Causal inference for continuous-time processes when covariates are observed only at discrete times

Most of the work on the structural nested model and g-estimation for causal inference in longitudinal data assumes a discrete-time underlying data generating process. However, in some observational studies, it is more reasonable to assume that the data are generated from a continuous-time process and are only observable at discrete time points. When these circumstances arise, the sequential randomization assumption in the observed discrete-time data, which is essential in justifying discrete-time g-estimation, may not be reasonable. Under a deterministic model, we discuss other useful assumptions that guarantee the consistency of discrete-time g-estimation. In more general cases, when those assumptions are violated, we propose a controlling-the-future method that performs at least as well as g-estimation in most scenarios and which provides consistent estimation in some cases where g-estimation is severely inconsistent. We apply the methods discussed in this paper to simulated data, as well as to a data set collected following a massive flood in Bangladesh, estimating the effect of diarrhea on children's height. Results from different methods are compared in both simulation and the real application.Comment: Published in at http://dx.doi.org/10.1214/10-AOS830 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Electronic, optical and transport properties of van der Waals Transition-metal Dichalcogenides Heterostructures: A First-principle Study

Two-dimensional (2D) transition-metal dichalcogenide (TMD) MX$_2$ (M = Mo, W; X= S, Se, Te) possess unique properties and novel applications. In this work, we perform first-principles calculations on the van der Waals (vdW) stacked MX$_2$ heterostructures to investigate their electronic, optical and transport properties systematically. We perform the so-called Anderson's rule to classify the heterostructures by providing the scheme of the construction of energy band diagrams for the heterostructure consisting of two semiconductor materials. For most of the MX$_2$ heterostructures, the conduction band maximum (CBM) and valence band minimum (VBM) reside in two separate semiconductors, forming type II band structure, thus the electron-holes pairs are spatially separated. We also find strong interlayer coupling at $\Gamma$ point after forming MX$_2$ heterostructures, even leading to the indirect band gap. While the band structure near $K$ point remain as the independent monolayer. The carrier mobilities of MX$_2$ heterostructures depend on three decisive factors, elastic modulus, effective mass and deformation potential constant, which are discussed and contrasted with those of monolayer MX$_2$, respectively.Comment: 7 figure

Knockdown of Brm and Baf170, Components of Chromatin Remodeling Complex, Facilitates Reprogramming of Somatic Cells

© Copyright 2015, Mary Ann Liebert, Inc. 2015. The SWI/SNF (SWItch/Sucrose NonFermentable or BAF, Brg/Brahma-associated factors) complexes are epigenetic modifiers of chromatin structure and undergo progressive changes in subunit composition during cellular differentiation. For example, in embryonic stem cells, esBAF contains Brg1 and Baf155, while their homologs, Brm and Baf170, are present in BAF of somatic cells. In this study, we sought to determine whether Brm and Baf170 play any roles in induced pluripotent stem cell (iPSC) reprogramming by using shRNA-mediated knockdown studies in the mouse model. We found that knocking down Brm during early, mid, and late stages (days 3, 6, and 9 after initial iPSC induction) and knocking down Baf170 during late-stage (day 9) reprogramming improve the numbers of iPSC colonies formed. We further showed that inhibition of these somatic BAF components also promotes complete reprogramming of partially reprogrammed somatic cells (pre-iPSCs). Finally, we found that the expression of Brm and Baf170 during reprogramming was regulated by Jak/Stat3 activity. Taken together, these data suggest that inhibiting somatic BAF improves complete reprogramming by facilitating the activation of the pluripotency circuitry

Viral subversion of selective autophagy is critical for biogenesis of virus replication organelles

Infection by many (+)RNA viruses is accompanied by ER-expansion and membrane remodelling to form viral replication organelles, followed by assembly and secretion of viral progenies. We previously identified that virus-triggered lipophagy was critical for flaviviral assembly, and is driven by the lipid droplet associated protein Ancient ubiquitin protein 1 (Aup1). A ubiquitin conjugating protein Ube2g2 that functions as a co-factor for Aup1 was identified as a host dependency factor in our study. Here we characterized its function: Ube2g2-deficient cells displayed a dramatic reduction in virus production, which could be rescued by reconstituting the wild-type but not the catalytically deficient (C89K) mutant of Ube2g2, suggesting that its enzymatic activity is necessary. Ube2g2 deficiency did not affect entry of virus particles but resulted in a profound loss in formation of replication organelles, and production of infectious progenies. This phenomenon resulted from its dual activity in (i) triggering lipophagy in conjunction with Aup1, and (ii) degradation of ER chaperones such as Herpud1, SEL1L, Hrd1, along with Sec62 to restrict ER-phagy upon Xbp1-IRE1 triggered ER expansion. Our results therefore underscore an exquisite fine-tuning of selective autophagy by flaviviruses that drive host membrane reorganization during infection to enable biogenesis of viral replication organelles

Responses of sequential and hierarchical phenological events to warming and cooling in alpine meadows

Organisms' life cycles consist of hierarchical stages, from a single phenological stage (for example, flowering within a season), to vegetative and reproductive phases, to the total lifespan of the individual. Yet phenological events are typically studied in isolation, limiting our understanding of life history responses to climate change. Here, we reciprocally transfer plant communities along an elevation gradient to investigate plastic changes in the duration of sequential phenological events for six alpine species. We show that prolonged flowering leads to longer reproductive phases and activity periods when plants are moved to warmer locations. In contrast, shorter post-fruiting leaf and flowering stages led to shorter vegetative and reproductive phases, respectively, which resulted in shorter activity periods when plants were moved to cooler conditions. Therefore, phenological responses to warming and cooling do not simply mirror one another in the opposite direction, and low temperature may limit reproductive allocation in the alpine region

Electrostatic phase separation: a review

The current understanding and developments in the electrostatic phase separation are reviewed. The literature covers predominantly two immiscible and inter-dispersed liquids following the last review on the topic some 15 years. Electrocoalescence kinetics and governing parameters, such as the applied field, liquid properties, drop shape and flow, are considered. The unfavorable effects, such as chain formation and partial coalescence, are discussed in detail. Moreover, the prospects of microfluidics platforms, non-uniform fields, coalescence on the dielectric surfaces to enhance the electrocoalescence rate are also considered. In addition to the electrocoalescence in water-in-oil emulsions the research in oil-in-oil coalescence is also discussed. Finally the studies in electrocoalescer development and commercial devices are also surveyed. The analysis of the literature reveals that the use of pulsed DC and AC electric fields is preferred over constant DC fields for efficient coalescence; but the selection of the optimum field frequency a priori is still not possible and requires further research. Some recent studies have helped to clarify important aspects of the process such as partial coalescence and drop–drop non-coalescence. On the other hand, some key phenomena such as thin film breakup and chain formation are still unclear. Some designs of inline electrocoalescers have recently been proposed; however with limited success: the inadequate knowledge of the underlying physics still prevents this technology from leaving the realm of empiricism and fully developing in one based on rigorous scientific methodology

Diverse Applications of Nanomedicine

The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic. \ua9 2017 American Chemical Society

Assessment of coastal management options by means of multilayered ecosystem models

This paper presents a multilayered ecosystem modelling approach that combines the simulation of the biogeochemistry of a coastal ecosystem with the simulation of the main forcing functions, such as catchment loading and aquaculture activities. This approach was developed as a tool for sustainable management of coastal ecosystems. A key feature is to simulate management scenarios that account for changes in multiple uses and enable assessment of cumulative impacts of coastal activities. The model was applied to a coastal zone in China with large aquaculture production and multiple catchment uses, and where management efforts to improve water quality are under way. Development scenarios designed in conjunction with local managers and aquaculture producers include the reduction of fish cages and treatment of wastewater. Despite the reduction in nutrient loading simulated in three different scenarios, inorganic nutrient concentrations in the bay were predicted to exceed the thresholds for poor quality defined by Chinese seawater quality legislation. For all scenarios there is still a Moderate High to High nutrient loading from the catchment, so further reductions might be enacted, together with additional decreases in fish cage culture. The model predicts that overall, shellfish production decreases by 10%–28% using any of these development scenarios, principally because shellfish growth is being sustained by the substances to be reduced for improvement of water quality. The model outcomes indicate that this may be counteracted by zoning of shellfish aquaculture at the ecosystem level in order to optimize trade-offs between productivity and environmental effects. The present case study exemplifies the value of multilayered ecosystem modelling as a tool for Integrated Coastal Zone Management and for the adoption of ecosystem approaches for marine resource management. This modelling approach can be applied worldwide, and may be particularly useful for the application of coastal management regulation, for instance in the implementation of the European Marine Strategy Framework Directive

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder