Supporting automatic recovery in offloaded distributed programming models through MPI-3 techniques

In this paper we describe the design of fault tolerance capabilities for general-purpose offload semantics, based on the OmpSs programming model. Using ParaStation MPI, a production MPI-3.1 implementation, we explore the features that, being standard compliant, an MPI stack must support to provide the necessary fault tolerance guarantees, based on MPI's dynamic process management. Our results, including synthetic benchmarks and applications, reveal low runtime overhead and efficient recovery, demonstrating that the existing MPI standard provided us with sufficient mechanisms to implement an effective and efficient fault-tolerant solution.This research received funding from the European Community’s 7th Framework Programme via the DEEP-ER project under Grant Agreement no. 610476. This work has also been supported by the Spanish Ministry of Science and Innovation (contract TIN2012-34557) and by Generalitat de Catalunya (contracts 2014-SGR-1051 and 2014-SGR-1272). Antonio J. Peña is cofinanced by the Spanish Ministry of Economy and Competitiveness under Juan de la Cierva fellowship number IJCI-2015-23266. The authors thank Jorge Bell´on, from BSC, for his technical support with the Nanos++ internals.Peer ReviewedPostprint (author's final draft

Rethinking marine plastics pollution: science diplomacy and multi-level governance

Although science diplomacy has been gaining relevance in foreign policy to solve environmental challenges, critical questions concerning what different instruments mean under the term ‘science diplomacy’ and whether science diplomacy does contribute to the progress in solving environmental issues remain unanswered. We explore those questions by linking science diplomacy salient features through documentary analysis of international instruments addressing the plastics pollution in the ocean. We find that from a science diplomacy and multi-level governance perspective, the responsibilities and capabilities of emergent actors of cross-level governance are also important, leading to more attention being paid to changes in the role of national authorities, away from passive leadership to cross-cutting coalitions supported by the salient features of science diplomacy, and redefining dominant discursive approaches that have framed plastics waste.info:eu-repo/semantics/publishedVersio

Immunotherapy for urothelial cancer: from the diagnostic pathologist's point of view

Inhibitory checkpoint proteins such as programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1) or cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) suppress anti-tumor T-cell resp..

Pentadienyl Complexes of Alkali Metals: Structure and Bonding

A systematic density functional study of the structure and bonding in the alkali-metal pentadienyl complexes C5H7E (E = Li-Cs) and their analogues derived from the 2,4-dimethylpentadienyl ligand is performed. The bonding in these structures has been analyzed in some detail with reference to molecular orbital analysis, and energy partition analysis, obtained by density functional calculations. An energy decomposition analysis indicates that the electrostatic interaction is the main factor to be considered in the stabilization of the gas-phase complexes we have studied. The stability of the U-shaped minimum energy structure decreases (the potential energy surface becomes more shallow) as the metal atom gets larger. We trace this behavior to a weakening of the metal–ligand binding due to the increasing diffuseness of the metal p orbitals on going down group 1. A significant pyramidalization at the terminal carbons in the coordinate U-shaped structure correlates with the strength of the metal–ligand binding. Initial results for the structural preferences of the complexes in solution for the lithium pentadienyl complex are examined in view of contrary experimental data. There still remains plenty of work to be done in modeling metal complexes in solution, and we suggest a way forward

Application of quality by design tools to upstream processing of platelet precursor cells to enable in vitro manufacture of blood products

Annually 4.5 million platelet units are transfused in Europe and the United States. These are obtained solely from allogeneic donations and have a shelf life of 5-7 days. To address the corresponding supply challenge, Moreau et al.1 devised a novel process for producing megakaryocytes (MKs, the platelet precursor cell) in vitro. A transcription-factor driven, forward-programming (FOP) approach converts human pluripotent stem cells into MKs. This strategy has the unique advantage of generating high yields of pure MKs in chemically defined medium which could lead to the production of a consistent, reliable supply of platelets which overcomes the logistical, financial and biosafety challenges for health organisations worldwide. Here we follow a Quality by Design (QbD) approach to enable improvements to the upstream processing of FOPMKs. Firstly, we created a process flow diagram for production of in vitro platelets for transfusion, which segregated processes into individual unit operations for control and optimisation. Next, we developed a Quality Target Product Profile (QTPP) and identified Critical Quality Attributes (CQAs) for each stage. We conducted a range of experiments utilising Design of Experiments (DOE) and mechanistic modelling2 tools to link Critical Process Parameters (CPPs) to CQAs. For adherent culture, we identified a productivity limit related to surface area available for growth and a cell loss phase which was dependent on cell seeding density, RhoK inhibitor usage and seed density. Using suspension cultures of FOPMK. We noted that TPO and Doxycycline concentration were CPPs as these impacted cell net growth rate and phenotype trajectory. Furthermore, we noted that medium exhaustion led to a 30% loss of viable cells over 8 hours. Proof of concept studies also showed that FOPMKs can be cultured in scaled-down suspension systems (ambr-15 and spinner flask culture) whilst retaining CQAs. 1. Moreau, T. et al. Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming. Nat. Commun. 7, 1–15 (2016). 2. Stacey, A. J., Cheeseman, E. A., Glen, K. E., Moore, R. L. L. & Thomas, R. J. Experimentally integrated dynamic modelling for intuitive optimisation of cell-based processes and manufacture. Biochem. Eng. J. 132, 130–138 (2018)

Müllerian Adenosarcoma of the Urinary Bladder: Clinicopathologic and Immunohistochemical Features with Novel Genetic Aberrations

Müllerian adenosarcoma is a biphasic neoplasm most commonly of the uterus and less frequently of the ovary. It has been rarely described to occur in other sites such as peritoneum and liver. In this study, we report the clinicopathologic, immunohistochemical and molecular features of a primary müllerian adenosarcoma of the urinary bladder in a 62-year-old woman. To our knowledge, this is the first report of müllerian adenosarcoma primary to the urinary bladder in the literature. Light microscopy showed a biphasic epithelial and stromal tumor with benign-appearing glands surrounded by endometrial-type stroma that is densely cellular with increased mitotic figures. The stroma surrounding the glands is more cellular than the intervening areas, which are more loose and edematous. Immunohistochemistry profile included positive staining for Pax2/8 within the glands, for CD10 and WT-1 within the spindled stroma, and for estrogen and progesterone receptors in both. Staining for desmin, GATA3, p63, and human papilloma virus (HPV) is negative. Molecular analyses identified mutations in AKT1 E17K, FLT3 D835N, KRAS G12D and HRAS G12S. These novel molecular aberrations have yet to be reported in the medical literature. X chromosome inactivation analysis revealed a clonal pattern in the stromal component and a non-clonal pattern in the epithelial component. Currently, the patient is disease/recurrence-free after regular follow-up of approximately 84 months. This case represents the first reported diagnosis of müllerian adenosarcoma arising in the urinary bladder with extensive clinicopathologic, immunohistochemical, and molecular analyses

The Epigenetic Regulatory Protein CBX2 Promotes mTORC1 Signalling and Inhibits DREAM Complex Activity to Drive Breast Cancer Cell Growth

Chromobox 2 (CBX2) is a chromatin-binding component of polycomb repressive complex 1, which causes gene silencing. CBX2 expression is elevated in triple-negative breast cancer (TNBC), for which there are few therapeutic options. Here, we aimed to investigate the functional role of CBX2 in TNBC. CBX2 knockdown in TNBC models reduced cell numbers, which was rescued by ectopic expression of wild-type CBX2 but not a chromatin binding-deficient mutant. Blocking CBX2 chromatin interactions using the inhibitor SW2_152F also reduced cell growth, suggesting CBX2 chromatin binding is crucial for TNBC progression. RNA sequencing and gene set enrichment analysis of CBX2-depleted cells identified downregulation of oncogenic signalling pathways, including mTORC1 and E2F signalling. Subsequent analysis identified that CBX2 represses the expression of mTORC1 inhibitors and the tumour suppressor RBL2. RBL2 repression, in turn, inhibits DREAM complex activity. The DREAM complex inhibits E2F signalling, causing cell senescence; therefore, inhibition of the DREAM complex via CBX2 may be a key oncogenic driver. We observed similar effects in oestrogen receptor-positive breast cancer, and analysis of patient datasets suggested CBX2 inhibits RBL2 activity in other cancer types. Therapeutic inhibition of CBX2 could therefore repress mTORC1 activation and promote DREAM complex-mediated senescence in TNBC and could have similar effects in other cancer types

Organized B cell sites in cartilaginous fishes reveal the evolutionary foundation of germinal centers

The absence of germinal centers (GCs) in cartilaginous fishes lies at odds with data showing that nurse sharks can produce robust antigen-specific responses and affinity mature their B cell repertoires. To investigate this apparent incongruity, we performed RNA sequencing on single nuclei, allowing us to characterize the cell types present in the nurse shark spleen, and RNAscope to provide in situ cellular resolution of key marker gene expression following immunization with R-phycoerythrin (PE). We tracked PE to the splenic follicles where it co-localizes with CXCR5high centrocyte-like B cells and a population of putative T follicular helper (Tfh) cells, surrounded by a peripheral ring of Ki67+ AID+ CXCR4+ centroblast-like B cells. Further, we reveal selection of mutations in B cell clones dissected from these follicles. We propose that the B cell sites iden tified here represent the evolutionary foundation of GCs, dating back to the jawed vertebrate ancestor

Higgs portal, fermionic dark matter, and a Standard Model like Higgs at 125 GeV

We show that fermionic dark matter (DM) which communicates with the Standard Model (SM) via the Higgs portal is a viable scenario, even if a SM-like Higgs is found at around 125 GeV. Using effective field theory we show that for DM with a mass in the range from about 60 GeV to 2 TeV the Higgs portal needs to be parity violating in order to be in agreement with direct detection searches. For parity conserving interactions we identify two distinct options that remain viable: a resonant Higgs portal, and an indirect Higgs portal. We illustrate both possibilities using a simple renormalizable toy model.Comment: 16 pages, 4 figures; references and discussion of Sommerfeld effect added; matches published versio

Low molecular weight organic acid salts, markers of old fungi activity in wall paintings

Micro-Infrared Spectroscopy (mSR-FTIR) and X-ray diffraction (mSR-XRD) with synchrotron light, Gas Chromatography/Mass Spectrometry (CG/MS), Optical Microscopy (OM) and Scanning Electron Microscopy (SEM/EDS) were used to identify and obtain the distribution of complex mixtures of calcium salts of low molecular weight organic acids (LMWOA) in micro-layered micro-samples. Filamentous fungi produce LMWOA that can react with metal cations producing stable salts. These substances were found in the dark spots covering the surfaces of Saint Michael's Chapel wall paintings of the Royal Monastery of Pedralbes in Barcelona linking them to old fungi activity. The presence of glycerol likewise related to the fungi activity is also identified in the layers.Postprint (author's final draft