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Computational steering refers to the real-time interaction of a scientist with their running simulation code. Despite the many benefits associated with computational steering, its uptake to date has been limited. In this paper we discuss the reasons for this and how the computational steering library and associated tools developed as part of the RealityGrid project aim to tackle them. We describe the functionality of the steering library and the use of Grid services in constructing a generic, dynamic architecture for discovering, steering and connecting visualization software to running simulations. The use of on-line visualization for providing feedback to the scientist is described, including the ways in which it may be enhanced through tools such as Chromium and Access Grid. Finally, we illustrate the flexibility of our approach by describing the functionality that has been added to various simulation codes as part of the RealityGrid project.

We describe the service architecture of the successful TeraGyroid experiment. In particular we discuss the use of the open Grid service infrastructure (OGSI) to build the services used during the experiment and illustrate the problems we encountered.

A powerful convergence of genetics, neuroimaging and epidemiological research has identified the biological pathways mediating individual differences in complex behavioral processes and the related risk for disease. Orthologous genetic variation in non-human primates (NHPs) represents a unique opportunity to characterize the detailed molecular and cellular mechanisms that bias behaviorally and clinically relevant brain function. We report that a rhesus macaque orthologue of a common polymorphism of the serotonin transporter gene (rh5-HTTLPR) has strikingly similar effects on behavior and brain morphology to those in humans. Specifically, the rh5-HTTLPR (S)hort allele broadly affects cognitive choice behavior and brain morphology without observably affecting the 5-hydroxytryptamine (5-HT) transporter or 5-HT 1A concentrations in vivo . Collectively, our findings indicate that 5-HTTLPR-associated behavioral effects reflect genotype-dependent biases in cortical development rather than static differences in serotonergic signaling mechanisms. Moreover, these data highlight the vast potential of NHP models in advancing our understanding of human genetic variation affecting behavior and neuropsychiatric disease liability.

Glioblastoma is one of the most aggressive types of cancer with success of therapy being hampered by the existence of treatment resistant populations of stem-like Tumour Initiating Cells (TICs) and poor blood–brain barrier drug penetration. Therapies capable of effectively targeting the TIC population are in high demand. Here, we synthesize spherical diketopyrrolopyrrole-based Conjugated Polymer Nanoparticles (CPNs) with an average diameter of 109 nm. CPNs were designed to include fluorescein-conjugated Hyaluronic Acid (HA), a ligand for the CD44 receptor present on one population of TICs. We demonstrate blood–brain barrier permeability of this system and concentration and cell cycle phase-dependent selective uptake of HA-CPNs in CD44 positive GBM-patient derived cultures. Interestingly, we found that uptake alone regulated the levels and signaling activity of the CD44 receptor, decreasing stemness, invasive properties and proliferation of the CD44-TIC populations in vitro and in a patient-derived xenograft zebrafish model . This work proposes a novel, CPN- based, and surface moiety-driven selective way of targeting of TIC populations in brain cancer.

In transition-edge sensors (TESs), the addition of normal metal stripes on top of the superconducting bilayer, perpendicular to the current direction, is known to globally alter the sensitivity of the resistance R to changes in temperature T and current I. Here, we describe measurements of the dependence of the TES current on magnetic field B, bath temperature and voltage bias in devices with various numbers of stripes. We show that the normal metal features have a profound effect on the appearance of localized regions of very large (T/R) dR/dT. We associate this with changes in the current distribution and corresponding changes in the oscillatory pattern of I (B). 140 μm TESs with no stripes are found to have a relatively smooth resistive transition and sufficiently low noise that the measured energy resolution is 1.6 eV for X-rays of 1.5 keV. The predicted energy resolution at 6 keV is better than 2 eV, once the heat capacity is optimized for these higher energies..

INTRODUCTION Despite significant advancements in the understanding of brain tumor biology, the successful management of Glioblastoma multiforme (GBM) remains unclear. The required high success rate in the clinical practice depends on the progress in patient-tailored approaches. METHODS A high-throughput BTO platform was developed, where individual nine GBM patient-derived low-propagated cell lines were grown and customized as mini-tumors. We optimized the microenvironment of the organoid by incorporating human endothelial cells (HUVECs) to better mimic that of the tumor in-vivo. We characterized the gene expression of the cultures separated via Fluorescence-activated cell sorting (FACS) and histopathology of organoids in comparison to the patient's neurosphere cultures. We tested the response of the generated BTO and co-cultured neurospheres to therapeutics used in the clinical practice compared to vehicle control. RESULTS We found that BTOs with endothelial components exhibit more aggressive features including proliferation and invasiveness. We found significant upregulation of poor prognosis markers including YKL-40, MDR-1, FLT-1, and PCNA expression in the co-culture of patient cells with increasing number of endothelial cells. There was a significant increase in the better prognosis markers (DLL-3) with low number of endothelial cells in the culture. Incorporation of HUVECs significantly increased YKL-40 expression in all mesenchymal subtype patients. Patients' cells co-cultured with HUVECs in the BTO system demonstrated a significant increase in resistance to novel therapies (dacomitinib and vorinostat) in comparison to cultured neurospheres. CONCLUSION This optimized BTO platform can potentially enable us to test a large number of drugs alone, and in combination, to stratify the best treatment regimens in a patient-tailored manner. Also, our model will answer several questions related to the role of the endothelial component in the GBM microenvironment to aid future discovery of new therapeutics.

We report on the development of multi-absorber transition-edge sensors (TESs), referred to as ‘hydras’. A hydra consists of multiple X-ray absorbers each with a different thermal conductance to a TES. Position information is encoded in the pulse shape. With some trade-off in performance, hydras enable very large format arrays without the prohibitive increase in bias and readout components associated with arrays of individual TESs. Hydras are under development for the next generation of space telescope such as Lynx. Lynx is a NASA concept under study that will combine a < 1″ angular resolution optic with 100,000-pixel microcalorimeter array with energy resolution of Δ E FWHM  ~ 3 eV in the soft X-ray energy range. We present first results from hydras with 25-pixels for Lynx. Designs with absorbers on a 25 μm and 50 μm pitch are studied. Arrays incorporate, for the first time, microstrip buried wiring layers of suitable pitch and density required to readout a full-scale Lynx array. The resolution from the coadded energy histogram including all 25-pixels was Δ E FWHM  = 1.66 ± 0.02 eV and 3.34 ± 0.06 eV at an energy of 1.5 keV for the 25 μm and 50 μm absorber designs, respectively. Position discrimination is demonstrated from parameterization of the rise-time.