Analysis and Control of Chain Mobility in Protein Hydrogels

Coiled-coil domains can direct the assembly of protein block copolymers into physically cross-linked, viscoelastic hydrogels. Here, we describe the use of fluorescence recovery after photobleaching (FRAP) to probe chain mobility in reversible hydrogels assembled from engineered proteins bearing terminal coiled-coil domains. We show that chain mobility can be related to the underlying dynamics of the coiled-coil domains by application of a three-state “hopping” model of chain migration. We further show that genetic programming allows the effective mobility of network chains to be varied 500-fold through modest changes in protein sequence. Destabilization of the coiled-coil domains by site-directed mutagenesis increases the effective diffusivity of probe chains. Conversely, probe mobility is reduced by expanding the hydrophobic surface area of the coiled-coil domains through introduction of the bulky leucine surrogate homoisoleucine. Predictions from the three-state model imply asymmetric sequential binding of the terminal domains. Brownian Dynamics simulations suggest that binding asymmetry is a general feature of reversible gels, arising from a loss in entropy as chains transition to a conformationally restricted bridged state

Hospital admissions from a pediatric HIV care and treatment program in Malawi

BACKGROUND: The scale up of pediatric antiretroviral treatment programs across Sub-Saharan Africa over the last decade has brought increasing numbers of children into HIV care. This patient population requiring life-long care presents new challenges in the outpatient and inpatient settings. We sought to describe hospitalizations from a large pediatric HIV treatment facility to better understand the scope of the situation and identify areas for improved care delivery. METHODS: We conducted a retrospective case series of all HIV-infected and exposed patients <18 years enrolled at Baylor College of Medicine Children’s Foundation Malawi, from October 2004-October 2010. Patients admitted to the hospital on or after the day of enrollment were included. Data were extracted from electronic clinic records. Analysis was done at the patient and admission level, as some patients had multiple admissions. RESULTS: Of 5062 patients enrolled in care, 877 (17.3 %) had 1137 admissions at median age 24 months (IQR: 12–62). 191 (21.8 %) patients had multiple admissions. A high proportion of admissions occurred in patients under two years (49.4 %), those within one month of clinic enrollment (32.9 %), those with severe immune suppression (44.0 %), and those not on ART (48.5 %). The frequency of primary admission diagnoses varied across these same variables, with malnutrition, pneumonia, and malaria being the most common. CONCLUSIONS: Illness requiring hospitalization is common in HIV-infected and exposed children and these results reinforce the need for a comprehensive care package with special attention to nutrition. Strengthened programs for malaria prevention and expanded access to pneumococcal vaccine are also needed. The high burden of admissions in children under 24 months and those newly enrolled in care suggests a need for continued improvement of early infant diagnosis and provider-initiated testing programs to link patients to care before they are symptomatic. Similarly, the high proportion of admissions in those not yet started on ART emphasizes the importance of rapid initiation of ART for eligible pediatric patients

Aerothermodynamic Analyses of Towed Ballutes

A ballute (balloon-parachute) is an inflatable, aerodynamic drag device for application to planetary entry vehicles. Two challenging aspects of aerothermal simulation of towed ballutes are considered. The first challenge, simulation of a complete system including inflatable tethers and a trailing toroidal ballute, is addressed using the unstructured-grid, Navier-Stokes solver FUN3D. Auxiliary simulations of a semi-infinite cylinder using the rarefied flow, Direct Simulation Monte Carlo solver, DSV2, provide additional insight into limiting behavior of the aerothermal environment around tethers directly exposed to the free stream. Simulations reveal pressures higher than stagnation and corresponding large heating rates on the tether as it emerges from the spacecraft base flow and passes through the spacecraft bow shock. The footprint of the tether shock on the toroidal ballute is also subject to heating amplification. Design options to accommodate or reduce these environments are discussed. The second challenge addresses time-accurate simulation to detect the onset of unsteady flow interactions as a function of geometry and Reynolds number. Video of unsteady interactions measured in the Langley Aerothermodynamic Laboratory 20-Inch Mach 6 Air Tunnel and CFD simulations using the structured grid, Navier-Stokes solver LAURA are compared for flow over a rigid spacecraft-sting-toroid system. The experimental data provides qualitative information on the amplitude and onset of unsteady motion which is captured in the numerical simulations. The presence of severe unsteady fluid - structure interactions is undesirable and numerical simulation must be able to predict the onset of such motion

NPAL04 OBS data analysis part 1 : kinematics of deep seafloor arrivals

These notes provide supporting information for a JASA (Journal of the Acoustical Society of America) LttE (Letter to the Editor) manuscript, "Deep seafloor arrivals: A new class of arrivals in long-range ocean acoustic propagation" (Stephen et al., submitted). It addresses five issues raised by the co-authors: 1) incorrect processing for the time-compressed traces at T2300 and T3200 that appeared in an early version of the LttE (T2300, T3200 … refer to transmissions at 2300, 3200km etc from the DVLA (Deep Vertical Line Array)), 2) processing issues, including the trade-offs between coherent and incoherent stacking and corrections for the effects of moving sources and receivers and tidal currents (Doppler), 4) the distinction between "deep shadow zone arrivals", which occur below the turning points in Parabolic Equation (PE) models, and "deep seafloor arrivals", which appear dominantly on the Ocean Bottom Seismometer (OBS) but are either very weak or absent on the deepest element in the DVLA and do not coincide with turning points in the PE model (some of these OBS late arrivals occur after the finale region), 4) the role of surface-reflected bottomreflected (SRBR) paths in explaining the late arriving energy, and 5) generally reconciling the OBS analysis with work by other North Pacific Acoustic Laboratory (NPAL) investigators and Dushaw et al (1999).Funding was provided by the Office of Naval Research through Contract No. N00014-06-1-0222

A Proposed Role of Aeroelasticity in NASA's New Exploration Vision

On 14 January 2004, NASA received a mandate to return astronauts to the Moon, evolve a sustained presence there, then head out into the solar system to Mars and perhaps beyond. This new space exploration initiative directs NASA to develop human and robotic technologies that can deliver payloads larger than Apollo to the Moon, to Mars, and bring astronauts and samples safely back to Earth at costs much lower than Apollo. These challenges require creative aerospace systems. On proposed technology for safely delivering payloads to the surface of Mars and returning samples to Earth involves deployed flexible and inflatable decelerators for atmospheric entry. Because inflatable decelerators provide the entry vehicle more drag surface area at smaller mass than traditional ablative devices, this class of decelerators can potentially accomodate larger mass payloads. The flexibility of these lightweight aeroshells can pose both vehicle and aeroelastic stability problems if not properly designed for the expected flight regimes. Computational tools need to be developed for modelling the large and nonlinear deformations of these highly flexible structures. Unlike wind tunnel testing, an integrated and efficient aeroelastic analysis tool can explore the entire flight environment. This paper will provide some background on flexible deployable decelerators, survey the current state of technology and outline the proposed development of an aeroelastic analysis and capability

Authigenic Iron Is a Significant Component of Oceanic Labile Particulate Iron Inventories

Particulate phases transport trace metals (TM) and thereby exert a major control on TM distribution in the ocean. Particulate TMs can be classified by their origin as lithogenic (crustal material), biogenic (cellular), or authigenic (formed in situ), but distinguishing these fractions analytically in field samples is a challenge often addressed using operational definitions and assumptions. These different phases require accurate characterization because they have distinct roles in the biogeochemical iron cycle. Particles collected from the upper 2,000 m of the northwest subtropical Atlantic Ocean over four seasonal cruises throughout 2019 were digested with a chemical leach to operationally distinguish labile particulate material from refractory lithogenics. Direct measurements of cellular iron (Fe) were used to calculate the biogenic contribution to the labile Fe fraction, and any remaining labile material was defined as authigenic. Total particulate Fe (PFe) inventories varied \u3c15% between seasons despite strong seasonality in dust inputs. Across seasons, the total PFe inventory (±1SD) was composed of 73 ± 13% lithogenic, 18 ± 7% authigenic, and 10 ± 8% biogenic Fe above the deep chlorophyll maximum (DCM), and 69 ± 8% lithogenic, 30 ± 8% authigenic, and 1.1 ± 0.5% biogenic Fe below the DCM. Data from three other ocean regions further reveal the importance of the authigenic fraction across broad productivity and Fe gradients, comprising ca. 20%-27% of total PFe

Atmospheric Input and Seasonal Inventory of Dissolved Iron in the Sargasso Sea: Implications for Iron Dynamics in Surface Waters of the Subtropical Ocean

Constraining the role of dust deposition in regulating the concentration of the essential micronutrient iron in surface ocean waters requires knowledge of the flux of seawater-soluble iron in aerosols and the replacement time of dissolved iron (DFe) in the euphotic zone. Here we estimate these quantities using seasonally resolved DFe data from the Bermuda Atlantic Time-series Study region and weekly-scale measurements of iron in aerosols and rain from Bermuda during 2019. In response to seasonal changes in vertical mixing, primary production and dust deposition, surface DFe concentrations vary from ∼0.2 nM in early spring to \u3e1 nM in late summer, with DFe inventories ranging from ∼30 to ∼80 μmol/m2, respectively, over the upper 200 m. Assuming the upper ocean approximates steady state for DFe on an annual basis, our aerosol and rainwater data require a mean euphotic-zone residence time of ∼0.8–1.9 years for DFe with respect to aeolian input

Deep seafloor arrivals : an unexplained set of arrivals in long-range ocean acoustic propagation

Author Posting. © Acoustical Society of America, 2009. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 126 (2009): 599-606, doi:10.1121/1.3158826.Receptions, from a ship-suspended source (in the band 50–100 Hz) to an ocean bottom seismometer (about 5000 m depth) and the deepest element on a vertical hydrophone array (about 750 m above the seafloor) that were acquired on the 2004 Long-Range Ocean Acoustic Propagation Experiment in the North Pacific Ocean, are described. The ranges varied from 50 to 3200 km. In addition to predicted ocean acoustic arrivals and deep shadow zone arrivals (leaking below turning points), “deep seafloor arrivals,” that are dominant on the seafloor geophone but are absent or very weak on the hydrophone array, are observed. These deep seafloor arrivals are an unexplained set of arrivals in ocean acoustics possibly associated with seafloor interface waves.The LOAPEX source deployments, the moored DVLA receiver deployments, and some post-cruise data reduction and analysis were funded by the Office of Naval Research under Award Nos. N00014-1403-1-0181, N00014-03-1-0182, and N00014-06-1-0222. Additional post-cruise analysis support was provided to RAS through the Edward W. and Betty J. Scripps Chair for Excellence in Oceanography. The OBS/Hs used in the experiment were provided by Scripps Institution of Oceanography under the U.S. National Ocean Bottom Seismic Instrumentation Pool (SIO-OBSIP—http://www.obsip.org). To cover the costs of the OBS/H deployments funds were paid to SIO-OBSIP from the National Science Foundation and from the Woods Hole Oceanographic Institution Deep Ocean Exploration Institute

Identification of hip fracture patients from radiographs using Fourier analysis of the trabecular structure: a cross-sectional study

Peer reviewedPublisher PD

End-stage renal disease preceded by rapid declines in kidney function: a case series

<p>Abstract</p> <p>Background</p> <p>Few studies have defined alternate pathways by which chronic kidney disease (CKD) patients transition into end-stage renal disease (ESRD).</p> <p>Methods</p> <p>We studied all consecutive patients initiated on maintenance hemodialysis or peritoneal dialysis over several years at two dialysis units in Northern California. Rapid decline in kidney function was considered to have occurred if a patient was documented to have estimated GFR > 30 ml/min/1.73 m²within three months prior to the initiation of chronic dialysis.</p> <p>Results</p> <p>We found that 8 out of 105 incident chronic dialysis patients one dialysis unit (7.6%; 95% confidence interval 3.4-14.5%) and 9 out of 71 incident patients at another (12.7%, 95% CI 6.0%-22.7%) suffered rapid decline in kidney function that was the immediate precipitant for the need for permanent renal replacement therapy. All these patients started hemodialysis and all relied on catheters for vascular access. Documentation submitted to United States Renal Data System did not fully reflect the health status of these patients during their "pre-ESRD" period.</p> <p>Conclusions</p> <p>A sizeable minority of ESRD cases are preceded by rapid declines in kidney function. The importance of these periods of rapid decline may have been under-appreciated in prior studies of the natural history of CKD and ESRD.</p