Toward the S3DVAR data assimilation software for the Caspian Sea

Data Assimilation (DA) is an uncertainty quantification technique used to incorporate observed data into a prediction model in order to improve numerical forecasted results. The forecasting model used for producing oceanographic prediction into the Caspian Sea is the Regional Ocean Modeling System (ROMS). Here we propose the computational issues we are facing in a DA software we are developing (we named S3DVAR) which implements a Scalable Three Dimensional Variational Data Assimilation model for assimilating sea surface temperature (SST) values collected into the Caspian Sea with observations provided by the Group of High resolution sea surface temperature (GHRSST). We present the algorithmic strategies we employ and the numerical issues on data collected in two of the months which present the most significant variability in water temperature: August and March

Influence of tumor microenvironment and fibroblast population plasticity on melanoma growth, therapy resistance and immunoescape

Cutaneous melanoma (CM) tissue represents a network constituted by cancer cells and tumor microenvironment (TME). A key feature of CM is the high structural and cellular plasticity of TME, allowing its evolution with disease and adaptation to cancer cell and environmental alter-ations. In particular, during melanoma development and progression each component of TME by interacting with each other and with cancer cells is subjected to dramatic structural and cellular modifications. These alterations affect extracellular matrix (ECM) remodelling, phenotypic profile of stromal cells, cancer growth and therapeutic response. The stromal fibroblast populations of the TME include normal fibroblasts and melanoma‐associated fibroblasts (MAFs) that are highly abun-dant and flexible cell types interacting with melanoma and stromal cells and differently influencing CM outcomes. The shift from the normal microenvironment to TME and from normal fibroblasts to MAFs deeply sustains CM growth. Hence, in this article we review the features of the normal mi-croenvironment and TME and describe the phenotypic plasticity of normal dermal fibroblasts and MAFs, highlighting their roles in normal skin homeostasis and TME regulation. Moreover, we dis-cuss the influence of MAFs and their secretory profiles on TME remodelling, melanoma progres-sion, targeted therapy resistance and immunosurveillance, highlighting the cellular interactions, the signalling pathways and molecules involved in these processes

IBtkα Activates the β‐Catenin‐Dependent Transcription of MYC through Ubiquitylation and Proteasomal Degradation of GSK3βin Cancerous B Cells

The IBTK gene encodes the IBtkα protein that is a substrate receptor of E3 ubiquitin ligase, Cullin 3. We have previously reported the pro‐tumorigenic activity of Ibtk in MYC‐dependent B‐ lymphomagenesis observed in Eμ‐myc transgenic mice. Here, we provide mechanistic evidence of the functional interplay between IBtkα and MYC. We show that IBtkα, albeit indirectly, activates the β‐catenin‐dependent transcription of the MYC gene. Of course, IBtkαassociates with GSK3β and promotes its ubiquitylation, which is associated with proteasomal degradation. This event increases the protein level of β‐catenin, a substrate of GSK3β, and results in the transcriptional activation of the MYC and CCND1 target genes of β‐catenin, which are involved in the control of cell division and apoptosis. In particular, we found that in Burkitt’s lymphoma cells, IBtkα silencing triggered the downregulation of both MYC mRNA and protein expression, as well as a strong decrease of cell survival, mainly through the induction of apoptotic events, as assessed by using flow cytometry‐based cell cycle and apoptosis analysis. Collectively, our results shed further light on the complex puzzle of IBtkα interactome and highlight IBtkα as a potential novel therapeutic target to be employed in the strategy for personalized therapy of B cell lymphoma

Insights into Thymus Development and Viral Thymic Infections

T-cell development in the thymus is a complex and highly regulated process, involving a wide variety of cells and molecules which orchestrate thymocyte maturation into either CD4+ or CD8+ single-positive (SP) T cells. Here, we briefly review the process regulating T-cell differentiation, which includes the latest advances in this field. In particular, we highlight how, starting from a pool of hematopoietic stem cells in the bone marrow, the sequential action of transcriptional factors and cytokines dictates the proliferation, restriction of lineage potential, T-cell antigen receptors (TCR) gene rearrangements, and selection events on the T-cell progenitors, ultimately leading to the generation of mature T cells. Moreover, this review discusses paradigmatic examples of viral infections affecting the thymus that, by inducing functional changes within this lymphoid gland, consequently influence the behavior of peripheral mature T-lymphocytes

A Bayesian Updating Scheme for Pandemics: Estimating the Infection Dynamics of COVID-19

Epidemic models play a key role in understanding and responding to the emerging COVID-19 pandemic. Widely used compartmental models are static and are of limited use to evaluate intervention strategies of combatting the pandemic. Applying the technology of data assimilation, we propose a Bayesian updating approach for estimating epidemiological parameters using observable information to assess the impacts of different intervention strategies. We adopt a concise renewal model and propose new parameters by disentangling the reduction of instantaneous reproduction number Rt into mitigation and suppression factors to quantify intervention impacts at a finer granularity. A data assimilation framework is developed to estimate these parameters including constructing an observation function and developing a Bayesian updating scheme. A statistical analysis framework is built to quantify the impacts of intervention strategies by monitoring the evolution of the estimated parameters. We reveal the intervention impacts in European countries and Wuhan and the resurgence risk in the United States

Computational fluid dynamics simulations of phase separation in dispersed oil-water pipe flows

The separation of liquid–liquid dispersions in horizontal pipes is common in many industrial sectors. It remains challenging, however, to predict the separation characteristics of the flow evolution due to the complex flow mechanisms. In this work, Computational Fluid Dynamics (CFD) simulations of the silicone oil and water two-phase flow in a horizontal pipe are performed. Several cases are explored with different mixture velocities and oil fractions (15%-60%). OpenFOAM (version 8.0) is used to perform Eulerian-Eulerian simulations coupled with population balance models. The ‘blending factor’ in the multiphaseEulerFoam solver captures the retardation of the droplet rising and coalescing due to the complex flow behaviour in the dense packed layer (DPL). The blending treatment provides a feasible compensation mechanism for the mesoscale uncertainties of droplet flow and coalescence through the DPL and its adjacent layers. In addition, the influence of the turbulent dispersion force is also investigated, which can improve the prediction of the radial distribution of concentrations but worsen the separation characteristics along the flow direction. Although the simulated concentration distribution and layer heights agree with the experiments only qualitatively, this work demonstrates how improvements in drag and coalescence modelling can be made to enhance the prediction accuracy

Oink: an Implementation and Evaluation of Modern Parity Game Solvers

Parity games have important practical applications in formal verification and synthesis, especially to solve the model-checking problem of the modal mu-calculus. They are also interesting from the theory perspective, as they are widely believed to admit a polynomial solution, but so far no such algorithm is known. In recent years, a number of new algorithms and improvements to existing algorithms have been proposed. We implement a new and easy to extend tool Oink, which is a high-performance implementation of modern parity game algorithms. We further present a comprehensive empirical evaluation of modern parity game algorithms and solvers, both on real world benchmarks and randomly generated games. Our experiments show that our new tool Oink outperforms the current state-of-the-art.Comment: Accepted at TACAS 201

Pancreatic cancer intrinsic PI3Kα activity accelerates metastasis and rewires macrophage component.

Pancreatic ductal adenocarcinoma (PDAC) patients frequently suffer from undetected micro-metastatic disease. This clinical situation would greatly benefit from additional investigation. Therefore, we set out to identify key signalling events that drive metastatic evolution from the pancreas. We searched for a gene signature that discriminate localised PDAC from confirmed metastatic PDAC and devised a preclinical protocol using circulating cell-free DNA (cfDNA) as an early biomarker of micro-metastatic disease to validate the identification of key signalling events. An unbiased approach identified, amongst actionable markers of disease progression, the PI3K pathway and a distinctive PI3Kα activation signature as predictive of PDAC aggressiveness and prognosis. Pharmacological or tumour-restricted genetic PI3Kα-selective inhibition prevented macro-metastatic evolution by hindering tumoural cell migratory behaviour independently of genetic alterations. We found that PI3Kα inhibition altered the quantity and the species composition of the produced lipid second messenger PIP3 , with a selective decrease of C36:2 PI-3,4,5-P3 . Tumoural PI3Kα inactivation prevented the accumulation of pro-tumoural CD206-positive macrophages in the tumour-adjacent tissue. Tumour cell-intrinsic PI3Kα promotes pro-metastatic features that could be pharmacologically targeted to delay macro-metastatic evolution

The higher-level phylogeny of Archosauria (Tetrapoda:Diapsida)

Crown group Archosauria, which includes birds, dinosaurs, crocodylomorphs, and several extinct Mesozoic groups, is a primary division of the vertebrate tree of life. However, the higher-level phylogenetic relationships within Archosauria are poorly resolved and controversial, despite years of study. The phylogeny of crocodile-line archosaurs (Crurotarsi) is particularly contentious, and has been plagued by problematic taxon and character sampling. Recent discoveries and renewed focus on archosaur anatomy enable the compilation of a new dataset, which assimilates and standardizes character data pertinent to higher-level archosaur phylogeny, and is scored across the largest group of taxa yet analysed. This dataset includes 47 new characters (25% of total) and eight taxa that have yet to be included in an analysis, and total taxonomic sampling is more than twice that of any previous study. This analysis produces a well-resolved phylogeny, which recovers mostly traditional relationships within Avemetatarsalia, places Phytosauria as a basal crurotarsan clade, finds a close relationship between Aetosauria and Crocodylomorpha, and recovers a monophyletic Rauisuchia comprised of two major subclades. Support values are low, suggesting rampant homoplasy and missing data within Archosauria, but the phylogeny is highly congruent with stratigraphy. Comparison with alternative analyses identifies numerous scoring differences, but indicates that character sampling is the main source of incongruence. The phylogeny implies major missing lineages in the Early Triassic and may support a Carnian-Norian extinction event.Marshall Scholarship for study in the United KingdomJurassic FoundationUniversity of BristolPaleontological Societ

A Basal Sauropodomorph (Dinosauria: Saurischia) from the Ischigualasto Formation (Triassic, Carnian) and the Early Evolution of Sauropodomorpha

BACKGROUND: The earliest dinosaurs are from the early Late Triassic (Carnian) of South America. By the Carnian the main clades Saurischia and Ornithischia were already established, and the presence of the most primitive known sauropodomorph Saturnalia suggests also that Saurischia had already diverged into Theropoda and Sauropodomorpha. Knowledge of Carnian sauropodomorphs has been restricted to this single species. METHODOLOGY/PRINCIPAL FINDINGS: We describe a new small sauropodomorph dinosaur from the Ischigualsto Formation (Carnian) in northwest Argentina, Panphagia protos gen. et sp. nov., on the basis of a partial skeleton. The genus and species are characterized by an anteroposteriorly elongated fossa on the base of the anteroventral process of the nasal; wide lateral flange on the quadrate with a large foramen; deep groove on the lateral surface of the lower jaw surrounded by prominent dorsal and ventral ridges; bifurcated posteroventral process of the dentary; long retroarticular process transversally wider than the articular area for the quadrate; oval scars on the lateral surface of the posterior border of the centra of cervical vertebrae; distinct prominences on the neural arc of the anterior cervical vertebra; distal end of the scapular blade nearly three times wider than the neck; scapular blade with an expanded posterodistal corner; and medial lamina of brevis fossa twice as wide as the iliac spine. CONCLUSIONS/SIGNIFICANCE: We regard Panphagia as the most basal sauropodomorph, which shares the following apomorphies with Saturnalia and more derived sauropodomorphs: basally constricted crowns; lanceolate crowns; teeth of the anterior quarter of the dentary higher than the others; and short posterolateral flange of distal tibia. The presence of Panphagia at the base of the early Carnian Ischigualasto Formation suggests an earlier origin of Sauropodomorpha during the Middle Triassic