Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with idiopathic gastroparesis

BACKGROUND: Gastric emptying is impaired in patients with gastroparesis whereas it is either unchanged or accelerated in obese individuals. The goal of the current study was to identify changes in gene expression in the stomach muscularis that may be contributing to altered gastric motility in idiopathic gastroparesis and obesity. METHODS: Quantitative real time RT-PCR and whole transcriptome sequencing were used to compare the transcriptomes of lean individuals, obese individuals and either lean or obese individuals with idiopathic gastroparesis. RESULTS: Obesity leads to an increase in mRNAs associated with muscle contractility whereas idiopathic gastroparesis leads to a decrease in mRNAs associated with PDGF BB signaling. Both obesity and idiopathic gastroparesis were also associated with similar alterations in pathways associated with inflammation. CONCLUSIONS: Our findings show that obesity and idiopathic gastroparesis result in overlapping but distinct changes in the gastric muscularis transcriptome. Increased expression of mRNAs encoding smooth muscle contractile proteins may be contributing to the increased gastric motility observed in obese subjects, whereas decreased PDGF BB signaling may be contributing to the impaired motility seen in subjects with idiopathic gastroparesis

First-principles equation of state of CHON resin for inertial confinement fusion applications

A wide-range (0 to 1044.0 g/cm3 and 0 to 109 K) equation-of-state (EOS) table for a CH1.72O0.37N0.086 quaternary compound has been constructed based on density-functional theory (DFT) molecular-dynamics (MD) calculations using a combination of Kohn-Sham DFT MD, orbital-free DFT MD, and numerical extrapolation. The first-principles EOS data are compared with predictions of simple models, including the fully ionized ideal gas and the Fermi-degenerate electron gas models, to chart their temperature-density conditions of applicability. The shock Hugoniot, thermodynamic properties, and bulk sound velocities are predicted based on the EOS table and compared to those of C-H compounds. The Hugoniot results show the maximum compression ratio of the C-H-O-N resin is larger than that of CH polystyrene due to the existence of oxygen and nitrogen; while the other properties are similar between CHON and CH. Radiation hydrodynamic simulations have been performed using the table for inertial confinement fusion targets with a CHON ablator and compared with a similar design with CH. The simulations show CHON outperforms CH as the ablator for laser-direct-drive target designs

Cyber Intelligence in the Era of Big Data

Three key moments have to be solved for this complex problem proper ap- proaching: (i) selection of suitable formalism for fast and easy modelling, im- plementing both experts’ data and cyber incidents statistics on past and future cyberattacks trends; (ii) model quantification is necessary to be added, achieving a suitable machine interpretation for discrete optimization; (iii) some probabilistic elements have also to be considered, in order to achieve realistic models, practi- cal implementation decision support, benefitting from the “big data” knowledge context of the task. Practical implementation of these moments will be given further

Моделирование спектров излучения импульсных рентгеновских трубок

Наведені результати моделювання спектрів гальмівного рентгенівського випромінювання в імпульсних трубках рефлекторного та трансмісійного типу, які враховують конструкцію анодно-катодного вузла, матеріали анода та вихідного вікна, змінювання анодної напруги і анодного струму під час імпульсу рентгенівського випромінювання в трубках з вибуховою емісією, а також кут нахилу траєкторій електронів до поверхні анода. З використанням програми MathCAD, в якій експериментальні залежності коефіцієнтів поглинання матеріалами анода і вихідного вікна від енергії фотонів, вольт-секундні та ампер-секундні характеристики анодної напруги та струму інтерполювалися кубічними та квадратичними сплайнами, а залежність константи Томсона-Віддінгтона від анодної напруги апроксимувалися експонентою, розраховані миттєві та сумарні (за тривалість імпульсу) спектри однонаправленого осьового) напрямку випромінювання і для різних кутів випромінювання, які утворюють панорамне тіньове зображення контрольованих матеріалів або виробів. Конкретні приклади змодельованих сумарних спектрів наведені для рефлекторних трубок з анодом у вигляді конусної поверхні і катода, утвореного одиночною загостреною з внутрішньої сторони шайбою, а в трубках трансмісійного типу анод має форму плоскої фольги.The results of modeling the spectra of X-ray braking radiation of pulsed tubes of reflex and transmission type have been shown. They consider the design of anode-cathode unit, material of anode and outlet window, changing of the anode voltage and anode current during the pulse in tubes with explosive emission and also angle between trajectories of electrons and anode surface. Using MathCAD software there were calculated instant and total (per pulse) spectra of single directional (axial) radiation and radiation for different angles, that form a panorama shadow image of controlled materials or products. The experimental dependence of the absorption of the anode material and the outlet window and the photon energy, volt-second and ampere-second characteristics of anode voltage and current were interpolated by cubic and quadratic splines. The dependence of Thomson-Viddington constants and anode voltage was exponential approximated. Specific examples of simulated total spectra of reflex tubes were shown with an anode as conical surface and the cathode formed by a solitary sharp washer on the inside, and transmission type anode tubes is shaped like a flat foil.Приведены результаты моделирования спектров тормозного рентгеновского излучения в импульсных трубках рефлекторного и трансмиссионного типа, которые учитывают конструкцию анодно-катодного узла, материалы анода и выпускного окна, изменения анодного напряжения и анодного тока в течение длительности импульса в трубках с взрывной эмиссией, а также угол наклона траекторий электронов к поверхности анода. С использованием программы MathCAD, в которой экспериментальные зависимости коэффициентов поглощения материалами анода и выпускного окна от энергии фотонов, вольт-секундные и ампер-секундные характеристики анодного напряжения и тока интерполировались кубическими и квадратичными сплайнами, а зависимость константы Томсона-Виддингтона от анодного напряжения аппроксимировались экспонентой. Рассчитаны мгновенные и суммарные (за длительность импульса) спектры однонаправленного (осевого) направления излучения и для разных углов излучения, которые образуют панорамное теневое изображение контролируемых материалов или изделий. Конкретные примеры смоделированных суммарных спектров приведены для рефлекторных трубок с анодом в виде конусной поверхности и катода, образованного одиночной заостренной с внутренней стороны шайбой, а в трубках трансмиссионного типа анод имеет форму плоской фольги

Geminin Is Required for Zygotic Gene Expression at the Xenopus Mid-Blastula Transition

In many organisms early development is under control of the maternal genome and zygotic gene expression is delayed until the mid-blastula transition (MBT). As zygotic transcription initiates, cell cycle checkpoints become activated and the tempo of cell division slows. The mechanisms that activate zygotic transcription at the MBT are incompletely understood, but they are of interest because they may resemble mechanisms that cause stem cells to stop dividing and terminally differentiate. The unstable regulatory protein Geminin is thought to coordinate cell division with cell differentiation. Geminin is a bi-functional protein. It prevents a second round of DNA replication during S and G2 phase by binding and inhibiting the essential replication factor Cdt1. Geminin also binds and inhibits a number of transcription factors and chromatin remodeling proteins and is thought to keep dividing cells in an undifferentiated state. We previously found that the cells of Geminin-deficient Xenopus embryos arrest in G2 phase just after the MBT then disintegrate at the onset of gastrulation. Here we report that they also fail to express most zygotic genes. The gene expression defect is cell-autonomous and is reproduced by over-expressing Cdt1 or by incubating the embryos in hydroxyurea. Geminin deficient and hydroxyurea-treated blastomeres accumulate DNA damage in the form of double stranded breaks. Bypassing the Chk1 pathway overcomes the cell cycle arrest caused by Geminin depletion but does not restore zygotic gene expression. In fact, bypassing the Chk1 pathway by itself induces double stranded breaks and abolishes zygotic transcription. We did not find evidence that Geminin has a replication-independent effect on transcription. We conclude that Geminin is required to maintain genome integrity during the rapid cleavage divisions, and that DNA damage disrupts zygotic gene transcription at the MBT, probably through activation of DNA damage checkpoint pathways

Study protocol: SPARCLE – a multi-centre European study of the relationship of environment to participation and quality of life in children with cerebral palsy

BACKGROUND: SPARCLE is a nine-centre European epidemiological research study examining the relationship of participation and quality of life to impairment and environment (physical, social and attitudinal) in 8–12 year old children with cerebral palsy. Concepts are adopted from the International Classification of Functioning, Disability and Health which bridges the medical and social models of disability. METHODS/DESIGN: A cross sectional study of children with cerebral palsy sampled from total population databases in 9 European regions. Children were visited by research associates in each country who had been trained together. The main instruments used were KIDSCREEN, Life-H, Strength and Difficulties Questionnaire, Parenting Stress Index. A measure of environment was developed within the study. All instruments were translated according to international guidelines. The potential for bias due to non response and missing data will be examined. After initial analysis using multivariate regression of how the data captured by each instrument relate to impairment and socio-economic characteristics, relationships between the latent traits captured by the instruments will then be analysed using structural equation modelling. DISCUSSION: This study is original in its methods by directly engaging children themselves, ensuring those with learning or communication difficulty are not excluded, and by studying in quantitative terms the crucial outcomes of participation and quality of life. Specification and publication of this protocol prior to analysis, which is not common in epidemiology but well established for randomised controlled trials and systematic reviews, should avoid the pitfalls of data dredging and post hoc analyses

Study protocol: Determinants of participation and quality of life of adolescents with cerebral palsy: a longitudinal study (SPARCLE2)

<p>Abstract</p> <p>Background</p> <p>Children and adults with impairments such as cerebral palsy have lower participation in life situations than able-bodied people. Less is known about their subjective perception of their lives, called their quality of life.</p> <p>During adolescence, rapid physical and psychological changes occur; although these may be more difficult for disabled than for able-bodied adolescents, little research has examined the lives of disabled adolescents.</p> <p>In 2003-4 a European Union funded project, SPARCLE, visited 818 children aged 8-12 years with cerebral palsy, sampled from population-based registers in nine European regions. The quality of life reported by these disabled children was similar to that of the general population but their participation was lower; levels of participation varied between countries even for children with similar severity of cerebral palsy.</p> <p>We are currently following up these children, now aged 13-17 years, to identify (i) to what extent contemporaneous factors (pain, impairment, psychological health and parental stress) predict their participation and quality of life, (ii) what factors modify how participation and quality of life at age 8-12 years are associated with participation and quality of life in adolescence, and (iii) whether differences between European countries in participation and quality of life can be explained by variations in environmental factors.</p> <p>Methods/Design</p> <p>Trained researchers will visit families to administer questionnaires to capture the adolescents' type and severity of impairment, socio-demographic characteristics, participation, quality of life, psychological health, pain, environmental access and parental stress. We will use multivariable models (linear, logistic or ordinal) to assess how adolescent participation, quality of life, psychological health, pain, environmental access and parental stress, vary with impairment and socio-demographic characteristics and, where possible, how these outcomes compare with general population data. For participation and quality of life, longitudinal analyses will assess to what extent these are predicted by corresponding levels in childhood and what factors modify this relationship. Structural equation modelling will be used to identify indirect relationships mediated by other factors.</p

Latest results on the production of hadronic resonances in ALICE at the LHC

Measurement of short-lived hadronic resonances are used to study different aspects of particle production and collision dynamics in pp, p–A and relativistic heavy-ion collisions. The yields of resonances are sensitive to the competing processes of hadron rescattering and regeneration, thus making these particles unique probes of the properties of the late hadronic phase. Measurements of resonances with different masses and quantum numbers also provide insight into strangeness production and processes that determine the shapes of particle momentum spectra at intermediate transverse momenta, as well as the species dependence of hadron suppression at high momentum. We present the comprehensive set of results in the ALICE experiment with unprecedented precision for ρ(770)0, K∗(892), φ(1020), Σ(1385)±, Λ(1520), and Ξ(1530)0 production in pp, p–Pb, Xe–Xe and Pb–Pb collisions in the energy range √sNN = 2.76-13 TeV, including the latest measurements from LHC Run 2. The obtained results are used to study the system-size and collision-energy evolution of transverse momentum spectra, particle ratios and nuclear modification factors and to search for the onset of collectivity in small collision systems. We compare these results to lower energy measurements and model calculations where available.publishedVersio