Virtue integrated platform : holistic support for distributed ship hydrodynamic design

Ship hydrodynamic design today is often still done in a sequential approach. Tools used for the different aspects of CFD (Computational Fluid Dynamics) simulation (e.g. wave resistance, cavitation, seakeeping, and manoeuvring), and even for the different levels of detail within a single aspect, are often poorly integrated. VIRTUE (the VIRtual Tank Utility in Europe) project has the objective to develop a platform that will enable various distributed CFD and design applications to be integrated so that they may operate in a unified and holistic manner. This paper presents an overview of the VIRTUE Integrated Platform (VIP), e.g. research background, objectives, current work, user requirements, system architecture, its implementation, evaluation, and current development and future work

Systems Engineering Leadership Development: Advancing Systems Engineering Excellence

This slide presentation reviews the Systems Engineering Leadership Development Program, with particular emphasis on the work being done in the development of systems engineers at Marshall Space Flight Center. There exists a lack of individuals with systems engineering expertise, in particular those with strong leadership capabilities, to meet the needs of the Agency's exploration agenda. Therefore there is a emphasis on developing these programs to identify and train systems engineers. The presentation reviews the proposed MSFC program that includes course work, and developmental assignments. The formal developmental programs at the other centers are briefly reviewed, including the Point of Contact (POC

Decellularised extracellular matrix-derived peptides from neural retina and retinal pigment epithelium enhance the expression of synaptic markers and light responsiveness of human pluripotent stem cell derived retinal organoids

Tissue specific extracellular matrices (ECM) provide structural support and enable access to molecular signals and metabolites, which are essential for directing stem cell renewal and differentiation. To mimic this phenomenon in vitro, tissue decellularisation approaches have been developed, resulting in the generation of natural ECM scaffolds that have comparable physical and biochemical properties of the natural tissues and are currently gaining traction in tissue engineering and regenerative therapies due to the ease of standardised production, and constant availability. In this manuscript we report the successful generation of decellularised ECM-derived peptides from neural retina (decel NR) and retinal pigment epithelium (decel RPE), and their impact on differentiation of human pluripotent stem cells (hPSCs) to retinal organoids. We show that culture media supplementation with decel RPE and RPE-conditioned media (CM RPE) significantly increases the generation of rod photoreceptors, whilst addition of decel NR and decel RPE significantly enhances ribbon synapse marker expression and the light responsiveness of retinal organoids. Photoreceptor maturation, formation of correct synapses between retinal cells and recording of robust light responses from hPSC-derived retinal organoids remain unresolved challenges for the field of regenerative medicine. Enhanced rod photoreceptor differentiation, synaptogenesis and light response in response to addition of decellularised matrices from RPE and neural retina as shown herein provide a novel and substantial advance in generation of retinal organoids for drug screening, tissue engineering and regenerative medicine

Development and evaluation of a biorelevant medium simulating porcine gastrointestinal fluids

Simulated human intestinal media, have proved to be a useful biopharmaceutics tool as a dissolution media for predicting in vivo dissolution and pharmacokinetic profile in humans. During drug product development preclinical animal models are also required to assess drug product performance, and there is a need to develop species specific intestinal media to similarly predict in vivo pharmacokinetic profiles in each preclinical model. Pigs, are increasingly being used in preclinical drug development, however to date there is a lack of quantitative information about the composition of porcine gastrointestinal (GI) fluids. As a result, a porcine biorelevant medium has not yet been developed, which is essential to improve interpretation and forecast of preclinical results using biorelevant in vitro dissolution studies. GI fluid samples, were collected from landrace pigs, and characterized. Fasted State Simulated Intestinal Fluid of pigs (FaSSIFp) was developed based on the physiological composition of the GI fluids in terms of pH, buffer capacity, osmolality, surface tension, as well as the bile salt, phospholipid and free fatty acid content. This study demonstrated that FaSSIFp was superior at predicting the solubility of the six model drugs in porcine intestinal fluids (PIF). A markedly high correlation (r2 0.98) was observed between the solubility obtained in PIF and FaSSIFp, whereas poor correlation (r2 0.12) was found for the solubility of the model drugs between human FaSSIF and PIF. This confirms that species specific biorelevant intestinal media are crucial to provide more accurate predictions of pharmacokinetic studies in preclinical models. Additionally, the availability of a species specific intestinal medium offers the potential to improve in vitro-in silico approaches to predict in vivo absorption and to reduce the overall number of animals needed in oral drug product development testing

Global birth defects app: An innovative tool for describing and coding congenital anomalies at birth in low resource settings

BACKGROUND: Surveillance programs in low- and middle-income countries (LMICs) have difficulty in obtaining accurate information about congenital anomalies. METHODS: As part of the ZikaPLAN project, an International Committee developed an app for the description and coding of congenital anomalies that are externally visible at birth, for use in low resource settings. The “basic” version of the app was designed for a basic clinical setting and to overcome language and terminology barriers by providing diagrams and photos, sourced mainly from international Birth Defects Atlases. The “surveillance” version additionally allows recording of limited pseudonymized data relevant to diagnosis, which can be uploaded to a secure server, and downloaded by the surveillance program data center. RESULTS: The app contains 98 (88 major and 10 minor) externally visible anomalies and 12 syndromes (including congenital Zika syndrome), with definitions and International Classification of Disease v10 -based code. It also contains newborn examination videos and links to further resources. The user taps a region of the body, then selects among a range of images to choose the congenital anomaly that best resembles what they observe, with guidance regarding similar congenital anomalies. The “basic” version of the app has been reviewed by experts and made available on the Apple and Google Play stores. Since its launch in November 2019, it has been downloaded in 39 countries. The "surveillance” version is currently being field-tested. CONCLUSION: The global birth defects app is a mHealth tool that can help in developing congenital anomaly surveillance in low resource settings to support prevention and care

Scale and intensity of intertidal habitat use by knots Calidris canutus in the Western Wadden Sea in relation to food, friends and foes

In August-October 1988-1992 we studied the distribution and abundance of knots Calidris canutus around Griend in the western Wadden Sea, and the extent to which these can be explained by benthic prey availability and presence of avian predators. Numbers in the nonbreeding season showed monthly averages of 10000 to 25000 birds. Over 100000 knots were recorded on three occasions. Knots feed in large flocks, individual birds usually experiencing 4000 to 15000 flock-mates. The Siberian-breeding/west-African wintering canutus subspecies passed through in late July and early August. Otherwise the Greenlandic/Canadian breeding islandica subspecies was present. Over the period 1964-1992 there were no clear trends in the number of knots, but canutus-knots were particularly abundant in July-August 1991, whereas in 1992 both subspecies were absent. Macoma balthica was the preferred prey of both subspecies. Hydrobia ulvae, Mytilus edulis and Cerastoderma edule were eaten when Macoma was absent close to the surface of the sediment. As Macoma buried deeper from July onwards, canutus faced better average feeding conditions than islandica later in the year. The spatial distribution of knots feeding on the intertidal flats around Griend was best explained by the harvestable biomass of the prevalent prey species in a particular year and season, i.e. Macoma (main prey when their harvestable biomass densities were greater than ca 0.8 g AFDM per m2) and Cerastoderma, and by the avoidance of situations where they run the risk of attack by bird-eating birds. Flocks of knots covered most of the intertidal flats in the western Dutch Wadden Sea in a couple of tidal cycles. This is about 800 km2, much larger than the equivalent area used by knots on their wintering grounds in Mauritania (10-15 km2), a difference that is correlated with prey spectrum, prey availability and predictability.

Adaptation of cortical activity to sustained pressure stimulation on the fingertip

Background Tactile adaptation is a phenomenon of the sensory system that results in temporal desensitization after an exposure to sustained or repetitive tactile stimuli. Previous studies reported psychophysical and physiological adaptation where perceived intensity and mechanoreceptive afferent signals exponentially decreased during tactile adaptation. Along with these studies, we hypothesized that somatosensory cortical activity in the human brain also exponentially decreased during tactile adaptation. The present neuroimaging study specifically investigated temporal changes in the human cortical responses to sustained pressure stimuli mediated by slow-adapting type I afferents. Methods We applied pressure stimulation for up to 15 s to the right index fingertip in 21 healthy participants and acquired functional magnetic resonance imaging (fMRI) data using a 3T MRI system. We analyzed cortical responses in terms of the degrees of cortical activation and inter-regional connectivity during sustained pressure stimulation. Results Our results revealed that the degrees of activation in the contralateral primary and secondary somatosensory cortices exponentially decreased over time and that intra- and inter-hemispheric inter-regional functional connectivity over the regions associated with tactile perception also linearly decreased or increased over time, during pressure stimulation. Conclusion These results indicate that cortical activity dynamically adapts to sustained pressure stimulation mediated by SA-I afferents, involving changes in the degrees of activation on the cortical regions for tactile perception as well as in inter-regional functional connectivity among them. We speculate that these adaptive cortical activity may represent an efficient cortical processing of tactile information.open

CDK4/6 inhibitor-mediated cell overgrowth triggers osmotic and replication stress to promote senescence

Summary. Abnormal increases in cell size are associated with senescence and cell cycle exit. The mechanisms by which overgrowth primes cells to withdraw from the cell cycle remain unknown. We address this question using CDK4/6 inhibitors, which arrest cells in G0/G1 and are licensed to treat advanced HR+/HER2− breast cancer. We demonstrate that CDK4/6-inhibited cells overgrow during G0/G1, causing p38/p53/p21-dependent cell cycle withdrawal. Cell cycle withdrawal is triggered by biphasic p21 induction. The first p21 wave is caused by osmotic stress, leading to p38- and size-dependent accumulation of p21. CDK4/6 inhibitor washout results in some cells entering S-phase. Overgrown cells experience replication stress, resulting in a second p21 wave that promotes cell cycle withdrawal from G2 or the subsequent G1. We propose that the levels of p21 integrate signals from overgrowth-triggered stresses to determine cell fate. This model explains how hypertrophy can drive senescence and why CDK4/6 inhibitors have long-lasting effects in patients

Tragicomic presentations of self : starring Phil Silvers as Bilko : the incomplete comic human

When a performer becomes over-associated with a particular, celebrated comic character can this lead to problems, not merely in terms of type-casting, but in creating confusions for the actor’s own perception of self? In instances where a comic creation is perceived to be an extension of the performer’s actual ‘self’, what dissonances in self construct may arise between the comic actor’s created persona and his/her own presentation of self? This article considers the nature of tensions created through the permeation of persona and person which can beset comedians who become closely identified with their particular mediated role. Can, indeed, over-association with their successful ‘signature’ comic role be seen to prove psychologically destabilising for certain performers whose own fragile, sense of identity becomes further compromised by presentation of their own most familiar and definitive, comic creations? Drawing specifically upon the career and comedy of Phil Silvers (aka ‘Sergeant ‘Bilko’), this article attempts to evaluate the forms of crises of identity that can arise between presentations of public and private selves for those performers who become, in effect, ‘public comic property’