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The ”2019 novel coronavirus” known as “ the 2019-nCoV” or simply “COVID-19” has been declared by the World Health organization (WHO), in first quarter of 2020, as a world pandemic and a public health emergency of international concern. Alas, many details related to the COVID-19 have remained unsolved completely. The success of government strategies in fighting the COVID-19 relays mainly on the results from epidemiological or statistical studies. Statistical models play a major role in providing reliable results based on appropriate analyses. Traditional (one-part) models, mixture models and mixed-effects models for counts are used to investigate effects of the WHO-regions and Cumulated COVID-19 cases on the outcome variable COVID-19 new deaths tolls. Overall result reveals there is a strong association between number of new deaths COVID-19 with predictors including the WHO regions and cumulated cases. Besides, models that account for the overdispersion feature have smallest AICs and have reasonable regression model fits.

Abstract Minimal residual disease (MRD) assessment is a known surrogate marker for survival in multiple myeloma (MM). Here, we present a single institution’s experience assessing MRD by NGS of Ig genes and the long-term impact of depth of response as well as clonal diversity on the clinical outcome of a large population of MM patients; 482 MM patients at the University of California, San Francisco (UCSF) diagnosed from 2008 to 2020 were analyzed retrospectively. MRD assessment was performed by NGS. PFS curves were plotted by the Kaplan–Meier method. In the newly diagnosed group, 119 of 304, achieved MRD negativity at the level of 10−6 at least once. These patients had a prolonged PFS versus patients who were persistently MRD positive at different levels (p > 0.0001). In the relapsed disease group, 64 of 178 achieved MRD negativity at 10−6, and PFS was prolonged versus patients who remained MRD positive (p = 0.03). Three categories of MRD dynamics were defined by artificial intelligence: (A) patients with ≥3 consistently MRD negative samples, (B) patients with continuously declining but detectable clones, and (C) patients with either increasing or a stable number of clones. Groups A and B had a more prolonged PFS than group C (p

As the climate warms, the grounded ice sheet and floating ice shelves surrounding Antarctica are melting and releasing additional freshwater into the Southern Ocean. Nonetheless, almost all existing coupled climate models have fixed ice sheets and lack the physics required to represent the dominant sources of Antarctic melt. These missing ice dynamics represent a key uncertainty that is typically unaccounted for in current global climate change projections. Previous modelling studies that have imposed additional Antarctic meltwater have demonstrated regional impacts on Southern Ocean stratification, circulation, and sea ice, as well as remote changes in atmospheric circulation, tropical precipitation, and global temperature. However, these previous studies have used widely varying rates of freshwater forcing, have been conducted using different climate models and configurations, and have reached differing conclusions on the magnitude of meltwater–climate feedbacks. The Southern Ocean Freshwater Input from Antarctica (SOFIA) initiative brings together a team of scientists to quantify the climate system response to Antarctic meltwater input along with key aspects of the uncertainty. In this paper, we summarize the state of knowledge on meltwater discharge from the Antarctic ice sheet and ice shelves to the Southern Ocean and explain the scientific objectives of our initiative. We propose a series of coupled and ocean–sea ice model experiments, including idealized meltwater experiments, historical experiments with observationally consistent meltwater input, and future scenarios driven by meltwater inputs derived from stand-alone ice sheet models. Through coordinating a multi-model ensemble of simulations using a common experimental design, open data archiving, and facilitating scientific collaboration, SOFIA aims to move the community toward better constraining our understanding of the climate system response to Antarctic melt.

Abstract Cyanophycin is a bacterial biopolymer used for storage of fixed nitrogen. It is composed of a backbone of L-aspartate residues with L-arginines attached to each of their side chains. Cyanophycin is produced by cyanophycin synthetase 1 (CphA1) using Arg, Asp and ATP, and is degraded in two steps. First, cyanophycinase breaks down the backbone peptide bonds, releasing β-Asp-Arg dipeptides. Then, these dipeptides are broken down into free Asp and Arg by enzymes with isoaspartyl dipeptidase activity. Two bacterial enzymes are known to possess promiscuous isoaspartyl dipeptidase activity: isoaspartyl dipeptidase (IadA) and isoaspartyl aminopeptidase (IaaA). We performed a bioinformatic analysis to investigate whether genes for cyanophycin metabolism enzymes cluster together or are spread around the microbial genomes. Many genomes showed incomplete contingents of known cyanophycin metabolizing genes, with different patterns in various bacterial clades. Cyanophycin synthetase and cyanophycinase are usually clustered together when recognizable genes for each are found within a genome. Cyanophycinase and isoaspartyl dipeptidase genes typically cluster within genomes lacking cphA1. About one-third of genomes with genes for CphA1, cyanophycinase and IaaA show these genes clustered together, while the proportion is around one-sixth for CphA1, cyanophycinase and IadA. We used X-ray crystallography and biochemical studies to characterize an IadA and an IaaA from two such clusters, in Leucothrix mucor and Roseivivax halodurans, respectively. The enzymes retained their promiscuous nature, showing that being associated with cyanophycin-related genes did not make them specific for β-Asp-Arg dipeptides derived from cyanophycin degradation.

Summary: Background: COVID-19 in paediatric ages could result in hospitalizations and death. In addition, excluding children from vaccination could turn them into reservoirs of the SARS-COV-2. Safe and effective COVID-19 vaccines are urgently needed for large-scale paediatric vaccination. ISMAELILLO study aimed to evaluate safety and immunogenicity of two strengths of a new recombinant receptor-binding domain (RBD) protein vaccine (Abdala) in paediatric population. Methods: A double-blinded, multicentre, randomised, phase 1/2 clinical trial was conducted in nine polyclinics in the province of Camagüey, Cuba. Healthy children and adolescents were stratified according to age (3–11 years old, or 12–18 years old) and they were randomly assigned (1:1; block size four) in two dosage level groups of vaccine to receive three intramuscular doses of 25 μg or 50 μg of RBD, 14 days apart. Main safety endpoint was analyzed as the percentage of serious adverse reactions during vaccination up to 28 days after the third dose (Day 56) in participants who received at least one dose vaccination. The primary immunogenicity endpoint assessed was seroconversion rate of anti-RBD IgG antibody at day 56. The immunogenicity outcomes were assessed in the per-protocol population. This trial is registered with Cuban Public Registry of Clinical Trials, RPCEC00000381. Findings: Between July 15, 2021, and August 16, 2021, 644 paediatric subjects were screened, of whom 592 were enrolled after verifying that they met the selection criteria: firstly 88 were included in Phase 1 of the study and 504 who completed Phase 2. The vaccine was well tolerated. Injection site pain was the most frequently reported local event (143 [8·4%] of 1707 total doses applied), taking place in 66/851 (7·8%) in the 25 μg group and in 77/856 (9·0%) in the 50 μg. The most common systemic adverse event (AE) was headache: 23/851 (2·7%) in the 25 μg group and 19/856 (2·2%) in the 50 μg. Reactogenicity was mild or moderate in severity, represented in 75% of cases by local symptoms, completely resolved in the first 24–48 h. Twenty-eight days after the third dose, seroconversion anti-RBD IgG were observed in 98·2% of the children and adolescents (231/234) for the 50 μg group and 98·7% (224/228) for the 25 μg group without differences between both strength. The specific IgG antibody geometric mean titres (GMT) showed higher titres between participants who received Abdala 50 μg (231·3; 95% CI 222·6–240·4) compared to those who received 25 μg (126·7; 95% CI 121·9–131·7). The mean ACE2 inhibition %, were 59·4% for 25 μg, and for 50 μg, 72·9% (p

Increasing Greenland Ice Sheet melting is anticipated to impact water mass transformation in the subpolar North Atlantic and ultimately the meridional overturning circulation. Complex ocean and climate models are widely applied to estimate magnitude and timing of related impacts under global warming. We discuss the role of the ocean mean state, subpolar water mass transformation, mesoscale eddies, and atmospheric coupling in shaping the response of the subpolar North Atlantic Ocean to enhanced Greenland runoff. In a suite of eight dedicated 60- to 100-year-long model experiments with and without atmospheric coupling, with eddy processes parameterized and explicitly simulated and with regular and significantly enlarged Greenland runoff, we find (1) a major impact by the interactive atmosphere in enabling a compensating temperature feedback, (2) a non-negligible influence by the ocean mean state biased towards greater stability in the coupled simulations, both of which make the Atlantic meridional overturning circulation less susceptible to the freshwater perturbation applied, and (3) a more even spreading and deeper mixing of the runoff tracer in the subpolar North Atlantic and enhanced inter-gyre exchange with the subtropics in the strongly eddying simulations. Overall, our experiments demonstrate the important role of mesoscale ocean dynamics and atmosphere feedback in projections of the climate system response to enhanced Greenland Ice Sheet melting and hence underline the necessity to advance scale-aware eddy parameterizations for next-generation climate models.

In appearance-based gait analysis studies, Gait Energy Images (GEI) have been shown to be an effective tool for human identification and gait pathology detection. In addition, model-based studies found kinematic and spatio-temporal features to be useful for gait recognition and Autism Spectrum Disorder (ASD) classification. Adapting the GEI to focus on the strong ASD features would improve the early screening of ASD by allowing the use of powerful appearance-based classifiers such as Convolutional Neural Networks (CNN). This paper introduces an enhanced GEI, by averaging images from a video sequence to produce a single image but by retention of a person’s joint positions only, instead of the full body silhouettes. Depth is encoded into the binary images before they are averaged using colour mapping, a technique used in the Chrono-Gait Image. The Joint Energy Image (JEI) therefore embeds both the temporal and depth information of the joints into a 2D image. The image was preprocessed using Principal Component Analysis before being applied to a Multi-Layer Perceptron, and a Random Forest classifier. The JEI was also applied to a CNN directly and accuracy was improved when using a Test Time Augmentation (TTA) measure. The CNN achieved a TTA accuracy of 95.56% when trained on a primary dataset of 100 subjects (50 with ASD and 50 that are typically developed), and 80% TTA accuracy on a secondary dataset of 20 subjects (10 ASD and 10 typically developed) across multiple tests.

Observations of the eastern subpolar North Atlantic in the 2010s show exceptional freshening and cooling of the upper ocean, peaking in 2016 with the lowest salinities recorded for 120 years. Published theories for the mechanisms driving the freshening include: reduced transport of saltier, warmer surface waters northwards from the subtropics associated with reduced meridional overturning; shifts in the pathways of fresher, cooler surface water from the Labrador Sea driven by changing patterns of wind stress; and the eastward expansion of the subpolar gyre. Using output from a high-resolution hindcast model simulation, we propose that the primary cause of the exceptional freshening and cooling is reduced surface heat loss in the Labrador Sea. Tracking virtual fluid particles in the model backwards from the eastern subpolar North Atlantic between 1990 and 2020 shows the major cause of the freshening and cooling to be an increased outflow of relatively fresh and cold surface waters from the Labrador Sea; with a minor contribution from reduced transport of warmer, saltier surface water northward from the subtropics. The cooling, but not the freshening, produced by these changing proportions of waters of subpolar and subtropical origin is mitigated by reduced along-track heat loss to the atmosphere in the North Atlantic Current. We analyse modelled boundary exchanges and water mass transformation in the Labrador Sea to show that since 2000, while inflows of lighter surface waters remain steady, the increasing output of these waters is due to reduced surface heat loss in the Labrador Sea beginning in the early 2000s. Tracking particles further upstream reveals that the primary source of the increased volume of lighter water transported out of the Labrador Sea is increased recirculation of water, and therefore longer residence times, in the upper 500–1000 m of the subpolar gyre.

Genomes from defective interfering (DI) particles following serial passaging of SARS-CoV-2 reveal a fusion protein that attenuates viral replication. Synthetic, recombinant DI genomes are designed to interfere with SARS-CoV-2 replication.

Engineered tissue currently lacks requisite capacity to sustain cell viability and functionality. Here we demonstrate that human RPE cell lines (ARPE-19) can be cultured on ultrathin suspended electrospun nanofibre scaffolds (ENS) composed of hydrophobic polymer polyacrylonitrile (PAN) and a water-soluble aliphatic diamine, without (untreated) or with (treated) fluocinolone acetonide (FA). Cells survived and retained their characteristic morphology for up to 150 days with FA-treated ENS and manifested a morphological epithelial phenotype with expression of biomarkers critical for maintaining retinal physiological characteristics. This novel technique for producing culture substrates provides suitable hydrophilicity and a protective environment for prolonged RPE culture and has immense potential for subretinal transplantation. The findings indicate that FA-treated ENS is an excellent matrix for retaining the differentiated and epithelial phenotype.

Cyanophycin synthetase CphA1 polymerizes Asp and Arg into the nitrogen reserve polymer cyanophycin using two active sites. Sharon et al. show CphA1 has a cryptic 3rd active site that cleaves cyanophycin into primers for self-sufficient biosynthesis.

Abstract Layered double hydroxides (LDHs) of magnesium (Mg) and aluminium (Al) are ion exchangers that can be used as slow release phosphorus (P) fertilisers. These LDHs can be used successfully to concentrate P from waste streams such as urine. This study was set up to test the fertiliser potential of P derived from urine and concentrated on LDHs. Ryegrass was grown in a pot trial using a P- and N-deficient soil where different urine derived fertilisers, i.e. LDH-P, stored urine and urine mixed with sludge as a source of P were compared to different mineral N and P doses in a full factorial design. Plants were grown for 75 days with four cuttings and did not exhibit salinity stress in stored urine treatments. Plant growth and P uptake responded to N, P doses in mineral fertilizer treatments with significant N-P interaction. The fertiliser use efficiency of urine fertilisers was lower than that of mineral fertilisers at equivalent total nutrient input for stored urine, due to lower N availability, and for urine mixed with sludge due to lower P availability. In contrast, the yield and P uptake of ryegrass grown on LDH loaded with P from urine (LDH-P) showed equal fertiliser P use as mineral fertiliser. Interestingly, the residual soil P after harvest, scored by the sum of isotopically exchangeable P in soil and the P uptake, was higher for LDH-P than for mineral P, confirming slow release properties of LDH that limit loss of P by fixation in soil.

Nonribosomal peptide synthetases work with additional enzymes to synthesise secondary metabolites and therapeutics. Here, the authors explore bacillamide D synthesis and show the oxidase action is done while the intermediate is attached to the synthetase and replicate this with an oxidase bound synthetase for bioengineering applications.

Mitosomes are highly reduced forms of mitochondria which have lost two of the ‘defining’ features of the canonical organelle, the mitochondrial genome, and the capacity to generate energy in the form of ATP. Mitosomes are found in anaerobic protists and obligate parasites and, in most of the studied organisms, have a conserved function in the biosynthesis of iron-sulfur clusters (ISC) that are indispensable cofactors of many essential proteins. The genomes of some mitosome-bearing human pathogenic Microsporidia encode homologues of an alternative oxidase (AOX). This mitochondrial terminal respiratory oxidase is absent from the human host, and hence is a potential target for the development of new antimicrobial agents. Here we present experimental evidence for the mitosomal localization of AOX in the microsporidian Trachipleistophora hominis and demonstrate that it has an important role during the parasite’s life cycle progression. Using a recently published methodology for synchronising T. hominis infection of mammalian cell lines, we demonstrated specific inhibition of T. hominis early meront growth and replication by an AOX inhibitor colletochlorin B. Treatment of T. hominis-infected host cells with the drug also inhibited re-infection by newly formed dispersive spores. Addition of the drug during the later stages of the parasite life cycle, when our methods suggest that AOX is not actively produced and T. hominis mitosomes are mainly active in Fe/S cluster biosynthesis, had no inhibitory effects on the parasites. Control experiments with the AOX-deficient microsporidian species Encephalitozoon cuniculi, further demonstrated the specificity of inhibition by the drug. Using the same methodology, we demonstrate effects of two clinically used anti-microsporidian drugs albendazole and fumagillin on the cell biology and life cycle progression of T. hominis infecting mammalian host cells. In summary, our results reveal that T. hominis mitosomes have an active role to play in the progression of the parasite life cycle as well as an important role in the biosynthesis of essential Fe/S clusters. Our work also demonstrates that T. hominis is a useful model for testing the efficacy of therapeutic agents and for studying the physiology and cell biology of microsporidian parasites growing inside infected mammalian cells. Author summary Microsporidia are increasingly appreciated as ubiquitous pathogens with ecological, veterinary and medical importance. Here we provide detailed protocol for establishing a synchronised infection of microsporidian parasites T. hominis and E. cuniculi inside host RK13 cell lines. We demonstrate how this protocol in combination with molecular and cell biology techniques can be utilised to test the effects of anti-microsporidian drugs, and specific protein inhibitors on the parasite’s cell biology and infection cycle progression. Using these techniques with bespoke specific antibodies against T. hominis alternative respiration (AR) components—alternative oxidase (AOX) and glycerol-3-phosphate dehydrogenase (mtG3PDH)—we demonstrate their life cycle stage-dependent mitosomal localisation, and in combination with the specific AOX-inhibitor colletochlorin B we show an essential function of the mitosomal AOX during an early phase of the T. hominis infection cycle. Using bioinformatics and specific inhibitors we show that the role of the microsporidian minimal mitochondria in AR was subsequently lost in the course of further reductive evolution in some lineages including that of E. cuniculi. Additional RNAseq across T. hominis life cycle and experiments using antibodies against the mitosomal iron-sulphur clusters biosynthesis (ISC) protein NFS indicated that unlike the phylogenetically-restricted AR, the conserved ISC function of the mitosome is active during T. hominis proliferation.

Abstract Background Cancer-related fatigue (CRF) is the most common side effect of cancer and cancer treatment. CRF prevalence is up to 50% in breast cancer patients and can continue several years after cancer remission. This persistent subjective sense of exhaustion is multifactorial. Numerous parameters have been evidenced to be related to CRF across biological, physical, psychological, social and/or behavioral dimensions. Although CRF has been studied for many years, the majority of previous studies focused on only one dimension, i.e., physical function. Moreover, few studies investigated CRF longitudinally with repeated measures. These are the two main obstacles that limit the understanding of CRF mechanisms. The purpose of this study is to create a biopsychosocial model of CRF with simultaneous and longitudinal anthropometric, clinical, biological, physical, psychological and sociological parameters. Methods BIOCARE FActory is a multicentric prospective study that will consist of an 18-month follow-up of 200 women diagnosed with breast cancer. Four visits will be scheduled at diagnosis, after treatments, and 12 and 18 months after diagnosis. The same procedure will be followed for each visit. Each session will be composed of anthropometric data collection, a semi-structured interview, cognitive tests, postural control tests, neuromuscular fatigability tests and a cardiorespiratory fitness test. Clinical and biological data will be collected during medical follow-ups. Participants will also complete questionnaires to assess psychological aspects and quality of life and wear an actigraphy device. Using a structural equation modeling analysis (SEM), collected data will build a biopsychosocial model of CRF, including the physiological, biological, psychological, behavioral and social dimensions of CRF. Discussion This study aims to highlight the dynamics of CRF and its correlates from diagnosis to post treatment. SEM analysis could examine some relations between potential mechanisms and CRF. Thus, the biopsychosocial model will contribute to a better understanding of CRF and its underlying mechanisms from diagnosis to the aftermaths of cancer and its treatments. Trial registration This study is registered at ClinicalTrials.gov ( NCT04391543 ), May 2020.

A hierarchy of global 1/4∘ (ORCA025) and Atlantic Ocean 1/20∘ nested (VIKING20X) ocean–sea-ice models is described. It is shown that the eddy-rich configurations performed in hindcasts of the past 50–60 years under CORE and JRA55-do atmospheric forcings realistically simulate the large-scale horizontal circulation, the distribution of the mesoscale, overflow and convective processes, and the representation of regional current systems in the North and South Atlantic. The representation of the Atlantic Meridional Overturning Circulation (AMOC), and in particular the long-term temporal evolution, strongly depends on numerical choices for the application of freshwater fluxes. The interannual variability of the AMOC instead is highly correlated among the model experiments and also with observations, including the 2010 minimum observed by RAPID at 26.5∘ N. This points to a dominant role of the wind forcing. The ability of the model to represent regional observations in western boundary current (WBC) systems at 53∘ N, 26.5∘ N and 11∘ S is explored. The question is investigated of whether WBC systems are able to represent the AMOC, and in particular whether these WBC systems exhibit similar temporal evolution to that of the zonally integrated AMOC. Apart from the basin-scale measurements at 26.5∘ N, it is shown that in particular the outflow of North Atlantic Deepwater at 53∘ N is a good indicator of the subpolar AMOC trend during the recent decades, once provided in density coordinates. The good reproduction of observed AMOC and WBC trends in the most reasonable simulations indicate that the eddy-rich VIKING20X is capable of representing realistic forcing-related and ocean-intrinsic trends.

Abstract In human cells under stress conditions, misfolded polypeptides can form potentially cytotoxic insoluble aggregates. To eliminate aggregates, the HSP70 chaperone machinery extracts and resolubilizes polypeptides for triage to refolding or degradation. Yeast and bacterial chaperones of the small heat-shock protein (sHSP) family can bind substrates at early stages of misfolding, during the aggregation process. The co-aggregated sHSPs then facilitate downstream disaggregation by HSP70. Because it is unknown whether a human sHSP has this activity, we investigated the disaggregation role of human HSPB1. HSPB1 co-aggregated with unfolded protein substrates, firefly luciferase and mammalian lactate dehydrogenase. The co-aggregates formed with HSPB1 were smaller and more regularly shaped than those formed in its absence. Importantly, co-aggregation promoted the efficient disaggregation and refolding of the substrates, led by HSP70. HSPB1 itself was also extracted during disaggregation, and its homo-oligomerization ability was not required. Therefore, we propose that a human sHSP is an integral part of the chaperone network for protein disaggregation.

Abstract A growing body of evidence supports an important role for alterations in the brain-gut-microbiome axis in the aetiology of depression and other psychiatric disorders. The potential role of the oral microbiome in mental health has received little attention, even though it is one of the most diverse microbiomes in the body and oral dysbiosis has been linked to systemic diseases with an underlying inflammatory aetiology. This study examines the structure and composition of the salivary microbiome for the first time in young adults who met the DSM-IV criteria for depression (n = 40) and matched controls (n = 43) using 16S rRNA gene-based next generation sequencing. Subtle but significant differences in alpha and beta diversity of the salivary microbiome were observed, with clear separation of depressed and healthy control cohorts into distinct clusters. A total of 21 bacterial taxa were found to be differentially abundant in the depressed cohort, including increased Neisseria spp. and Prevotella nigrescens, while 19 taxa had a decreased abundance. In this preliminary study we have shown that the composition of the oral microbiome is associated with depression in young adults. Further studies are now warranted, particuarly investigations into whether such shifts play any role in the underling aetiology of depression.

Golkar, Bassenden et al. report two structures of the latest generation aminoglycoside antibiotic plazomicin in complex with the bacterial 70S ribosome as well as in complex with AAC(2’)-la acetyltransferase, an antibiotic modification enzyme (AME). Their study can be useful in the development of newer aminoglycosides that are not modified by AMEs while being capable of targeting the bacterial ribosome.

Stratospheric HCl observations are an important diagnostic for the evaluation of catalytic processes that impact the ozone layer. We report here in situ balloon-borne observations of HCl employing an off-axis integrated cavity output spectrometer (OA-ICOS) fitted with a reinjection mirror. Laboratory assessments demonstrated that the spectrometer has a 90 % response time of 10 s to changes in HCl and a 30 s precision of 26 pptv. The instrument was deployed alongside an ozone instrument in August 2018 on a balloon-borne descent between 20–80 hPa (29–18 km altitude). The observations agreed with nearby satellite measurements made by the Earth Observing System Microwave Limb Sounder within 10 % on average. This is the first time that stratospheric measurements of HCl have been made with ICOS and the first time any cavity-enhanced HCl instrument has been tested in flight.

Andreev reflection is normally known to occur at a metal-superconductor interface. Here, Hashisaka et al. observe an Andreev-like process in a narrow junction between fractional and integer quantum Hall states originating from a topological quantum many-body effect instead of superconductivity.

The detection of moving objects is a trivial task performed by vertebrate retinas, yet a complex computer vision task. Object-motion-sensitive ganglion cells (OMS-GC) are specialised cells in the retina that sense moving objects. OMS-GC take as input continuous signals and produce spike patterns as output, that are transmitted to the Visual Cortex via the optic nerve. The Hybrid Sensitive Motion Detector (HSMD) algorithm proposed in this work enhances the GSOC dynamic background subtraction (DBS) algorithm with a customised 3-layer spiking neural network (SNN) that outputs spiking responses akin to the OMS-GC. The algorithm was compared against existing background subtraction (BS) approaches, available on the OpenCV library, specifically on the 2012 change detection (CDnet2012) and the 2014 change detection (CDnet2014) benchmark datasets. The results show that the HSMD was ranked overall first among the competing approaches and has performed better than all the other algorithms on four of the categories across all the eight test metrics. Furthermore, the HSMD proposed in this paper is the first to use an SNN to enhance an existing state of the art DBS (GSOC) algorithm and the results demonstrate that the SNN provides near real-time performance in realistic applications.

A new Earth system model, the Flexible Ocean and Climate Infrastructure (FOCI), is introduced. A first version of FOCI consists of a global high-top atmosphere (European Centre Hamburg general circulation model; ECHAM6.3) and an ocean model (Nucleus for European Modelling of the Ocean v3.6; NEMO3.6) as well as sea-ice (Louvain-la-Neuve sea Ice Model version 2; LIM2) and land surface model components (Jena Scheme for Biosphere Atmosphere Coupling in Hamburg; JSBACH), which are coupled through the OASIS3-MCT software package. FOCI includes a number of optional modules which can be activated depending on the scientific question of interest. In the atmosphere, interactive stratospheric chemistry can be used (ECHAM6-HAMMOZ) to study, for example, the effects of the ozone hole on the climate system. In the ocean, a biogeochemistry model (Model of Oceanic Pelagic Stoichiometry; MOPS) is available to study the global carbon cycle. A unique feature of FOCI is the ability to explicitly resolve mesoscale ocean eddies in specific regions. This is realized in the ocean through nesting; first examples for the Agulhas Current and the Gulf Stream systems are described here. FOCI therefore bridges the gap between coarse-resolution climate models and global high-resolution weather prediction and ocean-only models. It allows to study the evolution of the climate system on regional and seasonal to (multi)decadal scales. The development of FOCI resulted from a combination of the long-standing expertise in ocean and climate modeling in several research units and divisions at the Helmholtz Centre for Ocean Research Kiel (GEOMAR). FOCI will thus be used to complement and interpret long-term observations in the Atlantic, enhance the process understanding of the role of mesoscale oceanic eddies for large-scale oceanic and atmospheric circulation patterns, study feedback mechanisms with stratospheric processes, estimate future ocean acidification, and improve the simulation of the Atlantic Meridional Overturning Circulation changes and their influence on climate, ocean chemistry and biology. In this paper, we present both the scientific vision for the development of FOCI as well as some technical details. This includes a first validation of the different model components using several configurations of FOCI. Results show that the model in its basic configuration runs stably under pre-industrial control as well as under historical forcing and produces a mean climate and variability which compares well with observations, reanalysis products and other climate models. The nested configurations reduce some long-standing biases in climate models and are an important step forward to include the atmospheric response in multidecadal eddy-rich configurations.

When doing research on scientific issues, it is very significant if our research issues are closely connected to real applications. In reality, when analyzing data in practice, there are frequently several models that can appropriate to the survey data. Hence, it is necessary to have a standard criterion to choose the most ecient model. In this article, our primary interest is to compare and discuss about the criteria for selecting a model and its applications. The authors provide approaches and procedures of these methods and apply to the traffic violation data where we look for the most appropriate model among Poisson regression, Zero-inflated Poisson regression and Negative binomial regression to capture between number of violated speed regulations and some factors including distance covered, motorcycle engine and age of respondents by using AIC, BIC and Vuong's test. Based on results on the training, validation and test data set, we find that the criteria AIC and BIC are more consistent and robust performance in model selection than the Vuong's test. In the present paper, the authors also discuss about advantages and disadvantages of these methods and provide some of the suggestions with potential directions in future research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium provided the original work is properly cited.

Eigendecomposition is the factorization of a matrix into its canonical form, whereby the matrix is represented in terms of its eigenvalues and eigenvectors. A common step is the reduction of the data to a kernel matrix also known as a Gram matrix which is used for machine learning tasks. A significant drawback of kernel methods is the computational complexity associated with manipulating kernel matrices. This paper demonstrates that leading eigenvectors derived from singular value decomposition (SVD) and Nyström approximation methods can be utilized for classification tasks without the need to construct Gram matrices. Experiments were conducted with 14 biomedical datasets to compare classifier performance when taking as input into a classifier matrices containing: 1) leading eigenvectors which result from each approximation method, and 2) matrices which result from constructing the patient-by-patient Gram matrix. The results provide evidence to support the main hypothesis of this paper that using the leading eigenvectors as input into a classifier significantly (p

Morphometry has proven to be a useful tool, both for the clinician and horse owners, for evaluating the body condition in equids due to its objectivity, easiness and capacity for detection of important metabolic disturbances. However, limited information is available on the use of morphometric ratios to characterize regional and overall adiposity and much less about their application in different genders, ages and horses with different levels of obesity. The objectives were to evaluate body and neck absolute measurements and ratios; factors affecting them such as the influence of gender, age, appearance of the neck crest and overall body condition and; relationships among these measurements. A total of 154 Andalusian horses classified according to their gender, age, body score status and cresty neck condition were evaluated in this cross-sectional study. Two evaluators assigned a body condition score (BCS, 1 to 9) and a cresty neck score (CNS, 0 to 5) to each horse. Horses were divided into males and females; young (2 to 5 years) and adults (6 to 15 years); obese (BCS⩾7) and non-obese (BCS

The shrinking Arctic sea ice cover observed during the last decades is probably the clearest manifestation of ongoing climate change. While climate models in general reproduce the sea ice retreat in the Arctic during the 20th century and simulate further sea ice area loss during the 21st century in response to anthropogenic forcing, the models suffer from large biases and the results exhibit considerable spread. Here, we compare results from the two last generations of climate models, CMIP3 and CMIP5, with respect to total and regional Arctic sea ice change. Different characteristics of sea ice area (SIA) in March and September have been analysed for the Entire Arctic, Central Arctic and Barents Sea. Further, the sensitivity of SIA to changes in Northern Hemisphere (NH) temperature is investigated and dynamical links between SIA and some atmospheric variability modes are assessed.CMIP3 (SRES A1B) and CMIP5 (RCP8.5) models not only simulate a coherent decline of the Arctic SIA but also depict consistent changes in the SIA seasonal cycle. The spatial patterns of SIC variability improve in CMIP5 ensemble, most noticeably in summer when compared to HadISST1 data. A better simulation of summer SIA in the Entire Arctic by CMIP5 models is accompanied by a slightly increased bias for winter season in comparison to CMIP3 ensemble. SIA in the Barents Sea is strongly overestimated by the majority of CMIP3 and CMIP5 models, and projected SIA changes are characterized by a high uncertainty. Both CMIP ensembles depict a significant link between the SIA and NH temperature changes indicating that a part of inter-ensemble SIA spread comes from different temperature sensitivity to anthropogenic forcing. The results suggest that, in general, a sensitivity of SIA to external forcing is enhanced in CMIP5 models. Arctic SIA interannual variability in the end of the 20th century is on average well simulated by both ensembles. To the end of the 21st century, September variability is strongly reduced in CMIP5 models under RCP8.5 scenario, whereas variability changes in CMIP3 and in both ensembles in March are relatively small. The majority of models in both CMIP ensembles demonstrate an ability to capture a negative correlation of interannual SIA variations in the Barents Sea with North Atlantic Oscillation and sea level pressure gradient in the western Barents Sea opening serving as an index of oceanic inflow to the Sea.

The functions of the highly reduced mitochondria (mitosomes) of microsporidians are not well-characterized. Here, the authors show that theTrachipleistophora hominismitosome is the site of iron–sulfur cluster assembly and that its retention is likely linked to its role in cytosolic and nuclear iron–sulfur protein maturation.

Many anaerobic ciliated protozoa contain organelles of mitochondrial ancestry called hydrogenosomes. These organelles generate molecular hydrogen that is consumed by methanogenic Archaea, living in endosymbiosis within many of these ciliates. Here we describe a new species of anaerobic ciliate, Trimyema finlayi n. sp., by using silver impregnation and microscopy to conduct a detailed morphometric analysis. Comparisons with previously published morphological data for this species, as well as the closely related species, Trimyema compressum, demonstrated that despite them being similar, both the mean cell size and the mean number of somatic kineties are lower for T. finlayi than for T. compressum, which suggests that they are distinct species. This was also supported by analysis of the 18S rRNA genes from these ciliates, the sequences of which are 97.5% identical (6 substitutions, 1479 compared bases), and in phylogenetic analyses these sequences grouped with other 18S rRNA genes sequenced from previous isolates of the same respective species. Together these data provide strong evidence that T. finlayi is a novel species of Trimyema, within the class Plagiopylea. Various microscopic techniques demonstrated that T. finlayi n. sp. contains polymorphic endosymbiotic methanogens, and analysis of the endosymbionts’ 16S rRNA gene showed that they belong to the genus Methanocorpusculum, which was confirmed using fluorescence in situ hybridization with specific probes. Despite the degree of similarity and close relationship between these ciliates, T. compressum contains endosymbiotic methanogens from a different genus, Methanobrevibacter. In phylogenetic analyses of 16S rRNA genes, the Methanocorpusculum endosymbiont of T. finlayi n. sp. grouped with sequences from Methanomicrobia, including the endosymbiont of an earlier isolate of the same species, ‘Trimyema sp.,’ which was sampled approximately 22 years earlier, at a distant (∼400 km) geographical location. Identification of the same endosymbiont species in the two separate isolates of T. finlayi n. sp. provides evidence for spatial and temporal stability of the Methanocorpusculum–T. finlayi n. sp. endosymbiosis. T. finlayi n. sp. and T. compressum provide an example of two closely related anaerobic ciliates that have endosymbionts from different methanogen genera, suggesting that the endosymbionts have not co-speciated with their hosts.

Les actions d'une association comme Terres de Liens, qui œuvre pour la préservation des espaces agricoles et l'accompagnement vers une agriculture plus respectueuse de l'environnement, témoignent de l'entrée de la société civile dans la gouvernance du foncier agricole, aux côtés des collectivités territoriales et des acteurs fonciers plus traditionnels du milieu rural. Dans cet article, il est sujet ici de l'élaboration de conventions innovantes permettant d'agir collectivement pour faciliter l'accès au foncier de candidats à l'installation non issus du milieu agricole et souvent porteurs de projets en agriculture biologique.

Background: Patients with head and neck cancer undergoing surgery have a high incidence of ambulatory postoperative complications. Objective: The aim of our study was to investigate the influence of an oral immunoenhanced supplement (arginine and glutamine) on nutritional and biochemical parameters in postsurgical ambulatory patients with head and neck tumor. Design: A population of 39 ambulatory postsurgical patients with oral and laryngeal cancer was enrolled. At Hospital discharge postsurgical head and neck cancer patients were asked to consume two units per day of a specially designed enhanced supplement for a twelve week period. Results: The mean age was 60.2+/-13.1 years (9 female/30 males). Duration of supplementation was 90.8+20 days. A significant increase of albumin (3.1±0.6 g/dl vs 4.12+0.7g /dl;pAntecedentes: Los pacientes con tumores de cabeza y cuello sometidos a cirugía presentan una alta incidencia de complicaciones ambulatorias. Objetivo: El principal objetivo de nuestro trabajo fue evaluar la influencia de un suplemento oral inmunoenriquecido con arginina y glutamina en pacientes postquirúrgicos ambulatorios con tumores de cabeza y cuello. Diseño: Una muestra de 39 pacientes postquirúrgicos ambulatorios con tumores de cabeza y cuello fue evaluada. Tras el alta hospitalaria, los pacientes recibieron dos bricks al día de un suplemento inmunoenriquecido durante 12 semanas. Resultados: La edad media fue de 60,2+/-13,1 años (9 mujeres/30 varones). La duración media de la suplementación fue de 90,8+20 días. Se detectó un aumento significativo en los niveles de albúmina (3,1±0,6 g/dl vs 4,12+0,7 mg/dl;p

Using immunocytochemical techniques at light and electron microscopy, we analysed the distribution of phosphorylated c-Myc in actively proliferating human HeLa cells. The distribution pattern of c-Myc was also compared with those of other ribonucleoprotein (RNP)-containing components (PANA, hnRNP-core proteins, fibrillarin) or RNP-associated nuclear proteins (SC-35 splicing factor). Our results provide the first evidence that phosphorylated c-Myc accumulates in the nucleus of tumor cells, where it colocalizes with fibrillarin, both in the nucleolus and in extranucleolar structures.

As part of a major atmospheric chemistry and aerosol field program carried out in March 2006, a study was conducted in the area to the north and northeast of Mexico City to investigate the evolution of aerosols and their associated optical properties in the first few hours after their emission. The focus of the T1-T2 aerosol study was to investigate changes in the specific absorption αABS (absorption per unit mass, with unit of m2 g−1) of black carbon as it aged and became coated with compounds such as sulfate and organic carbon, evolving from an external to an internal mixture. Such evolution has been reported in previous studies. The T1 site was located just to the north of the Mexico City metropolitan area; the T2 site was situated approximately 35 km farther to the northeast. Nephelometers, particle soot absorption photometers, photoacoustic absorption spectrometers, and organic and elemental carbon analyzers were used to measure the optical properties of the aerosols and the carbon concentrations at each of the sites. Radar wind profilers and radiosonde systems helped to characterize the meteorology and to identify periods when transport from Mexico City over T1 and T2 occurred. Organic and elemental carbon concentrations at T1 showed diurnal cycles reflecting the nocturnal and early morning buildup from nearby sources, while concentrations at T2 appeared to be more affected by transport from Mexico City. Specific absorption during transport periods was lower than during other times, consistent with the likelihood of fresher emissions being found when the winds blew from Mexico City over T1 and T2. The specific absorption at T2 was larger than at T1, which is also consistent with the expectation of more aged particles with encapsulated black carbon being found at the more distant location. In situ measurements of single scattering albedo with an aircraft and a ground station showed general agreement with column-averaged values derived from rotating shadowband radiometer data, although some differences were found that may be related to boundary-layer evolution.

Since the function of the spinal cord depends on the proteins found there, better defing the normal Spinal Cord Proteome is an important and challenging task. Although brain and cerebrospinal fluid samples from patients with different central nervous system (CNS) disorders have been studied, a thorough examination of specific spinal cord proteins and the changes induced by injury or associated to conditions such as neurodegeneration, spasticity and neuropathies has yet to be performed. In the present study, we aimed to describe total protein content in the spinal cord of healthy rats, employing different proteomics tools. Accordingly, we have developed a fast, easy, and reproducible sequential protocol for protein extraction from rat spinal cords. We employed conventional two dimensional electrophoresis (2DE) in different pH ranges (eg. 4–7, 3–11 NL) combined with identification by mass spectrometry (MALDI-TOF/TOF), as well as first dimension protein separation combined with Liquid Chromatography Mass Spectrometry/Mass Spectrometry (LC-MS/MS) to maximise the benefits of this technology. The value of these techniques is demonstrated here by the identification of several proteins known to be associated with neuroglial structures, neurotransmission, cell survival and nerve growth in the central nervous system. Furthermore this study identified many spinal proteins that have not previously been described in the literature and which may play an important role as either sensitive biomarkers of dysfunction or of recovery after Spinal Cord Injury.

Drei Auerochsenskelette (Bos primigenius) und ein Bisonskelett (Bison priscus) aus dem Jungpleistozän bzw. Holozän Deutschlands werden osteologisch beschrieben. Gattungsunterschiede an den Langknochen werden an den mit Hilfe des Schädels sicher bestimmten Skelettfunden auf ihre Zuverlässigkeit hin überprüft. In die Untersuchung wird Vergleichsmaterial von Bos primigenius und Bison priscus aus dem Pleistozän von England sowie von Bison div. sp. aus Nordamerika einbezogen. Schlüsselmerkmale für eine Unterscheidung von Bos primigenius und Bison priscus existieren nicht. Die in einer früheren Arbeit an Material aus den Schottern der nördlichen Oberrheinebene (Martin 1987) ausgearbeiteten Merkmalskombinationen konnten als brauchbar bestätigt werden, wobei sich erneut zeigte, daß sehr zierliche Knochen in ihren Merkmalsausprägungen abweichen können. Die Unterscheidungsmerkmale lassen sich generell auch auf den nordamerikanischen Bison antiquus und Bison bison erfolgreich anwenden, sofern die Knochen in derselben Größenklasse wie die von Bison priscus liegen.