Gas containment for in situ sample analysis on the Moon: Utility of sealing materials in the presence of dust

Lunar dust presents a serious challenge to all operations on the Moon, whether human or robotic. It can be especially problematic in applications where it is necessary to make high integrity, gas-tight seals, such as within payloads designed for in situ analysis of lunar ices and volatiles. The challenge has been addressed within the context of the ProSPA instrument being developed for the Luna-27 mission. Soft sealing materials are preferred in order to minimise the required sealing force to enable use of lightweight actuators. JSC-1A simulant was used to test and compare the sealing performance of the elastomer Kalrez® 7075 and of Indium. It was found that both materials were able to seal at dust levels of up to 0.90 mg/cm2 with an applied force of up to 400 N. Indium offers the best sealing performance (better than 10-7 mbar.l.s-1) but Kalrez® is capable of operation at higher temperature, which may be beneficial in applications in which samples are heated to release gases for analysis

Caenorhabditis elegans Maintains Highly Compartmentalized Cellular Distribution of Metals and Steep Concentration Gradients of Manganese

Bioinorganic chemistry is critical to cellular function. Homeostasis of manganese (Mn), for example, is essential for life. A lack of methods for direct in situ visualization of Mn and other biological metals within intact multicellular eukaryotes limits our understanding of management of these metals. We provide the first quantitative subcellular visualization of endogenous Mn concentrations (spanning two orders of magnitude) associated with individual cells of the nematode, Caenorhabditis elegans

Diurnal Differences in Risk of Cardiac Arrhythmias during Spontaneous Hypoglycemia in Young People with Type 1 Diabetes

OBJECTIVE Hypoglycemia may exert proarrhythmogenic effects on the heart via sympathoadrenal stimulation and hypokalemia. Hypoglycemia-induced cardiac dysrhythmias are linked to the “dead-in-bed syndrome,” a rare but devastating condition. We examined the effect of nocturnal and daytime clinical hypoglycemia on electrocardiogram (ECG) in young people with type 1 diabetes. RESEARCH DESIGN AND METHODS Thirty-seven individuals with type 1 diabetes underwent 96 h of simultaneous ambulatory ECG and blinded continuous interstitial glucose monitoring (CGM) while symptomatic hypoglycemia was recorded. Frequency of arrhythmias, heart rate variability, and cardiac repolarization were measured during hypoglycemia and compared with time-matched euglycemia during night and day. RESULTS A total of 2,395 h of simultaneous ECG and CGM recordings were obtained; 159 h were designated hypoglycemia and 1,355 h euglycemia. A median duration of nocturnal hypoglycemia of 60 min (interquartile range 40–135) was longer than daytime hypoglycemia of 44 min (30–70) (P = 0.020). Only 24.1% of nocturnal and 51.0% of daytime episodes were symptomatic. Bradycardia was more frequent during nocturnal hypoglycemia compared with matched euglycemia (incident rate ratio [IRR] 6.44 [95% CI 6.26, 6.63], P < 0.001). During daytime hypoglycemia, bradycardia was less frequent (IRR 0.023 [95% CI 0.002, 0.26], P = 0.002) and atrial ectopics more frequent (IRR 2.29 [95% CI 1.19, 4.39], P = 0.013). Prolonged QTc, T-peak to T-end interval duration, and decreased T-wave symmetry were detected during nocturnal and daytime hypoglycemia. CONCLUSIONS Asymptomatic hypoglycemia was common. We identified differences in arrhythmic risk and cardiac repolarization during nocturnal versus daytime hypoglycemia in young adults with type 1 diabetes. Our data provide further evidence that hypoglycemia is proarrhythmogenic

Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis

Lipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis. We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism. We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR. HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3. We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol levels, with preferential suppression of cholesterol synthesis via lathosterol, associated with increasing hepatic steatosis. The genotype-specific lipid disturbances may shed light on genotypic variations in liver disease progression and promotion of hepatocellular cancer in HCV-G3

Learning is Like a Lava Lamp: The Student Journey to Critical Thinking

This paper explores the ways in which a university Foundation Degree programme supports undergraduate early years students to develop critical thinking, mindfulness and self-actualisation through their lived personal and professional experiences. It considers the impact of this on graduates employed within the Early Years sector. Findings inform future design of a University Foundation Degree programme situated within Early Childhood Education and Care (ECEC). As undergraduates, students engage in higher-level learning aligned to their practice within the workplace. An interpretive Participatory Qualitative Research methodology is used to gather the views of 6 alumni who completed their studies in 2014. They participated in the research freely within ethical parameters approved by a university ethics committee. Findings revealed that the development of critical thinking is empowered by having a personal or professional impetus, which in the case of Early Years is the child as being at the heart of values based practice. This, with the inclusion of mindfulness, drives students to a sustainable deeper layer of thinking to achieve self-actualisation. Through the acquisition of critical thinking students have been subsequently able to take up positions of authority within the early years workforce

L-DART: A Penetrator Mission for Lunar Permanently Shadowed Regions

Lunar Direct Analysis of Resource Traps (L‐DART) will address many current knowledge gaps concerning lunar volatiles and permanently shadowed regions (PSRs), providing in-situ ground truth data to calibrate numerous existing remote datasets. It builds on UK expertise in developing and testing penetrator system concepts for the Moon and Europa (e.g. MOONLITE). Following release of a Penetrator Descent Module in lunar orbit (Figure 1), its Penetrator Delivery System performs de-orbit and orientation before releasing the instrumented Penetrator to penetrate a few meters into target lunar surface at ~300 m/s. The penetrator itself serves as the sampling tool and an on-board mass spectrometer analyses in-situ the volatiles released both in the impact and in the subsequent thermal soak from lander to surrounding regolith. A pair of 3‐axis accelerometers measure regolith structure during the landing event and constrain penetrator final location. Temperature sensors enable regolith thermal properties to be deduced. Pre-and post impact imagery is obtained for context. Science is complete and data relayed to Earth within 1-2 hours, minimizing system mass and lifetime requirements. Possible landing sites include Cabeus (for comparison with LCROSS) or Shoemaker which exhibits excess hydrogen, or areas indicated by LRO to exhibit putative surface frost. Alternatively, L‐DART could target the hypothesised ancient (paleo) south pole and hence potentially ancient volatiles

Graphite flake self-retraction response based on potential seeking

The high elastic modulus and interlayer strengths of graphite flakes make them a durable solid superlubricant. Apart from this, they have configurable electrical properties, exhibit quantum Hall effects, and possess a myriad of useful photonic properties. The self-retraction behavior of graphite flakes can have significant impact on the creation of ordered stacks for various applications because any accidental or intentional displacement of the top flake over the stacks below may result in a misalignment of the carbon-carbon atomic arrangement which, in turn, can have influence over the electrical and photonic properties. It has also been revealed that there was a tendency of the displaced microflake to fail at times to return to its original starting position and orientation. Here, we elucidate this behavior by considering the influence of the interlayer potential forces based on minimal potential energy seeking. The maps of the parameters interrogated here provide the ability for precautions to be undertaken. They also potentially permit the creation of an array of microflake stacks in which the metastable states permit different information to be encoded by virtue of the differentiated photonic or electrical characteristics readable from each array site

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Emergent mechanical control of vascular morphogenesis

Vascularization is driven by morphogen signals and mechanical cues that coordinately regulate cellular force generation, migration, and shape change to sculpt the developing vascular network. However, it remains unclear whether developing vasculature actively regulates its own mechanical properties to achieve effective vascularization. We engineered tissue constructs containing endothelial cells and fibroblasts to investigate the mechanics of vascularization. Tissue stiffness increases during vascular morphogenesis resulting from emergent interactions between endothelial cells, fibroblasts, and ECM and correlates with enhanced vascular function. Contractile cellular forces are key to emergent tissue stiffening and synergize with ECM mechanical properties to modulate the mechanics of vascularization. Emergent tissue stiffening and vascular function rely on mechanotransduction signaling within fibroblasts, mediated by YAP1. Mouse embryos lacking YAP1 in fibroblasts exhibit both reduced tissue stiffness and develop lethal vascular defects. Translating our findings through biology-inspired vascular tissue engineering approaches will have substantial implications in regenerative medicine