Deformation of Silica Aerogel During Fluid Adsorption

Aerogels are very compliant materials - even small stresses can lead to large deformations. In this paper we present measurements of the linear deformation of high porosity aerogels during adsorption of low surface tension fluids, performed using a Linear Variable Differential Transformer (LVDT). We show that the degree of deformation of the aerogel during capillary condensation scales with the surface tension, and extract the bulk modulus of the gel from the data. Furthermore we suggest limits on safe temperatures for filling and emptying low density aerogels with helium.Comment: 8 pages, 5 figures, submitted to PR

Pump-probe differencing technique for cavity-enhanced, noise-canceling saturation laser spectroscopy

We present an experimental technique enabling mechanical-noise free, cavity-enhanced frequency measurements of an atomic transition and its hyperfine structure. We employ the 532nm frequency doubled output from a Nd:YAG laser and an iodine vapour cell. The cell is placed in a traveling-wave Fabry-Perot interferometer (FPI) with counter-propagating pump and probe beams. The FPI is locked using the Pound-Drever-Hall (PDH) technique. Mechanical noise is rejected by differencing pump and probe signals. In addition, this differenced error signal gives a sensitive measure of differential non-linearity within the FPI.Comment: 3 pages, 5 figures, submitted to Optics Letter

Phosphonopeptides Revisited, in an Era of Increasing Antimicrobial Resistance

Given the increase in resistance to antibacterial agents, there is an urgent need for the development of new agents with novel modes of action. As an interim solution, it is also prudent to reinvestigate old or abandoned antibacterial compounds to assess their efficacy in the context of widespread resistance to conventional agents. In the 1970s, much work was performed on the development of peptide mimetics, exemplified by the phosphonopeptide, alafosfalin. We investigated the activity of alafosfalin, di-alanyl fosfalin and β-chloro-L-alanyl-β-chloro-L-alanine against 297 bacterial isolates, including carbapenemase-producing Enterobacterales (CPE) (n = 128), methicillin-resistant Staphylococcus aureus (MRSA) (n = 37) and glycopeptide-resistant enterococci (GRE) (n = 43). The interaction of alafosfalin with meropenem was also examined against 20 isolates of CPE. The MIC50 and MIC90 of alafosfalin for CPE were 1 mg/L and 4 mg/L, respectively and alafosfalin acted synergistically when combined with meropenem against 16 of 20 isolates of CPE. Di-alanyl fosfalin showed potent activity against glycopeptide-resistant isolates of Enterococcus faecalis (MIC90; 0.5 mg/L) and Enterococcus faecium (MIC90; 2 mg/L). Alafosfalin was only moderately active against MRSA (MIC90; 8 mg/L), whereas β-chloro-L-alanyl-β-chloro-L-alanine was slightly more active (MIC90; 4 mg/L). This study shows that phosphonopeptides, including alafosfalin, may have a therapeutic role to play in an era of increasing antibacterial resistance

Engineering Resilient Space Systems

Several distinct trends will influence space exploration missions in the next decade. Destinations are becoming more remote and mysterious, science questions more sophisticated, and, as mission experience accumulates, the most accessible targets are visited, advancing the knowledge frontier to more difficult, harsh, and inaccessible environments. This leads to new challenges including: hazardous conditions that limit mission lifetime, such as high radiation levels surrounding interesting destinations like Europa or toxic atmospheres of planetary bodies like Venus; unconstrained environments with navigation hazards, such as free-floating active small bodies; multielement missions required to answer more sophisticated questions, such as Mars Sample Return (MSR); and long-range missions, such as Kuiper belt exploration, that must survive equipment failures over the span of decades. These missions will need to be successful without a priori knowledge of the most efficient data collection techniques for optimum science return. Science objectives will have to be revised ‘on the fly’, with new data collection and navigation decisions on short timescales. Yet, even as science objectives are becoming more ambitious, several critical resources remain unchanged. Since physics imposes insurmountable light-time delays, anticipated improvements to the Deep Space Network (DSN) will only marginally improve the bandwidth and communications cadence to remote spacecraft. Fiscal resources are increasingly limited, resulting in fewer flagship missions, smaller spacecraft, and less subsystem redundancy. As missions visit more distant and formidable locations, the job of the operations team becomes more challenging, seemingly inconsistent with the trend of shrinking mission budgets for operations support. How can we continue to explore challenging new locations without increasing risk or system complexity? These challenges are present, to some degree, for the entire Decadal Survey mission portfolio, as documented in Vision and Voyages for Planetary Science in the Decade 2013–2022 (National Research Council, 2011), but are especially acute for the following mission examples, identified in our recently completed KISS Engineering Resilient Space Systems (ERSS) study: 1. A Venus lander, designed to sample the atmosphere and surface of Venus, would have to perform science operations as components and subsystems degrade and fail; 2. A Trojan asteroid tour spacecraft would spend significant time cruising to its ultimate destination (essentially hibernating to save on operations costs), then upon arrival, would have to act as its own surveyor, finding new objects and targets of opportunity as it approaches each asteroid, requiring response on short notice; and 3. A MSR campaign would not only be required to perform fast reconnaissance over long distances on the surface of Mars, interact with an unknown physical surface, and handle degradations and faults, but would also contain multiple components (launch vehicle, cruise stage, entry and landing vehicle, surface rover, ascent vehicle, orbiting cache, and Earth return vehicle) that dramatically increase the need for resilience to failure across the complex system. The concept of resilience and its relevance and application in various domains was a focus during the study, with several definitions of resilience proposed and discussed. While there was substantial variation in the specifics, there was a common conceptual core that emerged—adaptation in the presence of changing circumstances. These changes were couched in various ways—anomalies, disruptions, discoveries—but they all ultimately had to do with changes in underlying assumptions. Invalid assumptions, whether due to unexpected changes in the environment, or an inadequate understanding of interactions within the system, may cause unexpected or unintended system behavior. A system is resilient if it continues to perform the intended functions in the presence of invalid assumptions. Our study focused on areas of resilience that we felt needed additional exploration and integration, namely system and software architectures and capabilities, and autonomy technologies. (While also an important consideration, resilience in hardware is being addressed in multiple other venues, including 2 other KISS studies.) The study consisted of two workshops, separated by a seven-month focused study period. The first workshop (Workshop #1) explored the ‘problem space’ as an organizing theme, and the second workshop (Workshop #2) explored the ‘solution space’. In each workshop, focused discussions and exercises were interspersed with presentations from participants and invited speakers. The study period between the two workshops was organized as part of the synthesis activity during the first workshop. The study participants, after spending the initial days of the first workshop discussing the nature of resilience and its impact on future science missions, decided to split into three focus groups, each with a particular thrust, to explore specific ideas further and develop material needed for the second workshop. The three focus groups and areas of exploration were: 1. Reference missions: address/refine the resilience needs by exploring a set of reference missions 2. Capability survey: collect, document, and assess current efforts to develop capabilities and technology that could be used to address the documented needs, both inside and outside NASA 3. Architecture: analyze the impact of architecture on system resilience, and provide principles and guidance for architecting greater resilience in our future systems The key product of the second workshop was a set of capability roadmaps pertaining to the three reference missions selected for their representative coverage of the types of space missions envisioned for the future. From these three roadmaps, we have extracted several common capability patterns that would be appropriate targets for near-term technical development: one focused on graceful degradation of system functionality, a second focused on data understanding for science and engineering applications, and a third focused on hazard avoidance and environmental uncertainty. Continuing work is extending these roadmaps to identify candidate enablers of the capabilities from the following three categories: architecture solutions, technology solutions, and process solutions. The KISS study allowed a collection of diverse and engaged engineers, researchers, and scientists to think deeply about the theory, approaches, and technical issues involved in developing and applying resilience capabilities. The conclusions summarize the varied and disparate discussions that occurred during the study, and include new insights about the nature of the challenge and potential solutions: 1. There is a clear and definitive need for more resilient space systems. During our study period, the key scientists/engineers we engaged to understand potential future missions confirmed the scientific and risk reduction value of greater resilience in the systems used to perform these missions. 2. Resilience can be quantified in measurable terms—project cost, mission risk, and quality of science return. In order to consider resilience properly in the set of engineering trades performed during the design, integration, and operation of space systems, the benefits and costs of resilience need to be quantified. We believe, based on the work done during the study, that appropriate metrics to measure resilience must relate to risk, cost, and science quality/opportunity. Additional work is required to explicitly tie design decisions to these first-order concerns. 3. There are many existing basic technologies that can be applied to engineering resilient space systems. Through the discussions during the study, we found many varied approaches and research that address the various facets of resilience, some within NASA, and many more beyond. Examples from civil architecture, Department of Defense (DoD) / Defense Advanced Research Projects Agency (DARPA) initiatives, ‘smart’ power grid control, cyber-physical systems, software architecture, and application of formal verification methods for software were identified and discussed. The variety and scope of related efforts is encouraging and presents many opportunities for collaboration and development, and we expect many collaborative proposals and joint research as a result of the study. 4. Use of principled architectural approaches is key to managing complexity and integrating disparate technologies. The main challenge inherent in considering highly resilient space systems is that the increase in capability can result in an increase in complexity with all of the 3 risks and costs associated with more complex systems. What is needed is a better way of conceiving space systems that enables incorporation of capabilities without increasing complexity. We believe principled architecting approaches provide the needed means to convey a unified understanding of the system to primary stakeholders, thereby controlling complexity in the conception and development of resilient systems, and enabling the integration of disparate approaches and technologies. A representative architectural example is included in Appendix F. 5. Developing trusted resilience capabilities will require a diverse yet strategically directed research program. Despite the interest in, and benefits of, deploying resilience space systems, to date, there has been a notable lack of meaningful demonstrated progress in systems capable of working in hazardous uncertain situations. The roadmaps completed during the study, and documented in this report, provide the basis for a real funded plan that considers the required fundamental work and evolution of needed capabilities. Exploring space is a challenging and difficult endeavor. Future space missions will require more resilience in order to perform the desired science in new environments under constraints of development and operations cost, acceptable risk, and communications delays. Development of space systems with resilient capabilities has the potential to expand the limits of possibility, revolutionizing space science by enabling as yet unforeseen missions and breakthrough science observations. Our KISS study provided an essential venue for the consideration of these challenges and goals. Additional work and future steps are needed to realize the potential of resilient systems—this study provided the necessary catalyst to begin this process

The Implementation and Validation of a Virtual Environment for Training Powered Wheelchair Manoeuvres

This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessible.Navigating a powered wheelchair and avoiding collisions is often a daunting task for new wheelchair users. It takes time and practice to gain the coordination needed to become a competent driver and this can be even more of a challenge for someone with a disability. We present a cost-effective virtual reality (VR) application that takes advantage of consumer level VR hardware. The system can be easily deployed in an assessment centre or for home use, and does not depend on a specialized high-end virtual environment such as a Powerwall or CAVE. This paper reviews previous work that has used virtual environments technology for training tasks, particularly wheelchair simulation. We then describe the implementation of our own system and the first validation study carried out using thirty three able bodied volunteers. The study results indicate that at a significance level of 5% then there is an improvement in driving skills from the use of our VR system. We thus have the potential to develop the competency of a wheelchair user whilst avoiding the risks inherent to training in the real world. However, the occurrence of cybersickness is a particular problem in this application that will need to be addressed

The CCAP KnowledgeBase : linking protistan and cyanobacterial biological resources with taxonomic and molecular data

Peer reviewe

Valsartan for attenuating disease evolution in early sarcomeric hypertrophic cardiomyopathy: the design of the Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) trial

Background: Hypertrophic cardiomyopathy (HCM) is often caused by sarcomere gene mutations, resulting in left ventricular hypertrophy (LVH), myocardial fibrosis, and increased risk of sudden cardiac death and heart failure. Studies in mouse models of sarcomeric HCM demonstrated that early treatment with an angiotensin receptor blocker (ARB) reduced development of LVH and fibrosis. In contrast, prior human studies using ARBs for HCM have targeted heterogeneous adult cohorts with well-established disease. The VANISH trial is testing the safety and feasibility of disease-modifying therapy with an ARB in genotyped HCM patients with early disease. Methods: A randomized, placebo-controlled, double-blind clinical trial is being conducted in sarcomere mutation carriers, 8 to 45 years old, with HCM and no/minimal symptoms, or those with early phenotypic manifestations but no LVH. Participants are randomly assigned to receive valsartan 80 to 320 mg daily (depending on age and weight) or placebo. The primary endpoint is a composite of 9 z-scores in domains representing myocardial injury/hemodynamic stress, cardiac morphology, and function. Total z-scores reflecting change from baseline to final visits will be compared between treatment groups. Secondary endpoints will assess the impact of treatment on mutation carriers without LVH, and analyze the influence of age, sex, and genotype. Conclusions: The VANISH trial is testing a new strategy of disease modification for treating sarcomere mutation carriers with early HCM, and those at risk for its development. In addition, further insight into disease mechanisms, response to therapy, and phenotypic evolution will be gained

Synthetic strategies for preparing BEDT-TTF derivatives functionalised with metal ion binding groups

The syntheses of BEDT-TTF (ET) derivatives with potential metal ion binding pyridyl, bipyridyl and terpyridyl groups are achieved either by stepwise construction of the organosulfur core or via reactions of hydroxymethyl-ET for which a cheap and efficient four step route is reported. The tosylate of hydroxymethyl-ET, reported for the first time, undergoes nucleophilic substitutions with pyridyl, bipyridyl- and terpyridyl-thiolates to give new donors. The X-ray crystal structures of two substituted ET derivatives show considerable deviation of the organosulfur donor system from planarity by bending about the short molecular axis of the ET group

Molecular epidemiology of NDM-1-producing Enterobacteriaceae and Acinetobacter baumannii isolates from Pakistan

The molecular epidemiology of 66 NDM-producing isolates from 2 Pakistani hospitals was investigated, with their genetic relatedness determined using repetitive sequence-based PCR (Rep-PCR). PCR-based replicon typing and screening for antibiotic resistance genes encoding carbapenemases, other β-lactamases, and 16S methylases were also performed. Rep-PCR suggested a clonal spread of Enterobacter cloacae and Escherichia coli. A number of plasmid replicon types were identified, with the incompatibility A/C group (IncA/C) being the most common (78%). 16S methylase-encoding genes were coharbored in 81% of NDM-producing Enterobacteriaceae. Copyrigh

The causes and consequences of changes in virulence following pathogen host shifts.

Emerging infectious diseases are often the result of a host shift, where the pathogen originates from a different host species. Virulence--the harm a pathogen does to its host-can be extremely high following a host shift (for example Ebola, HIV, and SARs), while other host shifts may go undetected as they cause few symptoms in the new host. Here we examine how virulence varies across host species by carrying out a large cross infection experiment using 48 species of Drosophilidae and an RNA virus. Host shifts resulted in dramatic variation in virulence, with benign infections in some species and rapid death in others. The change in virulence was highly predictable from the host phylogeny, with hosts clustering together in distinct clades displaying high or low virulence. High levels of virulence are associated with high viral loads, and this may determine the transmission rate of the virus.BL and FMJ are supported by a NERC grant (NE/L004232/1), a European Research Council grant (281668, DrosophilaInfection), a Junior Research Fellowship from Christ’s College, Cambridge (BL) and a Royal Society University Research Fellowship (FMJ). JDH is supported by a Royal Society University Research Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final published version. It first appeared at http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004728