Transportable setup for amplifier phase fidelity measurements

One possible laser source for the Laser Interferometer Space Antenna (LISA) consists of an Ytterbium-doped fiber amplifier originally developed for inter-satellite communication, seeded by the laser used for the technology demonstrator mission LISA Pathfinder. LISA needs to transmit clock information between its three spacecraft to correct for phase noise between the clocks on the individual spacecraft. For this purpose phase modulation sidebands at GHz frequencies will be imprinted on the laser beams between spacecraft. Differential phase noise between the carrier and a sideband introduced within the optical chain must be very low. We report on a transportable setup to measure the phase fidelity of optical amplifiers.DFG/EXC/QUESTDLR/50OQ1301DLR/50OQ060

Assaying the regulatory potential of mammalian conserved non-coding sequences in human cells

The fraction of experimentally active conserved non-coding sequences within any given cell type is low, so classical assays are unlikely to expose their potential

Nanopods: A New Bacterial Structure and Mechanism for Deployment of Outer Membrane Vesicles

Background: Bacterial outer membrane vesicles (OMV) are packets of periplasmic material that, via the proteins and other molecules they contain, project metabolic function into the environment. While OMV production is widespread in proteobacteria, they have been extensively studied only in pathogens, which inhabit fully hydrated environments. However, many (arguably most) bacterial habitats, such as soil, are only partially hydrated. In the latter, water is characteristically distributed as films on soil particles that are, on average thinner, than are typical OMV (ca. ≤10 nm water film vs. 20 to >200 nm OMV;). Methodology/Principal Findings: We have identified a new bacterial surface structure, termed a "nanopod", that is a conduit for projecting OMV significant distances (e.g., ≥6 µm) from the cell. Electron cryotomography was used to determine nanopod three-dimensional structure, which revealed chains of vesicles within an undulating, tubular element. By using immunoelectron microscopy, proteomics, heterologous expression and mutagenesis, the tubes were determined to be an assembly of a surface layer protein (NpdA), and the interior structures identified as OMV. Specific metabolic function(s) for nanopods produced by Delftia sp. Cs1-4 are not yet known. However, a connection with phenanthrene degradation is a possibility since nanopod formation was induced by growth on phenanthrene. Orthologs of NpdA were identified in three other genera of the Comamonadaceae family, and all were experimentally verified to form nanopods. Conclusions/Significance: Nanopods are new bacterial organelles, and establish a new paradigm in the mechanisms by which bacteria effect long-distance interactions with their environment. Specifically, they create a pathway through which cells can effectively deploy OMV, and the biological activity these transmit, in a diffusion-independent manner. Nanopods would thus allow environmental bacteria to expand their metabolic sphere of influence in a manner previously unknown for these organisms

A multidisciplinary stroke clinic for outpatient care of veterans with cerebrovascular disease

Background: Managing cerebrovascular risk factors is complex and difficult. The objective of this program evaluation was to assess the effectiveness of an outpatient Multidisciplinary Stroke Clinic model for the clinical management of veterans with cerebrovascular disease or cerebrovascular risk factors. Methods: The Multidisciplinary Stroke Clinic provided care to veterans with cerebrovascular disease during a one-half day clinic visit with interdisciplinary evaluations and feedback from nursing, health psychology, rehabilitation medicine, internal medicine, and neurology. We conducted a program evaluation of the clinic by assessing clinical care outcomes, patient satisfaction, provider satisfaction, and costs. Results: We evaluated the care and outcomes of the first consecutive 162 patients who were cared for in the clinic. Patients had as many as six clinic visits. Systolic and diastolic blood pressure decreased: 137.2 ± 22.0 mm Hg versus 128.6 ± 19.8 mm Hg, P = 0.007 and 77.9 ± 14.8 mm Hg versus 72.0 ± 10.2 mm Hg, P = 0.004, respectively as did low-density lipoprotein (LDL)-cholesterol (101.9 ± 23.1 mg/dL versus 80.6 ± 25.0 mg/dL, P = 0.001). All patients had at least one major change recommended in their care management. Both patients and providers reported high satisfaction levels with the clinic. Veterans with stroke who were cared for in the clinic had similar or lower costs than veterans with stroke who were cared for elsewhere. Conclusion: A Multidisciplinary Stroke Clinic model provides incremental improvement in quality of care for complex patients with cerebrovascular disease at costs that are comparable to usual post-stroke care

Tuning the 3D microenvironment of reprogrammed tubule cells enhances biomimetic modeling of polycystic kidney disease

Renal tubular cells frequently lose differentiation markers and physiological properties when propagated in conventional cell culture conditions. Embedding cells in 3D microenvironments or controlling their 3D assembly by bioprinting can enhance their physiological properties, which is beneficial for modeling diseases in vitro. A potential cellular source for modeling renal tubular physiology and kidney diseases in vitro are directly reprogrammed induced renal tubular epithelial cells (iRECs). iRECs were cultured in various biomaterials and as bioprinted tubular structures. They showed high compatibility with the embedding substrates and dispensing methods. The morphology of multicellular aggregates was substantially influenced by the 3D microenvironment. Transcriptomic analyses revealed signatures of differentially expressed genes specific to each of the selected biomaterials. Using a new cellular model for autosomal-dominant polycystic kidney disease, Pkd1$^{-/-}$ iRECs showed disrupted morphology in bioprinted tubules and a marked upregulation of the Aldehyde dehydrogenase 1a1 (Aldh1a1). In conclusion, 3D microenvironments strongly influence the morphology and expression profiles of iRECs, help to unmask disease phenotypes, and can be adapted to experimental demands. Combining a direct reprogramming approach with appropriate biomaterials will facilitate construction of biomimetic kidney tubules and disease models at the microscale

Observations and Hypotheses Related to Low to Middle Free Tropospheric Aerosol, Water Vapor and Altocumulus Cloud Layers within Convective Weather Regimes: A SEAC4RS Case Study

The NASA Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) project included goals related to aerosol particle life cycle in convective regimes. Using the University of Wisconsin High Spectral Resolution Lidar system at Huntsville, Alabama, USA, and the NASA DC-8 research aircraft, we investigate the altitude dependence of aerosol, water vapor and Altocumulus (Ac) properties in the free troposphere from a canonical 12 August 2013 convective storm case as a segue to a presentation of a mission-wide analysis. It stands to reason that any moisture detrainment from convection must have an associated aerosol layer. Modes of covariability between aerosol, water vapor and Ac are examined relative to the boundary layer entrainment zone, 0 ∘C level, and anvil, a region known to contain Ac clouds and a complex aerosol layering structure (Reid et al., 2017). Multiple aerosol layers in regions warmer than 0 ∘C were observed within the planetary boundary layer entrainment zone. At 0 ∘C there is a proclivity for aerosol and water vapor detrainment from storms, in association with melting level Ac shelves. Finally, at temperatures colder than 0 ∘C, weak aerosol layers were identified above Cumulus congestus tops (∼0 and ∼-20 role= presentation style= box-sizing: border-box; display: inline; line-height: normal; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; \u3e∼−20 ∘C). Stronger aerosol signals return in association with anvil outflow. In situ data suggest that detraining particles undergo aqueous-phase or heterogeneous chemical or microphysical transformations, while at the same time larger particles are being scavenged at higher altitudes leading to enhanced nucleation. We conclude by discussing hypotheses regarding links to aerosol emissions and potential indirect effects on Ac clouds

Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.http://deepblue.lib.umich.edu/bitstream/2027.42/78267/1/1748-5908-5-26.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/2/1748-5908-5-26.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/3/1748-5908-5-26-S3.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/4/1748-5908-5-26-S2.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/5/1748-5908-5-26-S1.TIFFPeer Reviewe

Stability and Fluctuations in Complex Ecological Systems

From 08-12 August, 2022, 32 individuals participated in a workshop, Stability and Fluctuations in Complex Ecological Systems, at the Lorentz Center, located in Leiden, The Netherlands. An interdisciplinary dialogue between ecologists, mathematicians, and physicists provided a foundation of important problems to consider over the next 5-10 years. This paper outlines eight areas including (1) improving our understanding of the effect of scale, both temporal and spatial, for both deterministic and stochastic problems; (2) clarifying the different terminologies and definitions used in different scientific fields; (3) developing a comprehensive set of data analysis techniques arising from different fields but which can be used together to improve our understanding of existing data sets; (4) having theoreticians/computational scientists collaborate closely with empirical ecologists to determine what new data should be collected; (5) improving our knowledge of how to protect and/or restore ecosystems; (6) incorporating socio-economic effects into models of ecosystems; (7) improving our understanding of the role of deterministic and stochastic fluctuations; (8) studying the current state of biodiversity at the functional level, taxa level and genome level.Comment: 22 page