Enhancing the significance of gravitational wave bursts through signal classification

The quest to observe gravitational waves challenges our ability to discriminate signals from detector noise. This issue is especially relevant for transient gravitational waves searches with a robust eyes wide open approach, the so called all- sky burst searches. Here we show how signal classification methods inspired by broad astrophysical characteristics can be implemented in all-sky burst searches preserving their generality. In our case study, we apply a multivariate analyses based on artificial neural networks to classify waves emitted in compact binary coalescences. We enhance by orders of magnitude the significance of signals belonging to this broad astrophysical class against the noise background. Alternatively, at a given level of mis-classification of noise events, we can detect about 1/4 more of the total signal population. We also show that a more general strategy of signal classification can actually be performed, by testing the ability of artificial neural networks in discriminating different signal classes. The possible impact on future observations by the LIGO-Virgo network of detectors is discussed by analysing recoloured noise from previous LIGO-Virgo data with coherent WaveBurst, one of the flagship pipelines dedicated to all-sky searches for transient gravitational waves

Challenges and opportunities of water quality monitoring and multi-stakeholder management in small islands: the case of Santa Cruz, Galápagos (Ecuador)

Sustainable water resources management roots in monitoring data reliability and a full engagement of all institutions involved in the water sector. When competences and interests are overlapping, however, coordination may be difficult, thus hampering cooperative actions. This is the case of Santa Cruz Island (Galápagos, Ecuador). A comprehensive assessment on water quality data (physico-chemical parameters, major elements, trace elements and coliforms) collected since 1985 revealed the need of optimizing monitoring efforts to fill knowledge gaps and to better target decision-making processes. A Water Committee (Comité de la gestión del Agua) was established to foster the coordinated action among stakeholders and to pave the way for joint monitoring in the island that can optimize the efforts for water quality assessment and protection. Shared procedures for data collection, sample analysis, evaluation and data assessment by an open-access geodatabase were proposed and implemented for the first time as a prototype in order to improve accountability and outreach towards civil society and water users. The overall results reveal the high potential of a well-structured and effective joint monitoring approach within a complex, multi-stakeholder framework.publishedVersio

Diffusion of biosimilar hemopoietic growth factors use in oncology practice: an Italian experience

Background: Biosimilars of hemopoietic growth factors present an important saving opportunity in oncology. However, while pharmacologists are aware of their potential benefits, biosimilars are still under-used in Italy. Improved information and guided clinical experience may help to increase the clinical acceptance of these drugs. To this aim, a collaborative educational project was set between an Hospital Oncology Unit and the Local Health Care Authority in Pavia, Italy. Methods: The project lasted 12 months. The strategy included an education-information seminar at startup, a reporting meeting at +6$+6$ months, electronic prescription monitoring and implementation of pharmacovigilance. The target was set to reach 90% of all naïve patients treated with biosimilars. Results: At the end of the study (2013), a dramatic relative increase in the prescription of biosimilar drugs was noted, with virtually 100% of new patients receiving biosimilar drugs during the last 4 months, with a positive impact on average per capita drug expenses. Active pharmacovigilance did not report any serious adverse drug reactions. An anonymous questionnaire showed that oncologists judged the experience quite positively, acquired a positive attitude toward these drugs and considered biosimilars a relevant saving opportunity, while adherence to prescription guidelines was maintained. Analysis of the year following the end of the project, 2014, showed a persistent prescription change. Conclusions: Results from this local experience suggests that specifically designed pragmatic interventions focused on information-education and monitoring may help in promoting the use and acceptance of biosimilar drugs in the real clinical setting

RAMPART: RowHammer Mitigation and Repair for Server Memory Systems

RowHammer attacks are a growing security and reliability concern for DRAMs and computer systems as they can induce many bit errors that overwhelm error detection and correction capabilities. System-level solutions are needed as process technology and circuit improvements alone are unlikely to provide complete protection against RowHammer attacks in the future. This paper introduces RAMPART, a novel approach to mitigating RowHammer attacks and improving server memory system reliability by remapping addresses in each DRAM in a way that confines RowHammer bit flips to a single device for any victim row address. When RAMPART is paired with Single Device Data Correction (SDDC) and patrol scrub, error detection and correction methods in use today, the system can detect and correct bit flips from a successful attack, allowing the memory system to heal itself. RAMPART is compatible with DDR5 RowHammer mitigation features, as well as a wide variety of algorithmic and probabilistic tracking methods. We also introduce BRC-VL, a variation of DDR5 Bounded Refresh Configuration (BRC) that improves system performance by reducing mitigation overhead and show that it works well with probabilistic sampling methods to combat traditional and victim-focused mitigation attacks like Half-Double. The combination of RAMPART, SDDC, and scrubbing enables stronger RowHammer resistance by correcting bit flips from one successful attack. Uncorrectable errors are much less likely, requiring two successful attacks before the memory system is scrubbed.Comment: 16 pages, 13 figures. A version of this paper will appear in the Proceedings of MEMSYS2

Properties of recombinant human cytosolic sialidase HsNEU2. The enzyme hydrolyzes monomerically dispersed GM1 ganglioside molecules

Recombinant human cytosolic sialidase (HsNEU2), expressed in Escherichia coli, was purified to homogeneity, and its substrate specificity was studied. HsNEU2 hydrolyzed 4-methylumbelliferyl alpha-NeuAc, alpha 2-->3 sialyllactose, glycoproteins (fetuin, alpha-acid glycoprotein, transferrin, and bovine submaxillary gland mucin), micellar gangliosides GD1a, GD1b, GT1b, and alpha 2-->3 paragloboside, and vesicular GM3. alpha 2-->6 sialyllactose, colominic acid, GM1 oligosaccharide, whereas micellar GM2 and GM1 were resistant. The optimal pH was 5.6, kinetics Michaelis-Menten type, V(max) varying from 250 IU/mg protein (GD1a) to 0.7 IU/mg protein (alpha(1)-acid glycoprotein), and K(m) in the millimolar range. HsNEU2 was activated by detergents (Triton X-100) only with gangliosidic substrates; the change of GM3 from vesicular to mixed micellar aggregation led to a 8.5-fold V(max) increase. HsNEU2 acted on gangliosides (GD1a, GM1, and GM2) at nanomolar concentrations. With these dispersions (studied in detailed on GM1), where monomers are bound to the tube wall or dilutedly associated (1:2000, mol/mol) to Triton X-100 micelles, the V(max) values were 25 and 72 microIU/mg protein, and K(m) was 10 and 15 x 10(-9) m, respectively. Remarkably, GM1 and GM2 were recognized only as monomers. HsNEU2 worked at pH 7.0 with an efficiency (compared with that at pH 5.6) ranging from 4% (on GD1a) to 64% (on alpha(1)-acid glycoprotein), from 7% (on GD1a) to 45% (on GM3) in the presence of Triton X-100, and from 30 to 40% on GM1 monomeric dispersion. These results show that HsNEU2 differentially recognizes the type of sialosyl linkage, the aglycone part of the substrate, and the supramolecular organization (monomer/micelle/vesicle) of gangliosides. The last ability might be relevant in sialidase interactions with gangliosides under physiological conditions

Sphingolipids : key regulators of apoptosis and pivotal players in cancer drug resistance

Drug resistance elicited by cancer cells still constitutes a huge problem that frequently impairs the efficacy of both conventional and novel molecular therapies. Chemotherapy usually acts to induce apoptosis in cancer cells; therefore, the investigation of apoptosis control and of the mechanisms used by cancer cells to evade apoptosis could be translated in an improvement of therapies. Among many tools acquired by cancer cells to this end, the de-regulated synthesis and metabolism of sphingolipids have been well documented. Sphingolipids are known to play many structural and signalling roles in cells, as they are involved in the control of growth, survival, adhesion, and motility. In particular, in order to increase survival, cancer cells: (a) counteract the accumulation of ceramide that is endowed with pro-apoptotic potential and is induced by many drugs; (b) increase the synthesis of sphingosine-1-phosphate and glucosylceramide that are pro-survivals signals; (c) modify the synthesis and the metabolism of complex glycosphingolipids, particularly increasing the levels of modified species of gangliosides such as 9-O acetylated GD3 (\u3b1Neu5Ac(2-8)\u3b1Neu5Ac(2-3)\u3b2Gal(1-4)\u3b2Glc(1-1)Cer) or N-glycolyl GM3 (\u3b1Neu5Ac (2-3)\u3b2Gal(1-4)\u3b2Glc(1-1)Cer) and de-N-acetyl GM3 (NeuNH(2)\u3b2Gal(1-4)\u3b2Glc(1-1)Cer) endowed with anti-apoptotic roles and of globoside Gb3 related to a higher expression of the multidrug resistance gene MDR1. In light of this evidence, the employment of chemical or genetic approaches specifically targeting sphingolipid dysregulations appears a promising tool for the improvement of current chemotherapy efficacy

External Validation of Equations to Estimate Resting Energy Expenditure in 2037 Children and Adolescents with and 389 without Obesity : a Cross-Sectional Study

We performed an external cross-validation study of 10 equations to estimate resting energy expenditure (REE) in 2037 children with and 389 without obesity. Inclusion criteria were Caucasian ethnicity, age 64 18 years, and availability of REE. REE was measured using indirect calorimetry. The correct classification fraction (CCF) of an equation was defined as the fraction of subjects whose estimated REE was within 10% of measured REE. The Moln\ue1r equation was the most accurate REE prediction equation with CCFs of 0.70 (95% CI 0.65 to 0.76) in girls without obesity, 0.64 (95% CI 0.61 to 0.66) in girls with obesity, 0.76 (95% CI 0.67 to 0.83) in boys without obesity, and 0.66 (95% CI 0.63 to 0.69) in boys with obesity. The Mifflin equation was the second most accurate equation with CCFs of 0.67 (95% CI 0.61 to 0.73) in girls without obesity, 0.61 (95% CI 0.58 to 0.64) in girls with obesity, 0.75 (95% CI 0.66 to 0.82) in boys without obesity, and 0.66 (95% CI 0.63 to 0.69) in boys with obesity