204 research outputs found
Warp-X: a new exascale computing platform for beam-plasma simulations
Turning the current experimental plasma accelerator state-of-the-art from a
promising technology into mainstream scientific tools depends critically on
high-performance, high-fidelity modeling of complex processes that develop over
a wide range of space and time scales. As part of the U.S. Department of
Energy's Exascale Computing Project, a team from Lawrence Berkeley National
Laboratory, in collaboration with teams from SLAC National Accelerator
Laboratory and Lawrence Livermore National Laboratory, is developing a new
plasma accelerator simulation tool that will harness the power of future
exascale supercomputers for high-performance modeling of plasma accelerators.
We present the various components of the codes such as the new Particle-In-Cell
Scalable Application Resource (PICSAR) and the redesigned adaptive mesh
refinement library AMReX, which are combined with redesigned elements of the
Warp code, in the new WarpX software. The code structure, status, early
examples of applications and plans are discussed
Endogenous protease nexin-1 protects against cerebral ischemia.
The serine protease thrombin plays a role in signalling ischemic neuronal death in the brain. Paradoxically, endogenous neuroprotective mechanisms can be triggered by preconditioning with thrombin (thrombin preconditioning, TPC), leading to tolerance to cerebral ischemia. Here we studied the role of thrombin's endogenous potent inhibitor, protease nexin-1 (PN-1), in ischemia and in tolerance to cerebral ischemia induced by TPC. Cerebral ischemia was modelled in vitro in organotypic hippocampal slice cultures from rats or genetically engineered mice lacking PN-1 or with the reporter gene lacZ knocked into the PN-1 locus PN-1HAPN-1-lacZ/HAPN-1-lacZ (PN-1 KI) exposed to oxygen and glucose deprivation (OGD). We observed increased thrombin enzyme activity in culture homogenates 24 h after OGD. Lack of PN-1 increased neuronal death in the CA1, suggesting that endogenous PN-1 inhibits thrombin-induced neuronal damage after ischemia. OGD enhanced β-galactosidase activity, reflecting PN-1 expression, at one and 24 h, most strikingly in the stratum radiatum, a glial cell layer adjacent to the CA1 layer of ischemia sensitive neurons. TPC, 24 h before OGD, additionally increased PN-1 expression 1 h after OGD, compared to OGD alone. TPC failed to induce tolerance in cultures from PN-1(-/-) mice confirming PN-1 as an important TPC target. PN-1 upregulation after TPC was blocked by the c-Jun N-terminal kinase (JNK) inhibitor, L-JNKI1, known to block TPC. This work suggests that PN-1 is an endogenous neuroprotectant in cerebral ischemia and a potential target for neuroprotection
Business and Information Technology Alignment Measurement -- a recent Literature Review
Since technology has been involved in the business context, Business and
Information Technology Alignment (BITA) has been one of the main concerns of IT
and Business executives and directors due to its importance to overall company
performance, especially today in the age of digital transformation. Several
models and frameworks have been developed for BITA implementation and for
measuring their level of success, each one with a different approach to this
desired state. The BITA measurement is one of the main decision-making tools in
the strategic domain of companies. In general, the classical-internal alignment
is the most measured domain and the external environment evolution alignment is
the least measured. This literature review aims to characterize and analyze
current research on BITA measurement with a comprehensive view of the works
published over the last 15 years to identify potential gaps and future areas of
research in the field.Comment: 12 pages, Preprint version, BIS 2018 International Workshops, Berlin,
Germany, July 18 to 20, 2018, Revised Paper
Changes in triggering of ST-elevation myocardial infarction by particulate air pollution in Monroe County, New York over time: a case-crossover study
Background
Previous studies have reported that fine particle (PM2.5) concentrations triggered ST elevation myocardial infarctions (STEMI). In Rochester, NY, multiple air quality policies and economic changes/influences from 2008 to 2013 led to decreased concentrations of PM2.5 and its major constituents (SO42−, NO3−, elemental and primary organic carbon). This study examined whether the rate of STEMI associated with increased ambient gaseous and PM component concentrations was different AFTER these air quality policies and economic changes (2014–2016), compared to DURING (2008–2013) and BEFORE these polices and changes (2005–2007).
Methods
Using 921 STEMIs treated at the University of Rochester Medical Center (2005–2016) and a case-crossover design, we examined whether the rate of STEMI associated with increased PM2.5, ultrafine particles (UFP, < 100 nm), accumulation mode particles (AMP, 100-500 nm), black carbon, SO2, CO, and O3 concentrations in the previous 1–72 h was modified by the time period related to these pollutant source changes (BEFORE, DURING, AFTER).
Results
Each interquartile range (3702 particles/cm3) increase in UFP concentration in the previous 1 h was associated with a 12% (95% CI = 3%, 22%) increase in the rate of STEMI. The effect size was larger in the AFTER period (26%) than the DURING (5%) or BEFORE periods (9%). There were similar patterns for black carbon and SO2.
Conclusions
An increased rate of STEMI associated with UFP and other pollutant concentrations was higher in the AFTER period compared to the BEFORE and DURING periods. This may be due to changes in PM composition (e.g. higher secondary organic carbon and particle bound reactive oxygen species) following these air quality policies and economic changes
Effect of Sm-, Gd- codoping on structural modifications in aluminoborosilicate glasses under beta-irradiation
Two series of Sm-, Gd-codoped aluminoborosilicate glasses with different
total rare earth content have been studied in order to examine the codoping
effect on the structural modifications of beta-irradiated glasses. The data
obtained by Electron Paramagnetic Resonance spectroscopy indicated that
relative amount of Gd3+ ions located in network former position reveals
non-linear dependence on Sm/Gd ratio. Besides, codoping leads to the evolution
of the EPR signal attributed to defects created by irradiation: superhyperfine
structure of boron oxygen hole centres EPR line becomes less noticeable and
resolved with increase of Gd amount. This fact manifests that Gd3+ ions are
mainly diluted in vicinity of the boron network. By Raman spectroscopy, we
showed that the structural changes induced by the irradiation also reveal
non-linear behaviour with Sm/Gd ratio. In fact, the shift of the Si-O-Si
bending vibration modes has a clear minimum for the samples containing equal
amount of Sm and Gd (50:50) in both series of the investigated glasses. In
contrast, for single doped glass there is no influence of dopant's content on
Si-O-Si shift (in case of Gd) or its diminution (in case of Sm) occurs which is
explained by the reduction process influence. At the same time, no noticeable
effect of codoping on Sm3+ intensity as well as on Sm2+ emission or on Sm
reduction process was observed
The Minimal Supersymmetric Standard Model: Group Summary Report
CONTENTS: 1. Synopsis, 2. The MSSM Spectrum, 3. The Physical Parameters, 4.
Higgs Boson Production and Decays, 5. SUSY Particle Production and Decays, 6.
Experimental Bounds on SUSY Particle Masses, 7. References.Comment: 121 pages, latex + epsfig, graphicx, axodraw, Report of the MSSM
working group for the Workshop "GDR-Supersym\'etrie",France. Rep. PM/98-4
Valoriser et conserver le pin de Salzmann en France -
Cet article fait le point sur l'état des connaissances disponibles sur le pin de Salzmann, dans les domaines écologique, sylvicole et de diversité génétique. Il fait aussi état des risques qui menacent cette ressource française originale, caractéristique de la forêt méditerranéenne et indique quelles sont les stratégies actuelles employées pour sauvegarder et utiliser durablement les populations naturelles
Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors
Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Conclusions Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11
A human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models
In patients with type 2 diabetes, pancreatic beta cells progressively degenerate and gradually lose their ability to produce insulin and regulate blood glucose. Beta cell dysfunction and loss is associated with an accumulation of aggregated forms of islet amyloid polypeptide (IAPP) consisting of soluble prefibrillar IAPP oligomers as well as insoluble IAPP fibrils in pancreatic islets. Here, we describe a human monoclonal antibody selectively targeting IAPP oligomers and neutralizing IAPP aggregate toxicity by preventing membrane disruption and apoptosis in vitro. Antibody treatment in male rats and mice transgenic for human IAPP, and human islet-engrafted mouse models of type 2 diabetes triggers clearance of IAPP oligomers resulting in beta cell protection and improved glucose control. These results provide new evidence for the pathological role of IAPP oligomers and suggest that antibody-mediated removal of IAPP oligomers could be a pharmaceutical strategy to support beta cell function in type 2 diabetes
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