Coordinated Ionospheric Reconstruction CubeSat Experiment (CIRCE), In situ and Remote Ionospheric Sensing (IRIS) suite

The UK’s Defence Science and Technology Laboratory (Dstl) is partnering with the US Naval Research Laboratory (NRL) on a joint mission to launch miniature sensors that will advance space weather measurement and modelling capabilities. The Coordinated Ionospheric Reconstruction Cubesat Experiment (CIRCE) comprises two 6U cube-satellites that will be launched into a near-polar low earth orbit (LEO), targeting 500 km altitude, in 2021. The UK contribution to CIRCE is the In situ and Remote Ionospheric Sensing (IRIS) suite, complementary to NRL sensors, and comprising three highly miniaturised payloads provided to Dstl by University College London (UCL), University of Bath, and University of Surrey/Surrey Satellite Technology Ltd (SSTL). One IRIS suite will be flown on each satellite, and incorporates an ion/neutral mass spectrometer, a tri-band global positioning system (GPS) receiver for ionospheric remote sensing, and a radiation environment monitor. From the US, NRL have provided two 1U Triple Tiny Ionospheric Photometers (Tri-TIPs) on each satellite (Nicholas et al., 2019), observing the ultraviolet 135.6 nm emission of atomic oxygen at night-time to characterize the two-dimensional distribution of electrons

Niclosamide Prevents the Formation of Large Ubiquitin-Containing Aggregates Caused by Proteasome Inhibition

Protein aggregation is a hallmark of many neurodegenerative diseases and has been linked to the failure to degrade misfolded and damaged proteins. In the cell, aberrant proteins are degraded by the ubiquitin proteasome system that mainly targets short-lived proteins, or by the lysosomes that mostly clear long-lived and poorly soluble proteins. Both systems are interconnected and, in some instances, autophagy can redirect proteasome substrates to the lysosomes.To better understand the interplay between these two systems, we established a neuroblastoma cell population stably expressing the GFP-ubiquitin fusion protein. We show that inhibition of the proteasome leads to the formation of large ubiquitin-containing inclusions accompanied by lower solubility of the ubiquitin conjugates. Strikingly, the formation of the ubiquitin-containing aggregates does not require ectopic expression of disease-specific proteins. Moreover, formation of these focused inclusions caused by proteasome inhibition requires the lysine 63 (K63) of ubiquitin. We then assessed selected compounds that stimulate autophagy and found that the antihelmintic chemical niclosamide prevents large aggregate formation induced by proteasome inhibition, while the prototypical mTORC1 inhibitor rapamycin had no apparent effect. Niclosamide also precludes the accumulation of poly-ubiquitinated proteins and of p62 upon proteasome inhibition. Moreover, niclosamide induces a change in lysosome distribution in the cell that, in the absence of proteasome activity, may favor the uptake into lysosomes of ubiquitinated proteins before they form large aggregates.Our results indicate that proteasome inhibition provokes the formation of large ubiquitin containing aggregates in tissue culture cells, even in the absence of disease specific proteins. Furthermore our study suggests that the autophagy-inducing compound niclosamide may promote the selective clearance of ubiquitinated proteins in the absence of proteasome activity

Metal-polymer composite sensors for volatile organic compounds: Part 1. Flow-through chemi-resistors

A new type of chemi-resistor based on a novel metal-polymer composite is described. The composite contains nickel particles with sharp nano-scale surface features, which are intimately coated by the polymer matrix so that they do not come into direct physical contact. No conductive chains of filler particles are formed even at loadings above the percolation threshold and the composite is intrinsically insulating. However, when subjected to compression the composite becomes conductive, with sample resistance falling from ≥ 1012 Ω to < 0.01 Ω. The composite can be formed into insulating granules, which display similar properties to the bulk form. A bed of granules compressed between permeable frits provides a porous structure with a start resistance set by the degree of compression while the granules are free to swell when exposed to volatile organic compounds (VOCs). The granular bed presents a large surface area for the adsorption of VOCs from the gas stream flowing through it. The response of this system to a variety of vapours has been studied for two different sizes of the granular bed and for different matrix polymers. Large responses, ΔR/R0 ≥ 10^7, are observed when saturated vapours are passed through the chemi-resistor. Rapid response allows real time sensing of VOCs and the initial state is recovered in a few seconds by purging with an inert gas stream. The variation in response as a function of VOC concentration is determined

ANALYTICAL DEVICE FOR TEST FLUIDS, COMPRISES A CONDUCTIVE POLYMER COMPOSITION

A sensor for chemical species or biological species or radiation presenting to test fluid a polymer composition comprises polymer and conductive filler metal, alloy or reduced metal oxide and having a first level of electrical conductance when quiescent and being convertible to a second level of conductance by change of stress applied by stretching or compression or electric field, in which the polymer composition is characterised by at least one of the features in the form of particles at least 90% w/w held on a 100 mesh sieve; and/or comprising a permeable body extending across a channel of fluid flow; and/or affording in-and-out diffusion of test fluid and/or mechanically coupled to a workpiece of polymer swellable by a constituent of test fluid

Histological correlates of carotid plaque surface morphology on lumen contrast imaging.

BACKGROUND: Carotid angiographic plaque surface morphology is a powerful risk factor for stroke and systemic vascular risk. However, the underlying pathology is unclear, and a better understanding is required both to evaluate other forms of carotid imaging and to develop new treatments. Previous studies comparing angiographic plaque surface morphology with pathology have been small and unblinded, and the vast majority assessed only the crude macroscopic appearance of the plaque. We performed the first large study comparing angiographic surface morphology with detailed histology. METHODS AND RESULTS: Carotid plaque surface morphology was classified as ulcerated, irregular, or smooth on 128 conventional selective carotid artery angiograms from consecutive patients undergoing endarterectomy for severe symptomatic stenosis. Blinded angiographic assessments were compared with 10 histological features recorded on detailed microscopy of the plaque using reproducible semiquantitative scales. Angiographic ulceration was associated with plaque rupture (P=0.001), intraplaque hemorrhage (P=0.001), large lipid core (P=0.005), less fibrous tissue (P=0.003), and increased instability overall (P=0.001). For example, angiographically ulcerated plaques were much more likely than smooth plaques to be ruptured (OR=15.4, 95% CI=2.7 to 87.3, P<0.001), show a large lipid core (OR=26.7, 95% CI=2.6 to 270, P<0.001) or a large hemorrhage (OR=17.0, 95% CI=2.0 to 147, P=0.02). The equivalent odds ratios for angiographically irregular versus smooth plaque were 6.3 (1.3 to 31, P=0.02), 6.7 (1.5 to 30, P=0.008), and 9.2 (1.1 to 77, P=0.02), respectively. CONCLUSIONS: In contrast to previous studies based on macroscopic assessment, we found very strong associations between detailed histology and carotid angiographic plaque surface morphology. Plaque surface morphology on carotid angiography is a highly sensitive marker of plaque instability. Studies of the predictive value of MR- and CT-based lumen contrast plaque surface imaging are required

A metal polymer composite with unusual properties

Electrically conductive composites that contain conductive filler dispersed in an insulating polymer matrix are usually prepared by the vigorous mixing of the components. This affects the structure of the filler particles and thereby the properties of the composite. It is shown that by careful mixing nano-scale features on the surface of the filler particles can be retained. The fillers used possess sharp surface protrusions similar to the tips used in scanning tunnelling microscopy. The electric field strength at these tips is very large and results in field assisted (Fowler–Nordheim) tunnelling. In addition the polymer matrix intimately coats the filler particles and the particles do not come into direct physical contact. This prevents the formation of chains of filler particles in close contact as the filler content increases. In consequence the composite has an extremely high resistance even at filler loadings above the expected percolation threshold. The retention of filler particle morphology and the presence of an insulating polymer layer between them endow the composite with a number of unusual properties. These are presented here together with appropriate physical models

Histological correlates of carotid plaque surface morphology on lumen contrast imaging.

BACKGROUND: Carotid angiographic plaque surface morphology is a powerful risk factor for stroke and systemic vascular risk. However, the underlying pathology is unclear, and a better understanding is required both to evaluate other forms of carotid imaging and to develop new treatments. Previous studies comparing angiographic plaque surface morphology with pathology have been small and unblinded, and the vast majority assessed only the crude macroscopic appearance of the plaque. We performed the first large study comparing angiographic surface morphology with detailed histology. METHODS AND RESULTS: Carotid plaque surface morphology was classified as ulcerated, irregular, or smooth on 128 conventional selective carotid artery angiograms from consecutive patients undergoing endarterectomy for severe symptomatic stenosis. Blinded angiographic assessments were compared with 10 histological features recorded on detailed microscopy of the plaque using reproducible semiquantitative scales. Angiographic ulceration was associated with plaque rupture (P=0.001), intraplaque hemorrhage (P=0.001), large lipid core (P=0.005), less fibrous tissue (P=0.003), and increased instability overall (P=0.001). For example, angiographically ulcerated plaques were much more likely than smooth plaques to be ruptured (OR=15.4, 95% CI=2.7 to 87.3, P&lt;0.001), show a large lipid core (OR=26.7, 95% CI=2.6 to 270, P&lt;0.001) or a large hemorrhage (OR=17.0, 95% CI=2.0 to 147, P=0.02). The equivalent odds ratios for angiographically irregular versus smooth plaque were 6.3 (1.3 to 31, P=0.02), 6.7 (1.5 to 30, P=0.008), and 9.2 (1.1 to 77, P=0.02), respectively. CONCLUSIONS: In contrast to previous studies based on macroscopic assessment, we found very strong associations between detailed histology and carotid angiographic plaque surface morphology. Plaque surface morphology on carotid angiography is a highly sensitive marker of plaque instability. Studies of the predictive value of MR- and CT-based lumen contrast plaque surface imaging are required

Vascular surgical society of great britain and ireland: twenty-three years of experience of carotid endarterectomy

BACKGROUND: Carotid endarterectomy (CEA) has been an evidence-based treatment for symptomatic severe carotid stenosis since 1991. Surgical techniques and patient selection have changed over the years. The results of CEA in a single centre over a 23-year period were reviewed. METHODS: Prospectively gathered preoperative, operative, postoperative and long-term follow-up data were analysed. Routine intraoperative shunting and patch closure has been used since 1988. Data were analysed using the chi2 test or by logistic regression, adjusting for age at operation and date of operation. RESULTS: Five hundred and seventy-three CEAs (37 bilateral and three repeat procedures) were carried out on 533 patients. Trainees performed an increasing proportion of CEAs from 1996 to 1998 (15, 50 and 56 per cent respectively). The perioperative death rate was 0.8 per cent and the rate of any perioperative neurological deficit was 6.9 per cent. Other causes of morbidity included nerve injury (5.1 per cent) of which the commonest was to the hypoglossal nerve (2.7 per cent). During follow-up (median 4 (range 0-22) years) there were 81 neurological events (15.9 per cent) which included 35 ipsilateral (6.6 per cent) and 18 contralateral (3.4 per cent) strokes. There was no significant difference in outcome for grade of surgeon, intraoperative shunting or patch closure. Major causes of death were cardiac death (74; 14.6 per cent) followed by stroke (23; 4.5 per cent) and cancer (20; 3.9 per cent). CONCLUSION: The introduction of routine intraoperative shunting and patch closure, as well as allowing surgical trainees to perform supervised CEAs, has not affected perioperative morbidity and mortality rates or long-term outcome