The single-stranded RNA Flavivirus, Zika virus (ZIKV), has recently re-emerged and spread rapidly across the western hemispheres equatorial countries, primarily through Aedes mosquito transmission. While symptoms in adult infections appear to be self-limiting and mild, severe birth defects, such as microcephaly, have been linked to infection during early pregnancy. Recently, Tang et al. (Cell Stem Cell 2016, doi: 10.1016/j.stem.2016.02.016 ) demonstrated that ZIKV efficiently infects induced pluripotent stem cell (iPSC) derived human neural progenitor cells (hNPCs), resulting in cell cycle abnormalities and apoptosis. Consequently, hNPCs are a suggested ZIKV target. We analyzed the transcriptomic sequencing (RNA-seq) data (GEO: GSE78711) of ZIKV (Strain: MR766) infected hNPCs. For comparison to the ZIKV-infected hNPCs, the expression data from hNPCs infected with human cytomegalovirus (CMV) (Strain: AD169) was used (GEO: GSE35295). Utilizing a combination of Gene Ontology, database of human diseases, and pathway analysis, we generated a putative systemic model of infection supported by known molecular pathways of other highly related viruses. We analyzed RNA-sequencing data for transcript expression alterations in ZIKV-infected hNPCs, and then compared them to expression patterns of iPSC-derived hNPCs infected with CMV, a virus that can also induce severe congenital neurological defects in developing fetuses. We demonstrate for the first time that many of cellular pathways correlate with clinical pathologies following ZIKV infection such as microcephaly, congenital nervous

Although stem cell therapy holds promise as a potential treatment in a number of diseases, the tumorigenicity of embryonic stem cells (ESC) and induced pluripotent stem cells remains a major obstacle. <i>In vitro</i> predifferentiation of ESCs can help prevent the risk of teratoma formation, yet proliferating neural progenitors can generate tumors, especially in the presence of immunosuppressive therapy. In this study, we investigated the effects of the microenvironment on stem cell growth and teratoma development using undifferentiated ESCs. Syngeneic ESC transplantation triggered an inflammatory response that involved the recruitment of bone marrow (BM)derived macrophages. These macrophages differentiated into an M2 or angiogenic phenotype that expressed multiple angiogenic growth factors and proteinases, such as macrophage migration inhibitory factor (MIF), VEGF, and matrix metalloproteinase 9

Consider a linear model Y= X + z, where X= X n, p and z~ N (0, I n). The vector is unknown and it is of interest to separate its nonzero coordinates from the zero ones (ie, variable selection). Motivated by examples in long-memory time series (Fan and Yao, 2003) and the change-point problem (Bhattacharya, 1994), we are primarily interested in the case where the Gram matrix G= X X is non-sparse but sparsifiable by a finite order linear filter. We focus on the regime where signals are both rare and weak so that successful variable selection is very challenging but is still possible.

Time- and state-domain methods are two common approaches to nonparametric prediction. Whereas the former uses data predominantly from recent history, the latter relies mainly on historical information. Combining these two pieces of valuable information is an interesting challenge in statistics. We surmount this problem by dynamically integrating information from both the time and state domains. The estimators from these two domains are optimally combined based on a data-driven weighting strategy, which provides a more efficient estimator of volatility. Asymptotic normality is separately established for the time domain, the state domain, and the integrated estimators. By comparing the efficiency of the estimators, we demonstrate that the proposed integrated estimator uniformly dominates the other two estimators. The proposed dynamic integration approach is also applicable to other estimation problems in time

The paper studies estimation of partially linear hazard regression models with varying coefficients for multivariate survival data. A profile pseudopartiallikelihood estimation method is proposed. The estimation of the parameters of the linear part is accomplished via maximization of the profile pseudopartiallikelihood, whereas the varyingcoefficient functions are considered as nuisance parameters that are profiled out of the likelihood. It is shown that the estimators of the parameters are root <i>n</i> consistent and the estimators of the nonparametric coefficient functions achieve optimal convergence rates. Asymptotic normality is obtained for the estimators of the finite parameters and varyingcoefficient functions. Consistent estimators of the asymptotic variances are derived and empirically tested, which facilitate inference for the model. We prove that the varyingcoefficient functions can be estimated as well as if the