Progress towards mammalian whole-brain cellular connectomics

Neurons are the fundamental structural units of the nervous system i.e., the Neuron Doctrine as the pioneering work of Santiago Ramon y Cajal in the 1880's clearly demonstrated through careful observation of Golgi-stained neuronal morphologies. However, at that time sample preparation, imaging methods and computational tools were either nonexistent or insufficiently developed to permit the precise mapping of an entire brain with all of its neurons and their connections. Some measure of the "mesoscopic" connectional organization of the mammalian brain has been obtained over the past decade by alignment of sparse subsets of labeled neurons onto a reference atlas or via MRI-based diffusion tensor imaging. Neither method, however, provides data on the complete connectivity of all neurons comprising an individual brain. Fortunately, whole-brain cellular connectomics now appears within reach due to recent advances in whole-brain sample preparation and high-throughput electron microscopy (EM), though substantial obstacles remain with respect to large volume electron microscopic acquisitions and automated neurite reconstructions. This perspective examines the current status and problems associated with generating a mammalian whole-brain cellular connectome and argues that the time is right to launch a concerted connectomic attack on a small mammalian whole-brain

X-ray spectra reveal the reawakening of the repeat changing-look AGN NGC 1566

We present simultaneous XMM-Newton and NuSTAR observations of the repeat changing-look AGN NGC 1566, which dramatically increased in brightness in the IR to X-ray bands in 2018. The broad-band X-ray spectrum was taken at the peak of the outburst and is typical of Seyfert 1 AGN. The spectrum shows a soft excess, Compton hump, warm absorption and reflection, ruling out tidal disruption as the cause of the outburst and demonstrating that a 'standard' accretion disk can develop very rapidly. The high resolution grating spectrum reveals that the outburst has launched a ~ 500 km/s outflow, and shows photoionised emission lines from rest-frame gas. We discuss possible mechanisms for the outburst, and conclude that it is most likely caused by a disk instability.Comment: 5 pages, 2 figures, accepted to MNRAS letter

An Investigation of the Longitudinal Proximity Effect in Superconducting and Normal Metal TES

As the TES volume and (effective) Tc become very small - for volume > the TES Tc, connected at opposite ends of TES approaches zero, superconductivity is induced parallel to the current flow, or longitudinally, and results in a much higher effective TES Te. Here we present effective Te measurements of Mo/Au TES bounded by Nb leads as a function of L which ranges between 4 and 36 micrometer. We observe that the effective Te is suppressed for current density of order 10(exp -6) A/sq micrometers. We also explore the possibility of using a normal metal TES

Development and modeling the heat exchange element concepts of convection high temperature compressed air heater

Рассмотрен способ интенсификации теплообмена, при рекуперативном нагреве воздуха до температур порядка 800-1000°С. Проанализировано влияние на процесс теплообмена высоты и толщины продольного ребра, а так же их стоимостные показатели. Выбрана конструкция теплообменного элемента для дальнейшей проработки. Проведено численное моделирование выбранной конструкции в пакете CFD.Тhe method heat transfer enhancement was considered in regenerative air heating to temperatures of about 800-1000 ° C. Impact the fins height and longitudinal thickness on heat transfer were analyzed, as well as their cost parameters were analyzed. The design of the heat exchanger element has been selected for further development. Numerical simulation of the chosen design conducted in CFD.Исследование выполнено в Уральском федеральном университете за счет гранта Российского научного фонда (проект №14-19-00524)

Tetrazine- and trans-cyclooctene-functionalised polypept(o)ides for fast bioorthogonal tetrazine ligation

The inverse electron demand Diets-Alder (IEDDA) reaction-initiated ligation between 1,2,4,5-tetra-zines (Tz) and trans-cyclooctenes (TCO) is one of the fastest bioorthogonal reactions known today and is therefore increasingly used for in vivo click chemistry. Described herein is the synthesis of Tz- and TCO-functionalised polypeptides, polypeptoids and polypeptide-block-polypeptoids (polypept(o) ides) by ring-opening polymerisation of the corresponding N-carboxyanhydrides using Tz- or TCO-functional amine initiators. Despite the reactivity of tetrazines, polymers with low dispersity and high end group integrity can be obtained as observed by gel permeation chromatography (GPC), nuclear magnetic resonance (NMR) spectroscopy and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Amphiphilic Tz-functionalised block copolypept(o)ides were used to prepare polymeric micelles and organic colloids by miniemulsion techniques, which may find an application as clearing agents in pretargeted nuclear imaging and therapy using efficient in vivo click chemistry. The reaction kinetics of the tetrazine ligation using the synthesised polymers and the accessibility of the Tz groups on the polymeric nanoparticles were evaluated using UV Vis and fluorescence correlation spectroscopy (FCS), and second-order rate constants were determined by stopped-flow spectrophotometry ensuring quantitative conversions in seconds at sub-millimolar concentrations (10-30 s).Drug Delivery Technolog

Measuring the health impact of human rights violations related to Australian asylum policies and practices: A mixed methods study

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Johnston et al.BACKGROUND: Human rights violations have adverse consequences for health. However, to date, there remains little empirical evidence documenting this association, beyond the obvious physical and psychological effects of torture. The primary aim of this study was to investigate whether Australian asylum policies and practices, which arguably violate human rights, are associated with adverse health outcomes. METHODS: We designed a mixed methods study to address the study aim. A cross-sectional survey was conducted with 71 Iraqi Temporary Protection Visa (TPV) refugees and 60 Iraqi Permanent Humanitarian Visa (PHV) refugees, residing in Melbourne, Australia. Prior to a recent policy amendment, TPV refugees were only given temporary residency status and had restricted access to a range of government funded benefits and services that permanent refugees are automatically entitled to. The quantitative results were triangulated with semi-structured interviews with TPV refugees and service providers. The main outcome measures were self-reported physical and psychological health. Standardised self-report instruments, validated in an Arabic population, were used to measure health and wellbeing outcomes. RESULTS: Forty-six percent of TPV refugees compared with 25% of PHV refugees reported symptoms consistent with a diagnosis of clinical depression (p = 0.003). After controlling for the effects of age, gender and marital status, TPV status made a statistically significant contribution to psychological distress (B = 0.5, 95% CI 0.3 to 0.71, p </= 0.001) amongst Iraqi refugees. Qualitative data revealed that TPV refugees generally felt socially isolated and lacking in control over their life circumstances, because of their experiences in detention and on a temporary visa. This sense of powerlessness and, for some, an implicit awareness they were being denied basic human rights, culminated in a strong sense of injustice. CONCLUSION: Government asylum policies and practices violating human rights norms are associated with demonstrable psychological health impacts. This link between policy, rights violations and health outcomes offers a framework for addressing the impact of socio-political structures on health.This research was supported by an Australian National and Medical Research Council PhD Scholarship (N. 251782) and a Victorian Health Promotion Foundation research grant (No. 2002-0280)