Mission Concept for the Single Aperture Far-Infrared (SAFIR) Observatory

The Single Aperture Far-InfraRed (SAFIR) Observatory's science goals are driven by the fact that the earliest stages of almost all phenomena in the universe are shrouded in absorption by and emission from cool dust and gas that emits strongly in the far-infrared and submillimeter. Over the past several years, there has been an increasing recognition of the critical importance of this spectral region to addressing fundamental astrophysical problems, ranging from cosmological questions to understanding how our own Solar System came into being. The development of large, far-infrared telescopes in space has become more feasible with the combination of developments for the James Webb Space Telescope and of enabling breakthroughs in detector technology. We have developed a preliminary but comprehensive mission concept for SAFIR, as a 10 m-class far-infrared and submillimeter observatory that would begin development later in this decade to meet the needs outlined above. Its operating temperature (<4K) and instrument complement would be optimized to reach the natural sky confusion limit in the far-infrared with diffraction-limited peformance down to at least 40 microns. This would provide a point source sensitivity improvement of several orders of magnitude over that of Spitzer or Herschel, with finer angular resolution, enabling imaging and spectroscopic studies of individual galaxies in the early universe. We have considered many aspects of the SAFIR mission, including the telescope technology, detector needs and technologies, cooling method and required technology developments, attitude and pointing, power systems, launch vehicle, and mission operations. The most challenging requirements for this mission are operating temperature and aperture size of the telescope, and the development of detector arrays.Comment: 36 page

A Vision for the Exploration of Mars: Robotic Precursors Followed by Humans to Mars Orbit in 2033

The reformulation of the Mars program gives NASA a rare opportunity to deliver a credible vision in which humans, robots, and advancements in information technology combine to open the deep space frontier to Mars. There is a broad challenge in the reformulation of the Mars exploration program that truly sets the stage for: 'a strategic collaboration between the Science Mission Directorate (SMD), the Human Exploration and Operations Mission Directorate (HEOMD) and the Office of the Chief Technologist, for the next several decades of exploring Mars'.Any strategy that links all three challenge areas listed into a true long term strategic program necessitates discussion. NASA's SMD and HEOMD should accept the President's challenge and vision by developing an integrated program that will enable a human expedition to Mars orbit in 2033 with the goal of returning samples suitable for addressing the question of whether life exists or ever existed on Mar

A Bio-Based Pro-Antimicrobial Polymer Network Via Degradable Acetal Linkages

The synthesis of a fully degradable, bio-based, sustained release, pro-antimicrobial polymer network comprised of degradable acetals (PANDA) is reported. The active antimicrobial agent – p-anisaldehyde (pA) (an extract from star anise) – was converted into a UV curable acetal containing pro-antimicrobial monomer and subsequently photopolymerized into a homogenous thiol-ene network. Under neutral to acidic conditions (pH \u3c 8), the PANDAs undergo surface erosion and exhibit sustained release of pA over 38 days. The release of pA from PANDAs was shown to be effective against both bacterial and fungal pathogens. From a combination of confocal microscopy and transmission electron microscopy, we observed that the released pA disrupts the cell membrane. Additionally, we demonstrated that PANDAs have minimal cytotoxicity towards both epithelial cells and macrophages. Although a model platform, these results point to promising pathways for the design of fully degradable sustained-release antimicrobial systems with potential applications in agriculture, pharmaceuticals, cosmetics, household/personal care, and food industries

The OptiMine feasibility study: a novel implementation strategy to electronically screen and signpost patients to health behaviour apps

Background: Behavior change apps have the potential to provide individual support on a population scale at low cost, but they face numerous barriers to implementation. Electronic health records (EHRs) in acute care hospitals provide a valuable resource for identifying patients at risk, who may benefit from behavior change apps. A novel, emerging implementation strategy is to use digital technologies not only for providing support to help-seeking individuals but also for signposting patients at risk to support services (also called proactive referral in the United States). Objective: The OptiMine study aimed to increase the reach of behavior change apps by implementing electronic signposting for smoking cessation and alcohol reduction in a large, at-risk population that was identified through an acute care hospital EHR. Methods: This 3-phase, mixed methods implementation study assessed the acceptability, feasibility, and reach of electronic signposting to behavior change apps by using a hospital’s EHR system to identify patients who are at risk. Phase 1 explored the acceptability of the implementation strategy among the patients and staff through focus groups. Phase 2 investigated the feasibility of using the hospital EHR to identify patients with target risk behaviors and contact them via SMS text message, email, or patient portal. Phase 3 assessed the impact of SMS text messages sent to patients who were identified as smokers or risky drinkers, which signposted them to behavior change apps. The primary outcome was the proportion of participants who clicked on the embedded link in the SMS text message to access information about the apps. The acceptability of the SMS text messages among the patients who had received them was also explored in a web-based survey. Results: Our electronic signposting strategy—using SMS text messages to promote health behavior change apps to patients at risk—was found to be acceptable and feasible and had good reach. The hospital sent 1526 SMS text messages, signposting patients to either the National Health Service Smokefree or Drink Free Days apps. A total of 13.56% (207/1526) of the patients clicked on the embedded link to the apps, which exceeded our 5% a priori success criterion. Patients and staff contributed to the SMS text message content and delivery approach, which were perceived as acceptable before and after the delivery of the SMS text messages. The feasibility of the SMS text message format was determined and the target population was identified by mining the EHR. Conclusions: The OptiMine study demonstrated the proof of concept for this novel implementation strategy, which used SMS text messages to signpost at-risk individuals to behavior change apps at scale. The level of reach exceeded our a priori success criterion in a non–help-seeking population of patients receiving unsolicited SMS text messages, disconnected from hospital visits. International Registered Report Identifier (IRRID): RR2-10.2196/2366

Novel implementation strategy to electronically screen and signpost patients to health behavior apps: Mixed methods implementation study (OptiMine study)

BACKGROUND: Behavior change apps have the potential to provide individual support on a population scale at low cost, but they face numerous barriers to implementation. Electronic health records (EHRs) in acute care hospitals provide a valuable resource for identifying patients at risk, who may benefit from behavior change apps. A novel, emerging implementation strategy is to use digital technologies not only for providing support to help-seeking individuals but also for signposting patients at risk to support services (also called proactive referral in the United States). OBJECTIVE: The OptiMine study aimed to increase the reach of behavior change apps by implementing electronic signposting for smoking cessation and alcohol reduction in a large, at-risk population that was identified through an acute care hospital EHR. METHODS: This 3-phase, mixed methods implementation study assessed the acceptability, feasibility, and reach of electronic signposting to behavior change apps by using a hospital\u27s EHR system to identify patients who are at risk. Phase 1 explored the acceptability of the implementation strategy among the patients and staff through focus groups. Phase 2 investigated the feasibility of using the hospital EHR to identify patients with target risk behaviors and contact them via SMS text message, email, or patient portal. Phase 3 assessed the impact of SMS text messages sent to patients who were identified as smokers or risky drinkers, which signposted them to behavior change apps. The primary outcome was the proportion of participants who clicked on the embedded link in the SMS text message to access information about the apps. The acceptability of the SMS text messages among the patients who had received them was also explored in a web-based survey. RESULTS: Our electronic signposting strategy-using SMS text messages to promote health behavior change apps to patients at risk-was found to be acceptable and feasible and had good reach. The hospital sent 1526 SMS text messages, signposting patients to either the National Health Service Smokefree or Drink Free Days apps. A total of 13.56% (207/1526) of the patients clicked on the embedded link to the apps, which exceeded our 5% a priori success criterion. Patients and staff contributed to the SMS text message content and delivery approach, which were perceived as acceptable before and after the delivery of the SMS text messages. The feasibility of the SMS text message format was determined and the target population was identified by mining the EHR. CONCLUSIONS: The OptiMine study demonstrated the proof of concept for this novel implementation strategy, which used SMS text messages to signpost at-risk individuals to behavior change apps at scale. The level of reach exceeded our a priori success criterion in a non-help-seeking population of patients receiving unsolicited SMS text messages, disconnected from hospital visits. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/23669

The Relationship Between Central Auditory Tests and Neurocognitive Domains in Adults Living With HIV

Objective: Tests requiring central auditory processing, such as speech perception-in-noise, are simple, time efficient, and correlate with cognitive processing. These tests may be useful for tracking brain function. Doing this effectively requires information on which tests correlate with overall cognitive function and specific cognitive domains. This study evaluated the relationship between selected central auditory focused tests and cognitive domains in a cohort of normal hearing adults living with HIV and HIV– controls. The long-term aim is determining the relationships between auditory processing and neurocognitive domains and applying this to analyzing cognitive function in HIV and other neurocognitive disorders longitudinally. Method: Subjects were recruited from an ongoing study in Dar es Salaam, Tanzania. Central auditory measures included the Gap Detection Test (Gap), Hearing in Noise Test (HINT), and Triple Digit Test (TDT). Cognitive measures included variables from the Test of Variables of Attention (TOVA), Cogstate neurocognitive battery, and Kiswahili Montreal Cognitive Assessment (MoCA). The measures represented three cognitive domains: processing speed, learning, and working memory. Bootstrap resampling was used to calculate the mean and standard deviation of the proportion of variance explained by the individual central auditory tests for each cognitive measure. The association of cognitive measures with central auditory variables taking HIV status and age into account was determined using regression models. Results: Hearing in Noise Tests and TDT were significantly associated with Cogstate learning and working memory tests. Gap was not significantly associated with any cognitive measure with age in the model. TDT explained the largest mean proportion of variance and had the strongest relationship to the MoCA and Cogstate tasks. With age in the model, HIV status did not affect the relationship between central auditory tests and cognitive measures. Age was strongly associated with multiple cognitive tests. Conclusion: Central auditory tests were associated with measures of learning and working memory. Compared to the other central auditory tests, TDT was most strongly related to cognitive function. These findings expand on the association between auditory processing and cognitive domains seen in other studies and support evaluating these tests for tracking brain health in HIV and other neurocognitive disorders

Hif-1α regulates differentiation of limb bud mesenchyme and joint development

Recent evidence suggests that low oxygen tension (hypoxia) may control fetal development and differentiation. A crucial mediator of the adaptive response of cells to hypoxia is the transcription factor Hif-1α. In this study, we provide evidence that mesenchymal condensations that give origin to endochondral bones are hypoxic during fetal development, and we demonstrate that Hif-1α is expressed and transcriptionally active in limb bud mesenchyme and in mesenchymal condensations. To investigate the role of Hif-1α in mesenchymal condensations and in early chondrogenesis, we conditionally inactivated Hif-1α in limb bud mesenchyme using a Prx1 promoter-driven Cre transgenic mouse. Conditional knockout of Hif-1α in limb bud mesenchyme does not impair mesenchyme condensation, but alters the formation of the cartilaginous primordia. Late hypertrophic differentiation is also affected as a result of the delay in early chondrogenesis. In addition, mutant mice show a striking impairment of joint development. Our study demonstrates a crucial, and previously unrecognized, role of Hif-1α in early chondrogenesis and joint formation

Stability analysis of the GAL regulatory network in Saccharomyces cerevisiae and Kluyveromyces lactis

<p>Abstract</p> <p>Background</p> <p>In the yeast <it>Saccharomyces cerevisiae</it>, interactions between galactose, Gal3p, Gal80p, and Gal4p determine the transcriptional status of the genes required for the galactose utilization. Increase in the cellular galactose concentration causes the galactose molecules to bind onto Gal3p which, via Gal80p, activates Gal4p, which induces the GAL3 and GAL80 gene transcription. Recently, a linear time-invariant multi-input multi-output (MIMO) model of this GAL regulatory network has been proposed; the inputs being galactose and Gal4p, and the outputs being the active Gal4p and galactose utilization. Unfortunately, this model assumes the cell culture to be homogeneous, although it is not so in practice. We overcome this drawback by including more biochemical reactions, and derive a quadratic ordinary differential equation (ODE) based model.</p> <p>Results</p> <p>We show that the model, referred to above, does not exhibit bistability. We establish sufficiency conditions for the domain of attraction of an equilibrium point of our ODE model for the special case of full-state feedback controller. We observe that the GAL regulatory system of <it>Kluyveromyces lactis </it>exhibits an aberration of monotone nonlinearity and apply the Rantzer multipliers to establish a class of stabilizing controllers for this system.</p> <p>Conclusion</p> <p>Feedback in a GAL regulatory system can be used to enhance the cellular memory. We show that the system can be modeled as a quadratic nonlinear system for which the effect of feedback on the domain of attraction of the equilibrium point can be characterized using <it>linear matrix inequality </it>(LMI) conditions that are easily implementable in software. The benefit of this result is that a mathematically sound approach to the synthesis of full-state and partial-state feedback controllers to regulate the cellular memory is now possible, irrespective of the number of state-variables or parameters of interest.</p