A parallel Block Lanczos algorithm and its implementation for the evaluation of some eigenvalues of large sparse symmetric matrices on multicomputers

In the present work we describe HPEC (High Performance Eigenvalues Computation), a parallel software package for the evaluation of some eigenvalues of a large sparse symmetric matrix. It implements an efficient and portable Block Lanczos algorithm for distributed memory multicomputers. HPEC is based on basic linear algebra operations for sparse and dense matrices, some of which have been derived by ScaLAPACK library modules. Numerical experiments have been carried out to evaluate HPEC performance on a cluster of workstations with test matrices from Matrix Market and Higham’s collections. A comparison with a PARPACKroutine is also detailed. Finally, parallel performance is evaluated on random matrices, using standard parameters

Transfer of particulate matter from the Northwestern Mediterranean continental margin: Variability and controlling factors

International audienceLong-term observations of monthly downward particle fluxes and hourly currents and temperaturewere initiated in 1993 in two canyons of the continental margin of the Gulf of Lion. The goals of thissurvey were to estimate its contribution to the CO 2 global budget and to understand the role offorcing factors in the control of present-day particle exchange across this margin. A previousstatistical analysis of the long-term time series suggested that variability in the transfer of particulatematter to the deep ocean could be the result of the effect of the meandering of the Northern Currentand by dense water formation in winter rather than variations in the sources of matter. Numericalsimulations have been carried out to consider these hypotheses. A model is used to examine theimpact of local atmospheric forcing (wind stress, heat fluxes, precipitation–evaporation budget) onthe variability of the oceanic circulation and of mass fluxes within the canyons from December toApril, for five consecutive years between 1996 and 2001. Results show an east-west gradient of massexport on the shelf and a positive correlation between anomalies of dense water formation rates andinterannual variability of particle fluxes. However, in the eastern part of the Gulf, the simulated massexport from the shelf is not significant, even during a winter of strong convection, when the measuredparticle fluxes are at maxima. Moreover, although the model suggests that the dense water formationcould be the major hydrodynamic forcing factor, this process is not sufficient to completely explainthe space and time variations of observed particle fluxes, especially at depth

P1367Effects of levosimendan therapy in patients with severe functional mitral regurgitation and chronic heart failure undergoing mitraclip implantation: a single-centre experience

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Quantitative lung ultrasonography: A putative new algorithm for automatic detection and quantification of B-lines

Background: This pilot study was designed to develop a fully automatic and quantitative scoring system of B-lines (QLUSS: quantitative lung ultrasound score) involving the pleural line and to compare it with previously described semi-quantitative scores in the measurement of extravascular lung water as determined by standard thermo-dilution. Methods: This was a prospective observational study of 12 patients admitted in the intensive care unit with acute respiratory distress and each provided with 12 lung ultrasound (LUS) frames. Data collected from each patient consisted in five different scores, four semi-quantitative (nLUSS, cLUSS, qLUSS, %LUSS) and quantitative scores (QLUSS). The association between LUS scores and extravascular lung water (EVLW) was determined by simple linear regression (SLR) and robust linear regression (RLR) methods. A correlation analysis between the LUS scores was performed by using the Spearman rank test. Inter-observer variability was tested by computing intraclass correlation coefficient (ICC) in two-way models for agreement, basing on scores obtained by different raters blinded to patients' conditions and clinical history. Results: In the SLR, QLUSS showed a stronger association with EVLW (R 2 = 0.57) than cLUSS (R 2 = 0.45) and nLUSS (R 2 = 0.000), while a lower association than qLUSS (R 2 = 0.85) and %LUSS (R 2 = 0.72) occurred. By applying RLR, QLUSS showed an association for EVLW (R 2 = 0.86) comparable to qLUSS (R 2 = 0.85) and stronger than %LUSS (R 2 = 0.72). QLUSS was significantly correlated with qLUSS (r = 0.772; p = 0.003) and %LUSS (r = 0.757; p = 0.005), but not with cLUSS (r = 0.561; p = 0.058) and nLUSS (r = 0.105; p = 0.744). Moreover, QLUSS showed the highest ICC (0.998; 95%CI from 0.996 to 0.999) among the LUS scores. Conclusions: This study demonstrates that computer-aided scoring of the pleural line percentage affected by B-lines has the potential to assess EVLW. QLUSS may have a significant impact, once validated with a larger dataset composed by multiple real-time frames. This approach has the potentials to be advantageous in terms of faster data analysis and applicability to large sets of data without increased costs. On the contrary, it is not useful in pleural effusion or consolidations

Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion

In cardiac surgery, postoperative low cardiac output has been shown to correlate with increased rates of organ failure and mortality. Catecholamines have been the standard therapy for many years, although they carry substantial risk for adverse cardiac and systemic effects, and have been reported to be associated with increased mortality. On the other hand, the calcium sensitiser and potassium channel opener levosimendan has been shown to improve cardiac function with no imbalance in oxygen consumption, and to have protective effects in other organs. Numerous clinical trials have indicated favourable cardiac and non-cardiac effects of preoperative and perioperative administration of levosimendan. A panel of 27 experts from 18 countries has now reviewed the literature on the use of levosimendan in on-pump and off-pump coronary artery bypass grafting and in heart valve surgery. This panel discussed the published evidence in these various settings, and agreed to vote on a set of questions related to the cardioprotective effects of levosimendan when administered preoperatively, with the purpose of reaching a consensus on which patients could benefit from the preoperative use of levosimendan and in which kind of procedures, and at which doses and timing should levosimendan be administered. Here, we present a systematic review of the literature to report on the completed and ongoing studies on levosimendan, including the newly commenced LEVO-CTS phase III study (NCT02025621), and on the consensus reached on the recommendations proposed for the use of preoperative levosimendan

Jugular vein distensibility predicts fluid responsiveness in septic patients

Introduction: The purpose of the study was to verify the efficacy of using internal jugular vein (IJV) size and distensibility as a reliable index of fluid responsiveness in mechanically ventilated patients with sepsis. Methods: Hemodynamic data of mechanically ventilated patients with sepsis were collected through a radial arterial indwelling catheter connected to continuous hemodynamic monitoring system (Most Care®, Vytech Health, Padova, Italy), including cardiac index (CI) (L/min/M2), heart rate (beats/min), mean arterial pressure (MAP) (mmHg), central venous pressure (CVP) (mmHg) and arterial pulse pressure variation (PPV), coupled with ultrasound evaluation of IJV distensibility (%), defined as a ratio of the difference between IJV maximal antero-posterior diameter during inspiration and minimum expiratory diameter to minimum expiratory diameter x100. Patients were retrospectively divided into two groups; fluid responders (R), if CI increase of more than or equal to 15% after a 7 ml/kg crystalloid infusion, and non-responders (NR) if CI increased more than 15%. We compared differences in measured variables between R and NR groups and calculated receiver-operator-characteristic (ROC) curves of optimal IJV distensibility and PPV sensitivity and specificity to predicting R. We also calculated a combined inferior vena cava distensibility-PPV ROC curve to predict R. Results: We enrolled 50 patients, of these, 30 were R. Responders presented higher IJV distensibility and PPV before fluid challenge than NR (P <0.05). An IJV distensibility more than 18% prior to volume challenge had an 80% sensitivity and 85% specificity to predict R. Pairwise comparison between IJV distensibility and PPV ROC curves revealed similar ROC area under the curve results. Interestingly, combining IJV distensibility more than 9.7% and PPV more than 12% predicted fluid responsiveness with a sensitivity of 100% and specificity of 95%. Conclusion: IJV distensibility is an accurate, easily acquired non-invasive parameter of fluid responsiveness in mechanically ventilated septic patients with performance similar to PPV. The combined use of IJV distensibility with left-sided indexes of fluid responsiveness improves their predictive value

Influenza A triggered status asthmaticus requiring emergency ECMO

We describe a case of acute respiratory failure due to severe pneumonia triggered by the influenza A virus, rapidly evolving into a refractory status asthmaticus requiring emergent ECMO assistance, in order to facilitate the clinical management of patients suffering from this rare but life-threatening condition. This case report demonstrates that infection with influenza A virus can present with severe pneumonia and status asthmaticus refractory to medical and ventilatory treatment. When medical treatment and mechanical ventilation fail, extracorporeal membrane oxygenation therapy should not be delayed as it will avoid injury resulting from inadequate mechanical ventilation and lung hyperinflation

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

Los sistemas de gobierno corporativo y su vigencia en la Argentina

Si bien el campo de estudio del Gobierno Corporativo es muy amplio, la mayor proporción de sus desarrollos ha tenido lugar en el ámbito de las empresas que adoptan forma societaria. En esos casos, se analizan las estructuras económicas de las empresas, y se alinean con las superestructuras jurídicas más adecuadas. En su seno, son estudiados los principales conflictos de intereses que moldean su funcionamiento, usualmente modelándolos como relaciones de agencia. Éstas, junto a las asimetrías informativas y a la incompletitud contractual típicas de este tipo de organizaciones (Hart, 1995), brindan el contexto donde surgen endógenamente los sistemas de Gobierno Corporativo.Facultad de Ciencias Económica

Control of replication stress and mitosis in colorectal cancer stem cells through the interplay of PARP1, MRE11 and RAD51

Cancer stem cells (CSCs) are tumor subpopulations driving disease development, progression, relapse and therapy resistance, and their targeting ensures tumor eradication. CSCs display heterogeneous replication stress (RS), but the functionality/relevance of the RS response (RSR) centered on the ATR-CHK1 axis is debated. Here, we show that the RSR is efficient in primary CSCs from colorectal cancer (CRC-SCs), and describe unique roles for PARP1 and MRE11/RAD51. First, we demonstrated that PARP1 is upregulated in CRC-SCs resistant to several replication poisons and RSR inhibitors (RSRi). In these cells, PARP1 modulates replication fork speed resulting in low constitutive RS. Second, we showed that MRE11 and RAD51 cooperate in the&nbsp;genoprotection and mitosis execution of PARP1-upregulated CRC-SCs. These roles represent therapeutic vulnerabilities for CSCs. Indeed, PARP1i sensitized CRC-SCs to ATRi/CHK1i, inducing replication catastrophe, and prevented the development of&nbsp;resistance to&nbsp;CHK1i. Also, MRE11i + RAD51i selectively killed PARP1-upregulated CRC-SCs via mitotic catastrophe. These results provide the rationale for biomarker-driven clinical trials in CRC using distinct RSRi combinations