Observation of Andreev Reflection Enhanced Shot Noise

We have experimentally investigated the quasiparticle shot noise in NbN/MgO/NbN superconductor - insulator - superconductor tunnel junctions. The observed shot noise is significantly larger than theoretically expected. We attribute this to the occurrence of multiple Andreev reflection processes in pinholes present in the MgO barrier. This mechanism causes the current to flow in large charge quanta (Andreev clusters), with a voltage dependent average value of m = 1+ 2 Delta/eV times the electron charge. Because of this charge enhancement effect, the shot noise is increased by the factor m.Comment: 4 pages, 5 figures include

Sphingosine 1-Phosphate Receptor 2 Signals Through Leukemia-Associated RhoGEF (LARG), to Promote Smooth Muscle Cell Differentiation

The goals of this study were to identify the signaling pathway by which S1P activates RhoA in SMC and to evaluate the contribution of this pathway to the regulation of SMC phenotype

Chapter 15 - National and sub-national policies and institutions

This chapter assesses national and sub-national mitigation policies and their institutional settings. There has been a marked increase in national policies and legislation on climate change since the AR4 with a diversity of approaches and a multiplicity of objectives (see Section 15.2). However, Figure 1.9 of Chapter 1 suggests that these policies, taken together, have not yet achieved a substantial deviation in emissions from the past trend. Limiting concentrations to levels that would be consistent with a likely probability of maintaining temperature increases below 2 degrees C this century (scenarios generally in the range of 430-480 ppmv CO2eq) would require that emissions break from these trends and be decreased substantially. In contrast, concentrations exceed 1000 ppmv CO2eq by 2100 in many baseline scenarios (that is, scenarios without additional efforts to reduce emissions). The literature on mitigation scenarios provides a wide range of CO2 shadow price levels consistent with these goals, with estimates of less than US$50/tCO2 in 2020 in many studies and exceeding US$100/tCO2 in others, assuming a globally-efficient and immediate effort to reduce emissions. These shadow prices exhibit a strongly increasing trend thereafter. Policies and instruments are assessed in this light. Section 15.2 assesses the role of institutions and governance. Section 15.3 lays out the classification of policy instruments and packages, while 15.4 discusses the methodologies used to evaluate policies and institutions. The performance of various policy instruments and measures are individually assessed in Sections 15.5 and 15.6. The two main types of economic instruments are price instruments, that is, taxes and subsidies (including removal of subsidies on fossil fuels), and quantity instruments - emission-trading systems. These are assessed in Sections 15.5.2 and 15.5.3 respectively. An important feature of both these instruments is that they can be applied at a very broad, economy-wide scale. This is in contrast to the regulation and information policies and voluntary agreements which are usually sector- specific. These policies are assessed in Sections 15.5.4, 15.5.5, and 15.5.7. Government provision and planning is discussed in 15.5.6. The next section, 15.6, provides a focused discussion on technology policy including research and development and the deployment and diffusion of clean energy technologies. In addition to technology policy, longer-term effects of the policies assessed in Section 15.5 are addressed in Section 15.6. Both these sections, 15.5 and 15.6, bring together lessons from policies and policy packages used at the sectoral level from Chapters 7 (Energy), 8 (Transport), 9 (Buildings), 10 (Industry), 11 (Agriculture, Forestry and Land Use) and Chapter 12 (Human Settlements, Infrastructure, and Spatial Planning). The following sections further assess the interaction among policy instruments, as they are not usually used in isolation, and the impacts of particular instruments depend on the entire package of policies and the institutional context. Section 15.7 reviews interactions, both beneficial and harmful, that may not have been planned. The presence of such interactions is in part a consequence of the multi-jurisdictional nature of climate governance as well as the use of multiple policy instruments within a jurisdiction. Section 15.8 examines the deliberate linkage of policies across national and sub-national jurisdictions. Other key issues are further discussed in dedicated sections. They are: the role of stakeholders including non-governmental organizations (NGOs) (15.9), capacity building (15.10), links between adaptation and mitigation policies (15.11), and investment and finance (15.12). Gaps in knowledge are collected in 15.13

The place of strategic environmental assessment in the privatised electricity industry

The private sector has given relatively little attention to the emergence of strategic environmental assessment (SEA); even recently privatised utilities, where SEA might be deemed particularly appropriate, and whose activities are likely to fall within the scope of the European Union SEA Directive, have shown less interest than might be expected. However, the global trend towards the privatisation of state-owned enterprises makes the adaptation of SEA towards these industries all the more pressing. This paper addresses the place that SEA might take within the electricity sector, taking the privatised UK electricity industry as an example. Particular challenges are posed by the radical restructuring of the industry, designed to introduce competitive behaviour, making the development of comprehensive SEA processes problematic, and requiring SEA to be placed in the context of corporate environmental policy and objectives.</p

The Small GTPase RhoA Localizes to the Nucleus and Is Activated by Net1 and DNA Damage Signals

Rho GTPases control many cellular processes, including cell survival, gene expression and migration. Rho proteins reside mainly in the cytosol and are targeted to the plasma membrane (PM) upon specific activation by guanine nucleotide exchange factors (GEFs). Accordingly, most GEFs are also cytosolic or associated with the PM. However, Net1, a RhoA-specific GEF predominantly localizes to the cell nucleus at steady-state. Nuclear localization for Net1 has been seen as a mechanism for sequestering the GEF away from RhoA, effectively rendering the protein inactive. However, considering the prominence of nuclear Net1 and the fact that a biological stimulus that promotes Net1 translocation out the nucleus to the cytosol has yet to be discovered, we hypothesized that Net1 might have a previously unidentified function in the nucleus of cells.Using an affinity precipitation method to pulldown the active form of Rho GEFs from different cellular fractions, we show here that nuclear Net1 does in fact exist in an active form, contrary to previous expectations. We further demonstrate that a fraction of RhoA resides in the nucleus, and can also be found in a GTP-bound active form and that Net1 plays a role in the activation of nuclear RhoA. In addition, we show that ionizing radiation (IR) specifically promotes the activation of the nuclear pool of RhoA in a Net1-dependent manner, while the cytoplasmic activity remains unchanged. Surprisingly, irradiating isolated nuclei alone also increases nuclear RhoA activity via Net1, suggesting that all the signals required for IR-induced nuclear RhoA signaling are contained within the nucleus.These results demonstrate the existence of a functional Net1/RhoA signaling pathway within the nucleus of the cell and implicate them in the DNA damage response

GPU-based ultra fast dose calculation using a finite pencil beam model

Online adaptive radiation therapy (ART) is an attractive concept that promises the ability to deliver an optimal treatment in response to the inter-fraction variability in patient anatomy. However, it has yet to be realized due to technical limitations. Fast dose deposit coefficient calculation is a critical component of the online planning process that is required for plan optimization of intensity modulated radiation therapy (IMRT). Computer graphics processing units (GPUs) are well-suited to provide the requisite fast performance for the data-parallel nature of dose calculation. In this work, we develop a dose calculation engine based on a finite-size pencil beam (FSPB) algorithm and a GPU parallel computing framework. The developed framework can accommodate any FSPB model. We test our implementation on a case of a water phantom and a case of a prostate cancer patient with varying beamlet and voxel sizes. All testing scenarios achieved speedup ranging from 200~400 times when using a NVIDIA Tesla C1060 card in comparison with a 2.27GHz Intel Xeon CPU. The computational time for calculating dose deposition coefficients for a 9-field prostate IMRT plan with this new framework is less than 1 second. This indicates that the GPU-based FSPB algorithm is well-suited for online re-planning for adaptive radiotherapy.Comment: submitted Physics in Medicine and Biolog

Rgnef (p190RhoGEF) Knockout Inhibits RhoA Activity, Focal Adhesion Establishment, and Cell Motility Downstream of Integrins

Cell migration is a highly regulated process that involves the formation and turnover of cell-matrix contact sites termed focal adhesions. Rho-family GTPases are molecular switches that regulate actin and focal adhesion dynamics in cells. Guanine nucleotide exchange factors (GEFs) activate Rho-family GTPases. Rgnef (p190RhoGEF) is a ubiquitous 190 kDa GEF implicated in the control of colon carcinoma and fibroblast cell motility.Rgnef exon 24 floxed mice (Rgnef(flox)) were created and crossed with cytomegalovirus (CMV)-driven Cre recombinase transgenic mice to inactivate Rgnef expression in all tissues during early development. Heterozygous Rgnef(WT/flox) (Cre+) crosses yielded normal Mendelian ratios at embryonic day 13.5, but Rgnef(flox/flox) (Cre+) mice numbers at 3 weeks of age were significantly less than expected. Rgnef(flox/flox) (Cre+) (Rgnef-/-) embryos and primary mouse embryo fibroblasts (MEFs) were isolated and verified to lack Rgnef protein expression. When compared to wildtype (WT) littermate MEFs, loss of Rgnef significantly inhibited haptotaxis migration, wound closure motility, focal adhesion number, and RhoA GTPase activation after fibronectin-integrin stimulation. In WT MEFs, Rgnef activation occurs within 60 minutes upon fibronectin plating of cells associated with RhoA activation. Rgnef-/- MEF phenotypes were rescued by epitope-tagged Rgnef re-expression.Rgnef-/- MEF phenotypes were due to Rgnef loss and support an essential role for Rgnef in RhoA regulation downstream of integrins in control of cell migration

Regaining momentum for international climate policy beyond Copenhagen

The 'Copenhagen Accord' fails to deliver the political framework for a fair, ambitious and legally-binding international climate agreement beyond 2012. The current climate policy regime dynamics are insufficient to reflect the realities of topical complexity, actor coalitions, as well as financial, legal and institutional challenges in the light of extreme time constraints to avoid 'dangerous' climate change of more than 2°C. In this paper we analyze these stumbling blocks for international climate policy and discuss alternatives in order to regain momentum for future negotiations

Feasible mitigation actions in developing countries

Energy use is not only crucial for economic development, but is also the main driver of greenhouse-gas emissions. Developing countries can reduce emissions and thrive only if economic growth is disentangled from energy-related emissions. Although possible in theory, the required energy-system transformation would impose considerable costs on developing nations. Developed countries could bear those costs fully, but policy design should avoid a possible 'climate rent curse', that is, a negative impact of financial inflows on recipients' economies. Mitigation measures could meet further resistance because of adverse distributional impacts as well as political economy reasons. Hence, drastically re-orienting development paths towards low-carbon growth in developing countries is not very realistic. Efforts should rather focus on 'feasible mitigation actions' such as fossil-fuel subsidy reform, decentralized modern energy and fuel switching in the power sector