Investigation of a Liquefaction Methodology to Enable the Utilization of In-Situ Produced Propellant on the Lunar and Martian Surfaces

To enable NASAs plans to return astronauts to the lunar surface and eventually to Mars, the agency is putting emphasis on reusable cryogenic systems. Such systems will require replenishing of cryogens on-orbit via a cryogenic tanker or refueling depot, and potentially on the lunar or Martian surfaces with the utilization of in-situ resources. Surface replenishing requires the in-situ production of gaseous oxygen (and hydrogen if on the lunar surface), followed by liquefaction and storage. The liquefaction system can be integrated into the propulsion system propellant tanks, or in a separate storage facility and transferred to the propulsion system when needed. In interest of developing a liquefaction and storage system that is efficient, reliable and scalable, a multicenter team of NASA engineers was formed. The team conducted trade studies on various system level concepts including multiple heat exchanger configurations to be integrated with active cooling (cryocoolers). When the trade studies concluded, the team settled on a system level configuration which included a propellant tank outfitted with a tube-on-tank heat exchanger integrated with a cryocooler. The team executed a development plan to include: 1) a brassboard level test series to demonstrate proof of concept, 2) model development to predict system performance, 3) model validation utilizing brassboard test results, 4) the design, development and demonstration of a Mars surface liquefaction and storage system prototype, and 5) eventually conduct an end-to-end demonstration to include in-situ production, liquefaction, and long duration storage of cryogens with zero boil-off. The effort is currently in the brassboard level testing phase which will be discussed here

The birth place of the type Ic Supernova 2007gr

We report our attempts to locate the progenitor of the peculiar type Ic SN 2007gr in HST pre-explosion images of the host galaxy, NGC 1058. Aligning adaptive optics Altair/NIRI imaging of SN 2007gr from the Gemini (North) Telescope with the pre-explosion HST WFPC2 images, we identify the SN position on the HST frames with an accuracy of 20 mas. Although nothing is detected at the SN position we show that it lies on the edge of a bright source, 134+/-23 mas (6.9 pc) from its nominal centre. Based on its luminosity we suggest that this object is possibly an unresolved, compact and coeval cluster and that the SN progenitor was a cluster member, although we note that model profile fitting favours a single bright star. We find two solutions for the age of this assumed cluster; 7-/+0.5 Myrs and 20-30 Myrs, with turn-off masses of 28+/-4 Msun and 12-9 Msun respectively. Pre-explosion ground-based K-band images marginally favour the younger cluster age/higher turn-off mass. Assuming the SN progenitor was a cluster member, the turn-off mass provides the best estimate for its initial mass. More detailed observations, after the SN has faded, should determine if the progenitor was indeed part of a cluster, and if so allow an age estimate to within ~2 Myrs thereby favouring either a high mass single star or lower mass interacting binary progenitor.Comment: 12 pages, 3 figures, resolution of fig 1. has been reduced, some revision based on referee's comments, Accepted ApJL 27 Nov 200

Vented Chill / No-Vent Fill of Cryogenic Propellant Tanks

Architectures for extended duration missions often include an on-orbit replenishment of the space vehicle's cryogenic liquid propellants. Such a replenishment could be accomplished via a tank-to-tank transfer from a dedicated tanker or a more permanent propellant depot storage tank. Minimizing the propellant loss associated with transfer line and receiver propellant tank thermal conditioning is essential for mass savings. A new methodology for conducting tank-to-tank transfer while minimizing such losses has been demonstrated. Charge-Hold-Vent is the traditional methodology for conducting a tank-to-tank propellant transfer. A small amount of cryogenic liquid is introduced to chill the transfer line and propellant tank. As the propellant absorbs heat and undergoes a phase change, the tank internal pressure increases. The tank is then vented to relieve pressure prior to another charge of cryogenic liquid being introduced. This cycle is repeated until the transfer lines and tank are sufficiently chilled and the replenishment of the propellant tank is complete. This method suffers inefficiencies due to multiple chill and vent cycles within the transfer lines and associated feed system components. Additionally, this system requires precise measuring of cryogenic fluid delivery for each transfer, multiple valve cycling events, and other complexities associated with cycled operations. To minimize propellant loss and greatly simplify on-orbit operations, an alternate methodology has been designed and demonstrated. The Vented Chill / No Vent Fill method is a simpler, constant flow approach in which the propellant tank and transfer lines are only chilled once. The receiver tank is continuously vented as cryogenic liquid chills the transfer lines, tank mass and ullage space. Once chilled sufficiently, the receiver tank valve is closed and the tank is completely filled. Interestingly, the vent valve can be closed prior to receiver tank components reaching liquid saturation temperature. An incomplete fill results if insufficient energy is removed from the tank's thermal mass and ullage space. The key to successfully conducting the no vent fill is to assure that sufficient energy is removed from the system prior to closing the receiver tank vent valve. This paper will provide a description of the transfer methodology and test article, and will provide a discussion of test results

The Life Science Exchange: a case study of a sectoral and sub-sectoral knowledge exchange programme

Background: Local and national governments have implemented sector-specific policies to support economic development through innovation, entrepreneurship and knowledge exchange. Supported by the Welsh Government through the European Regional Development Fund, The Life Science Exchange® project was created with the aim to increase interaction between stakeholders, to develop more effective knowledge exchange mechanisms, and to stimulate the formation and maintenance of long-term collaborative relationships within the Welsh life sciences ecosystem. The Life Science Exchange allowed participants to interact with other stakeholder communities (clinical, academic, business, governmental), exchange perspectives and discover new opportunities.Methods: Six sub-sector focus groups comprising over 200 senior stakeholders from academia, industry, the Welsh Government and National Health Service were established. Over 18 months, each focus group provided input to inform healthcare innovation policy and knowledge mapping exercises of their respective sub-sectors. Collaborative projects identified during the focus groups and stakeholder engagement were further developed through sandpit events and bespoke support.Results: Each sub-sector focus group produced a report outlining the significant strengths and opportunities in their respective areas of focus, made recommendations to overcome any ‘system failures’, and identified the stakeholder groups which needed to take action. A second outcome was a stakeholder-driven knowledge mapping exercise for each area of focus. Finally, the sandpit events and bespoke support resulted in participants generating more than £1.66 million in grant funding and inward investment. This article outlines four separate outcomes from the Life Science Exchange programme.Conclusions: The Life Science Exchange process has resulted in a multitude of collaborations, projects, inward investment opportunities and special interest group formations, in addition to securing over ten times its own costs in funding for Wales. The Life Science Exchange model is a simple and straightforward mechanism for a regional or national government to adapt and implement in order to improve innovation, skills, networks and knowledge exchange

In B cells, phosphatidylinositol 5-phosphate 4-kinase-α synthesizes PI(4,5)P2 to impact mTORC2 and Akt signaling.

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are enigmatic lipid kinases with physiological functions that are incompletely understood, not the least because genetic deletion and cell transfection have led to contradictory data. Here, we used the genetic tractability of DT40 cells to create cell lines in which endogenous PI5P4Kα was removed, either stably by genetic deletion or transiently (within 1 h) by tagging the endogenous protein genomically with the auxin degron. In both cases, removal impacted Akt phosphorylation, and by leaving one PI5P4Kα allele present but mutating it to be kinase-dead or have PI4P 5-kinase activity, we show that all of the effects on Akt phosphorylation were dependent on the ability of PI5P4Kα to synthesize phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] rather than to remove PI5P. Although stable removal of PI5P4Kα resulted in a pronounced decrease in Akt phosphorylation at Thr308 and Ser473, in part because of reduced plasma membrane PIP3, its acute removal led to an increase in Akt phosphorylation only at Ser473. This process invokes activation primarily of mammalian target of rapamycin complex 2 (mTORC2), which was confirmed by increased phosphorylation of other mTORC2 substrates. These findings establish PI5P4Kα as a kinase that synthesizes a physiologically relevant pool of PI(4,5)P2 and as a regulator of mTORC2, and show a phenomenon similar to the "butterfly effect" described for phosphatidylinositol 3-kinase Iα [Hart JR, et al. (2015) Proc Natl Acad Sci USA 112(4):1131-1136], whereby through apparently the same underlying mechanism, the removal of a protein's activity from a cell can have widely divergent effects depending on the time course of that removal.S.J.B. was supported by an A.J. Clark Studentship from the British Pharmacological Society, A.D. by Sidney Sussex College, the Cambridge Overseas Trust and the Säid Foundation, and J.H.C by the MRC (Grant RG64071).This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Proceedings of the National Academy of Sciences (PNAS)

Epigenetic modifications are associated with inter-species gene expression variation in primates

Abstract Background Changes in gene regulation have long been thought to play an important role in evolution and speciation, especially in primates. Over the past decade, comparative genomic studies have revealed extensive inter-species differences in gene expression levels, yet we know much less about the extent to which regulatory mechanisms differ between species. Results To begin addressing this gap, we perform a comparative epigenetic study in primate lymphoblastoid cell lines, to query the contribution of RNA polymerase II and four histone modifications, H3K4me1, H3K4me3, H3K27ac, and H3K27me3, to inter-species variation in gene expression levels. We find that inter-species differences in mark enrichment near transcription start sites are significantly more often associated with inter-species differences in the corresponding gene expression level than expected by chance alone. Interestingly, we also find that first-order interactions among the five marks, as well as chromatin states, do not markedly contribute to the degree of association between the marks and inter-species variation in gene expression levels, suggesting that the marginal effects of the five marks dominate this contribution. Conclusions Our observations suggest that epigenetic modifications are substantially associated with changes in gene expression levels among primates and may represent important molecular mechanisms in primate evolution.http://deepblue.lib.umich.edu/bitstream/2027.42/110207/1/13059_2014_Article_547.pd

Understanding the influences on successful quality improvement in emergency general surgery: learning from the RCS Chole-QuIC project.

BACKGROUND: Acute gallstone disease is the highest volume Emergency General Surgical presentation in the UK. Recent data indicate wide variations in the quality of care provided across the country, with national guidance for care delivery not implemented in most UK hospitals. Against this backdrop, the Royal College of Surgeons of England set up a 13-hospital quality improvement collaborative (Chole-QuIC) to support clinical teams to reduce time to surgery for patients with acute gallstone disease requiring emergency cholecystectomy. METHODS: Prospective, mixed-methods process evaluation to answer the following: (1) how was the collaborative delivered by the faculty and received, understood and enacted by the participants; (2) what influenced teams' ability to improve care for patients requiring emergency cholecystectomy? We collected and analysed a range of data including field notes, ethnographic observations of meetings, and project documentation. Analysis was based on the framework approach, informed by Normalisation Process Theory, and involved the creation of comparative case studies based on hospital performance during the project. RESULTS: Chole-QuIC was delivered as planned and was well received and understood by participants. Four hospitals were identified as highly successful, based upon a substantial increase in the number of patients having surgery in line with national guidance. Conversely, four hospitals were identified as challenged, achieving no significant improvement. The comparative analysis indicate that six inter-related influences appeared most associated with improvement: (1) achieving clarity of purpose amongst site leads and key stakeholders; (2) capacity to lead and effective project support; (3) ideas to action; (4) learning from own and others' experience; (5) creating additional capacity to do emergency cholecystectomies; and (6) coordinating/managing the patient pathway. CONCLUSION: Collaborative-based quality improvement is a viable strategy for emergency surgery but success requires the deployment of effective clinical strategies in conjunction with improvement strategies. In particular, achieving clarity of purpose about proposed changes amongst key stakeholders was a vital precursor to improvement, enabling the creation of additional surgical capacity and new pathways to be implemented effectively. Protected time, testing ideas, and the ability to learn quickly from data and experience were associated with greater impact within this cohort

Who Needs Inpatient Detox? Development and Implementation of a Hospitalist Protocol for the Evaluation of Patients for Alcohol Detoxification

BACKGROUND: Clinicians caring for patients seeking alcohol detoxification face many challenges, including lack of evidence-based guidelines for treatment and high recidivism rates. OBJECTIVES: To develop a standardized protocol for determining which alcohol dependent patients seeking detoxification need inpatient versus outpatient treatment, and to study the protocol's implementation. DESIGN: Review of best evidence by ad hoc task force and subsequent creation of standardized protocol. Prospective observational evaluation of initial protocol implementation. PARTICIPANTS: Patients presenting for alcohol detoxification. INTERVENTION: Development and implementation of a protocol for evaluation and treatment of patients requesting alcohol detoxification. MAIN MEASURES: Number of admissions per month with primary alcohol related diagnosis (DRG), 30-day readmission rate, and length of stay, all measured before and after protocol implementation. RESULTS: We identified one randomized clinical trial and three cohort studies to inform the choice of inpatient versus outpatient detoxification, along with one prior protocol in this population, and combined that data with clinical experience to create an institutional protocol. After implementation, the average number of alcohol related admissions was 15.9 per month, compared with 18.9 per month before implementation (p = 0.037). There was no difference in readmission rate or length of stay. CONCLUSIONS: Creation and utilization of a protocol led to standardization of care for patients requesting detoxification from alcohol. Initial evaluation of protocol implementation showed a decrease in number of admissions

Cysteinyl-tRNA Deacylation Can Be Uncoupled from Protein Synthesis

Aminoacyl-tRNA synthetases (ARSs) are critical components of protein translation, providing ribosomes with aminoacyl-tRNAs. In return, ribosomes release uncharged tRNAs as ARS substrates. Here, we show that tRNA deacylation can be uncoupled from protein synthesis in an amino acid specific manner. While tRNAs coupled to radiolabeled Met, Leu Lys, or Ser are stable in cells following translation inhibition with arsenite, radiolabeled Cys is released from tRNA at a high rate. We discuss possible translation independent functions for tRNACys