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

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

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

Demonstration of tunability of HOFI waveguides via start-to-end simulations

In recent years, hydrodynamic optical-field-ionized (HOFI) channels have emerged as a promising technique to create laser waveguides suitable for guiding tightly focused laser pulses in a plasma, as needed for laser-plasma accelerators. While experimental advances in HOFI channels continue to be made, the underlying mechanisms and the roles of the main parameters remain largely unexplored. In this paper, we propose a start-to-end simulation pipeline of the HOFI channel formation and the resulting laser guiding and use it to explore the underlying physics and the tunability of HOFI channels. This approach is benchmarked against experimental measurements. HOFI channels are shown to feature excellent guiding properties over a wide range of parameters, making them a promising and tunable waveguide option for laser-plasma accelerators

The future for Mediterranean wetlands: 50 key issues and 50 important conservation research questions

Wetlands are critically important for biodiversity and human wellbeing, but face a range of challenges. This is especially true in the Mediterranean region, where wetlands support endemic and threatened species and remain integral to human societies, but have been severely degraded in recent decades. Here, in order to raise awareness of future challenges and opportunities for Mediterranean wetlands, and to inform proactive research and management, we identified (a) 50 key issues that might affect Mediterranean wetlands between 2020 and 2050, and (b) 50 important research questions that, if answered, would have the greatest impact on the conservation of Mediterranean wetlands between 2020 and 2050. We gathered ideas through an online survey and review of recent literature. A diverse assessment panel prioritised ideas through an iterative, anonymised, Delphi-like process of scoring, voting and discussion. The prioritised issues included some that are already well known but likely to have a large impact on Mediterranean wetlands in the next 30 years (e.g. the accumulation of dams and reservoirs, plastic pollution and weak governance), and some that are currently overlooked in the context of Mediterranean wetlands (e.g. increasing desalination capacity and development of antimicrobial resistance). Questions largely focused on how best to carry out conservation interventions, or understanding the impacts of threats to inform conservation decision-making. This analysis will support research, policy and practice related to environmental conservation and sustainable development in the Mediterranean, and provides a model for similar analyses elsewhere in the world

Term birth weight and ambient air pollutant concentrations during pregnancy, among women living in Monroe County, New York

Increased ambient air pollutant concentrations during pregnancy have been associated with reduced birth weight, but the etiologically relevant pregnancy time window(s) is/are unclear. In 76,500 singleton births in Monroe County, NY (2005–2016), who were 37–42 gestational weeks at delivery, we used generalized linear models to regress term birth weight against mean gestational month pollutant concentrations, adjusting for mean temperature, and maternal, infant, and medical service use characteristics. Overall, there were no clear patterns of term birth weight change associated with increased concentrations of any pollutant across gestational months. However, among Hispanic women only, increases in all pollutants, except O3, in multiple gestational months, were associated with decreased term birth weight. Each 3.25 µg/m3 increase in PM2.5 concentration in the 6th gestational month was associated with a −20.4 g (95% CI = −34.0, −6.8) reduction in term birth weight among Hispanic women, but a 4.1 g (95% CI = −2.5, 10.8) increase among non-Hispanic mothers (p for interaction &lt; 0.001). Although ambient air pollutant concentrations during pregnancy were not associated with reduced term birth weight among women of all ethnicities living in Monroe County, this observed association in Hispanic mothers may be a result of less exposure misclassification and bias (due to closer residential proximity to the monitoring site)

Sucrose Monoester Micelles Size Determined by Fluorescence Correlation Spectroscopy (FCS)

One of the several uses of sucrose detergents, as well as other micelle forming detergents, is the solubilization of different membrane proteins. Accurate knowledge of the micelle properties, including size and shape, are needed to optimize the surfactant conditions for protein purification and membrane characterization. We synthesized sucrose esters having different numbers of methylene subunits on the substituent to correlate the number of methylene groups with the size of the corresponding micelles. We used Fluorescence Correlation Spectroscopy (FCS) and two photon excitation to determine the translational D of the micelles and calculate their corresponding hydrodynamic radius, Rh. As a fluorescent probe we used LAURDAN (6-dodecanoyl-2-dimethylaminonaphthalene), a dye highly fluorescent when integrated in the micelle and non-fluorescent in aqueous media. We found a linear correlation between the size of the tail and the hydrodynamic radius of the micelle for the series of detergents measured