To translate, or not to translate: viral and host mRNA regulation by interferon-stimulated genes.

Type I interferon (IFN) is one of the first lines of cellular defense against viral pathogens. As a result of IFN signaling, a wide array of IFN-stimulated gene (ISG) products is upregulated to target different stages of the viral life cycle. We review recent findings implicating a subset of ISGs in translational regulation of viral and host mRNAs. Translation inhibition is mediated either by binding to viral RNA or by disrupting physiological interactions or levels of the translation complex components. In addition, many of these ISGs localize to translationally silent cytoplasmic granules, such as stress granules and processing bodies, and intersect with the microRNA (miRNA)-mediated silencing pathway to regulate translation of cellular mRNAs

End-to-End Localization and Ranking for Relative Attributes

We propose an end-to-end deep convolutional network to simultaneously localize and rank relative visual attributes, given only weakly-supervised pairwise image comparisons. Unlike previous methods, our network jointly learns the attribute's features, localization, and ranker. The localization module of our network discovers the most informative image region for the attribute, which is then used by the ranking module to learn a ranking model of the attribute. Our end-to-end framework also significantly speeds up processing and is much faster than previous methods. We show state-of-the-art ranking results on various relative attribute datasets, and our qualitative localization results clearly demonstrate our network's ability to learn meaningful image patches.Comment: Appears in European Conference on Computer Vision (ECCV), 201

ZAP's stress granule localization is correlated with its antiviral activity and induced by virus replication.

Cellular antiviral programs encode molecules capable of targeting multiple steps in the virus lifecycle. Zinc-finger antiviral protein (ZAP) is a central and general regulator of antiviral activity that targets pathogen mRNA stability and translation. ZAP is diffusely cytoplasmic, but upon infection ZAP is targeted to particular cytoplasmic structures, termed stress granules (SGs). However, it remains unclear if ZAP's antiviral activity correlates with SG localization, and what molecular cues are required to induce this localization event. Here, we use Sindbis virus (SINV) as a model infection and find that ZAP's localization to SGs can be transient. Sometimes no apparent viral infection follows ZAP SG localization but ZAP SG localization always precedes accumulation of SINV non-structural protein, suggesting virus replication processes trigger SG formation and ZAP recruitment. Data from single-molecule RNA FISH corroborates this finding as the majority of cells with ZAP localization in SGs contain low levels of viral RNA. Furthermore, ZAP recruitment to SGs occurred in ZAP-expressing cells when co-cultured with cells replicating full-length SINV, but not when co-cultured with cells replicating a SINV replicon. ZAP recruitment to SGs is functionally important as a panel of alanine ZAP mutants indicate that the anti-SINV activity is correlated with ZAP's ability to localize to SGs. As ZAP is a central component of the cellular antiviral programs, these data provide further evidence that SGs are an important cytoplasmic antiviral hub. These findings provide insight into how antiviral components are regulated upon virus infection to inhibit virus spread

Coordinated operation of electric vehicle charging and wind power generation as a virtual power plant: A multi-stage risk constrained approach

© 2019 Elsevier Ltd As the number of electric vehicles (EVs) is steadily increasing, their aggregation can offer significant storage to improve the electric system operation in many aspects. To this end, a comprehensive stochastic optimization framework is proposed in this paper for the joint operation of a fleet of EVs with a wind power producer (WPP) in a three-settlement pool-based market. An aggregator procures enough energy for the EVs based on their daily driving patterns, and schedules the stored energy to counterbalance WPP fluctuations. Different sources of uncertainty including the market prices and WPP generation are modeled through proper scenarios, and the risk is hedged by adding a risk measure to the formulation. To obtain more accurate results, the battery degradation costs are also included in the problem formulation. A detailed case study is presented based on the Iberian electricity market data as well as the technical information of three different types of EVs. The proposed approach is benchmarked against the disjoint operation of EVs and WPP. Numerical simulations demonstrate that the proposed strategy can effectively benefit EV owners and WPP by reducing the energy costs and increasing the profits

Interferon regulatory factor 2 protects mice from lethal viral neuroinvasion.

The host responds to virus infection by activating type I interferon (IFN) signaling leading to expression of IFN-stimulated genes (ISGs). Dysregulation of the IFN response results in inflammatory diseases and chronic infections. In this study, we demonstrate that IFN regulatory factor 2 (IRF2), an ISG and a negative regulator of IFN signaling, influences alphavirus neuroinvasion and pathogenesis. A Sindbis virus strain that in wild-type (WT) mice only causes disease when injected into the brain leads to lethal encephalitis in Irf2-/- mice after peripheral inoculation. Irf2-/- mice fail to control virus replication and recruit immune infiltrates into the brain. Reduced B cells and virus-specific IgG are observed in the Irf2-/- mouse brains despite the presence of peripheral neutralizing antibodies, suggesting a defect in B cell trafficking to the central nervous system (CNS). B cell-deficient μMT mice are significantly more susceptible to viral infection, yet WT B cells and serum are unable to rescue the Irf2-/- mice. Collectively, our data demonstrate that proper localization of B cells and local production of antibodies in the CNS are required for protection. The work advances our understanding of host mechanisms that affect viral neuroinvasion and their contribution to immunity against CNS infections

Active Power Sharing and Frequency Restoration in an Autonomous Networked Microgrid

© 1969-2012 IEEE. Microgrid (MG) concept is considered as the best solution for future power systems, which are expected to receive a considerable amount of power through renewable energy resources and distributed generation units. Droop control systems are widely adopted in conventional power systems and recently in MGs for power sharing among generation units. However, droop control causes frequency fluctuations, which leads to poor power quality. This paper deals with frequency fluctuation and stability concerns of f-P droop control loop in MGs. Inspired from conventional synchronous generators, virtual damping is proposed to diminish frequency fluctuation in MGs. Then, it is demonstrated that the conventional frequency restoration method inserts an offset to the phase angle, which is in conflict with accurate power sharing. To this end, a novel control method, based on phase angle feedback, is proposed for frequency restoration in conjunction with a novel method for adaptively tuning the feedback gains to preserve precise active power sharing. Nonlinear stability analysis is conducted by drawing the phase variations of the nonlinear second-order equation of the δ-P droop loop and it is proved that the proposed method improves the stability margin of f-P control loop. Simulation results demonstrate the effectiveness of the proposed method

Fast Locality-Sensitive Hashing Frameworks for Approximate Near Neighbor Search

The Indyk-Motwani Locality-Sensitive Hashing (LSH) framework (STOC 1998) is a general technique for constructing a data structure to answer approximate near neighbor queries by using a distribution $\mathcal{H}$ over locality-sensitive hash functions that partition space. For a collection of $n$ points, after preprocessing, the query time is dominated by $O(n^{\rho} \log n)$ evaluations of hash functions from $\mathcal{H}$ and $O(n^{\rho})$ hash table lookups and distance computations where $\rho \in (0,1)$ is determined by the locality-sensitivity properties of $\mathcal{H}$. It follows from a recent result by Dahlgaard et al. (FOCS 2017) that the number of locality-sensitive hash functions can be reduced to $O(\log^2 n)$, leaving the query time to be dominated by $O(n^{\rho})$ distance computations and $O(n^{\rho} \log n)$ additional word-RAM operations. We state this result as a general framework and provide a simpler analysis showing that the number of lookups and distance computations closely match the Indyk-Motwani framework, making it a viable replacement in practice. Using ideas from another locality-sensitive hashing framework by Andoni and Indyk (SODA 2006) we are able to reduce the number of additional word-RAM operations to $O(n^\rho)$.Comment: 15 pages, 3 figure

Genetic components of grey cattle in Estonia as revealed by microsatellite analysis using two Bayesian clustering methods

<p>Abstract</p> <p>Background</p> <p>It was recently postulated that a few individual grey cattle still found in Estonia might be a relict of the old native cattle stock. Genotypes at 17 microsatellite loci from a total of 243 cattle from North European breeds and 11 grey cattle in Estonia were used in an attempt to clarify the genetic composition of the grey cattle.</p> <p>Findings</p> <p>We characterize the genetic components of 11 examples of the grey cattle in Estonia at the population and individual levels. Our results show that the grey cattle in Estonia are most genetically similar to the Holstein-Friesian breed and secondarily to the Estonian Red cattle.</p> <p>Conclusions</p> <p>Both Bayesian approaches gave similar results in terms of the identification of numbers of clusters and the estimation of proportions of genetic components. This study suggested that the Estonian grey cattle included in the analysis are a genetic composite resulting from cross-breeding of European dairy breeds.</p

Cell-Cycle-Based Strategies to Drive Myocardial Repair

Cardiomyocytes exhibit robust proliferative activity during development. After birth, cardiomyocyte proliferation is markedly reduced. Consequently, regenerative growth in the postnatal heart via cardiomyocyte proliferation (and, by inference, proliferation of stem-cell-derived cardiomyocytes) is limited and often insufficient to affect repair following injury. Here, we review studies wherein cardiomyocyte cell cycle proliferation was induced via targeted expression of cyclin D2 in postnatal hearts. Cyclin D2 expression resulted in a greater than 500-fold increase in cell cycle activity in transgenic mice as compared to their nontransgenic siblings. Induced cell cycle activity resulted in infarct regression and concomitant improvement in cardiac hemodynamics following coronary artery occlusion. These studies support the notion that cell-cycle-based strategies can be exploited to drive myocardial repair following injury

Towards precision medicine for hypertension: a review of genomic, epigenomic, and microbiomic effects on blood pressure in experimental rat models and humans

Compelling evidence for the inherited nature of essential hypertension has led to extensive research in rats and humans. Rats have served as the primary model for research on the genetics of hypertension resulting in identification of genomic regions that are causally associated with hypertension. In more recent times, genome-wide studies in humans have also begun to improve our understanding of the inheritance of polygenic forms of hypertension. Based on the chronological progression of research into the genetics of hypertension as the "structural backbone," this review catalogs and discusses the rat and human genetic elements mapped and implicated in blood pressure regulation. Furthermore, the knowledge gained from these genetic studies that provide evidence to suggest that much of the genetic influence on hypertension residing within noncoding elements of our DNA and operating through pervasive epistasis or gene-gene interactions is highlighted. Lastly, perspectives on current thinking that the more complex "triad" of the genome, epigenome, and the microbiome operating to influence the inheritance of hypertension, is documented. Overall, the collective knowledge gained from rats and humans is disappointing in the sense that major hypertension-causing genes as targets for clinical management of essential hypertension may not be a clinical reality. On the other hand, the realization that the polygenic nature of hypertension prevents any single locus from being a relevant clinical target for all humans directs future studies on the genetics of hypertension towards an individualized genomic approach