CSIP - a Novel Photon-Counting Detector Applicable for the SPICA Far-Infrared Instrument

We describe a novel GaAs/AlGaAs double-quantum-well device for the infrared photon detection, called Charge-Sensitive Infrared Phototransistor (CSIP). The principle of CSIP detector is the photo-excitation of an intersubband transition in a QW as an charge integrating gate and the signal amplification by another QW as a channel with very high gain, which provides us with extremely high responsivity (10^4 -- 10^6 A/W). It has been demonstrated that the CSIP designed for the mid-infrared wavelength (14.7 um) has an excellent sensitivity; the noise equivalent power (NEP) of 7x10^-19 W/rHz with the quantum efficiency of ~2%. Advantages of the CSIP against the other highly sensitive detectors are, huge dynamic range of >10^6, low output impedance of 10^3 -- 10^4 Ohms, and relatively high operation temperature (>2K). We discuss possible applications of the CSIP to FIR photon detection covering 35 -- 60 um waveband, which is a gap uncovered with presently available photoconductors.Comment: To appear in Proc. Workshop "The Space Infrared Telescope for Cosmology & Astrophysics: Revealing the Origins of Planets and Galaxies". Eds. A.M. Heras, B. Swinyard, K. Isaak, and J.R. Goicoeche

The Influence of Spatial Resolution due to Hot-Wire Sensors on Measurements in Wall-Bounded Turbulence.

Reassessment of compiled data reveal that recorded scatter in the hot-wire measured near-wall peak in viscous-scaled streamwise turbulence intensity is due in large part to the simultaneous competing effects of Reynolds number and viscous-scaled wire-length l ( lUt n, where l is the wirelength, Ut is friction velocity and n is kinematic viscosity). These competing factors can explain much of the disparity in existing literature, in particular explaining how previous studies have incorrectly concluded that the inner-scaled near-wall peak is independent of Re. We also investigate the appearance of the, so-called, ‘outerpeak’ in the broadband streamwise intensity, found by some researchers to occur within the log-region of high Reynolds number boundary layers. We show that this ‘outer-peak’ is most likely a symptom of attenuation of small-scales due to large l . Fully mapped energy spectra, obtained with two different l , are presented to demonstrate this phenomena. The spatial attenuation resulting from wires with large l effectively filters small-scale fluctuations from the recorded signal

Exercise is delayed in critically ill patients: a five year observational study in an Australian tertiary intensive care unit

Duration of bed rest among critically ill patients in ICU has been associated with development of persistent weakness that can last for more than five years. Commencing early exercise interventions in ICU is likely to reduce critically ill patients’ physical dysfunction. However, critically ill patients often experience prolonged periods of bed rest and inactivity. This study examined the timing of commencement of exercise interventions, including sitting out of bed and upright mobilisation, following physiological stability in critically ill patients and describes key clinical outcomes. Participants included consecutive patients admitted for >48 hours to a 25-bed Australian mixed medical and surgical adult ICU between July 2009 and June 2014. Time taken for patients to achieve neurological, cardiorespiratory and cardiovascular (physiological) stability was calculated and timing of initial sitting out of bed and upright mobilisation was recorded. A small number of patients (n=206, 6.0%) did not achieve physiological stability. A substantial proportion of patients (n=1377, 40.1%) did not complete any mobilisation or sitting activities. For patients (n=1851, 53.9%) who did undertake mobilisation or sitting activities, activity commenced a median (IQR) of 3.6 (2.0, 7.7) days after ICU admission. This represented a median (IQR) delay after physiological stability of 2.3 (1.3, 4.4) days for mobilisation and 2.7 (1.5, 5.7) days for sitting. In-hospital mortality was 14.3% (n=491) for patients who did not participate in exercise interventions, compared to 2.6% (n=89) for patients who exercised whilst in ICU

Critical Care Cycling Study (CYCLIST) trial protocol: a randomised controlled trial of usual care plus additional in-bed cycling sessions versus usual care in the critically ill

Introduction In-bed cycling with patients with critical illness has been shown to be safe and feasible, and improves physical function outcomes at hospital discharge. The effects of early in-bed cycling on reducing the rate of skeletal muscle atrophy, and associations with physical and cognitive function are unknown. Methods and analysis A single-centre randomised controlled trial in a mixed medical-surgical intensive care unit (ICU) will be conducted. Adult patients (n=68) who are expected to be mechanically ventilated for more than 48 hours and remain in ICU for a further 48 hours from recruitment will be randomly allocated into either (1) a usual care group or (2) a group that receives usual care and additional in-bed cycling sessions. The primary outcome is change in rectus femoris cross-sectional area at day 10 in comparison to baseline measured by blinded assessors. Secondary outcome measures include muscle strength, incidence of ICU-acquired weakness, handgrip strength, time to achieve functional milestones (sitting out of bed, walking), Functional Status Score in ICU, ICU Mobility Scale, 6 min walk test 1week postICU discharge, incidence of delirium and quality of life (EuroQol Five Dimensions questionnaire Five Levels scale). Quality of life assessments will be conducted post-ICU admission at day 10, 3 and 6 months after acute hospital discharge. Participants in the intervention group will complete an acceptability of intervention questionnaire. Ethics and dissemination Appropriate ethical approval from Metro South Health Human Research Ethics Committee has been attained. Results will be published in peer-reviewed publications and presented at scientific conferences to assist planning of future multicentre randomised controlled trials (if indicated) that will test in-bed cycling as an intervention to improve the physical, cognitive and health-related quality of life outcomes of patients with critical illness

124-Color Super-resolution Imaging by Engineering DNA-PAINT Blinking Kinetics

Optical super-resolution techniques reach unprecedented spatial resolution down to a few nanometers. However, efficient multiplexing strategies for the simultaneous detection of hundreds of molecular species are still elusive. Here, we introduce an entirely new approach to multiplexed super-resolution microscopy by designing the blinking behavior of targets with engineered binding frequency and duration in DNA-PAINT. We assay this kinetic barcoding approach in silico and in vitro using DNA origami structures, show the applicability for multiplexed RNA and protein detection in cells, and finally experimentally demonstrate 124-plex super-resolution imaging within minutes.We thank Martin Spitaler and the imaging facility of the MPI of Biochemistry for confocal imaging support

Highly efficient 5\u27 capping of mitochondrial RNA with NAD+ and NADH by yeast and human mitochondrial RNA polymerase

Bacterial and eukaryotic nuclear RNA polymerases (RNAPs) cap RNA with the oxidized and reduced forms of the metabolic effector nicotinamide adenine dinucleotide, NAD+ and NADH, using NAD+ and NADH as non-canonical initiating nucleotides for transcription initiation. Here, we show that mitochondrial RNAPs (mtRNAPs) cap RNA with NAD+ and NADH, and do so more efficiently than nuclear RNAPs. Direct quantitation of NAD+- and NADH-capped RNA demonstrates remarkably high levels of capping in vivo: up to ~60% NAD+ and NADH capping of yeast mitochondrial transcripts, and up to ~15% NAD+ capping of human mitochondrial transcripts. The capping efficiency is determined by promoter sequence at, and upstream of, the transcription start site and, in yeast and human cells, by intracellular NAD+ and NADH levels. Our findings indicate mtRNAPs serve as both sensors and actuators in coupling cellular metabolism to mitochondrial transcriptional outputs, sensing NAD+ and NADH levels and adjusting transcriptional outputs accordingly. © 2018, Bird et al

Interaction of CarD with RNA polymerase mediates Mycobacterium tuberculosis viability, rifampin resistance, and pathogenesis

Mycobacterium tuberculosis infection continues to cause substantial human suffering. New chemotherapeutic strategies, which require insight into the pathways essential for M. tuberculosis pathogenesis, are imperative. We previously reported that depletion of the CarD protein in mycobacteria compromises viability, resistance to oxidative stress and fluoroquinolones, and pathogenesis. CarD associates with the RNA polymerase (RNAP), but it has been unknown which of the diverse functions of CarD are mediated through the RNAP; this question must be answered to understand the CarD mechanism of action. Herein, we describe the interaction between the M. tuberculosis CarD and the RNAP β subunit and identify point mutations that weaken this interaction. The characterization of mycobacterial strains with attenuated CarD/RNAP β interactions demonstrates that the CarD/RNAP β association is required for viability and resistance to oxidative stress but not for fluoroquinolone resistance. Weakening the CarD/RNAP β interaction also increases the sensitivity of mycobacteria to rifampin and streptomycin. Surprisingly, depletion of the CarD protein did not affect sensitivity to rifampin. These findings define the CarD/RNAP interaction as a new target for chemotherapeutic intervention that could also improve the efficacy of rifampin treatment of tuberculosis. In addition, our data demonstrate that weakening the CarD/RNAP β interaction does not completely phenocopy the depletion of CarD and support the existence of functions for CarD independent of direct RNAP binding