copper. Finally, an SSU1 over-expressing strain exhibited increased sensitivity to moderately elevated copper concentrations in sulfur-limited medium, demonstrating that SSU1 over-expression burdens the sulfate assimilation pathway. Over-expression of MET 3/14/16, genes upstream of H2S production in the sulfate assimilation pathway increased the production of SO2 and H2S but did not improve copper sensitivity in an SSU1 over-expressing background. We conclude that copper and SO2 tolerance are conditional traits in S. cerevisiae and provide evidence of the metabolic basis for their mutual exclusivity. These findings suggest an evolutionary driver for the extreme amplification of CUP1 observed in some yeasts. Author summary: Completing a commercial wine fermentation is a tough job for a yeast. Grape juice is a highly variable environment and to cope with that variability, a large number of different yeast strains have been generated exhibiting different features. Two of the most distinguishing physical characteristics of wine yeast are copper and SO2 tolerance, which appear to be mutually exclusive. The genetic underpinnings of these two traits are individually well-characterised, but there doesn't appear to be an obvious reason why copper tolerance and SO2 tolerance could not co-exist. We performed a genetic analysis that showed how over-expression of the SO2 transporters responsible for SO2 tolerance induced copper sensitivity. Our analysis of RNA and protein levels in SO2-tolerant yeast showed that they could still produce the molecules that would usually protect them when exposed to copper stress. However, the constant activation of the transporter that provides SO2 tolerance also induced a sulfur limitation that could not be overcome when combined with copper stress. [ABSTRACT FROM AUTHOR]

Background and Aims. An OIV resolution provides guidelines on using glutathione as a prefermentation additive when the amount of yeast assimilable nitrogen (YAN) of a juice or must is adequate, to avoid the metabolism of glutathione by the yeast. The effect of YAN concentration on glutathione metabolism by yeast had not been determined. This study explored whether nitrogen management could be used to control glutathione consumption during fermentation. Methods and Results. An HPLC-UV method was developed to quantify reduced L-glutathione (GSH) and oxidised glutathione (GSSG) and used to monitor yeast GSH metabolism during alcoholic fermentation with two yeast strains (AWRI 1688 and AWRI 2861). The addition of GSH had no impact on the fermentation rate of the chemically defined medium, even in a limited YAN environment; however, a decrease in glutathione concentration occurred regardless of YAN concentration. The effect of GSH on volatile sulfur compound formation was yeast strain-dependent. Conclusions. Increasing the YAN status of a chemically defined medium led to a decrease in GSH consumption during fermentation, but the loss of GSH could not be prevented entirely, even with a low initial GSH concentration and high initial YAN. Significance of the Study. In the presence of higher concentrations of GSH during fermentation, there is a risk of forming undesirable fermentative sulfur compounds that are not mitigated through nitrogen supplementation. Thus, it seems unlikely that an argument could be made for the inclusion of GSH in relevant food standards codes as a wine additive especially if a lack of GSH metabolism was a criterion. [ABSTRACT FROM AUTHOR]

The domination game is played on a graph G by Dominator and Staller. The game domination number γg(G) of G is the number of moves played when Dominator starts and both players play optimally. Similarly, γ'g(G) is the number of moves played when Staller starts. Graphs G with γg(G) = 2, graphs with γ'g(G) = 2, as well as graphs extremal with respect to the diameter among these graphs are characterized. In particular, γ'g(G) = 2 and diam(G) = 3 hold for a graph G if and only if G is a so-called gamburger. Graphs G with ?(G) = 3 and diam(G) = 6, as well as graphs G with γ'g(G) = 3 and diam(G) = 5 are also characterized. [ABSTRACT FROM AUTHOR]

Pd-catalyzed direct arylation (DA) reaction conditions have been established for unsubstituted foran (Fu) and thiophene (fh) with three popular acceptor building blocks to be used in materials for organic electronics, namely 4,7-dibromo- 2,1,3-benzothiadiazole (BTBr2), N,N'-dialkylated 2,6-dibromonaphthalene-1,4,5,8-bis(dicarboximide) (NDIBr2), and 1,4- dibromotetrafluorobenzene (F4Br2). Reactions with BTBr2 F4Br2 and NDIBr2 require different solvents to obtain high yields. The use of dimethylacetamide (DMAc) is essential for the successful coupling of BTBr2 and F4 r2 but detrimental for NDIBr2 as the electron-deficient NDI core is prone to nucleophilic core substitution in DMAc as solvent but not in toluene. ND1Fu2 is much more planar compared to ND1Th2) resulting in an enhanced charge-transfer character, which makes it an interesting building block for conjugated systems designed for organic electronics. This study highlights direct arylation as a simple and inexpensive method to construct a series o f important donor-acceptor-donor building blocks to be forther used for the preparation of a variety of conjugated materials. [ABSTRACT FROM AUTHOR]

Aureobasidium pullulans has been observed as one of the most abundant species in freshly pressed grape juice. Despite this, little is known about the consequences for the wine-making process associated with the presence and proliferation of this fungus, including its interaction with other ferment-derived microorganisms and impact on the composition of the resulting wine. In this study, the physiology of abundant A. pullulans grape juice isolates was investigated through lab scale fermentation trials, demonstrating the ability of this species to survive in grape juice while producing polysaccharides, polymers of malic acid (poly β-malic acid) and enzymes with pectinase, β - glucosidase and tannase activity. A possible antagonistic effect against yeast through competition for metals including Fe and Zn was also observed. Overall, the data suggests this abundant species could have important implications for wine production and quality. • Aureobasidium pullulans has a fructophilic phenotype when growing in grape juice. • Poly-malic acid and glucose-based polysaccharides were produced by this species. • β - glucosidase, pectinase and tannase activities were observed in grape juice growing conditions. • Fermentation derived volatiles were affected by the presence of A. pullulans. • An antagonistic effect against yeast through competition for metals including Fe and Zn was observed. [ABSTRACT FROM AUTHOR]

In most yeast-driven biotechnological applications, biomass is separated from the aqueous phase after fermentation or production has finished. During winemaking, yeasts are removed after fermentation by racking, filtration, or centrifugation, which add costs to the overall process and may reduce product yield. Theoretically, clarification and filtration can be aided through use of yeast strains that form flocs due to cell-cell binding, a process known as flocculation. However, because early flocculation can cause stuck/sluggish fermentations, this phenotype is not common amongst commercially available wine yeasts. In this study we sought to identify wine strains that exhibit late-fermentation flocculant behaviour using two complementary approaches; a high-throughput sedimentation rate assay of individual strains and a competitive sedimentation assay using a barcoded yeast collection. Amongst 103 wine strains, several exhibited strong sedimentation at the end of the wine fermentation process under various environmental conditions. Two of these strains, AWRI1688 and AWRI1759, were further characterised during red winemaking trials. Shiraz wines produced with both strains displayed improved filtration-related properties. AWRI1759 produced wines with greater filterability, whereas AWRI1688 enabled the recovery of larger wine volumes after racking. Thus, this study demonstrates the effective use of sedimentation screening assays to identify wine yeasts with practical winemaking applications. [ABSTRACT FROM AUTHOR]

Chardonnay is the basis of some of the world’s most iconic wines and its success is underpinned by a historic program of clonal selection. There are numerous clones of Chardonnay available that exhibit differences in key viticultural and oenological traits that have arisen from the accumulation of somatic mutations during centuries of asexual propagation. However, the genetic variation that underlies these differences remains largely unknown. To address this knowledge gap, a high-quality, diploid-phased Chardonnay genome assembly was produced from single-molecule real time sequencing, and combined with re-sequencing data from 15 different Chardonnay clones. There were 1620 markers identified that distinguish the 15 clones. These markers were reliably used for clonal identification of independently sourced genomic material, as well as in identifying a potential genetic basis for some clonal phenotypic differences. The predicted parentage of the Chardonnay haplomes was elucidated by mapping sequence data from the predicted parents of Chardonnay (Gouais blanc and Pinot noir) against the Chardonnay reference genome. This enabled the detection of instances of heterosis, with differentially-expanded gene families being inherited from the parents of Chardonnay. Most surprisingly however, the patterns of nucleotide variation present in the Chardonnay genome indicate that Pinot noir and Gouais blanc share an extremely high degree of kinship that has resulted in the Chardonnay genome displaying characteristics that are indicative of inbreeding. [ABSTRACT FROM AUTHOR]

Objective: To evaluate long-term safety and effectiveness of continued treatment with aripiprazole once-monthly 400mg (AOM 400) in patients with schizophrenia.Methods: Patients who completed the QUALIFY study (NCT01795547) in the AOM 400 arm were eligible for 6 additional once-monthly injections of AOM 400 during an open-label, 24-week extension (NCT01959035). Safety data were collected at each visit. Effectiveness measures included change from baseline in health-related qualify of life and functioning on the Heinrichs-Carpenter Quality of Life scale (QLS) and Clinical Global Impression - Severity (CGI-S) scale.Results: Of the 88 patients enrolled, 77 (88%) completed the extension study. Most common treatment-emergent adverse events (incidence ≥2%) were weight increased (6/88, 7%), toothache (3/88, 3%) and headache (3/88, 3%). Effectiveness was maintained during the extension study, with small but continued improvements from baseline: the least squares mean (LSM) change (95% CI) from baseline to week 24 was 2.32 (-1.21 to 5.85) for the QLS total score and -0.10 (-0.26 to 0.06) for the CGI-S score. The aggregated LSM change (95% CI) from baseline of the lead-in study to week 24 of the extension study was 11.54 (7.45 to 15.64) for the QLS total score and -0.98 (-1.18 to -0.79) for the CGI-S score.Conclusions: AOM 400 was well tolerated in patients continuing AOM treatment during the extension phase of the QUALIFY study. Robust and clinically meaningful improvements in health-related quality of life and functioning were maintained, further supporting the long-term clinical benefits of AOM 400 for the treatment of patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Schizophrenia is a chronic disease with negative impact on patients’ employment status and quality of life. This post-hoc analysis uses data from the QUALIFY study to elucidate the relationship between work readiness and health-related quality of life and functioning. QUALIFY was a 28-week, randomized study (NCT01795547) comparing the treatment effectiveness of aripiprazole once-monthly 400 mg and paliperidone palmitate once-monthly using the Heinrichs-Carpenter Quality-of-Life Scale as the primary endpoint. Also, patients’ capacity to work and work readiness (Yes/No) was assessed with the Work Readiness Questionnaire. We categorized patients, irrespective of treatment, by work readiness at baseline and week 28: No to Yes (n = 41), Yes to Yes (n = 49), or No at week 28 (n = 118). Quality-of-Life Scale total, domains, and item scores were assessed with a mixed model of repeated measures. Patients who shifted from No to Yes in work readiness showed robust improvements on Quality-of-Life Scale total scores, significantly greater than patients not ready to work at week 28 (least squares mean difference: 11.6±2.6, p<0.0001). Scores on Quality-of-Life Scale instrumental role domain and items therein–occupational role, work functioning, work levels, work satisfaction–significantly improved in patients shifting from No to Yes in work readiness (vs patients No at Week 28). Quality-of-Life Scale total scores also significantly predicted work readiness at week 28. Overall, these results highlight a strong association between improvements in health-related quality of life and work readiness, and suggest that increasing patients’ capacity to work is an achievable and meaningful goal in the treatment of impaired functioning in schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of vortioxetine in adolescents with major depressive disorder (MDD).Method: After 4 weeks of single-blind lead-in treatment with a Brief Psychosocial Intervention (BPI) plus placebo, patients (aged 12-17 years) with MDD (DSM-5) who did not meet response criteria (Children's Depression Rating Scale-Revised [CDRS-R]; total score ≥40 plus <40% reduction and a Parent Global Assessment score >2) were randomized 1:1:1:1 to 8 weeks of BPI plus double-blind treatment with vortioxetine 10 mg, vortioxetine 20 mg, fluoxetine 20 mg, or placebo. The primary endpoint was change from randomization in CDRS-R total score at week 8; the primary comparison was the average effect of 2 vortioxetine doses vs placebo.Results: Of 784 patients enrolled in the lead-in, 616 were randomized. At week 8, the mean change in CDRS-R total score averaged for vortioxetine doses was -18.01 (SE = 0.98) and the mean difference vs placebo was 0.21 (P = .878; not significant). For fluoxetine, the mean change in CDRS-R total score was -21.95 and the mean difference vs placebo was -3.73 (P = .015). Treatment-emergent adverse events occurring in ≥5% of patients in either vortioxetine arm and at least twice more frequently than placebo were nausea, headache, vomiting, and dizziness.Conclusion: Patients in all groups showed reduction in CDRS-R scores by the end of the study, with no difference between combined doses of vortioxetine and placebo. The primary endpoint was not met, thereby rendering the study negative. The overall favorable safety profile of vortioxetine in an adolescent patient population was consistent with that seen in adults.Clinical Trial Registration Information: Active Reference (Fluoxetine) Fixed-Dose Study of Vortioxetine in Paediatric Patients Aged 12 to 17 Years With Major Depressive Disorder (MDD); http://clinicaltrials.gov; NCT02709746. [ABSTRACT FROM AUTHOR]

Humans have been consuming wines for more than 7000 yr. For most of this time, fermentations were presumably performed by strains of Saccharomyces cerevisiae that naturally found their way into the fermenting must. In contrast, most commercial wines are now produced by inoculation with pure yeast monocultures, ensuring consistent, reliable and reproducible fermentations, and there are now hundreds of these yeast starter cultures commercially available. In order to thoroughly investigate the genetic diversity that has been captured by over 50 yr of commercial wine yeast development and domestication, whole genome sequencing has been performed on 212 strains of S. cerevisiae, including 119 commercial wine and brewing starter strains, and wine isolates from across seven decades. Comparative genomic analysis indicates that, despite their large numbers, commercial strains, and wine strains in general, are extremely similar genetically, possessing all of the hallmarks of a population bottle-neck, and high levels of inbreeding. In addition, many commercial strains from multiple suppliers are nearly genetically identical, suggesting that the limits of effective genetic variation within this genetically narrow group may be approaching saturation. [ABSTRACT FROM AUTHOR]