Spin-Polarization Mechanisms of the Nitrogen-Vacancy Center in Diamond

The nitrogen-vacancy (NV) center in diamond has shown great promise for quantum information due to the ease of initializing the qubit and of reading out its state. Here we show the leading mechanism for these effects gives results opposite from experiment; instead both must rely on new physics. Furthermore, NV centers fabricated in nanometer-sized diamond clusters are stable, motivating a bottom-up qubit approach, with the possibility of quite different optical properties to bulk.

New molecular targets in radiotherapy: DNA damage signalling and repair in targeted and non-targeted cells

Ionising radiation plays a key role in therapy due to its ability to directly induce DNA damage, in particular DNA double-strand breaks leading to cell death. Cells have multiple repair pathways which attempt to maintain genomic stability. DNA repair proteins have become key targets for therapy, using small molecule inhibitors, in combination with radiation and or chemotherapeutic agents as a means of enhancing cell killing. Significant advances in our understanding of the response of cells to radiation exposures has come from the observation of non-targeted effects where cells respond via mechanisms other than those which are a direct consequence of energy-dependent DNA damage. Typical of these is bystander signalling where cells respond to the fact that their neighbours have been irradiated. Bystander cells show a DNA damage response which is distinct from directly irradiated cells. In bystander cells, ATM- and Rad3-related (ATR) protein kinase-dependent signalling in response to stalled replication forks is an early event in the DNA damage response. The ATM protein kinase is activated downstream of ATR in bystander cells. This offers the potential for differential approaches for the modulation of bystander and direct effects with repair inhibitors which may impact on the response of tumours and on the protection of normal tissues during radiotherapy. (C) 2009 Elsevier B.V. All rights reserved.

A commentary on climate change, stone decay dynamics and the ‘greening’ of natural stone buildings: new perspectives on ‘deep wetting’

Environmental controls on stone decay processes are rapidly changing as a result of changing climate. UKCP09 projections for the 2020s (2010–2039) indicate that over much of the UK seasonality of precipitation will increase. Summer dryness and winter wetness are both set to increase, the latter linked to projected precipitation increases in autumn and spring months. If so, this could increase the time that stone structures remain wet and possibly the depth of moisture penetration, and it appears that building stone in Northern Ireland has already responded through an increased incidence of algal ‘greening’.This paper highlights the need for understanding the effects of climate change through a series of studies of largely sandstone structures. Current and projected climatic trends are therefore considered to have aesthetic, physical and chemical implications that are not currently built into our models of sandstone decay, especially with respect to the role played by deep-seated wetness on sandstone deterioration and decay progression and the feedbacks associated with, for example surface algal growth. In particular,it is proposed that algal biofilms will aid moisture retention and further facilitate moisture and dissolved salt penetration to depth. Thus, whilst the outer surface of stone may continue to experience frequent wetting and drying associated with individual precipitation events, the latter is less likely to be complete, and the interiors of building blocks may only experience wetting/drying in response to seasonal cycling. A possible consequence of deeper salt penetration could be a delay in the onset of surface deterioration,but more rapid and effective retreat once it commences as decay mechanisms ‘tap into a reservoir of deep salt’.

Runx2, p53, and pRB Status as Diagnostic Parameters for Deregulation of Osteoblast Growth and Differentiation in a New Pre-Chemotherapeutic Osteosarcoma Cell Line (OS1)

Osteosarcomas are the most prevalent primary bone tumors found in pediatric patients. To understand their molecular etiology, cell culture models are used to define disease mechanisms under controlled conditions. Many osteosarcoma cell lines (e.g., SAOS-2, U2OS, MG63) are derived from Caucasian patients. However, patients exhibit individual and ethnic differences in their responsiveness to irradiation and chemotherapy. This motivated the establishment of osteosarcoma cell lines (OS1, OS2, OS3) from three ethnically Chinese patients. OS1 cells, derived from a pre-chemotherapeutic tumor in the femur of a 6-year-old female, were examined for molecular markers characteristic for osteoblasts, stem cells, and cell cycle control by immunohistochemistry, reverse transcriptase-PCR, Western blotting and flow cytometry. OS I have aberrant G-banded karyotypes, possibly reflecting chromosomal abnormalities related to p53 deficiency. OS I had ossification profiles similar to human fetal osteoblasts rather than SAOS-2 which ossifies ab initio, (P

Reaction Mechanisms of Crotonaldehyde Hydrogenation on Pt(111): Density Functional Theory and Microkinetic Modeling

The microkinetics based on density function theory (DFT) calculations is utilized to investigate the reaction mechanism of crotonaldehyde hydrogenation on Pt(111) in the free energy landscape. The dominant reaction channel of each hydrogenation product is identified. Each of them begins with the first surface hydrogenation of the carbonyl oxygen of crotonaldehyde on the surface. A new mechanism, 1,4-addition mechanism generating enols (butenol), which readily tautomerize to saturated aldehydes (butanal), is identified as a primary mechanism to yield saturated aldehydes instead of the 3,4-addition via direct hydrogenation of the ethylenic bond. The calculation results also show that the full hydrogenation product, butylalcohol, mainly stems from the deep hydrogenation of surface open-shell dihydrogenation intermediates. It is found that the apparent barriers of the dominant pathways to yield three final products are similar on P(111), which makes it difficult to achieve a high selectivity to the desired crotyl alcohol (COL).

Non-genetic mechanisms communicating antibiotic resistance:rethinking strategies for antimicrobial drug design

Introduction: Infections by multidrug-resistant bacteria are of great concern worldwide. In many cases, resistance is not due to the presence of specific antibiotic-modifying enzymes, but rather associated with a general impermeability of the bacterial cell envelope. The molecular bases of this intrinsic resistance are not completely understood. Moreover, horizontal gene transfers cannot solely explain the spread of intrinsic resistance among bacterial strains. Areas covered: This review focuses on the increased intrinsic antibiotic resistance mediated by small molecules. These small molecules can either be secreted from bacterial cells of the same or different species (e.g., indole, polyamines, ammonia, and the Pseudomonas quinolone signal) or be present in the bacterial cell milieu, whether in the environment, such as indole acetic acid and other plant hormones, or in human tissues and body fluids, such as polyamines. These molecules are metabolic byproducts that act as infochemicals and modulate bacterial responses toward antibiotics leading to increasing or decreasing resistance levels. Expert opinion: The non-genetic mechanisms of antibiotic response modulation and communication discussed in this review should reorient our thinking of the mechanisms of intrinsic resistance to antibiotics and its spread across bacterial cell populations. The identification of chemical signals mediating increased intrinsic antibiotic resistance will expose novel critical targets for the development of new antimicrobial strategies.

European Law and New Health Technologies

Health is a matter of fundamental importance in European societies, both as a human right in itself, and as a factor in a productive workforce and therefore a healthy economy. New health technologies promise improved quality of life for patients suffering from a range of diseases, and the potential for the prevention of incidence of disease in the future. At the same time, new health technologies pose significant challenges for governments, particularly in relation to ensuring the technologies are safe, effective, and provide appropriate value for (public) money.

To guard against the possible dangers arising from new health technologies, and to maximize the benefits, all European governments regulate their development, marketing, and public financing. In addition, several international institutions operating at European level, in particular the European Union, the Council of Europe, and the European Patent Office, have become involved in the regulation of new health technologies. They have done so both through traditional 'command and control' legal measures, and through other regulatory mechanisms, including guidelines, soft law, 'steering' through redistribution of resources, and private or quasi-private regulation.

This collection analyses European law and its relationships with new health technologies. It uses interdisciplinary insights, particularly from law but also drawing on regulation theory, and science and technology studies, to shed new light on some of the key defining features of the relationships and especially the roles of risk, rights, ethics, and markets. The collection explores the way in which European law's engagement with new health technologies is to be legitimized, and discusses the implications for biological or biomedical citizenship.

Migratory navigation in birds: new opportunities in an era of fast-developing tracking technology

Birds have remained the dominant model for studying the mechanisms of animal navigation for decades, with much of what has been discovered coming from laboratory studies or model systems. The miniaturisation of tracking technology in recent years now promises opportunities for studying navigation during migration itself (migratory navigation) on an unprecedented scale. Even if migration tracking studies are principally being designed for other purposes, we argue that attention to salient environmental variables during the design or analysis of a study may enable a host of navigational questions to be addressed, greatly enriching the field. We explore candidate variables in the form of a series of contrasts (e. g. land vs ocean or night vs day migration), which may vary naturally between migratory species, populations or even within the life span of a migrating individual. We discuss how these contrasts might help address questions of sensory mechanisms, spatiotemporal representational strategies and adaptive variation in navigational ability. We suggest that this comparative approach may help enrich our knowledge about the natural history of migratory navigation in birds.

New susceptibility Loci associated with kidney disease in type 1 diabetes

Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ~2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P?=?1.2×10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P?=?2.0×10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-ß1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P?=?2.1×10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

Epigenetics in Vascular Disease - Therapeutic Potential of New Agents

Vascular diseases, including atherosclerosis, angioplasty-induced restenosis, vessel graft arteriosclerosis and hypertension-related stenosis, remain the most prevalent cause of death in the developed world. The aetiology of vascular diseases is multifactorial with both genetic and environmental factors. Recently, some of the most promising research identifies the epigenetic modification of the genome to play a major role in the disease development, linking the environmental insults with gene regulation. In this process, modification of DNA by methylation, and histone modification by acetylation, methylation, phosphorylation and/or SUMOylation are reported. Importantly, recent studies demonstrated that histone deacetylase (HDAC) enzymes are crucial in endothelial integrity, smooth muscle proliferation and in the formation of arteriosclerosis in animal models. The study of HDACs has shown remarkable specificity of HDAC family members in vascular cell growth/death that influences the disease process. Interestingly, the effects of HDACs on arteriosclerosis development in animal models have been observed after HDAC inhibition using specific inhibitors. This provides a new approach for the treatment of vascular disease using the agents that influence the epigenetic process in vascular cells. This review updates the rapid advances in epigenetics of vascular diseases focusing on the role of HDAC family in atherosclerosis. It will also discuss the underlying mechanisms of histone acetylation in vascular cells and highlight the therapeutic potential of such agents.

Chaotropic and hydrophobic stress mechanisms of antifungal substances

Growth and metabolism of fungi can be curtailed by chaotropic solutes and hydrophobic substances, both of which can weaken or inhibit non-covalent interactions within and between macromolecular systems. Here we explore the potential to utilize the fungistatic and fungicidal activities of such stressors as the basis for commercial formulations. A method was developed for the quantification of chaotropicity, which can be used for chemically diverse substances, in order elucidate roles of chaotropicity and hydrophobicity in microbial ecology (both of which are sufficiently potent to limit the Earth’s microbial biosphere). A large number of naturally occurring substances act as chaotropic or hydrophobic stressors including aliphatic alcohols, salts such as MgCl2, aromatics such as phenol, and hydrocarbons such as hexane and octene. We suggest that these stress parameters provide the (hitherto unidentified) modes-of-action for some extant antifungal products. The findings are discussed in relation to the development of a new generation of antifungals.

A New Mechanism for Hydroxyl Radical Production in Irradiated Nanoparticle Solutions

The absolute yield of hydroxyl radicals per unit of deposited X-ray energy is determined for the first time for irradiated aqueous solutions containing metal nanoparticles based on a “reference” protocol. Measurements are made as a function of dose rate and nanoparticle concentration. Possible mechanisms for hydroxyl radical production are considered in turn: energy deposition in the nanoparticles followed by its transport into the surrounding environment is unable to account for observed yield whereas energy deposition in the water followed by a catalytic-like reaction at the water-nanoparticle interface can account for the total yield and its dependence on dose rate and nanoparticle concentration. This finding is important because current models used to account for nanoparticle enhancement to radiobiological damage only consider the primary interaction with the nanoparticle, not with the surrounding media. Nothing about the new mechanism appears to be specific to gold, the main requirements being the formation of a structured water layer in the vicinity of the nanoparticle possibly through the interaction of its charge and the water dipoles. The massive hydroxyl radical production is relevant to a number of application fields, particularly nanomedicine since the hydroxyl radical is responsible for the majority of radiation-induced DNA damage.

Old truths and new politics:Does truth commission 'publicness' impact democratization?

This article analyzes the relationship between truth and politics by asking whether the 'publicness' of a truth commission - defined by whether it has public hearings, releases a public report, and names perpetrators - contributes to democratization. The article reviews scholarship relevant to the potential democratizing effects of truth commissions and derives mechanisms that help explain this relationship. Work from the transitional justice field as well as democratization and political transition more generally is considered. Using a newly-constructed Truth Commission Publicness Dataset (TCPD), the analysis finds that even after statistically controlling for initial levels of democracy, democratic trends in the years prior to a commission, level of wealth, amnesties and/or trials, the influence of the South African Truth and Reconciliation Commission, and different cutoff points for measuring democratization across a number of models, more publicness predicts higher levels of democracy years after the commission has finished its work. The more public a truth commission is, the more it will contribute to democratization. The finding that more public truth commissions are associated with higher levels of democratization indicates particular strategies that policymakers, donors, and civil society activists may take to improve prospects for democracy in a country planning a truth commission in the wake of violence and/or government abuse. © The Author(s) 2012.