An Estimation of U.S. Industry-Level Capital-Labor Substitution

A key parameter that determines the distributional impacts of a policy shift in general equilibrium models is the elasticity of substitution between capital and labor. Despite the importance of this parameter in applied modeling, its identification continues to pose a challenge. Given the structure of most growth models, we posit that the true relationship between capital and labor is likely to be close to Cobb- Douglas. Using a rich new data set from the Bureau of Economic Analysis, we estimate substitution elasticities for 28 industries, which cover the entire economy, and provide an indication of the long- and short-run estimates. We fail to reject the Cobb-Douglas specification in 20 of the 28 industries. These findings lend support to the Cobb-Douglas specification as a transparent starting point in simulation analysis.Econometric Methods; Time Series Models; Computable General Equilibrium Models

Energy and system dependence of high-pTp_T triggered two-particle near-side correlations

Previous studies have indicated that the near-side peak of high-$p_T$ triggered correlations can be decomposed into two parts, the \textit{Jet} and the \textit{Ridge}. We present data on the yield per trigger of the \textit{Jet} and the \textit{Ridge} from $d+Au$, $Cu+Cu$ and $Au+Au$ collisions at $\sqrt{s_{NN}}$ = 62.4 GeV and 200 GeV and compare data on the \textit{Jet} to PYTHIA 8.1 simulations for $p+p$. PYTHIA describes the \textit{Jet} component up to a scaling factor, meaning that PYTHIA can provide a better understanding of the \textit{Ridge} by giving insight into the effects of the kinematic cuts. We present collision energy and system dependence of the \textit{Ridge} yield, which should help distinguish models for the production mechanism of the \textit{Ridge}.Comment: 4 pages, 6 figures, proceedings for Hot Quarks in Estes Park, Colorad

Identifying cell class specific losses from serially generated electroretinogram components

Purpose. Processing of information through the cellular layers of the retina occurs in a serial manner. In the electroretinogram (ERG), this complicates interpretation of inner retinal changes as dysfunction may arise from “upstream” neurons or may indicate a direct loss to that neural generator. We propose an approach that addresses this issue by defining ERG gain relationships. Methods. Regression analyses between two serial ERG parameters in a control cohort of rats are used to define gain relationships. These gains are then applied to two models of retinal disease. Results. The to gain is unity whereas the to and to gains are greater than unity, indicating “amplification” (). Timing relationships show amplification between to and compression for to and to , (). Application of these gains to -3-deficiency indicates that all timing changes are downstream of photoreceptor changes, but a direct pSTR amplitude loss occurs (). Application to diabetes indicates widespread inner retinal dysfunction which cannot be attributed to outer retinal changes (). Conclusions. This simple approach aids in the interpretation of inner retinal ERG changes by taking into account gain characteristics found between successive ERG components of normal animals

Heterogeneity in HIV and cellular transcription profiles in cell line models of latent and productive infection: implications for HIV latency.

BackgroundHIV-infected cell lines are widely used to study latent HIV infection, which is considered the main barrier to HIV cure. We hypothesized that these cell lines differ from each other and from cells from HIV-infected individuals in the mechanisms underlying latency.ResultsTo quantify the degree to which HIV expression is inhibited by blocks at different stages of HIV transcription, we employed a recently-described panel of RT-ddPCR assays to measure levels of 7 HIV transcripts ("read-through," initiated, 5' elongated, mid-transcribed/unspliced [Pol], distal-transcribed [Nef], polyadenylated, and multiply-sliced [Tat-Rev]) in bulk populations of latently-infected (U1, ACH-2, J-Lat) and productively-infected (8E5, activated J-Lat) cell lines. To assess single-cell variation and investigate cellular genes associated with HIV transcriptional blocks, we developed a novel multiplex qPCR panel and quantified single cell levels of 7 HIV targets and 89 cellular transcripts in latently- and productively-infected cell lines. The bulk cell HIV transcription profile differed dramatically between cell lines and cells from ART-suppressed individuals. Compared to cells from ART-suppressed individuals, latent cell lines showed lower levels of HIV transcriptional initiation and higher levels of polyadenylation and splicing. ACH-2 and J-Lat cells showed different forms of transcriptional interference, while U1 cells showed a block to elongation. Single-cell studies revealed marked variation between/within cell lines in expression of HIV transcripts, T cell phenotypic markers, antiviral factors, and genes implicated in latency. Expression of multiply-spliced HIV Tat-Rev was associated with expression of cellular genes involved in activation, tissue retention, T cell transcription, and apoptosis/survival.ConclusionsHIV-infected cell lines differ from each other and from cells from ART-treated individuals in the mechanisms governing latent HIV infection. These differences in viral and cellular gene expression must be considered when gauging the suitability of a given cell line for future research on HIV. At the same time, some features were shared across cell lines, such as low expression of antiviral defense genes and a relationship between productive infection and genes involved in survival. These features may contribute to HIV latency or persistence in vivo, and deserve further study using novel single cell assays such as those described in this manuscript

Using the electroretinogram to understand how intraocular pressure elevation affects the rat retina

Intraocular pressure (IOP) elevation is a key risk factor for glaucoma. Our understanding of the effect that IOP elevation has on the eye has been greatly enhanced by the application of the electroretinogram (ERG). In this paper, we describe how the ERG in the rodent eye is affected by changes in IOP magnitude, duration, and number of spikes. We consider how the variables of blood pressure and age can modify the effect of IOP elevation on the ERG. Finally, we contrast the effects that acute and chronic IOP elevation can have on the rodent ERG

Patient- and population-level health consequences of discontinuing antiretroviral therapy in settings with inadequate HIV treatment availability

Background In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART) after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes. Methods In settings with two available ART regimens, we assessed two strategies: (1) continue ART after second-line failure (Status Quo) and (2) discontinue ART after second-line failure (Alternative). A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the Alternative strategy, discontinuation of second-line ART occurred upon detection of antiretroviral failure, specified by WHO guidelines. Those discontinuing failed ART experienced an increased risk of AIDS-related mortality compared to those continuing ART. Results At the population level, the Alternative strategy increased the mean number initiating ART annually by 1,100 individuals (+18.7%) to 6,980 compared to the Status Quo. More individuals initiating ART under the Alternative strategy increased total life-years by 15,000 (+2.8%) to 555,000, compared to the Status Quo. Although more individuals received treatment under the Alternative strategy, life expectancy for those treated decreased by 0.7 years (−8.0%) to 8.1 years compared to the Status Quo. In a cohort of treated patients only, 600 more individuals (+27.1%) died by 5 years under the Alternative strategy compared to the Status Quo. Results were sensitive to the timing of detection of ART failure, number of ART regimens, and treatment capacity. Although we believe the results robust in the short-term, this analysis reflects settings where HIV case detection occurs late in the disease course and treatment capacity and the incidence of newly detected patients are stable. Conclusions In settings with inadequate HIV treatment availability, trade-offs emerge between maximizing outcomes for individual patients already on treatment and ensuring access to treatment for all people who may benefit. While individuals may derive some benefit from ART even after virologic failure, the aggregate public health benefit is maximized by providing effective therapy to the greatest number of people. These trade-offs should be explicit and transparent in antiretroviral policy decisions

Robust inducible Cre recombinase activity in the human malaria parasite Plasmodium falciparum enables efficient gene deletion within a single asexual erythrocytic growth cycle.

Asexual blood stages of the malaria parasite, which cause all the pathology associated with malaria, can readily be genetically modified by homologous recombination, enabling the functional study of parasite genes that are not essential in this part of the life cycle. However, no widely applicable method for conditional mutagenesis of essential asexual blood-stage malarial genes is available, hindering their functional analysis. We report the application of the DiCre conditional recombinase system to Plasmodium falciparum, the causative agent of the most dangerous form of malaria. We show that DiCre can be used to obtain rapid, highly regulated site-specific recombination in P. falciparum, capable of excising loxP-flanked sequences from a genomic locus with close to 100% efficiency within the time-span of a single erythrocytic growth cycle. DiCre-mediated deletion of the SERA5 3' UTR failed to reduce expression of the gene due to the existence of alternative cryptic polyadenylation sites within the modified locus. However, we successfully used the system to recycle the most widely used drug resistance marker for P. falciparum, human dihydrofolate reductase, in the process producing constitutively DiCre-expressing P. falciparum clones that have broad utility for the functional analysis of essential asexual blood-stage parasite genes

Parent and Household Influences on Calcium Intake Among Early Adolescents

Background: Calcium intake during early adolescence falls short of requirements for maximum bone accretion. Parents and the home food environment potentially influence children’s calcium intakes. This study aimed to quantify parental psychosocial factors (PSF) predicting calcium intakes of Asian, Hispanic, and non-Hispanic white (NHW) early adolescent children from a parental perspective. Methods: This was a cross-sectional study involving the administration of a validated calcium-specific food frequency questionnaire to a convenience sample of children aged 10–13 years and the primary individual responsible for food acquisition in the child’s household. Based on Social Cognitive Theory, parental factors potentially associated with children’s calcium intake were also assessed via parent questionnaires. The total study sample consisted of 633 parent-child pairs (Asian = 110, Hispanic = 239, NHW = 284). Questionnaires were completed at community-based centers/sites. Outcome measures were the association between parent-child calcium (mg), milk (cups/day), and soda (cans/day) intakes and the predictive value of significant parental PSF towards calcium intakes of their children. Sex-adjusted linear regression and multivariate analyses were performed. Results: Calcium intakes of parent-child pairs were positively associated among all ethnic groups (r = 0.296; P \u3c 0.001). Soda intakes were positively associated among Hispanic parent-child pairs only (r = 0.343; P \u3c 0.001). Home availability of calcium-rich foods (CRF), parental rules and expectations for their child’s intake of beverages, and parents’ calcium intake/role modeling were positively associated with children’s calcium intake and overwhelmed all other PSF in multivariate analyses. Significant cultural differences were observed. Parental role modeling was a significant factor among Hispanic dyads only. Multivariate models explained 19–21% of the variance in children’s calcium intakes. Conclusions: Nutrition interventions to improve children’s calcium intakes should focus on parents and provide guidance on improving home availability of CRF and increasing rules and expectations for the consumption of CRF. Among Hispanic families, interventions promoting parental modeling of desired dietary behaviors may be most successful

Cellular Origins of EGFR-Driven Lung Cancer Cells Determine Sensitivity to Therapy

Targeting the epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors (TKIs) is one of the major precision medicine treatment options for lung adenocarcinoma. Due to common development of drug resistance to first- and second-generation TKIs, third-generation inhibitors, including osimertinib and rociletinib, have been developed. A model of EGFR-driven lung cancer and a method to develop tumors of distinct epigenetic states through 3D organotypic cultures are described here. It is discovered that activation of the EGFR T790M/L858R mutation in lung epithelial cells can drive lung cancers with alveolar or bronchiolar features, which can originate from alveolar type 2 (AT2) cells or bronchioalveolar stem cells, but not basal cells or club cells of the trachea. It is also demonstrated that these clones are able to retain their epigenetic differences through passaging orthotopically in mice and crucially that they have distinct drug vulnerabilities. This work serves as a blueprint for exploring how epigenetics can be used to stratify patients for precision medicine decisions