Ultra-Sensitive Hot-Electron Nanobolometers for Terahertz Astrophysics

The background-limited spectral imaging of the early Universe requires spaceborne terahertz (THz) detectors with the sensitivity 2-3 orders of magnitude better than that of the state-of-the-art bolometers. To realize this sensitivity without sacrificing operating speed, novel detector designs should combine an ultrasmall heat capacity of a sensor with its unique thermal isolation. Quantum effects in thermal transport at nanoscale put strong limitations on the further improvement of traditional membrane-supported bolometers. Here we demonstrate an innovative approach by developing superconducting hot-electron nanobolometers in which the electrons are cooled only due to a weak electron-phonon interaction. At T<0.1K, the electron-phonon thermal conductance in these nanodevices becomes less than one percent of the quantum of thermal conductance. The hot-electron nanobolometers, sufficiently sensitive for registering single THz photons, are very promising for submillimeter astronomy and other applications based on quantum calorimetry and photon counting.Comment: 19 pages, 3 color figure

Forecasting stroke-like episodes and outcomes in mitochondrial disease

In this retrospective, multicentre, observational cohort study, we sought to determine the clinical, radiological, EEG, genetics and neuropathological characteristics of mitochondrial stroke-like episodes and to identify associated risk predictors. Between January 1998 and June 2018, we identified 111 patients with genetically-determined mitochondrial disease who developed stroke-like episodes. Post-mortem cases of mitochondrial disease (n = 26) were identified from Newcastle Brain Tissue Resource. The primary outcome was to interrogate the clinic-radio-pathological correlates and prognostic indicators of stroke-like episode in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome. The secondary objective was to develop a multivariable prediction model to forecast stroke-like episode risk. The most common genetic cause of stroke-like episodes was the m.3243A>G variant in MT-TL1 (n = 66), followed by recessive pathogenic POLG variants (n = 22), and 11 other rarer pathogenic mitochondrial DNA (mtDNA) variants (n = 23). The age of first stroke-like episode was available for 105 patients (mean [SD] age: 31.8 [16.1]); a total of 35 patients (32%) presented with their first stroke-like episode ≥40 years of age. The median interval (interquartile range) between first and second stroke-like episodes was 1.33 (2.86) years; 43% of patients developed recurrent stroke-like episodes within 12 months. Clinico-radiological, electrophysiological and neuropathological findings of stroke-like episodes were consistent with the hallmarks of medically refractory epilepsy. Patients with POLG-related stroke-like episodes demonstrated more fulminant disease trajectories than cases of m.3243A>G and other mtDNA pathogenic variants, in terms of the frequency of refractory status epilepticus, rapidity of progression and overall mortality. In multivariate analysis, baseline factors of body mass index, age-adjusted blood m.3243A>G heteroplasmy, sensorineural hearing loss and serum lactate were significantly associated with risk of stroke-like episodes in patients with the m.3243A>G variant. These factors informed the development of a prediction model to assess the risk of developing stroke-like episodes that demonstrated good overall discrimination (area under the curve = 0.87, 95% CI 0.82-0.93; c-statistic = 0.89). Significant radiological and pathological features of neurodegeneration was more evident in patients harbouring pathogenic mtDNA variants compared with POLG: brain atrophy on cranial MRI (90% vs 44%, p G variant can help inform more tailored genetic counselling and prognostication in routine clinical practice

Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma

Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265Funder: Good Will CauseFunder: MRC/EPSRC Newcastle Pathology NodeFunder: Newcastle upon Tyne Hospitals NHS Foundation Trust (Newcastle upon Tyne Hospitals NHS Trust); doi: https://doi.org/10.13039/501100003776Funder: Blood Cancer UK - Senior Bennett Fellowship #12005 North East Promenaders Against Cancer (NEPAC) The Little Princess Trust JGW Patterson FoundationAbstract: Children with B-cell non-Hodgkin lymphoma (B-NHL) have an excellent chance of survival, however, current clinical risk stratification places as many as half of patients in a high-risk group receiving very intensive chemo-immunotherapy. TP53 alterations are associated with adverse outcome in many malignancies; however, whilst common in paediatric B-NHL, their utility as a risk classifier is unknown. We evaluated the clinical significance of TP53 abnormalities (mutations, deletion and/or copy number neutral loss of heterozygosity) in a large UK paediatric B-NHL cohort and determined their impact on survival. TP53 abnormalities were present in 54.7% of cases and were independently associated with a significantly inferior survival compared to those without a TP53 abnormality (PFS 70.0% vs 100%, p < 0.001, OS 78.0% vs 100%, p = 0.002). Moreover, amongst patients clinically defined as high-risk (stage III with high LDH or stage IV), those without a TP53 abnormality have superior survival compared to those with TP53 abnormalities (PFS 100% vs 55.6%, p = 0.005, OS 100% vs 66.7%, p = 0.019). Biallelic TP53 abnormalities were either maintained from the presentation or acquired at progression in all paired diagnosis/progression Burkitt lymphoma cases. TP53 abnormalities thus define clinical risk groups within paediatric B-NHL and offer a novel molecular risk stratifier, allowing more personalised treatment protocols

Computing, Design, Art: Reflections on an Innovative Moment in History

The paper is concerned with the role of art and design in the history and philosophy of computing. It offers insights arising from research into a period in the 1960s and 70s, particularly in the UK, when computing became more available to artists and designers, focusing on John Lansdown (1929-1999) and Bruce Archer (1922-2005) in London. Models of computing interacted with conceptualisations of art, design and related creative activities in important ways

Resupply of mesopelagic dissolved iron controlled by particulate iron composition

The dissolved iron supply controls half of the oceans’ primary productivity. Resupply by the remineralization of sinking particles, and subsequent vertical mixing, largely sustains this productivity. However, our understanding of the drivers of dissolved iron resupply, and their influence on its vertical distribution across the oceans, is still limited due to sparse observations. There is a lack of empirical evidence as to what controls the subsurface iron remineralization due to difficulties in studying mesopelagic biogeochemistry. Here we present estimates of particulate transformations to dissolved iron, concurrent oxygen consumption and iron-binding ligand replenishment based on in situ mesopelagic experiments. Dissolved iron regeneration efficiencies (that is, replenishment over oxygen consumption) were 10- to 100-fold higher in low-dust subantarctic waters relative to higher-dust Mediterranean sites. Regeneration efficiencies are heavily influenced by particle composition. Their make-up dictates ligand release, controls scavenging, modulates ballasting and may lead to the differential remineralization of biogenic versus lithogenic iron. At high-dust sites, these processes together increase the iron remineralization length scale. Modelling reveals that in oceanic regions near deserts, enhanced lithogenic fluxes deepen the ferricline, which alter the vertical patterns of dissolved iron replenishment, and set its redistribution at the global scale. Such wide-ranging regeneration efficiencies drive different vertical patterns in dissolved iron replenishment across oceanic provinces

The role of place branding and image in the development of sectoral clusters: the case of Dubai

This paper contextualizes how place branding and image influence the development of Dubai’s key sectoral clusters, including the key determinants of growth and success under the impression of Porter’s cluster theory. The approach is exploratory and of a qualitative inductive nature. Data was collected through conducting 21 semi-structured interviews with Dubai’s marketing/communication managers and stakeholders. Findings suggest that Dubai’s traditional clusters, namely, trading, tourism and logistics that have strong place branding and image show strong signs of success owing to Dubai’s geographical location (i.e., physical conditions). Among the new clusters, the financial sector is also benefitting from place branding. The results suggest that the success of traditional clusters have a positive spill over effect on the new clusters, in particular on construction and real estate. For policy makers it is worth to note that the recent success of the financial services cluster in Dubai will have positive impact on both, the traditional as well new clusters. The marketing and brand communication managers must consider the correlation and interplay of strength of activities amongst trading, tourism and logistics clusters and its implication while undertaking place branding for clients in their sector

Modeling the accretion history of supermassive black holes

There is overwhelming evidence for the presence of supermassive black holes (SMBHs) in the centers of most nearby galaxies. The mass estimates for these remnant black holes from the stellar kinematics of local galaxies and the quasar phenomenon at high redshifts point to the presence of assembled SMBHs. The accretion history of SMBHs can be reconstructed using observations at high and low redshifts as model constraints. Observations of galaxies and quasars in the submillimeter, infrared, optical, and X-ray wavebands are used as constraints, along with data from the demography of local black holes. Theoretical modeling of the growth of black hole mass with cosmic time has been pursued thus far in two distinct directions: a phenomenological approach that utilizes observations in various wavebands, and a semi-analytic approach that starts with a theoretical framework and a set of assumptions with a view to matching observations. Both techniques have been pursued in the context of the standard paradigm for structure formation in a Cold Dark Matter dominated universe. Here, we examine the key issues and uncertainties in the theoretical understanding of the growth of SMBHs.Comment: 19 pages, 4 figures, to appear as Chapter 4 in "Supermassive Black Holes in the Distant Universe" (2004), ed. A. J. Barger, Kluwer Academic Publishers, in pres

Major Role of Microbes in Carbon Fluxes during Austral Winter in the Southern Drake Passage

Carbon cycling in Southern Ocean is a major issue in climate change, hence the need to understand the role of biota in the regulation of carbon fixation and cycling. Southern Ocean is a heterogeneous system, characterized by a strong seasonality, due to long dark winter. Yet, currently little is known about biogeochemical dynamics during this season, particularly in the deeper part of the ocean. We studied bacterial communities and processes in summer and winter cruises in the southern Drake Passage. Here we show that in winter, when the primary production is greatly reduced, Bacteria and Archaea become the major producers of biogenic particles, at the expense of dissolved organic carbon drawdown. Heterotrophic production and chemoautotrophic CO2 fixation rates were substantial, also in deep water, and bacterial populations were controlled by protists and viruses. A dynamic food web is also consistent with the observed temporal and spatial variations in archaeal and bacterial communities that might exploit various niches. Thus, Southern Ocean microbial loop may substantially maintain a wintertime food web and system respiration at the expense of summer produced DOC as well as regenerate nutrients and iron. Our findings have important implications for Southern Ocean ecosystem functioning and carbon cycle and its manipulation by iron enrichment to achieve net sequestration of atmospheric CO2