Casimir forces on a silicon micromechanical chip

Quantum fluctuations give rise to van der Waals and Casimir forces that dominate the interaction between electrically neutral objects at sub-micron separations. Under the trend of miniaturization, such quantum electrodynamical effects are expected to play an important role in micro- and nano-mechanical devices. Nevertheless, utilization of Casimir forces on the chip level remains a major challenge because all experiments so far require an external object to be manually positioned close to the mechanical element. Here, by integrating a force-sensing micromechanical beam and an electrostatic actuator on a single chip, we demonstrate the Casimir effect between two micromachined silicon components on the same substrate. A high degree of parallelism between the two near-planar interacting surfaces can be achieved because they are defined in a single lithographic step. Apart from providing a compact platform for Casimir force measurements, this scheme also opens the possibility of tailoring the Casimir force using lithographically defined components of non-conventional shapes

Accelerating Low Carbon Development in the World’s Cities

Cities are engines of economic growth and social change. About 85% of global GDP in 2015 was generated in cities. By 2050, two-thirds of the global population will live in urban areas. Compact, connected and efficient cities can generate stronger growth and job creation, alleviate poverty and reduce investment costs, as well as improve quality of life through lower air pollution and traffic congestion. Better, more resilient models of urban development are particularly critical for rapidly urbanizing cities in the developing world. International city networks, such as the C40 Cities Climate Leadership Group, Local Governments for Sustainability (ICLEI) and United Cities and Local Governments (UCLG), are scaling up the sharing of best practices and developing initiatives to facilitate new flows of finance, enabling more ambitious action on climate change. Altogether, low-carbon urban actions available today could generate a stream of savings in the period to 2050 with a current value of US$16.6 trillion

Human preferences for sexually dimorphic faces may be evolutionarily novel

This article has been made available through the Brunel Open Access Publishing Fund.A large literature proposes that preferences for exaggerated sex typicality in human faces (masculinity/femininity) reflect a long evolutionary history of sexual and social selection. This proposal implies that dimorphism was important to judgments of attractiveness and personality in ancestral environments. It is difficult to evaluate, however, because most available data come from largescale, industrialized, urban populations. Here, we report the results for 12 populations with very diverse levels of economic development. Surprisingly, preferences for exaggerated sex-specific traits are only found in the novel, highly developed environments. Similarly, perceptions that masculine males look aggressive increase strongly with development, specifically, urbanization. These data challenge the hypothesis that facial dimorphism was an important ancestral signal of heritable mate value. One possibility is that highly developed environments provide novel opportunities to discern relationships between facial traits and behavior by exposing individuals to large numbers of unfamiliar faces, revealing patterns too subtle to detect with smaller samples

The Search for Higher TcT_c in Houston

It is a great pleasure to be invited to join the chorus on this auspicious occasion to celebrate Professor K. Alex Mueller's 90th birthday by Professors Annette Bussman-Holder, Hugo Keller, and Antonio Bianconi. As a student in high temperature superconductivity, I am forever grateful to Professor Alex Mueller and Dr. Georg Bednorz "for their important breakthrough in the discovery of superconductivity in the ceramic materials" in 1986 as described in the citation of their 1987 Nobel Prize in Physics. It is this breakthrough discovery that has ushered in the explosion of research activities in high temperature superconductivity (HTS) and has provided immense excitement in HTS science and technology in the ensuing decades till now. Alex has not been resting on his laurels and has continued to search for the origin of the unusual high temperature superconductivity in cuprates.Comment: Dedicated to Alex Mueller, whose "important breakthrough in the discovery of superconductivity in ceramic materials" in 1986 has changed the world of superconductivit

MultiMetEval: comparative and multi-objective analysis of genome-scale metabolic models

Comparative metabolic modelling is emerging as a novel field, supported by the development of reliable and standardized approaches for constructing genome-scale metabolic models in high throughput. New software solutions are needed to allow efficient comparative analysis of multiple models in the context of multiple cellular objectives. Here, we present the user-friendly software framework Multi-Metabolic Evaluator (MultiMetEval), built upon SurreyFBA, which allows the user to compose collections of metabolic models that together can be subjected to flux balance analysis. Additionally, MultiMetEval implements functionalities for multi-objective analysis by calculating the Pareto front between two cellular objectives. Using a previously generated dataset of 38 actinobacterial genome-scale metabolic models, we show how these approaches can lead to exciting novel insights. Firstly, after incorporating several pathways for the biosynthesis of natural products into each of these models, comparative flux balance analysis predicted that species like Streptomyces that harbour the highest diversity of secondary metabolite biosynthetic gene clusters in their genomes do not necessarily have the metabolic network topology most suitable for compound overproduction. Secondly, multi-objective analysis of biomass production and natural product biosynthesis in these actinobacteria shows that the well-studied occurrence of discrete metabolic switches during the change of cellular objectives is inherent to their metabolic network architecture. Comparative and multi-objective modelling can lead to insights that could not be obtained by normal flux balance analyses. MultiMetEval provides a powerful platform that makes these analyses straightforward for biologists. Sources and binaries of MultiMetEval are freely available from https://github.com/PiotrZakrzewski/MetEv​al/downloads

Epigenetic memory in induced pluripotent stem cells.

Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer

The contractile actin-myosin cytoskeleton provides much of the force required for numerous cellular activities such as motility, adhesion, cytokinesis and changes in morphology. Key elements that respond to various signal pathways are the myosin II regulatory light chains (MLC), which participate in actin-myosin contraction by modulating the ATPase activity and consequent contractile force generation mediated by myosin heavy chain heads. Considerable effort has focussed on the role of MLC kinases, and yet the contributions of the myotonic dystrophy-related Cdc42-binding kinases (MRCK) proteins in MLC phosphorylation and cytoskeleton regulation have not been well characterized. In contrast to the closely related ROCK1 and ROCK2 kinases that are regulated by the RhoA and RhoC GTPases, there is relatively little information about the CDC42-regulated MRCKα, MRCKβ and MRCKγ members of the AGC (PKA, PKG and PKC) kinase family. As well as differences in upstream activation pathways, MRCK and ROCK kinases apparently differ in the way that they spatially regulate MLC phosphorylation, which ultimately affects their influence on the organization and dynamics of the actin-myosin cytoskeleton. In this review, we will summarize the MRCK protein structures, expression patterns, small molecule inhibitors, biological functions and associations with human diseases such as cancer

A powerful bursting radio source towards the Galactic Centre

Transient astronomical sources are typically powered by compact objects and usually signify highly explosive or dynamic events. While radio astronomy has an impressive record of obtaining high time resolution observations, usually it is achieved in quite narrow fields-of-view. Consequently, the dynamic radio sky is poorly sampled, in contrast to the situation in the X- and gamma-ray bands in which wide-field instruments routinely detect transient sources. Here we report a new transient source, GCRT J1745-3009, detected in 2002 during a moderately wide-field radio transient monitoring program of the Galactic center (GC) region at 0.33 GHz. The characteristics of its bursts are unlike those known for any other class of radio transient. If located in or near the GC, its brightness temperature (~10^16 K) and the implied energy density within GCRT J1745-3009 vastly exceeds that observed in most other classes of radio astronomical sources, and is consistent with coherent emission processes rarely observed. We conclude that GCRT J1745-3009 is the first member of a new class of radio transient sources, the first of possibly many new classes to be identified through current and upcoming radio surveys.Comment: 16 pages including 3 figures. Appears in Nature, 3 March 200

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression