Study of the performance of a large scale water-Cherenkov detector (MEMPHYS)

MEMPHYS (MEgaton Mass PHYSics) is a proposed large-scale water Cherenkov experiment to be performed deep underground. It is dedicated to nucleon decay searches, neutrinos from supernovae, solar and atmospheric neutrinos, as well as neutrinos from a future Super-Beam or Beta-Beam to measure the CP violating phase in the leptonic sector and the mass hierarchy. A full simulation of the detector has been performed to evaluate its performance for beam physics. The results are given in terms of "Migration Matrices" of reconstructed versus true neutrino energy, taking into account all the experimental effects.Comment: Updated after JCAP's referee's comment

Future large-scale water-Cherenkov detector

MEMPHYS (MEgaton Mass PHYSics) is a proposed large-scale water-Cherenkov experiment to be performed deep underground. It is dedicated to nucleon decay searches and the detection of neutrinos from supernovae, solar, and atmospheric neutrinos, as well as neutrinos from a future beam to measure the CP violating phase in the leptonic sector and the mass hierarchy. This paper provides an overview of the latest studies on the expected performance of MEMPHYS in view of detailed estimates of its physics reach, mainly concerning neutrino beams

Atmospheric predictability revisited

This article examines the potential to improve numerical weather prediction (NWP) by estimating upper and lower bounds on predictability by re-visiting the original study of Lorenz (1982) but applied to the most recent version of the European Centre for Medium Range Weather Forecasts (ECMWF) forecast system, for both the deterministic and ensemble prediction systems (EPS). These bounds are contrasted with an older version of the same NWP system to see how they have changed with improvements to the NWP system. The computations were performed for the earlier seasons of DJF 1985/1986 and JJA 1986 and the later seasons of DJF 2010/2011 and JJA 2011 using the 500-hPa geopotential height field. Results indicate that for this field, we may be approaching the limit of deterministic forecasting so that further improvements might only be obtained by improving the initial state. The results also show that predictability calculations with earlier versions of the model may overestimate potential forecast skill, which may be due to insufficient internal variability in the model and because recent versions of the model are more realistic in representing the true atmospheric evolution. The same methodology is applied to the EPS to calculate upper and lower bounds of predictability of the ensemble mean forecast in order to explore how ensemble forecasting could extend the limits of the deterministic forecast. The results show that there is a large potential to improve the ensemble predictions, but for the increased predictability of the ensemble mean, there will be a trade-off in information as the forecasts will become increasingly smoothed with time. From around the 10-d forecast time, the ensemble mean begins to converge towards climatology. Until this point, the ensemble mean is able to predict the main features of the large-scale flow accurately and with high consistency from one forecast cycle to the next. By the 15-d forecast time, the ensemble mean has lost information with the anomaly of the flow strongly smoothed out. In contrast, the control forecast is much less consistent from run to run, but provides more detailed (unsmoothed) but less useful information

Crosstalk between the ubiquitin-proteasome system and autophagy in a human cellular model of Alzheimer's disease

Alzheimer's disease is the most common progressive neurodegenerative disorder characterized by the abnormal deposition of amyloid plaques, likely as a consequence of an incorrect processing of the amyloid-β precursor protein (AβPP). Dysfunctions in both the ubiquitin-proteasome system and autophagy have also been observed. Recently, an extensive cross-talk between these two degradation pathways has emerged, but the exact implicated processes are yet to be clarified. In this work, we gained insight into such interplay by analyzing human SH-SY5Y neuroblastoma cells stably transfected either with wild-type AβPP gene or 717 valine-to-glycine AβPP-mutated gene. The over-expression of the AβPP mutant isoform correlates with an increase in oxidative stress and a remodeled pattern of protein degradation, with both marked inhibition of proteasome activities and impairment in the autophagic flux. To compensate for this altered scenario, cells try to promote the autophagy activation in a HDAC6-dependent manner. The treatment with amyloid-β(42) oligomers further compromises proteasome activity and also contributes to the inhibition of cathepsin-mediated proteolysis, finally favoring the neuronal degeneration and suggesting the existence of an Aβ(42) threshold level beyond which proteasome-dependent proteolysis becomes definitely dysfunctional

Theory and computation of covariant Lyapunov vectors

Lyapunov exponents are well-known characteristic numbers that describe growth rates of perturbations applied to a trajectory of a dynamical system in different state space directions. Covariant (or characteristic) Lyapunov vectors indicate these directions. Though the concept of these vectors has been known for a long time, they became practically computable only recently due to algorithms suggested by Ginelli et al. [Phys. Rev. Lett. 99, 2007, 130601] and by Wolfe and Samelson [Tellus 59A, 2007, 355]. In view of the great interest in covariant Lyapunov vectors and their wide range of potential applications, in this article we summarize the available information related to Lyapunov vectors and provide a detailed explanation of both the theoretical basics and numerical algorithms. We introduce the notion of adjoint covariant Lyapunov vectors. The angles between these vectors and the original covariant vectors are norm-independent and can be considered as characteristic numbers. Moreover, we present and study in detail an improved approach for computing covariant Lyapunov vectors. Also we describe, how one can test for hyperbolicity of chaotic dynamics without explicitly computing covariant vectors.Comment: 21 pages, 5 figure

Conformational altered p53 affects neuronal function: relevance for the response to toxic insult and growth-associated protein 43 expression

The role of p53 in neurodegenerative diseases is essentially associated with neuronal death. Recently an alternative point of view is emerging, as altered p53 conformation and impaired protein function have been found in fibroblasts and blood cells derived from Alzheimer's disease patients. Here, using stable transfected SH-SY5Y cells overexpressing APP751wt (SY5Y-APP) we demonstrated that the expression of an unfolded p53 conformation compromised neuronal functionality. In particular, these cells showed (i) augmented expression of amyloid precursor protein (APP) and its metabolites, including the C-terminal fragments C99 and C83 and β-amyloid peptide (ii) high levels of oxidative markers, such as 4-hydroxy-2-nonenal Michael-adducts and 3-nitro-tyrosine and (iii) altered p53 conformation, mainly due to nitration of its tyrosine residues. The consequences of high-unfolded p53 expression resulted in loss of p53 pro-apoptotic activity, and reduction of growth-associated protein 43 (GAP-43) mRNA and protein levels. The role of unfolded p53 in cell death resistance and lack of GAP-43 transcription was demonstrated by ZnCl(2) treatment. Zinc supplementation reverted p53 wild-type tertiary structure, increased cells sensitivity to acute cytotoxic injury and GAP-43 levels in SY5Y-APP clone

Ejaculation-sparing thulium laser enucleation of the prostate (ES-ThuLEP): outcomes on a large cohort

Purpose: To assess the effects of a new ejaculation-sparing thulium laser enucleation of the prostate (ES-ThuLEP) technique on sexual functions and micturition, in patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) and to evaluate how the surgical technique of ES-ThuLEP can lead to ejaculation preservation. Methods: A prospective study was carried out between January 2015 and January 2018 on patients with surgical indication for BPH, who wished to preserve ejaculation. The patients were treated with ES-ThuLEP and were evaluated before and 3 and 6 months after surgery. Three validated questionnaires (ICIQ-MLUTSsex, IIEF-5 and IPSS) were used to assess changes in ejaculation, erectile function and urinary symptoms. Uroflowmetry (Qmax and Qavg), post-void residual volume and voided volume were also evaluated, to assess micturition improvement. Patients with moderate to severe erectile dysfunction were excluded. Statistical analysis was performed with the Student\u2019s t test, Chi-square test and logistic regression analysis. Results: Two hundred and eighty three patients were enrolled. Ejaculation was spared in 203 and 219 patients at 3 and 6 months after surgery. No significant differences were observed between erectile function before and after surgery: baseline IIEF-5 = 16.2 \ub1 4.47 vs 16.7 \ub1 2.9 (p = 0.419) and 17.7 \ub1 3.2 (p = 0.410) at 3 and 6 months. Significant improvement in urinary symptoms was achieved: baseline IPSS = 19.4 \ub1 7.24 vs 5.8 \ub1 4.3 (p = 0.032) and 3.9 \ub1 4.1 (p = 0.029) at 3 and 6 months. Conclusion: ES-ThuLEP effectively preserved ejaculation in over two thirds of the patients without compromising micturition improvement or erectile function. ES-ThuLEP could be a valid treatment option for BPH in young and sexually active men

Is psychiatric residential facility discharge possible and predictable? A multivariate analytical approach applied to a prospective study in Italy

A growing number of severely ill patients require long-term care in non-hospital residential facilities (RFs). Despite the magnitude of this development, longitudinal studies surveying fairly large resident samples and yielding important information on this population have been very few

A prospective multicenter randomized comparison between Holmium Laser Enucleation of the Prostate (HoLEP) and Thulium Laser Enucleation of the Prostate (ThuLEP)

Purpose: To compare intra and perioperative parameters between HoLEP and ThuLEP in the treatment of benign prostatic hyperplasia and to evaluate clinical and functional outcomes of the two procedures with a 12-month follow-up. Methods: A prospective randomized study was performed on 236 consecutive patients who underwent ThuLEP (n = 115), or HoLEP (n = 121) in three different centers. Intra and perioperative parameters were analyzed: operative time, enucleated tissue weight, irrigation volume, blood loss, catheterization time, hospital stay and complications. Patients were evaluated preoperatively and 3 and 12 months postoperatively with the international prostate symptom score (IPSS), the quality of life (QoL) score, post-void residual volume (PVR), PSA and maximum flow rate (Qmax). Results: Preoperative variables in each study arm did not show any significant difference. Compared to HoLEP, ThuLEP showed similar operative time (63.69 vs 71.66 min, p = 0.245), enucleated tissue weight (48.84 vs 51.13 g, p = 0.321), catheterization time (1.9 vs 2.0 days, p = 0.450) and hospital stay (2.2 vs 2.8 days, p = 0.216), but resulted in less haemoglobin decrease (0.45 vs 2.77 g/dL, p = 0.005). HoLEP presented a significantly higher number of patients with postoperative acute urinary retention and stress incontinence. No significant differences were found in PSA, Qmax, PVR, IPSS and QoL score during follow-up. Conclusion: ThuLEP and HoLEP both relieved lower urinary tract symptoms equally, with high efficacy and safety. ThuLEP detemined reduced blood loss and early postoperative complications. Catheterization time, enucleated tissue, hospital stay, operative time and follow-up parameters did not show any significant difference

Flow Index: a novel, non-invasive, continuous, quantitative method to evaluate patient inspiratory effort during pressure support ventilation

Background: The evaluation of patient effort is pivotal during pressure support ventilation, but a non-invasive, continuous, quantitative method to assess patient inspiratory effort is still lacking. We hypothesized that the concavity of the inspiratory flow-time waveform could be useful to estimate patient’s inspiratory effort. The purpose of this study was to assess whether the shape of the inspiratory flow, as quantified by a numeric indicator, could be associated with inspiratory effort during pressure support ventilation. Methods: Twenty-four patients in pressure support ventilation were enrolled. A mathematical relationship describing the decay pattern of the inspiratory flow profile was developed. The parameter hypothesized to estimate effort was named Flow Index. Esophageal pressure, airway pressure, airflow, and volume waveforms were recorded at three support levels (maximum, minimum and baseline). The association between Flow Index and reference measures of patient effort (pressure time product and pressure generated by respiratory muscles) was evaluated using linear mixed effects models adjusted for tidal volume, respiratory rate and respiratory rate/tidal volume. Results: Flow Index was different at the three pressure support levels and all group comparisons were statistically significant. In all tested models, Flow Index was independently associated with patient effort (p < 0.001). Flow Index prediction of inspiratory effort agreed with esophageal pressure-based methods. Conclusions: Flow Index is associated with patient inspiratory effort during pressure support ventilation, and may provide potentially useful information for setting inspiratory support and monitoring patient-ventilator interactions