Phenomenology of D-Brane Inflation with General Speed of Sound

A characteristic of D-brane inflation is that fluctuations in the inflaton field can propagate at a speed significantly less than the speed of light. This yields observable effects that are distinct from those of single-field slow roll inflation, such as a modification of the inflationary consistency relation and a potentially large level of non-Gaussianities. We present a numerical algorithm that extends the inflationary flow formalism to models with general speed of sound. For an ensemble of D-brane inflation models parameterized by the Hubble parameter and the speed of sound as polynomial functions of the inflaton field, we give qualitative predictions for the key inflationary observables. We discuss various consistency relations for D-brane inflation, and compare the qualitative shapes of the warp factors we derive from the numerical models with analytical warp factors considered in the literature. Finally, we derive and apply a generalized microphysical bound on the inflaton field variation during brane inflation. While a large number of models are consistent with current cosmological constraints, almost all of these models violate the compactification constraint on the field range in four-dimensional Planck units. If the field range bound is to hold, then models with a detectable level of non-Gaussianity predict a blue scalar spectral index, and a tensor component that is far below the detection limit of any future experiment.Comment: 23 pages, 11 figures, v2: version accepted by PRD; minor clarifications and references added to the text. Higher resolution figures are available in the published version. v3: post-publication correction of typo in Eq. 87. No results/conclusions change

What is the initial work-up in the diagnosis of hypertension?

Patients with a new diagnosis of hypertension should be evaluated with a history and physical exam and the following initial studies: serum potassium and creatinine, fasting serum glucose and lipid panel, hematocrit, urinalysis, and electrocardiogram (strength of recommendation [SOR]: C, based on a consensus of expert opinion). Consensus is lacking for measuring serum sodium, calcium, and uric acid. Testing for microalbuminuria is optional in the work-up for a patient without diabetes (SOR: C, expert consensus). Some expert panels list limited echocardiography as another option

Modeling the spatial distribution of grazing intensity in Kazakhstan

<div><p>With increasing affluence in many developing countries, the demand for livestock products is rising and the increasing feed requirement contributes to pressure on land resources for food and energy production. However, there is currently a knowledge gap in our ability to assess the extent and intensity of the utilization of land by livestock, which is the single largest land use in the world. We developed a spatial model that combines fine-scale livestock numbers with their associated energy requirements to distribute livestock grazing demand onto a map of energy supply, with the aim of estimating where and to what degree pasture is being utilized. We applied our model to Kazakhstan, which contains large grassland areas that historically have been used for extensive livestock production but for which the current extent, and thus the potential for increasing livestock production, is unknown. We measured the grazing demand of Kazakh livestock in 2015 at 286 Petajoules, which was 25% of the estimated maximum sustainable energy supply that is available to livestock for grazing. The model resulted in a grazed area of 1.22 million km², or 48% of the area theoretically available for grazing in Kazakhstan, with most utilized land grazed at low intensities (average off-take rate was 13% of total biomass energy production). Under a conservative scenario, our estimations showed a production potential of 0.13 million tons of beef additional to 2015 production (31% increase), and much more with utilization of distant pastures. This model is an important step forward in evaluating pasture use and available land resources, and can be adapted at any spatial scale for any region in the world.</p></div

Fluorescent penetration enhancers for transdermal applications

Chemical penetration enhancers are often used to enhance transdermal drug delivery. However, the fundamental mechanisms that govern the interactions between penetration enhancers and skin are not fully understood. Therefore, the goal of this work was to identify naturally fluorescent penetration enhancers (FPEs) in order to utilize well-established fluorescence techniques to directly study the behavior of FPEs within skin. In this study, 12 fluorescent molecules with amphiphilic characteristics were evaluated as skin penetration enhancers. Eight of the molecules exhibited significant activity as skin penetration enhancers, determined using skin current enhancement ratios. In addition, to illustrate the novel, direct, and non-invasive visualization of the behavior of FPEs within skin, three case studies involving the use of two-photon fluorescence microscopy (TPM) are presented, including visualizing glycerol-mitigated and ultrasound-enhanced FPE skin penetration. Previous TPM studies have indirectly visualized the effect of penetration enhancers on the skin by using a fluorescent dye to probe the transdermal pathways of the enhancer. These effects can now be directly visualized and investigated using FPEs. Finally, future studies are proposed for generating FPE design principles. The combination of FPEs with fluorescence techniques represents a useful novel approach for obtaining physical insights on the behavior of penetration enhancers within the skin.National Institutes of Health (U.S.) (Grant EB-00351)Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Grant DAAD-19-02-D-002)National Science Foundation (U.S.). Graduate Research FellowshipConselho Nacional de Pesquisas (Brazil)Fundacao de Amparo a Pesquisa do Estado de Sao Paul

Effect of frequent hemodialysis on residual kidney function.

Frequent hemodialysis can alter volume status, blood pressure, and the concentration of osmotically active solutes, each of which might affect residual kidney function (RKF). In the Frequent Hemodialysis Network Daily and Nocturnal Trials, we examined the effects of assignment to six compared with three-times-per-week hemodialysis on follow-up RKF. In both trials, baseline RKF was inversely correlated with number of years since onset of ESRD. In the Nocturnal Trial, 63 participants had non-zero RKF at baseline (mean urine volume 0.76 liter/day, urea clearance 2.3 ml/min, and creatinine clearance 4.7 ml/min). In those assigned to frequent nocturnal dialysis, these indices were all significantly lower at month 4 and were mostly so at month 12 compared with controls. In the frequent dialysis group, urine volume had declined to zero in 52% and 67% of patients at months 4 and 12, respectively, compared with 18% and 36% in controls. In the Daily Trial, 83 patients had non-zero RKF at baseline (mean urine volume 0.43 liter/day, urea clearance 1.2 ml/min, and creatinine clearance 2.7 ml/min). Here, treatment assignment did not significantly influence follow-up levels of the measured indices, although the range in baseline RKF was narrower, potentially limiting power to detect differences. Thus, frequent nocturnal hemodialysis appears to promote a more rapid loss of RKF, the mechanism of which remains to be determined. Whether RKF also declines with frequent daily treatment could not be determined

Large-scale Structural Rearrangement of a Serine Hydrolase from Francisella Tularensis Facilitates Catalysis

Tularemia is a deadly, febrile disease caused by infection by the gram-negative bacterium, Francisella tularensis. Members of the ubiquitous serine hydrolase protein family are among current targets to treat diverse bacterial infections. Herein we present a structural and functional study of a novel bacterial carboxylesterase (FTT258) from F. tularensis, a homologue of human acyl protein thioesterase (hAPT1). The structure of FTT258 has been determined in multiple forms, and unexpectedly large conformational changes of a peripheral flexible loop occur in the presence of a mechanistic cyclobutanone ligand. The concomitant changes in this hydrophobic loop and the newly exposed hydrophobic substrate binding pocket suggest that the observed structural changes are essential to the biological function and catalytic activity of FTT258. Using diverse substrate libraries, site-directed mutagenesis, and liposome binding assays, we determined the importance of these structural changes to the catalytic activity and membrane binding activity of FTT258. Residues within the newly exposed hydrophobic binding pocket and within the peripheral flexible loop proved essential to the hydrolytic activity of FTT258, indicating that structural rearrangement is required for catalytic activity. Both FTT258 and hAPT1 also showed significant association with liposomes designed to mimic bacterial or human membranes, respectively, even though similar structural rearrangements for hAPT1 have not been reported. The necessity for acyl protein thioesterases to have maximal catalytic activity near the membrane surface suggests that these conformational changes in the protein may dually regulate catalytic activity and membrane association in bacterial and human homologues

Access, Socioeconomic Environment, and Death from COVID-19 in Nebraska

Our study assesses whether factors related to healthcare access in the first year of the pandemic affect mortality and length of stay (LOS). Our cohort study examined hospitalized patients at Nebraska Medicine between April and October 2020 who were tested for SARS-CoV-2 and had a charted sepsis related diagnostic code. Multivariate logistic was used to analyze the odds of mortality and linear regression was used to calculate the parameter estimates of LOS associated with COVID-19 status, age, gender, race/ethnicity, median household income, admission month, and residential distance from definitive care. Among 475 admissions, the odds of mortality is greater among those with older age (OR: 1.04, 95% CI: 1.02-1.07) and residence in an area with low median household income (OR: 2.11, 95% CI: 0.52-8.57), however, the relationship between mortality and wealth was not statistically significant. Those with non-COVID-19 sepsis had longer LOS (Parameter Estimate: -5.11, adjusted 95% CI: -7.92 to -2.30). Distance from definitive care had trends toward worse outcomes (Parameter Estimate: 0.164, adjusted 95% CI: -1.39 to 1.97). Physical and social aspects of access to care are linked to poorer COVID-19 outcomes. Non-COVID-19 healthcare outcomes may be negatively impacted in the pandemic. Strategies to advance patient-centered outcomes in vulnerable populations should account for varied aspects (socioeconomic, residential setting, rural populations, racial, and ethnic factors). Indirect impacts of the pandemic on non-COVID-19 health outcomes require further study

Layer-by-Layer Spray-Coating of Cellulose Nanofibrils and Silver Nanoparticles for Hydrophilic Interfaces

Silver nanoparticles (AgNPs) and AgNP-based composite materials have attracted growing interest due to their structure-dependent optical, electrical, catalytic, and stimuli-responsive properties. For practical applications, polymeric materials are often combined with AgNPs to provide flexibility and offer a scaffold for homogenous distribution of the AgNPs. However, the control over the assembly process of AgNPs on polymeric substrates remains a big challenge. Herein, we report the fabrication of AgNP/cellulose nanofibril (CNF) thin films via layer-by-layer (LBL) spray-coating. The morphology and self-assembly of AgNPs with increasing number of spray cycles are characterized by atomic force microscopy (AFM), grazing-incidence small-angle X-ray scattering (GISAXS), and grazing-incidence wide-angle X-ray scattering (GIWAXS). We deduce that an individual AgNP (radius = 15 ± 3 nm) is composed of multiple nanocrystallites (diameter = 2.4 ± 0.9 nm). Our results suggest that AgNPs are assembled into large agglomerates on SiO2 substrates during spray-coating, which is disadvantageous for AgNP functionalization. However, the incorporation of CNF substrates contributes to a more uniform distribution of AgNP agglomerates and individual AgNPs by its network structure and by absorbing the partially dissolved AgNP agglomerates. Furthermore, we demonstrate that the spray-coating of the AgNP/CNF mixture results in similar topography and agglomeration patterns of AgNPs compared to depositing AgNPs onto a precoated CNF thin film. Contact-angle measurements and UV/vis spectroscopy suggest that the deposition of AgNPs onto or within CNFs could increase the hydrophilicity of AgNP-containing surfaces and the localized surface plasmon resonance (LSPR) intensity of AgNP compared to AgNPs sprayed on SiO2 substrates, suggesting their potential applications in antifouling coatings or label-free biosensors. Thereby, our approach provides a platform for a facile and scalable production of AgNP/CNF films with a low agglomeration rate by two different methods as follows: (1) multistep layer-by-layer (LBL) spray-coating and (2) direct spray-coating of the AgNP/CNF mixture. We also demonstrate the ability of CNFs as a flexible framework for directing the uniform assembly of AgNPs with tailorable wettability and plasmonic properties

Declining human pressure and opportunities for rewilding in the steppes of Eurasia

Large and ecologically functioning steppe complexes have been lost historically across the globe, but recent land‐use changes may allow the reversal of this trend in some regions. We aimed to develop and map indicators of changing human influence using satellite imagery and historical maps, and to use these indicators to identify areas for broad‐scale steppe rewilding.Peer Reviewe