28232 research outputs found
Sort by
Characterization and modeling of aerosol-cloud interactions toward the improvement of rainfall estimation in high mountains
No full textIn high elevated regions, ground-based precipitation measurements are scarce or non-existing. Remote sensing estimates are prone to underestimation due to a lack of sensitivity to light precipitation and ground-clutter contamination of radar signals by steep terrain. The latter creates a blind zone extending up a few kilometers above the ground for the vertical profiling radars onboard the Global Precipitation Measurement mission (GPM) core satellite that serves as a reference standard to unify precipitation measurements from research and operational satellites. Ground radars which are not affected by the blind zone, show an increase in effective reflectivity factor (ERF) from the melting layer below the isotherm of zero towards the surface. The blind zone is critical as rainfall characteristics at the ground results from the vertical evolution of the rain drop-size distributions (RDSDs). Explicit modeling of the rainfall microphysics from the top of the blind zone, if located below the zero-degree isotherm, towards the surface can improve rainfall estimation at the ground, as demonstrated in the Southern Appalachian Mountains. However, if the top of the blind zone is located above the zero-degree isotherm, ice and mix-phase hydrometeors coexist at the top boundary condition precluding explicit modeling because the microphysics of these hydrometeors is yet an active research topic. This work has three parts. The first part is devoted to characterizing precipitating systems and the blind zone in the Central Andes of Peru. Twenty years of TRMM and GPM radar measurements reveal that stratiform precipitation is the most frequent type in the Central Andes. Long-lasting precipitating systems (LDPSs) having a stratiform structure with embedded convection determine the interannual variability of the diurnal cycle of precipitation. Moisture availability at high elevations in the Central Andes is scarce. Moisture sources that sustain LDPSs are located in the adjacent eastern foothills of the Andes (Western Amazon basin) that result from enhanced moisture convergence and low and mid-levels due to the interplay of the South American low-level jet and cold air incursions. In the Central Andes of Peru, the top of the GPM blind zone is 46 % of the time above the zero-degree isotherm located at 5000 masl missing liquid precipitation, and a comparison with ground disdrometer data shows that GPM DPR does not capture the variability of the rain drop size distribution. These findings show that rainfall in the Central Andes depends on the dynamics of atmospheric circulation and microphysics at multiple spatial and temporal scales. These scales cannot be modeled explicitly by one single model nor validated with current observations. However, progress in that direction can be made by using different models to simulate different weather regimes to elucidate the role of different microphysics and dynamic processes. Observations needed to validate the models are lacking in the Andes but available in the Southern Appalachian Mountains (SAM). So, the modeling part of this work is focused on the SAM, and the knowledge gained by modeling the SAM region can be used to improve the representation of dynamical and microphysical processes in numerical models to be used in the Andes.Changes in the cloud drop size distribution ultimately capture the interplay of microphysics, dynamics, and thermodynamics in clouds. The chain of microphysical mechanisms from aerosol activation to cloud drop size distribution (CDSD) evolution during cloud development to the raindrop size distribution (RDSD) dynamics spans a scale range of four orders of magnitude from fractions of micrometers to millimeters. It can be modeled explicitly in cloud parcel and rain-shaft models (for liquid hydrometeors), and it is described using different parameterizations with varying degrees of complexity in Numerical Weather Prediction (NWP) models. However, in the Weather Research and Forecast (WRF) model, parameterized microphysics often fail to capture the diurnal cycle and spatial distribution of precipitation, rainfall intensity, and duration depending on the weather regime, regional topography, and regional aerosol characteristics. Besides, the representation of the dynamical processes affecting the aerosol activation and the CDSDs evolution during cloud formation and of the cloud-droplet-raindrop continuum in precipitating clouds is lacking in NWP models. In the second part of this work, a two-moment bulk microphysics scheme in WRF is modified to add an aerosol activation spectrum from in-situ measurement and compared to the default activation spectrum to characterize the impact of aerosol activation in the onset of precipitation in different weather conditions. WRF simulations show that using the in-situ aerosol activation spectrum yields higher cloud droplet number concentrations (CDNC) than the default WRF aerosol activation spectrum, with smaller cloud droplets and delayed onset of rainfall under weak synoptic forcing conditions. For large-scale systems with strong and sustained moisture convergence at low levels (frontal and tropical systems), mechanically forced rainfall efficiency is enhanced despite high CDNC, there is no delay in the onset of precipitation, and the impact of ACPI on the spatial and temporal variability of rainfall is negligible (significant) at onset (hours later) consistent with rainfall observations. The simulated cloud vertical structure from CDNC indicates that convective development is more intense in the inner SAM region than in the adjacent plains. In the inner region, valley-ridge circulations organize the spatial patterns of cloudiness under weak synoptic forcing conditions. The formation of early afternoon low-level clouds over the ridges in the summertime reflects the high sensitivity of cloud mixing ratios and cloud droplet concentrations to aerosol activation properties.
In the third part of this work, the dynamical and microphysical processes not resolved by WRF are modeled using a large eddy simulation coupled with a spectrum bin microphysics that permits aerosol replenishment to characterize the heterogeneity of cloud microstructure associated with cloud circulations and entrainment in non-precipitating cumulus clouds. Furthermore, the sensitivity of cloud variables to different vertical profiles of aerosol loading is tested and validated with aircraft observations. The coupled model simulated a convective case under weak synoptic conditions, and the spatial variability of the LWC, CDNC, and CDSD was characterized. Simulations show large differences between the region around the updraft and regions of entrainment located at cloud edges and preferred locations. The interplay of environmental wind and cloud circulations explains these locations. More and larger droplets towards the location of the updraft and towards but before the cloud's top result in large LWC in the upper half of the cloud. The opposite in regions of entrainment, having small droplets in minor concentrations resulting in low LWC. Different initial vertical profiles of aerosol concentrations result in significantly different values of CDNC; as larger the aerosol loading, the larger the CDNC. The updraft transport aerosols and moisture up to the cloud altitude from near the ground elevation. In the updraft, a sharp CDSD with a small standard deviation has small values of relative dispersion. In regions of entrainment, the CDSD has smaller droplets in minor concentrations due to the evaporation of droplets. Its shape resembles the distribution of interstitial aerosols with a large standard deviation resulting in large values of relative dispersion and smaller values of LWC. Aircraft measurements show agreement with the simulated CDNC and relative dispersion for the simulation with an initial vertical profile of aerosol concentration that decays exponentially with height and has a scale height of 500m. The significant impact of aerosol loading in the CDNC affects the cloud optical thickness (COT). The COT in the cloud mature stage for a scale height of 2000m is approximately 1.75 times the COT for a scale height of 500m.
</p
Clinical and radiographic parameters that distinguish between the best and worst outcomes of scoliosis surgery for adults.
No full textPurposePredictors of marked improvement versus failure to improve following surgery for adult scoliosis have not been identified. Our objective was to identify factors that distinguish between patients with the best and worst outcomes following surgery for adult scoliosis.MethodsThis is a secondary analysis of a prospective, multicenter spinal deformity database. Inclusion criteria included: age 18-85, scoliosis (Cobb ≥ 30°), and 2-year follow-up. Based on the Oswestry Disability Index (ODI) and the SRS-22 at 2-year follow-up, patients with the best and worst outcomes were identified for younger (18-45) and older (46-85) adults with scoliosis. Clinical and radiographic factors were compared between patients with the best and worst outcomes.Results276 patients met inclusion criteria (89 younger and 187 older patients). Among younger patients, predictors of poor outcome included: depression/anxiety, smoking, narcotic medication use, older age, greater body mass index (BMI) and greater severity of pain prior to surgery. Among older patients, predictors of poor outcome included: depression/anxiety, narcotic medication use, greater BMI and greater severity of pain prior to surgery. None of the other baseline or peri-operative factors assessed distinguished the best and worst outcomes for younger or older patients, including severity of deformity, operative parameters, or the occurrence of complications.ConclusionsNot all patients achieve favorable outcomes following surgery for adult scoliosis. Baseline and peri-operative factors distinguishing between patients with the best and worst outcomes were predominantly patient factors, including BMI, depression/anxiety, smoking, and pain severity; not comorbidities, severity of deformity, operative parameters, or complications
Accelerating crystal structure determination with iterative AlphaFold prediction.
No full textExperimental structure determination can be accelerated with artificial intelligence (AI)-based structure-prediction methods such as AlphaFold. Here, an automatic procedure requiring only sequence information and crystallographic data is presented that uses AlphaFold predictions to produce an electron-density map and a structural model. Iterating through cycles of structure prediction is a key element of this procedure: a predicted model rebuilt in one cycle is used as a template for prediction in the next cycle. This procedure was applied to X-ray data for 215 structures released by the Protein Data Bank in a recent six-month period. In 87% of cases our procedure yielded a model with at least 50% of Cα atoms matching those in the deposited models within 2 Å. Predictions from the iterative template-guided prediction procedure were more accurate than those obtained without templates. It is concluded that AlphaFold predictions obtained based on sequence information alone are usually accurate enough to solve the crystallographic phase problem with molecular replacement, and a general strategy for macromolecular structure determination that includes AI-based prediction both as a starting point and as a method of model optimization is suggested
Powerful, scalable and resource-efficient meta-analysis of rare variant associations in large whole genome sequencing studies.
No full textMeta-analysis of whole genome sequencing/whole exome sequencing (WGS/WES) studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with complex phenotypes. Existing rare variant meta-analysis approaches are not scalable to biobank-scale WGS data. Here we present MetaSTAAR, a powerful and resource-efficient rare variant meta-analysis framework for large-scale WGS/WES studies. MetaSTAAR accounts for relatedness and population structure, can analyze both quantitative and dichotomous traits and boosts the power of rare variant tests by incorporating multiple variant functional annotations. Through meta-analysis of four lipid traits in 30,138 ancestrally diverse samples from 14 studies of the Trans Omics for Precision Medicine (TOPMed) Program, we show that MetaSTAAR performs rare variant meta-analysis at scale and produces results comparable to using pooled data. Additionally, we identified several conditionally significant rare variant associations with lipid traits. We further demonstrate that MetaSTAAR is scalable to biobank-scale cohorts through meta-analysis of TOPMed WGS data and UK Biobank WES data of ~200,000 samples
Effectiveness of Tax and Non-Tax Incentives and Investments: Evidence and Policy Implications
No full textLessons for Modernizing Energy Access Finance, Part 1: What the Electrification Experiences of Seven Countries Tell Us about the Future of Connection Costs, Subsidies, and Integrated Planning
No full textCountries facing electricity access challenges today have more options and potential electrification pathways than ever before. Technology developments in distributed renewable electricity systems, monitoring and payment systems, and end-use equipment efficiency have made off-grid electricity systems the lowest-cost and most expedient option for the majority of unconnected rural populations. However, the initial cost of connecting new rural customers remains an expensive proposition, and public financing that addresses the affordability issue will be required for most countries to achieve universal access, just as it always has. This brief explores the successful rural electrification experiences of seven case countries—Brazil, Chile, Laos, Peru, South Africa, Thailand, and Tunisia—looking specifically at the cost of connections and how subsidies and public financing were deployed to address the affordability challenge and facilitate energy access. The analysis finds that connecting rural customers has been costly—more than $1,500 per connection on average—far more than the cost of distributed systems today. The rural electrification programs examined subsidized 70–100 percent of connection costs. Maintaining these public investments and adapting funding mechanisms to address the unique nature of the off-grid sector, will dictate the extent to which distributed systems are able to scale in the coming decade
Dynamics of a qubit in a high-impedance transmission line from a bath perspective
No full textWe investigate the quantum dynamics of a generic model of light-matter interaction in the context of high-impedance waveguides, focusing on the behavior of the photonic states generated in the waveguide. The model treated consists simply of a two-level system coupled to a bosonic bath (the Ohmic spin-boson model). Quantum quenches as well as scattering of an incident coherent pulse are studied using two complementary methods. First, we develop an approximate ansatz for the electromagnetic waves based on a single multimode coherent state wave function; formally, this approach combines in a single framework ideas from adiabatic renormalization, the Born-Markov approximation, and input-output theory. Second, we present numerically exact results for scattering of a weak intensity pulse by using numerical renormalization group (NRG) calculations. NRG provides a benchmark for any linear response property throughout the ultrastrong-coupling regime. We find that in a sudden quantum quench, the coherent state approach produces physical artifacts, such as improper relaxation to the steady state. These previously unnoticed problems are related to the simplified form of the ansatz that generates spurious correlations within the bath. In the scattering problem, NRG is used to find the transmission and reflection of a single photon, as well as the inelastic scattering of that single photon. Simple analytical formulas are established and tested against the NRG data that predict quantitatively the transport coefficients for up to moderate environmental impedance. These formulas resolve pending issues regarding the presence of inelastic losses in the spin-boson model near absorption resonances, and could be used for comparison to experiments in Josephson waveguide quantum electrodynamics. Finally, the scattering results using the coherent state wave-function approach are compared favorably to the NRG results for very weak incident intensity. We end our study by presenting results at higher power where the response of the system is nonlinear
The association between renal recovery after acute kidney injury and long-term mortality after transcatheter aortic valve replacement.
No full textBackgroundThis study aimed to examine the association between renal recovery status at hospital discharge after acute kidney injury (AKI) and long-term mortality following transcatheter aortic valve replacement (TAVR).MethodsWe screened all adult patients who survived to hospital discharge after TAVR for aortic stenosis at a quaternary referral medical center from January 1, 2008, through June 30, 2014. An AKI was defined as an increase in serum creatinine level of 0.3 mg/dL or a relative increase of 50% from baseline. Renal outcome at the time of discharge was evaluated by comparing the discharge serum creatinine level to the baseline level. Complete renal recovery was defined as no AKI at discharge, whereas partial renal recovery was defined as AKI without a need for renal replacement therapy at discharge. No renal recovery was defined as a need for renal replacement therapy at discharge.ResultsThe study included 374 patients. Ninty-eight (26%) patients developed AKI during hospitalization: 55 (56%) had complete recovery; 39 (40%), partial recovery; and 4 (4%), no recovery. AKI development was significantly associated with increased risk of 2-year mortality (hazard ratio [HR], 2.20 [95% CI, 1.37-3.49]). For patients with AKI, the 2-year mortality rate for complete recovery was 34%; for partial recovery, 43%; and for no recovery, 75%; compared with 20% for patients without AKI (P ConclusionThe mortality rate increased for all patients with AKI undergoing TAVR. A reverse correlation existed for progressively higher risk of death and the extent of AKI recovery
Evolving Adeno-Associated Virus for Editing T-Lymphocytes
No full textAdeno-Associated Virus (AAV) is a gene therapy vector with immense clinical importance. However, its use as a template for homology directed repair has come under greater examination particularly for the generation of site-specific recombined Chimeric antigen receptor or CAR T-cells. This is because traditional CAR T-cells generated from retro- or lentiviral vectors have risks for insertional oncogenesis or exhaustion from tonic signaling due to use of a constitutively active promoter, both problems which AAV directed knockins may overcome. In fact, the use of site-specific knockin CAR T-cells have now entered clinical trials for the treatment of CD19+ blood-borne cancers. While the use of these next-gen AAV generated CARs have excelled for liquid tumors, their use for the treatment of solid tumors has lagged. This is due to poor preclinical modeling for solid-tumor directed CARs which take place in immunocompromised mouse models that do not fully recapitulate the tumor microenvironment known to be problematic for infiltrating lymphocytes. Thus, there is a clear need to evaluate these therapeutics in immunocompetent hosts, however, there exist no known AAV serotype that can effectively target murine T-lymphocytes to generate these site-specific knockins.
To ameliorate this problem, we employed a capsid evolution from the AAV6 background to generate a murine T-lymphocyte tropic AAV variant dubbed Ark313. Ark313 is vastly superior to the parent serotype in transducing, gene editing and site-specific knockins in murine T-cells. To characterize how this was happening, we employed a genome wide CRISPR knockout screen in murine primary T-cells to reveal the essential factor for Ark313 transduction to be Qa-2, a non-classical MHC-1b molecule. Due to the restricted tissue expression of the Qa-2 antigen, we injected mice systemically with Ark313 and saw it could transduce up to 25% of spleen resident T-cells including naïve/memory/effector subsets when using a self-complementary transgene. Additionally, Ark313 displayed a liver de-targeted tropism reducing potential off target tissue transduction when employing an ubiquitous promoter.
Together we have generated a novel tool for the facile genetic manipulation of murine T-cells both ex and in vivo. We believe Ark313 will be a fundamental reagent to employ when interrogating T-lymphocyte immunotherapeutic questions and for investigating immune basic biology. This work lays the groundwork for the development of human lymphocyte targeting AAVs for generating CARs to combat liquid and solid tumors via systemic dosing.
</p
Stable condition: Traumatic injury, coma, and vital traffic in a Mumbai hospital ward
No full textBased on five years of research in a public-hospital trauma ward in Mumbai, this article examines the fraught case study of comatose states that result from traffic-accident injuries. It focuses on a relationship between two brothers, one injured in a motorcycle accident and in a coma, and the other caring for him. The article asks: How do people navigate life-and-death situations through both stillness and motion? Addressing this question requires recasting traumatic injury from a wound that lodges in a single body to an intersubjective problem of discontinuous and relational traffic. In moments of transfer to the hospital, prognosis about vital signs, and reflections on death, the embodiment of and care for traumatic injury materializes through uneven relationships of intermittent motion. The article develops the analytic of vital traffic to describe these relationships and analyzes the temporal and spatial discontinuities that shape and undermine stability after injury occurs. Differences in vital traffic matter to patients, families, providers, and to the very possibility of survival. The implication of this finding is a better understanding of the sociality of injury and its care. Beyond the case of medicine, attention to vital traffic can illuminate the flux of ethnography itself