Assessment of space proton radiation-induced charge transfer inefficiency in the CCD204 for the Euclid space observatory

Euclid is a medium class European Space Agency mission candidate for launch in 2019 with a primary goal to study the dark universe using the weak lensing and baryonic acoustic oscillations techniques. Weak lensing depends on accurate shape measurements of distant galaxies. Therefore it is beneficial that the effects of radiation-induced charge transfer inefficiency (CTI) in the Euclid CCDs over the course of the 5 year mission at L2 are understood. This will allow, through experimental analysis and modelling techniques, the effects of radiation induced CTI on shape to be decoupled from those of mass inhomogeneities along the line-of-sight. This paper discusses a selection of work from the study that has been undertaken using the e2v CCD204 as part of the initial proton radiation damage assessment for Euclid. The experimental arrangement and procedure are described followed by the results obtained, thereby allowing recommendations to be made on the CCD operating temperature, to provide an insight into CTI effects using an optical background, to assess the benefits of using charge injection on CTI recovery and the effect of the use of two different methods of serial clocking on serial CTI. This work will form the basis of a comparison with a p-channel CCD204 fabricated using the same mask set as the n-channel equivalent. A custom CCD has been designed, based on this work and discussions between e2v technologies plc. and the Euclid consortium, and designated the CCD273

Pontine stroke presenting as isolated facial nerve palsy mimicking Bell's palsy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Isolated facial nerve palsy usually manifests as Bell's palsy. Lacunar infarct involving the lower pons is a rare cause of solitary infranuclear facial paralysis. The present unusual case is one in which the patient appeared to have Bell's palsy but turned out to have a pontine infarct.</p> <p>Case presentation</p> <p>A 47-year-old Asian Indian man with a medical history of hypertension presented to our institution with nausea, vomiting, generalized weakness, facial droop, and slurred speech of 14 hours' duration. His physical examination revealed that he was conscious, lethargic, and had mildly slurred speech. His blood pressure was 216/142 mmHg. His neurologic examination showed that he had loss of left-sided forehead creases, inability to close his left eye, left facial muscle weakness, rightward deviation of the angle of the mouth on smiling, and loss of the left nasolabial fold. Afferent corneal reflexes were present bilaterally. MRI of the head was initially read as negative for acute stroke. Bell's palsy appeared less likely because of the acuity of his presentation, encephalopathy-like imaging, and hypertension. The MRI was re-evaluated with a neurologist's assistance, which revealed a tiny 4 mm infarct involving the left dorsal aspect of the pons. The final diagnosis was isolated facial nerve palsy due to lacunar infarct of dorsal pons and hypertensive encephalopathy.</p> <p>Conclusion</p> <p>The facial nerve has a predominant motor component which supplies all muscles concerned with unilateral facial expression. Anatomic knowledge is crucial for clinical localization. Bell's palsy accounts for around 72% of facial palsies. Other causes such as tumors and pontine infarcts can also present as facial palsy. Isolated dorsal infarct presenting as isolated facial palsy is very rare. Our case emphasizes that isolated facial palsy should not always be attributed to Bell's palsy. It can be a presentation of a rare dorsal pontine infarct as observed in our patient.</p

Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition

BACKGROUND:Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.METHODS:We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.RESULTS:All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.CONCLUSIONS:Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations

Cloud computing mobile application for remote monitoring of Bell's palsy

Mobile applications provide the healthcare industry with a means of connecting with patients in their own home utilizing their own personal mobile devices such as tablets and phones. This allows therapists to monitor the progress of people under their care from a remote location and all with the added benefit that patients are familiar with their own mobile devices; thereby reducing the time required to train patients with the new technology. There is also the added benefit to the health service that there is no additional cost required to purchase devices for use. The Facial Remote Activity Monitoring Eyewear (FRAME) mobile application and web service framework has been designed to work on the IOS and android platforms, the two most commonly used today. Results: The system utilizes secure cloud based data storage to collect, analyse and store data, this allows for near real time, secure access remotely by therapists to monitor their patients and intervene when required. The underlying framework has been designed to be secure, anonymous and flexible to ensure compliance with the data protection act and the latest General Data Protection Regulation (GDPR); this new standard came into effect in April 2018 and replaces the Data Protection Act in the UK and Europe

Bridging the gap between energy and the environment

Meeting the world’s energy demand is a major challenge for society over the coming century. To identify the most sustainable energy pathways to meet this demand, analysis of energy systems on which policy is based must move beyond the current primary focus on carbon to include a broad range of ecosystem services on which human well-being depends. Incorporation of a broad set of ecosystem services into the design of energy policy will differentiates between energy technology options to identify policy options that reconcile national and international obligations to address climate change and the loss of biodiversity and ecosystem services. In this paper we consider our current understanding of the implications of energy systems for ecosystem services and identify key elements of an assessment. Analysis must consider the full life cycle of energy systems, the territorial and international footprint, use a consistent ecosystem service framework that incorporates the value of both market and non-market goods, and consider the spatial and temporal dynamics of both the energy and environmental system. While significant methodological challenges exist, the approach we detail can provide the holistic view of energy and ecosystem services interactions required to inform the future of global energy policy

Population dynamics of an RNA virus and its defective interfering particles in passage cultures

<p>Abstract</p> <p>Background</p> <p>Viruses can fall prey to their defective interfering (DI) particles. When viruses are cultured by serial passage on susceptible host cells, the presence of virus-like DI particles can cause virus populations to rise and fall, reflecting predator-prey interactions between DI and virus particles. The levels of virus and DI particles in each population passage can be determined experimentally by plaque and yield-reduction assays, respectively.</p> <p>Results</p> <p>To better understand DI and virus particle interactions we measured vesicular stomatitis virus and DI particle production during serial-passage culture on BHK cells. When the multiplicity of infection (MOI, or ratio of infectious virus particles to cells) was fixed, virus yields followed a pattern of progressive decline, with higher MOI driving earlier and faster drops in virus level. These patterns of virus decline were consistent with predictions from a mathematical model based on single-passage behavior of cells co-infected with virus and DI particles. By contrast, the production of virus during fixed-volume passages exhibited irregular fluctuations that could not be described by either the steady-state or regular oscillatory dynamics of the model. However, these irregularities were, to a significant degree, reproduced when measured host-cell levels were incorporated into the model, revealing a high sensitivity of virus and DI particle populations to fluctuations in available cell resources.</p> <p>Conclusions</p> <p>This study shows how the development of mathematical models, when guided by quantitative experiments, can provide new insight into the dynamic behavior of virus populations.</p

Atmospheric oxygen regulation at low Proterozoic levels by incomplete oxidative weathering of sedimentary organic carbon

It is unclear why atmospheric oxygen remained trapped at low levels for more than 1.5 billion years following the Paleoproterozoic Great Oxidation Event. Here, we use models for erosion, weathering and biogeochemical cycling to show that this can be explained by the tectonic recycling of previously accumulated sedimentary organic carbon, combined with the oxygen sensitivity of oxidative weathering. Our results indicate a strong negative feedback regime when atmospheric oxygen concentration is of order pO2∼0.1 PAL (present atmospheric level), but that stability is lost at pO2<0.01 PAL. Within these limits, the carbonate carbon isotope (δ13C) record becomes insensitive to changes in organic carbon burial rate, due to counterbalancing changes in the weathering of isotopically light organic carbon. This can explain the lack of secular trend in the Precambrian δ13C record, and reopens the possibility that increased biological productivity and resultant organic carbon burial drove the Great Oxidation Event

Microevolution of Helicobacter pylori during prolonged infection of single hosts and within families

Our understanding of basic evolutionary processes in bacteria is still very limited. For example, multiple recent dating estimates are based on a universal inter-species molecular clock rate, but that rate was calibrated using estimates of geological dates that are no longer accepted. We therefore estimated the short-term rates of mutation and recombination in Helicobacter pylori by sequencing an average of 39,300 bp in 78 gene fragments from 97 isolates. These isolates included 34 pairs of sequential samples, which were sampled at intervals of 0.25 to 10.2 years. They also included single isolates from 29 individuals (average age: 45 years) from 10 families. The accumulation of sequence diversity increased with time of separation in a clock-like manner in the sequential isolates. We used Approximate Bayesian Computation to estimate the rates of mutation, recombination, mean length of recombination tracts, and average diversity in those tracts. The estimates indicate that the short-term mutation rate is 1.4×10−6 (serial isolates) to 4.5×10−6 (family isolates) per nucleotide per year and that three times as many substitutions are introduced by recombination as by mutation. The long-term mutation rate over millennia is 5–17-fold lower, partly due to the removal of non-synonymous mutations due to purifying selection. Comparisons with the recent literature show that short-term mutation rates vary dramatically in different bacterial species and can span a range of several orders of magnitude

Ferric quinate (QPLEX) inhibits the interaction of major outer membrane protein (MOMP) with the Lewis b (Leb) antigen and limits Campylobacter colonization in broilers

Campylobacter jejuni colonizes hosts by interacting with Blood Group Antigens (BgAgs) on the surface of gastrointestinal epithelia. Genetic variations in BgAg expression affects host susceptibility to C. jejuni. Here, we show that the essential major outer membrane protein (MOMP) of C. jejuni NCTC11168 binds to the Lewis b (Leb) antigen on the gastrointestinal epithelia of host tissues and this interaction can be competitively inhibited by ferric quinate (QPLEX), a ferric chelate structurally similar to bacterial siderophores. We provide evidence that QPLEX competitively inhibits the MOMP-Leb interaction. Furthermore, we demonstrate that QPLEX can be used as a feed additive in broiler farming to significantly reduce C. jejuni colonization. Our results indicate that QPLEX can be a viable alternative to the preventative use of antibiotics in broiler farming to combat C. jejuni infections

Calmodulin-like proteins localized to the conoid regulate motility and cell invasion by Toxoplasma gondii

Toxoplasma gondii contains an expanded number of calmodulin (CaM)-like proteins whose functions are poorly understood. Using a combination of CRISPR/Cas9-mediated gene editing and a plant-like auxin-induced degron (AID) system, we examined the roles of three apically localized CaMs. CaM1 and CaM2 were individually dispensable, but loss of both resulted in a synthetic lethal phenotype. CaM3 was refractory to deletion, suggesting it is essential. Consistent with this prediction auxin-induced degradation of CaM3 blocked growth. Phenotypic analysis revealed that all three CaMs contribute to parasite motility, invasion, and egress from host cells, and that they act downstream of microneme and rhoptry secretion. Super-resolution microscopy localized all three CaMs to the conoid where they overlap with myosin H (MyoH), a motor protein that is required for invasion. Biotinylation using BirA fusions with the CaMs labeled a number of apical proteins including MyoH and its light chain MLC7, suggesting they may interact. Consistent with this hypothesis, disruption of MyoH led to degradation of CaM3, or redistribution of CaM1 and CaM2. Collectively, our findings suggest these CaMs may interact with MyoH to control motility and cell invasion