The structure of M.EcoKI Type I DNA methyltransferase with a DNA mimic antirestriction protein

Type-I DNA restriction–modification (R/M) systems are important agents in limiting the transmission of mobile genetic elements responsible for spreading bacterial resistance to antibiotics. EcoKI, a Type I R/M enzyme from Escherichia coli, acts by methylation- and sequence-specific recognition, leading to either methylation of DNA or translocation and cutting at a random site, often hundreds of base pairs away. Consisting of one specificity subunit, two modification subunits, and two DNA translocase/endonuclease subunits, EcoKI is inhibited by the T7 phage antirestriction protein ocr, a DNA mimic. We present a 3D density map generated by negative-stain electron microscopy and single particle analysis of the central core of the restriction complex, the M.EcoKI M2S1 methyltransferase, bound to ocr. We also present complete atomic models of M.EcoKI in complex with ocr and its cognate DNA giving a clear picture of the overall clamp-like operation of the enzyme. The model is consistent with a large body of experimental data on EcoKI published over 40 years

Towards global sustainability: Education on environmentally clean energy technologies

The recent climate change agreement in Paris highlights the imperative to aggressively decarbonize the energy economy and develop new technologies, especially for the generation of electrical energy that are environmentally clean. This challenge can only be addressed by a multi-pronged approach to research and education of the next generation of scientists and engineers as well as informed public discourse. Consequently this requires the introduction of new and comprehensive education programs on sustainable energy technologies for universities and, possibly, high schools. Among others, the new programs should provide in-depth knowledge in the development of new materials for more efficient energy conversion systems and devices. The enhanced level of education is also needed for properly assessing the competing technologies in terms of their economic and social benefits. The increasing recognition of the significance of clean and efficient energy conversion indicates the need for a comprehensive education program to be developed. The purpose of the present work is to consider the structure of both an education program and the related textbook where the energy-related fundamental and applied subjects are presented in a concentrated and uniform manner. Such a textbook could be an education aid for students of energy-related courses as well as the teachers involved in the formulation of the education programs. The textbook, which should be dedicated mainly for students at the undergraduate levels at universities, and possibly high schools, should include in-depth interdisciplinary sections dedicated to energy experts and graduate students. This paper considers the present international efforts in reducing the impact of climate change and the need to develop new technologies for clean energy generation. It is argued that progress in this area requires recognition of hydrogen as the main energy carrier of the future. This work also delineates the goals of the Sustainable Energy Network, SEN, involved in the UN program of Future Earth

Lie families: theory and applications

We analyze families of non-autonomous systems of first-order ordinary differential equations admitting a common time-dependent superposition rule, i.e., a time-dependent map expressing any solution of each of these systems in terms of a generic set of particular solutions of the system and some constants. We next study relations of these families, called Lie families, with the theory of Lie and quasi-Lie systems and apply our theory to provide common time-dependent superposition rules for certain Lie families.Comment: 23 pages, revised version to appear in J. Phys. A: Math. Theo

Molecular signatures associated with the treatment of triple-negative MDA-MB231 breast cancer cells with the histone deacetylase inhibitors JAHA and SAHA

Jay Amin Hydroxamic Acid (JAHA; N8-ferrocenylN1-hydroxy-octanediamide) is a ferrocene-containing analogue of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA). JAHA’s cytotoxic activity on MDA-MB231 triple negative breast cancer (TNBC) cells at 72 h has been previously demonstrated with an IC50 of 8.45 M. JAHA’s lethal effect was found linked to perturbations of cell cycle, mitochondrial activity, signal transduction and autophagy mechanisms. In order to glean novel insights on how MDA-MB231 breast cancer cells respond to the cytotoxic effect induced by JAHA, and to compare the biological effect with the related compound SAHA, we have employed a combination of differential display-PCR, proteome analysis and COMET assay techniques and shown some differences in the molecular signature profiles induced by exposure to either HDACis. In particular, in contrast to the more numerous and diversified changes induced by SAHA, JAHA has shown a more selective impact on expression of molecular signatures involved in anti-oxidant activity and DNA repair. Besides expanding the biological knowledge of the effect exerted by the modifications in compound structures on cell phenotype, the molecular elements put in evidence in our study may provide promising targets for therapeutic interventions on TNBCs

Vertical integration and firm boundaries : the evidence

Since Ronald H. Coase's (1937) seminal paper, a rich set of theories has been developed that deal with firm boundaries in vertical or input–output structures. In the last twenty-five years, empirical evidence that can shed light on those theories also has been accumulating. We review the findings of empirical studies that have addressed two main interrelated questions: First, what types of transactions are best brought within the firm and, second, what are the consequences of vertical integration decisions for economic outcomes such as prices, quantities, investment, and profits. Throughout, we highlight areas of potential cross-fertilization and promising areas for future work

What Consensus? Ideology, Politics and Elections Still Matter

This article, which was prepared for an ABA Antitrust Section Panel, discusses the role of ideology and politics in antitrust enforcement and the impact of elections in the last twenty year on enforcement and policy at the federal antitrust agencies. The article explains the differences in antitrust ideologies and their impact on policy preferences. The article then uses a database of civil non-merger complaints by the DOJ and FTC over the last three Presidential administrations to analyze changes in the number, type and other characteristics of antitrust enforcement. It also discusses change in vertical merger enforcement and other antirust policies such as amicus briefs, reports and guidelines. The article concludes that elections do matter and that the impact of elections on the DOJ and FTC has differed significantly

Methane emissions from Alaska in 2012 from CARVE airborne observations

We determined methane (CH4) emissions from Alaska, USA using airborne measurements from the Carbon Arctic Reservoirs Vulnerability Experiment (CARVE). Atmospheric sampling was conducted between May and September 2012, and analyzed using a customized version of the Polar Weather Research and Forecast model linked to a Lagrangian particle dispersion model (Stochastic Time-Inverted Lagrangian Transport Model). We estimated growing season CH4 fluxes of 8 2 mg CH4 m 2 d 1 averaged over all of Alaska, corresponding to fluxes from wetlands of 56+22 13 20 mg CH4 m 2 d 1 if we assumed that wetlands are the only source from the land surface (all uncertainties are 95% confidence intervals from a bootstrapping analysis). Fluxes roughly doubled from May to July, then decreased gradually in August and September. Integrated emissions totaled 25 2:1 0:5 Tg CH4 for Alaska from May to September 2012, close to the average (2.3, range 0.7-6 Tg CH4) predicted by various land surface models and inversion analyses for the growing season. Methane emissions from boreal Alaska were larger than from the North Slope; the monthly regional flux estimates show no evidence of enhanced 30 emissions during early spring or late fall, although these bursts may be more localized in time and space than can be detected by our analysis. These results provide an important baseline to which future studies can be compared.Engineering and Applied Science

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes

Status Report of the DPHEP Study Group: Towards a Global Effort for Sustainable Data Preservation in High Energy Physics

Data from high-energy physics (HEP) experiments are collected with significant financial and human effort and are mostly unique. An inter-experimental study group on HEP data preservation and long-term analysis was convened as a panel of the International Committee for Future Accelerators (ICFA). The group was formed by large collider-based experiments and investigated the technical and organisational aspects of HEP data preservation. An intermediate report was released in November 2009 addressing the general issues of data preservation in HEP. This paper includes and extends the intermediate report. It provides an analysis of the research case for data preservation and a detailed description of the various projects at experiment, laboratory and international levels. In addition, the paper provides a concrete proposal for an international organisation in charge of the data management and policies in high-energy physics