New and Notable, 10 December 2014

Here is another selection of recently published articles highly rated by our reviewers. Do you agree with them?

Euthanasia Assessment in Ebola Virus Infected Nonhuman Primates

Travis K. Warren, John C. Trefry, Shannon T. Marko, Taylor B. Chance, Jay B. Wells, William D. Pratt, Joshua C. Johnson, Eric M. Mucker, Sarah L. Norris, Mark Chappell, John M. Dye and Anna N. Honko

Multiple products are being developed for use against filoviral infections. Efficacy for these products will likely be demonstrated in nonhuman primate models of filoviral disease to satisfy licensure requirements under the Animal Rule, or to supplement human data. Typically, the endpoint for efficacy assessment will be survival following challenge; however, there exists no standardized approach for assessing the health or euthanasia criteria for filovirus-exposed nonhuman primates. Consideration of objective criteria is important to (a) ensure test subjects are euthanized without unnecessary distress; (b) enhance the likelihood that animals exhibiting mild or moderate signs of disease are not prematurely euthanized; (c) minimize the occurrence of spontaneous deaths and loss of end-stage samples; (d) enhance the reproducibility of experiments between different researchers; and (e) provide a defensible rationale for euthanasia decisions that withstands regulatory scrutiny. Historic records were compiled for 58 surviving and non-surviving monkeys exposed to Ebola virus at the US Army Medical Research Institute of Infectious Diseases. Clinical pathology parameters were statistically analyzed and those exhibiting predicative value for survival are reported. These findings may be useful for standardization of objective euthanasia assessments in rhesus monkeys exposed to Ebola virus and may serve as a useful approach for other standardization efforts.

Exploration of Preterm Birth Rates Using the Public Health Exposome Database and Computational Analysis Methods

Anne D. Kershenbaum, Michael A. Langston, Robert S. Levine, Arnold M. Saxton, Tonny J. Oyana, Barbara J. Kilbourne, Gary L. Rogers, Lisaann S. Gittner, Suzanne H. Baktash, Patricia Matthews-Juarez and Paul D. Juarez

Recent advances in informatics technology has made it possible to integrate, manipulate, and analyze variables from a wide range of scientific disciplines allowing for the examination of complex social problems such as health disparities. This study used 589 county-level variables to identify and compare geographical variation of high and low preterm birth rates. Data were collected from a number of publically available sources, bringing together natality outcomes with attributes of the natural, built, social, and policy environments. Singleton early premature county birth rate, in counties with population size over 100,000 persons provided the dependent variable. Graph theoretical techniques were used to identify a wide range of predictor variables from various domains, including black proportion, obesity and diabetes, sexually transmitted infection rates, mother’s age, income, marriage rates, pollution and temperature among others. Dense subgraphs (paracliques) representing groups of highly correlated variables were resolved into latent factors, which were then used to build a regression model explaining prematurity (R-squared = 76.7%). Two lists of counties with large positive and large negative residuals, indicating unusual prematurity rates given their circumstances, may serve as a starting point for ways to intervene and reduce health disparities for preterm births.

Ectopic Noggin in a Population of Nfatc1 Lineage Endocardial Progenitors Induces Embryonic Lethality

Paige Snider, Olga Simmons, Jian Wang, Chinh Q. Hoang and Simon J. Conway

The initial heart is composed of a myocardial tube lined by endocardial cells. The TGFβ superfamily is known to play an important role, as BMPs from the myocardium signal to the overlying endocardium to create an environment for EMT. Subsequently, BMP and TGFβ signaling pathways synergize to form primitive valves and regulate myocardial growth. In this study, we investigated the requirement of BMP activity by transgenic over-expression of extracellular BMP antagonist Noggin. Using Nfatc1Cre to drive lineage-restricted Noggin within the endocardium, we show that ectopic Noggin arrests cardiac development in E10.5-11 embryos, resulting in small hearts which beat poorly and die by E12.5. This is coupled with hypoplastic endocardial cushions, reduced trabeculation and fewer mature contractile fibrils in mutant hearts. Moreover, Nfatc1Cre-mediated diphtheria toxin fragment-A expression in the endocardium resulted in genetic ablation and a more severe phenotype with lethality at E11 and abnormal linear hearts. Molecular analysis demonstrated that endocardial Noggin resulted in a specific alteration of TGFβ/BMP-mediated signal transduction, in that, both Endoglin and ALK1 were downregulated in mutant endocardium. Combined, these results demonstrate the cell-autonomous requirement of the endocardial lineage and function of unaltered BMP levels in facilitating endothelium-cardiomyocyte cross-talk and promoting endocardial cushion formation.

A Generalized Approach for the Steady-State Analysis of Dual-Bridge Resonant Converters

Gao-Yuan Hu, Xiaodong Li and Bo-Yue Luan

In this paper, a dual-bridge DC/DC resonant converter with a generalized series and parallel resonant tank is analyzed. A general approach based on Fundamental Harmonic Approximation is used to find the universal steady-state solutions. The analysis results for particular resonant tank configurations are exemplified with several typical resonant tank configurations respectively. The corresponded soft-switching conditions are discussed too. To illustrate the usefulness of the generalized approach, a dual-bridge (LC)(L)-type resonant converter working in below resonance mode is designed based on the analysis results. Finally, simulation and experimental plots of the design example are included to evaluate the validity and the accuracy of the proposed analysis approach.

A New Quantum f-Divergence for Trace Class Operators in Hilbert Spaces

Silvestru Sever Dragomir

A new quantum f-divergence for trace class operators in Hilbert Spaces is introduced. It is shown that for normalised convex functions it is nonnegative. Some upper bounds are provided. Applications for some classes of convex functions of interest are also given.