Simulation of optical interstellar scintillation

Stars twinkle because their light propagates through the atmosphere. The same phenomenon is expected on a longer time scale when the light of remote stars crosses an interstellar turbulent molecular cloud, but it has never been observed at optical wavelengths. The aim of the study described in this paper is to fully simulate the scintillation process, starting from the molecular cloud description as a fractal object, ending with the simulations of fluctuating stellar light curves. Fast Fourier transforms are first used to simulate fractal clouds. Then, the illumination pattern resulting from the crossing of background star light through these refractive clouds is calculated from a Fresnel integral that also uses fast Fourier transform techniques. Regularisation procedure and computing limitations are discussed, along with the effect of spatial and temporal coherency (source size and wavelength passband). We quantify the expected modulation index of stellar light curves as a function of the turbulence strength --characterised by the diffraction radius $R_{diff}$-- and the projected source size, introduce the timing aspects, and establish connections between the light curve observables and the refractive cloud. We extend our discussion to clouds with different structure functions from Kolmogorov-type turbulence. Our study confirms that current telescopes of ~4m with fast-readout, wide-field detectors have the capability of discovering the first interstellar optical scintillation effects. We also show that this effect should be unambiguously distinguished from any other type of variability through the observation of desynchronised light curves, simultaneously measured by two distant telescopes.Comment: 11 pages, 11 figures, accepted for publication in Astronomy and Astrophysic

A new method to improve photometric redshift reconstruction. Applications to the Large Synoptic Survey Telescope

In the next decade, the LSST will become a major facility for the astronomical community. However accurately determining the redshifts of the observed galaxies without using spectroscopy is a major challenge. Reconstruction of the redshifts with high resolution and well-understood uncertainties is mandatory for many science goals, including the study of baryonic acoustic oscillations. We investigate different approaches to establish the accuracy that can be reached by the LSST six-band photometry. We construct a realistic mock galaxy catalog, based on the GOODS survey luminosity function, by simulating the expected apparent magnitude distribution for the LSST. To reconstruct the photometric redshifts (photo-z's), we consider a template-fitting method and a neural network method. The photo-z reconstruction from both of these techniques is tested on real CFHTLS data and also on simulated catalogs. We describe a new method to improve photo-z reconstruction that efficiently removes catastrophic outliers via a likelihood ratio statistical test. This test uses the posterior probability functions of the fit parameters and the colors. We show that the photometric redshift accuracy will meet the stringent LSST requirements up to redshift $\sim2.5$ after a selection that is based on the likelihood ratio test or on the apparent magnitude for galaxies with $S/N>5$ in at least 5 bands. The former selection has the advantage of retaining roughly 35% more galaxies for a similar photo-z performance compared to the latter. Photo-z reconstruction using a neural network algorithm is also described. In addition, we utilize the CFHTLS spectro-photometric catalog to outline the possibility of combining the neural network and template-fitting methods. We conclude that the photo-z's will be accurately estimated with the LSST if a Bayesian prior probability and a calibration sample are used.Comment: 19 pages, 25 figures, accepted for publication in Astronomy and Astrophysics Astronomy and Astrophysics, 201

Pseudoprogression after proton beam irradiation for a choroid plexus carcinoma in pediatric patient: MRI and PET imaging patterns

Purpose: Pseudoprogression is a rare complication of radiation therapy, and discrimination between true progression and pseudoprogression is of paramount importance for further medical care. We present a case of intra-axial pseudoprogression following complementary proton radiation therapy for a choroid plexus carcinoma in a child. We aim to highlight radiological patterns of pseudoprogression after proton beam therapy. Case report: A 6-year-old girl presented with choroid plexus carcinoma, manifesting as change in behavior, tremor, and balance disorder. Partial resection and chemotherapy were performed. Complementary localized proton beam therapy (54Gy) was administered on the residual tumor. Eight month follow-up MRI showed an abnormal, irregular, rim-like enhancement in the pons and both temporal lobes within the field of irradiation. These lesions had a low cerebral blood volume (CBV) on perfusion MR imaging and no restricted diffusion. However, the lesions were hypermetabolic on O-(2-[18F]fluoroethyl)-l-tyrosine (FET)-PET MRI. Follow-up MRI showed disappearance of these lesions confirming the perfusion MR diagnosis of pseudoprogression. Conclusion: Based on this case, radiological patterns of pseudoprogression after proton beam therapy may be a low CBV and no restricted diffusion. Lesions can be hypermetabolic on FET-PET imagin

Language, reading, and math learning profiles in an epidemiological sample of school age children.

Dyscalculia, dyslexia, and specific language impairment (SLI) are relatively specific developmental learning disabilities in math, reading, and oral language, respectively, that occur in the context of average intellectual capacity and adequate environmental opportunities. Past research has been dominated by studies focused on single impairments despite the widespread recognition that overlapping and comorbid deficits are common. The present study took an epidemiological approach to study the learning profiles of a large school age sample in language, reading, and math. Both general learning profiles reflecting good or poor performance across measures and specific learning profiles involving either weak language, weak reading, weak math, or weak math and reading were observed. These latter four profiles characterized 70% of children with some evidence of a learning disability. Low scores in phonological short-term memory characterized clusters with a language-based weakness whereas low or variable phonological awareness was associated with the reading (but not language-based) weaknesses. The low math only group did not show these phonological deficits. These findings may suggest different etiologies for language-based deficits in language, reading, and math, reading-related impairments in reading and math, and isolated math disabilities

Rich-club structure contributes to individual variance of reading skills via feeder connections in children with reading disabilities

The present work considers how connectome-wide differences in brain organization might distinguish good and poor readers. The connectome comprises a ‘rich-club’ organization in which a small number of hub regions play a focal role in assisting global communication across the whole brain. Prior work indicates that this rich-club structure is associated with typical and impaired cognitive function although no work so far has examined how this relates to skilled reading or its disorders. Here we investigated the rich-club structure of brain\u27s white matter connectome and its relationship to reading subskills in 64 children with and without reading disabilities. Among three types of white matter connections, the strength of feeder connections that connect hub and non-hub nodes was significantly correlated with word reading efficiency and phonemic decoding. Phonemic decoding was also positively correlated with connectivity between connectome-wide hubs and nodes within the left-hemisphere reading network, as well as the local efficiency of the reading network. Exploratory analyses also identified sex differences indicating these effects were stronger in girls. This work highlights the independent roles of connectome-wide structure and the more narrowly-defined reading network in understanding the neural bases of skilled and impaired reading in children

In silico and in vitro investigations on the protein–protein interactions of glutathione S-transferases with mitogen-activated protein kinase 8 and apoptosis signal-regulating kinase 1

Cytosolic glutathione S-transferase (GST) enzymes participate in several cellular processes in addition to facilitating glutathione conjugation reactions that eliminate endogenous and exogenous toxic compounds, especially electrophiles. GSTs are thought to interact with various kinases, resulting in the modulation of apoptotic processes and cellular proliferation. The present research used a combination of in silico and in vitro studies to investigate protein–protein interactions between the seven most abundant cytosolic GSTs—GST alpha-1 (GST-A1), GST alpha-2 (GST-A2), GST mu-1 (GST-M1), GST mu-2 (GST-M2), GST mu-5 (GST-M5), GST theta-1 (GST-T1) and GST pi-1 (GST-P1)—and Mitogen-activated protein kinase 8 (MAPK8) and Apoptosis signal-regulating kinase 1 (ASK1). MAPK8 and ASK1 were chosen as this study’s protein interaction partners because of their predominant role in electrophile or cytokine-induced stress-mediated apoptosis, inflammation and fibrosis. The highest degree of sequence homology or sequence similarity was observed in two GST subgroups: the GST-A1, GST-A2 and GST-P1 isoforms constituted subgroup1; the GST-M1, GST-M2 and GST-M5 isoforms constituted subgroup 2. The GST-T1 isoform diverged from these isoforms. In silico investigations revealed that GST-M1 showed a significantly higher binding affinity to MAPK8, and its complex was more structurally stable than the other isoforms, in the order GST-M1 > GST-M5 > GST-P1 > GST-A2 > GST-A1 > GST-M2 > GST-T1. Similarly, GST-A1, GST-P1 and GST-T1 actively interacted with ASK1, and their structural stability was also better, in the order GST-T1 > GST-A1 > GST-P1 > GST-A2 > GST-M5 > GST-M1 > GST-M2. To validate in silico results, we performed in vitro crosslinking and mass spectroscopy experiments. Results indicated that GST-M1 interacted with GST-T1 to form heterodimers and confirmed the predicted interaction between GST-M1 and MAPK8. Communicated by Ramaswamy H. Sarma.publishersversioninpres

Identification of putative substrates and inhibitors for Glutathione S-transferases using computational methods

Glutathione S-transferases (GSTs) comprise a family of enzymes that utilizes glutathione (GSH) in many enzymatic reactions that involved in transformation of several compounds including therapeutic drug molecules and carcinogens. In addition, GSTs influence cellular survival and proliferation, by repressing apoptosis signal-regulating kinase 1 (ASK1) thus affecting the activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) in response to various intra and extracellular stresses. Molecules inhibiting the function of GSTs received attention as an adjuvant therapy to the highly toxic electrophilic agents to avoid usage of high doses and toxicity for better outcomes. There is no detailed in silico analysis exists in literature to describe the binding patterns of known inhibitors to all GST isoforms. This study is aimed at providing details of binding patterns of known and putative substrates (Busulfan, Treosulfan, SS-EBDM, SS-DEB), inhibitors (Ethacrynic acid, Sulfolane and Curcumin) with predominately-expressed seven isoforms of GST (Alpha1, Alpha2, Pi1, Mu1, Mu2, Mu5 and Theta1). In silico methodology include six steps namely (a) Retrieval of three-dimensional structure of GSTs and Ligand molecules from RCSB-PDB and NCBI-PubChem databases, (b) Protein and Ligand preparation using Auto Dock Tools (ADT), (c) Receptor grid preparation based on known binding site (Direct docking protocol) of GSTs using AutoDock/Vina plugin in PyMOL, (d) Preparation of Auto Dock Vina configuration file, (e) Running of docking calculation using Auto Dock Vina and (f) Analysis of docking results using ADT, PyMOL and LigPlus programs. Molecular docking studies of substrates/inhibitors are performed with both Apo and GSH bounded forms of GSTs. Structural parameters such as estimated free energy of binding (ΔH), estimated inhibition constant (Ki), binding orientation, intermolecular interactions were noted for all the docking interaction models. Then the parameters were compared against each substrate or inhibitor for the affinity towards a selective GST isoform. Out of the three putative or known inhibitors screened, Curcumin showed a significant high binding affinity towards all the classes of GSTs, particularly GST Alpha1 (ΔH: -9.7 kcal/mol and Ki: 0.08 µM). Ethacrynic acid also showed better binding affinity towards GST Alpha1 (ΔH: -7.6 kcal/mol and Ki: 2.7 uM). Sulfolane did not exhibited a stronger affinity towards all the seven GST isoforms. Busulfan and Treosulfan exhibited a reasonable binding affinity towards GST Alpha1 (ΔH: -5.2 and -5.3 kcal/mol) and weakened affinity for the remaining six GST isoforms. Thus, treosulfan could be a possible substrate for GST Alpha1. Manual inspection of three-dimensional structures of the docking complexes revealed that binding-sites for inhibitor and substrate are different. In an on-going study, we are evaluating the inhibitory potential of Curcumin and Ethacrynic acid against GSTs in in vitro studies. The detailed description of the binding interactions may be useful to screen new putative GST substrates and inhibitors. Presence or absence of variants in these binding pockets also can define the amount of inhibitor required and the affinity and potency of an inhibitor and or substrate. This poster is presented at " ESPT 2017 in Catania, Italy from Oct 4th-7th 2017