Water and protein dynamics in protein-water mixtures over wide range of composition

© 2012 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.[EN] Water and protein dynamics in two globular protein-water systems, water-lysozyme and water-BSA (bovine serum albumine), were studied by differential scanning calorimetry (DSC), dielectric relaxation spectroscopy (DRS) and thermally stimulated depolarization currents (TSDC) techniques. Water equilibrium sorption isotherms (ESI) measurements were also recorded at room temperature. The samples covered a wide range of composition, from practically dry solid pellets (2wt% of water) to dilute solutions (82wt% of water). Crystallization and melting events of water were studied by DSC and the amount of uncrystallized water was calculated. The evolution of dynamics with hydration level was followed for various dielectric relaxation processes, the emphasis being given to relaxation processes of polar groups on the surface of the proteins and of uncrystallized water molecules. A relationship between the formation of a conductive percolating water cluster and the saturation of the water process was found.This research has been co-financed by the European Union (European Social Fund - ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program: Heracleitus II. Investing in knowledge society through the European Social Fund.Kyritsis, A.; Panagopoulou, A.; Pissis, P.; Sabater I Serra, R.; Gómez Ribelles, JL.; Shinyashiki, N. (2012). Water and protein dynamics in protein-water mixtures over wide range of composition. IEEE Transactions on Dielectrics and Electrical Insulation. 19(4):1239-1246. https://doi.org/10.1109/TDEI.2012.6259997S1239124619

Local Commutativity and Causality in Interacting PP-wave String Field Theory

In this paper, we extend our previous study of causality and local commutativity of string fields in the pp-wave lightcone string field theory to include interaction. Contrary to the flat space case result of Lowe, Polchinski, Susskind, Thorlacius and Uglum, we found that the pp-wave interaction does not affect the local commutativity condition. Our results show that the pp-wave lightcone string field theory is not continuously connected with the flat space one. We also discuss the relation between the condition of local commutativity and causality. While the two notions are closely related in a point particle theory, their relation is less clear in string theory. We suggest that string local commutativity may be relevant for an operational defintion of causality using strings as probes.Comment: Latex, JHEP3.cls, 18 pages, no figures. v2: add comments about the UV-IR mixing effect displayed in our result. version to appear in JHE

Machine Intelligence Identifies Soluble TNFa as a Therapeutic Target for Spinal Cord Injury

Traumatic spinal cord injury (SCI) produces a complex syndrome that is expressed across multiple endpoints ranging from molecular and cellular changes to functional behavioral deficits. Effective therapeutic strategies for CNS injury are therefore likely to manifest multi-factorial effects across a broad range of biological and functional outcome measures. Thus, multivariate analytic approaches are needed to capture the linkage between biological and neurobehavioral outcomes. Injury-induced neuroinflammation (NI) presents a particularly challenging therapeutic target, since NI is involved in both degeneration and repair. Here, we used big-data integration and large-scale analytics to examine a large dataset of preclinical efficacy tests combining five different blinded, fully counter-balanced treatment trials for different acute anti-inflammatory treatments for cervical spinal cord injury in rats. Multi-dimensional discovery, using topological data analysis (TDA) and principal components analysis (PCA) revealed that only one showed consistent multidimensional syndromic benefit: intrathecal application of recombinant soluble TNFα receptor 1 (sTNFR1), which showed an inverse-U dose response efficacy. Using the optimal acute dose, we showed that clinically-relevant 90 min delayed treatment profoundly affected multiple biological indices of NI in the first 48 h after injury, including reduction in pro-inflammatory cytokines and gene expression of a coherent complex of acute inflammatory mediators and receptors. Further, a 90 min delayed bolus dose of sTNFR1 reduced the expression of NI markers in the chronic perilesional spinal cord, and consistently improved neurological function over 6 weeks post SCI. These results provide validation of a novel strategy for precision preclinical drug discovery that is likely to improve translation in the difficult landscape of CNS trauma, and confirm the importance of TNFα signaling as a therapeutic target

Dielectric relaxations of nanocomposites composed of HEUR polymers and magnetite nanoparticles

We investigate the dynamics of nanocomposites composed of hydrophobically modified ethoxylated urethanes (HEUR) and magnetite nanoparticles (MNPs) as dry films. Weemployed dielectric relaxation spectroscopy (DRS) in combination with differential scanning calorimetry (DSC) and thermally stimulated depolarization currents (TSDC).The three techniques reveal a strong heterogeneity of the matrix of the nanocomposites, consisting of (i) a crystalline poly(ethyleneoxide) PEO bulk phase, (ii) an amorphous PEO portion, and (iii) small PEO crystallites which experience different constraints than the PEO bulk phase. TSDC and DRS reveal a very high direct current (DC)-conductivity of the pure matrix, which increases with MNPs concentration. The increase of the DCconductivity is not related to an increase of the segmental mobility, but most likely to the change of the morphology of the hydrophobic domains of the polymer matrix, due to the formation of large MNPs clusters. Indeed, the MNPs neither influence the segmental dynamics of the polymer nor the phase behavior of the polymer matrix. The addition of MNPs slightly increases the activation energy related to the γ-relaxation of the polymer. This effect might be related to the changes in nano-morphology as demonstrated by the slight increase of the degree of crystallinity. The analysis of the DRS data with the electrical modulus M’’(ω) and the derivative ε’’der formalism allow us to identify a low-frequency process in addition to the conductivity relaxation. This low-frequency dispersion is also revealed by TSDC. It is most likely related to the Maxwell-Wagner- Sillars relaxation, which typically occurs in systems which feature phase separation. The detailed investigation of the dielectric properties of these novel nanocomposites with increasing MNPs concentration will be useful for their practical application, for example as absorbers of electromagnetic waves

RoboPol: AGN polarimetric monitoring data

We present uniformly reprocessed and re-calibrated data from the RoboPol programme of optopolarimetric monitoring of active galactic nuclei (AGN), covering observations between 2013, when the instrument was commissioned, and 2017. In total, the dataset presented in this paper includes 5068 observations of 222 AGN with Dec > -25 deg. We describe the current version of the RoboPol pipeline that was used to process and calibrate the entire dataset, and we make the data publicly available for use by the astronomical community. Average quantities summarising optopolarimetric behaviour (average degree of polarization, polarization variability index) are also provided for each source we have observed and for the time interval we have followed it.Comment: Accepted to MNRA

Efficacy and acceptability of selective serotonin reuptake inhibitors for the treatment of depression in Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials

<p>Abstract</p> <p>Background</p> <p>Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants for the treatment of depression in patients with Parkinson's Disease (PD) but data on their efficacy are controversial.</p> <p>Methods</p> <p>We conducted a systematic review and meta-analysis of randomized controlled trials to investigate the efficacy and acceptability of SSRIs in the treatment of depression in PD.</p> <p>Results</p> <p>Ten studies were included. In the comparison between SSRIs and Placebo (n = 6 studies), the combined risk ratio (random effects) was 1.08 (95% confidence interval: 0.77 - 1.55, p = 0.67). In the comparison between SSRIs and Tricyclic Antidepressants (TCAs) (n = 3 studies) the combined risk ratio was 0.75 (0.39 - 1.42, p = 0.37). An acceptability analysis showed that SSRIs were generally well tolerated.</p> <p>Conclusions</p> <p>These results suggest that there is insufficient evidence to reject the null hypothesis of no differences in efficacy between SSRIs and placebo in the treatment of depression in PD. Due to the limited number of studies and the small sample sizes a type II error (false negative) cannot be excluded. The comparison between SSRIs and TCAs is based on only three studies and further trials with more pragmatic design are needed.</p

Pushing the high count rate limits of scintillation detectors for challenging neutron-capture experiments

One of the critical aspects for the accurate determination of neutron capture cross sections when combining time-of-flight and total energy detector techniques is the characterization and control of systematic uncertainties associated to the measuring devices. In this work we explore the most conspicuous effects associated to harsh count rate conditions: dead-time and pile-up effects. Both effects, when not properly treated, can lead to large systematic uncertainties and bias in the determination of neutron cross sections. In the majority of neutron capture measurements carried out at the CERN n\_TOF facility, the detectors of choice are the C$_{6}$D$_{6}$ liquid-based either in form of large-volume cells or recently commissioned sTED detector array, consisting of much smaller-volume modules. To account for the aforementioned effects, we introduce a Monte Carlo model for these detectors mimicking harsh count rate conditions similar to those happening at the CERN n\_TOF 20~m fligth path vertical measuring station. The model parameters are extracted by comparison with the experimental data taken at the same facility during 2022 experimental campaign. We propose a novel methodology to consider both, dead-time and pile-up effects simultaneously for these fast detectors and check the applicability to experimental data from $^{197}$Au($n$,$\gamma$), including the saturated 4.9~eV resonance which is an important component of normalization for neutron cross section measurements

Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma

Contains fulltext : 79699.pdf (publisher's version ) (Closed access)BACKGROUND: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). METHODS: A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary end point was radiographic response rate and secondary end points were safety, progression-free survival at 6 months (PFS-6), and overall survival (OS). RESULTS: The radiographic response rate after centralised review was 3.4%. Progression-free survival at 6 months and median OS were 10.6% and 26.0 weeks, respectively. Outcome did not appear to differ based on EIAED status. The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%). CONCLUSIONS: Imatinib in addition to hydroxyurea was well tolerated among patients with recurrent GBM but did not show clinically meaningful anti-tumour activity

Advances and new ideas for neutron-capture astrophysics experiments at CERN n_TOF

This article presents a few selected developments and future ideas related to the measurement of (n,γ) data of astrophysical interest at CERN n_TOF. The MC-aided analysis methodology for the use of low-efficiency radiation detectors in time-of-flight neutron-capture measurements is discussed, with particular emphasis on the systematic accuracy. Several recent instrumental advances are also presented, such as the development of total-energy detectors with γ-ray imaging capability for background suppression, and the development of an array of small-volume organic scintillators aimed at exploiting the high instantaneous neutron-flux of EAR2. Finally, astrophysics prospects related to the intermediate i neutron-capture process of nucleosynthesis are discussed in the context of the new NEAR activation area