Can Polarity-Inverted Surfactants Self-Assemble in Nonpolar Solvents

We investigate the self-assembly process of a surfactant with inverted polarity in water and cyclohexane using both all-atom and coarse grained hybrid particle-field molecular dynamics simulations. Unlike conventional surfactants, the molecule under study, proposed in a recent experiment, is formed by a rigid and compact hydrophobic adamantane moiety, and a long and floppy triethylene glycol tail. In water, we report the formation of stable inverted micelles with the adamantane heads grouping together into a hydrophobic core, and the tails forming hydrogen bonds with water. By contrast, microsecond simulations do not provide evidence of stable micelle formation in cyclohexane. Validating the computational results by comparison with experimental diffusion constant and small-angle X-ray scattering intensity, we show that at laboratory thermodynamic conditions the mixture resides in the supercritical region of the phase diagram, where aggregated and free surfactant states co-exist in solution. Our simulations also provide indications about how to escape this region, to produce thermodynamically stable micellar aggregates.Comment: 14 pages, 10 Figures, accepted for publication (2020

Influence of conformational fluctuations on enzymatic activity: modelling the functional motion of beta-secretase

Considerable insight into the functional activity of proteins and enzymes can be obtained by studying the low-energy conformational distortions that the biopolymer can sustain. We carry out the characterization of these large scale structural changes for a protein of considerable pharmaceutical interest, the human $\beta$-secretase. Starting from the crystallographic structure of the protein, we use the recently introduced beta-Gaussian model to identify, with negligible computational expenditure, the most significant distortion occurring in thermal equilibrium and the associated time scales. The application of this strategy allows to gain considerable insight into the putative functional movements and, furthermore, helps to identify a handful of key regions in the protein which have an important mechanical influence on the enzymatic activity despite being spatially distant from the active site. The results obtained within the Gaussian model are validated through an extensive comparison against an all-atom Molecular Dynamics simulation.Comment: To be published in a special issue of J. Phys.: Cond. Mat. (Bedlewo Workshop

Overview of the molecular determinants contributing to the expression of Psoriasis and Psoriatic Arthritis phenotypes

Psoriasis and psoriatic arthritis are multifactorial chronic disorders whose etiopathogenesis essentially derives from the alteration of several signalling pathways and the co-occurrence of genetic, epigenetic and non-genetic susceptibility factors that altogether affect the functional and structural property of the skin. Although shared and differential susceptibility genes and molecular pathways are known to contribute to the onset of pathological phenotypes, further research is needed to dissect the molecular causes of psoriatic disease and its progression towards Psoriatic Arthritis. This review will therefore be addressed to explore differences and similarities in the etiopathogenesis and progression of both disorders, with a particular focus on genes involved in the maintenance of the skin structure and integrity (keratins and collagens), modulation of patterns of recognition (through Toll-like receptors and dectin-1) and immuno-inflammatory response (by NLRP3-dependent inflammasome) to microbial pathogens. In addition, special emphasis will be given to the contribution of epigenetic elements (methylation pattern, non-coding RNAs, chromatin modifiers and 3D genome organization) to the etiopathogenesis and progression of psoriasis and psoriatic arthritis. The evidence discussed in this review highlights how the knowledge of patients' clinical and (epi)genomic make-up could be helpful for improving the available therapeutic strategies for psoriasis and psoriatic arthritis treatment

Dual-readout Calorimetry

The RD52 Project at CERN is a pure instrumentation experiment whose goal is to understand the fundamental limitations to hadronic energy resolution, and other aspects of energy measurement, in high energy calorimeters. We have found that dual-readout calorimetry provides heretofore unprecedented information event-by-event for energy resolution, linearity of response, ease and robustness of calibration, fidelity of data, and particle identification, including energy lost to binding energy in nuclear break-up. We believe that hadronic energy resolutions of {\sigma}/E $\approx$ 1 - 2% are within reach for dual-readout calorimeters, enabling for the first time comparable measurement preci- sions on electrons, photons, muons, and quarks (jets). We briefly describe our current progress and near-term future plans. Complete information on all aspects of our work is available at the RD52 website http://highenergy.phys.ttu.edu/dream/.Comment: 10 pages, 10 figures, Snowmass White pape

MEG Upgrade Proposal

We propose the continuation of the MEG experiment to search for the charged lepton flavour violating decay (cLFV) \mu \to e \gamma, based on an upgrade of the experiment, which aims for a sensitivity enhancement of one order of magnitude compared to the final MEG result, down to the $6 \times 10^{-14}$ level. The key features of this new MEG upgrade are an increased rate capability of all detectors to enable running at the intensity frontier and improved energy, angular and timing resolutions, for both the positron and photon arms of the detector. On the positron-side a new low-mass, single volume, high granularity tracker is envisaged, in combination with a new highly segmented, fast timing counter array, to track positron from a thinner stopping target. The photon-arm, with the largest liquid xenon (LXe) detector in the world, totalling 900 l, will also be improved by increasing the granularity at the incident face, by replacing the current photomultiplier tubes (PMTs) with a larger number of smaller photosensors and optimizing the photosensor layout also on the lateral faces. A new DAQ scheme involving the implementation of a new combined readout board capable of integrating the diverse functions of digitization, trigger capability and splitter functionality into one condensed unit, is also under development. We describe here the status of the MEG experiment, the scientific merits of the upgrade and the experimental methods we plan to use.Comment: A. M. Baldini and T. Mori Spokespersons. Research proposal submitted to the Paul Scherrer Institute Research Committee for Particle Physics at the Ring Cyclotron. 131 Page

ALADYN: a web server for aligning proteins by matching their large-scale motion

The ALADYN web server aligns pairs of protein structures by comparing their internal dynamics and detecting regions that sustain similar large-scale movements. The latter often accompany functional conformational changes in proteins and enzymes. The ALADYN dynamics-based alignment can therefore highlight functionally-oriented correspondences that could be more elusive to sequence- or structure-based comparisons. The ALADYN server takes the structure files of the two proteins as input. The optimal relative positioning of the molecules is found by maximizing the similarity of the pattern of structural fluctuations which are calculated via an elastic network model. The resulting alignment is presented via an interactive graphical Java applet and is accompanied by a number of quantitative indicators and downloadable data files. The ALADYN web server is freely accessible at the http://aladyn.escience-lab.org address

Calibration of ATLAS Tile Calorimeter at Electromagnetic Scale

In this paper we summarize the measurement of the electromagnetic (EM) scale calibration constant for 11% of the Tile Calorimeter modules exposed to electron and muon test beams at CERN SPS accelerator. The Tile Calorimeter modules are currently installed in the ATLAS detector. The analysis presented in this paper takes into account the recent improvements in the Tile Calorimeter cesium calibration, charge injection system calibration and Fit Method energy reconstruction. The overall conversion factor between the measured charge and the energy deposited by measured particles for Tile Calorimeter cells is $1.050pm0.003$~pC/GeV, with spread of $2.4pm0.1$%. We discuss in detail the sources of uncertainties of EM scale calibration constant. We also show, that after inter-calibrating all the Tile Calorimeter cells with a~radioactive cesium source and setting the EM scale in the first calorimeter sampling with electron beams, the values of signals measured in the second and third calorimeter sampling need to be increased by 1--9% to keep the EM scale uniform in the whole calorimeter