3,593 research outputs found
Sequential featureâbased mesh movement and adjoint errorâbased mesh refinement
Nowadays, aerodynamic computational modeling is carried out on a daily basis in an industrial setting. This is done with the aim of predicting the performance and flow characteristics of new components. However, limited resources in terms of time and hardware force the engineer to employ relatively coarse computational grids, thus achieving results with variable degree of inaccuracy. In this article, a novel combination of feature and adjointâbased mesh adaptation methods is investigated and applied to typical threeâdimensional turbomachinery cases, such as compressor and fan blades. The proposed process starts by employing featureâbased mesh movement to improve the global flow solution and then adjoint refinement to tune the mesh for each quantity of interest. Comparison of this process with one utilizing only the adjoint refinement procedure shows significant benefits in terms of accuracy of the performance quantity
Cancer management during COVID-19 pandemic: is immune checkpoint inhibitors-based immunotherapy harmful or beneficial?
The coronavirus disease 2019 (COVID-19) is currently representing a global health threat especially for fragile individuals, such as cancer patients. It was demonstrated that cancer patients have an increased risk of developing a worse symptomatology upon severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) infection, often leading to hospitalization and intensive care. The consequences of this pandemic for oncology are really heavy, as the entire healthcare system got reorganized. Both oncologists and cancer patients are experiencing rescheduling of treatments and disruptions of appointments with a concurrent surge of fear and stress. In this review all the up-to-date findings, concerning the association between COVID-19 and cancer, are reported. A remaining very debated question regards the use of an innovative class of anti-cancer molecules, the immune checkpoint inhibitors (ICIs), given their modulating effects on the immune system. For that reason, administration of ICIs to cancer patients represents a question mark during this pandemic, as its correlation with COVID-19-associated risks is still under investigation. Based on the mechanisms of action of ICIs and the current evidence, we suggest that ICIs not only can be safely administered to cancer patients, but they might even be beneficial in COVID-19-positive cancer patients, by exerting an immune-stimulating action
RIP Links TLR4 to Akt and Is Essential for Cell Survival in Response to LPS Stimulation
Receptor-interacting protein (RIP) has been reported to associate with tumor necrosisâassociated factor (TRAF)2 and TRAF6. Since TRAF2 and TRAF6 play important roles in CD40 signaling and TRAF6 plays an important role in TLR4 signaling, we examined the role of RIP in signaling via CD40 and TLR4. Splenocytes from RIPâ/â mice proliferated and underwent isotype switching normally in response to anti-CD40âIL-4 but completely failed to do so in response to LPSâIL-4. However, they normally up-regulated TNF-Îą and IL-6 gene expression and CD54 and CD86 surface expression after LPS stimulation. RIPâ/â splenocytes exhibited increased apoptosis and impaired Akt phosphorylation after LPS stimulation. These results suggest that RIP is essential for cell survival after TLR4 signaling and links TLR4 to the phosphatidylinositol 3 kinaseâAkt pathway
Prospects for the Search for a Standard Model Higgs Boson in ATLAS using Vector Boson Fusion
The potential for the discovery of a Standard Model Higgs boson in the mass
range m_H < 2 m_Z in the vector boson fusion mode has been studied for the
ATLAS experiment at the LHC. The characteristic signatures of additional jets
in the forward regions of the detector and of low jet activity in the central
region allow for an efficient background rejection. Analyses for the H -> WW
and H -> tau tau decay modes have been performed using a realistic simulation
of the expected detector performance. The results obtained demonstrate the
large discovery potential in the H -> WW decay channel and the sensitivity to
Higgs boson decays into tau-pairs in the low-mass region around 120 GeV.Comment: 20 pages, 13 ps figures, uses EPJ style fil
The 68âkDa subunit of mammalian cleavage factor I interacts with the U7 small nuclear ribonucleoprotein and participates in 3â˛-end processing of animal histone mRNAs
Metazoan replication-dependent histone pre-mRNAs undergo a unique 3â˛-cleavage reaction which does not result in mRNA polyadenylation. Although the cleavage site is defined by histone-specific factors (hairpin binding protein, a 100-kDa zinc-finger protein and the U7 snRNP), a large complex consisting of cleavage/polyadenylation specificity factor, two subunits of cleavage stimulation factor and symplekin acts as the effector of RNA cleavage. Here, we report that yet another protein involved in cleavage/polyadenylation, mammalian cleavage factor I 68-kDa subunit (CF Im68), participates in histone RNA 3â˛-end processing. CF Im68 was found in a highly purified U7 snRNP preparation. Its interaction with the U7 snRNP depends on the N-terminus of the U7 snRNP protein Lsm11, known to be important for histone RNA processing. In vivo, both depletion and overexpression of CF Im68 cause significant decreases in processing efficiency. In vitro 3â˛-end processing is slightly stimulated by the addition of low amounts of CF Im68, but inhibited by high amounts or by anti-CF Im68 antibody. Finally, immunoprecipitation of CF Im68 results in a strong enrichment of histone pre-mRNAs. In contrast, the small CF Im subunit, CF Im25, does not appear to be involved in histone RNA processin
The 68âkDa subunit of mammalian cleavage factor I interacts with the U7 small nuclear ribonucleoprotein and participates in 3â˛-end processing of animal histone mRNAs
Metazoan replication-dependent histone pre-mRNAs undergo a unique 3â˛-cleavage reaction which does not result in mRNA polyadenylation. Although the cleavage site is defined by histone-specific factors (hairpin binding protein, a 100-kDa zinc-finger protein and the U7 snRNP), a large complex consisting of cleavage/polyadenylation specificity factor, two subunits of cleavage stimulation factor and symplekin acts as the effector of RNA cleavage. Here, we report that yet another protein involved in cleavage/polyadenylation, mammalian cleavage factor I 68-kDa subunit (CF Im68), participates in histone RNA 3â˛-end processing. CF Im68 was found in a highly purified U7 snRNP preparation. Its interaction with the U7 snRNP depends on the N-terminus of the U7 snRNP protein Lsm11, known to be important for histone RNA processing. In vivo, both depletion and overexpression of CF Im68 cause significant decreases in processing efficiency. In vitro 3â˛-end processing is slightly stimulated by the addition of low amounts of CF Im68, but inhibited by high amounts or by anti-CF Im68 antibody. Finally, immunoprecipitation of CF Im68 results in a strong enrichment of histone pre-mRNAs. In contrast, the small CF Im subunit, CF Im25, does not appear to be involved in histone RNA processing
Immune-checkpoint inhibitors from cancer to COVIDâ19: A promising avenue for the treatment of patients with COVIDâ19
The severe acute respiratory syndrome associated coronavirusâ2 (SARSâCoVâ2) poses a threat to human life worldwide. Since early March, 2020, coronavirus disease 2019 (COVIDâ19), characterized by an acute and often severe form of pneumonia, has been declared a pandemic. This has led to a boom in biomedical research studies at all stages of the pipeline, from the in vitro to the clinical phase. In line with this global effort, known drugs, currently used for the treatment of other pathologies, including antivirals, immunomodulating compounds and antibodies, are currently used offâlabel for the treatment of COVIDâ19, in association with the supportive standard care. Yet, no effective treatments have been identified. A new hope stems from medical oncology and relies on the use of immuneâcheckpoint inhibitors (ICIs). In particular, amongst the ICIs, antibodies able to block the programmed deathâ1 (PDâ1)/PD ligand-1 (PDâL1) pathway have revealed a hidden potential. In fact, patients with severe and critical COVIDâ19, even prior to the appearance of acute respiratory distress syndrome, exhibit lymphocytopenia and suffer from Tâcell exhaustion, which may lead to viral sepsis and an increased mortality rate. It has been observed that cancer patients, who usually are immunocompromised, may restore their antiâtumoral immune response when treated with ICIs. Moreover, viral-infected mice and humans, exhibit a Tâcell exhaustion, which is also observed following SARSâCoVâ2 infection. Importantly, when treated with antiâPDâ1 and antiâPDâL1 antibodies, they restore their Tâcell competence and efficiently counteract the viral infection. Based on these observations, four clinical trials are currently open, to examine the efficacy of antiâPDâ1 antibody administration to both cancer and nonâcancer individuals affected by COVIDâ19. The results may prove the hypothesis that restoring exhausted Tâcells may be a winning strategy to beat SARSâCoVâ2 infection
Co-carcinogenic effects of vitamin E in prostate
A large number of basic researches and observational studies suggested the cancer preventive activity of vitamin E, but large-scale human intervention trials have yielded disappointing results and actually showed a higher incidence of prostate cancer although the mechanisms underlying the increased risk remain largely unknown. Here we show through in vitro and in vivo studies that vitamin E produces a marked inductive effect on carcinogen-bioactivating enzymes and a pro-oxidant status promoting both DNA damage and cell transformation frequency. First, we found that vitamin E in the human prostate epithelial RWPE-1 cell line has the remarkable ability to upregulate the expression of various phase-I activating cytochrome P450 (CYP) enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), giving rise to supraphysiological levels of reactive oxygen species. Furthermore, our rat model confirmed that vitamin E in the prostate has a powerful booster effect on CYP enzymes associated with the generation of oxidative stress, thereby favoring lipid-derived electrophile spread that covalently modifies proteins. We show that vitamin E not only causes DNA damage but also promotes cell transformation frequency induced by the PAH-prototype benzo[a]pyrene. Our findings might explain why dietary supplementation with vitamin E increases the prostate cancer risk among healthy men
Management of congenital nephrotic syndrome: consensus recommendations of the ERKNet-ESPN Working Group
Congenital nephrotic syndrome (CNS) is a heterogeneous group of disorders characterized by nephrotic-range proteinuria, hypoalbuminaemia and oedema, which manifest in utero or during the first 3 months of life. The main cause of CNS is genetic defects in podocytes; however, it can also be caused, in rare cases, by congenital infections or maternal allo-immune disease. Management of CNS is very challenging because patients are prone to severe complications, such as haemodynamic compromise, infections, thromboses, impaired growth and kidney failure. In this consensus statement, experts from the European Reference Network for Kidney Diseases (ERKNet) and the European Society for Paediatric Nephrology (ESPN) summarize the current evidence and present recommendations for the management of CNS, including the use of reninâangiotensin system inhibitors, diuretics, anticoagulation and infection prophylaxis. Therapeutic management should be adapted to the clinical severity of the condition with the aim of maintaining intravascular euvolaemia and adequate nutrition, while preventing complications and preserving central and peripheral vessels. We do not recommend performing routine early nephrectomies but suggest that they are considered in patients with severe complications despite optimal conservative treatment, and before transplantation in patients with persisting nephrotic syndrome and/or a WT1-dominant pathogenic variant
A PMT-Block test bench
The front-end electronics of the ATLAS hadronic calorimeter (Tile Cal) is
housed in a unit, called {\it PMT-Block}. The PMT-Block is a compact instrument
comprising a light mixer, a PMT together with its divider and a {\it 3-in-1}
card, which provides shaping, amplification and integration for the signals.
This instrument needs to be qualified before being assembled on the detector. A
PMT-Block test bench has been developed for this purpose. This test bench is a
system which allows fast, albeit accurate enough, measurements of the main
properties of a complete PMT-Block. The system, both hardware and software, and
the protocol used for the PMT-Blocks characterisation are described in detail
in this report. The results obtained in the test of about 10000 PMT-Blocks
needed for the instrumentation of the ATLAS (LHC-CERN) hadronic Tile
Calorimeter are also reported.Comment: 23 pages, 10 figure
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