A Tunable Two-impurity Kondo system in an atomic point contact

Two magnetic atoms, one attached to the tip of a Scanning Tunneling Microscope (STM) and one adsorbed on a metal surface, each constituting a Kondo system, have been proposed as one of the simplest conceivable systems potentially exhibiting quantum critical behaviour. We have succeeded in implementing this concept experimentally for cobalt dimers clamped between an STM tip and a gold surface. Control of the tip-sample distance with sub-picometer resolution allows us to tune the interaction between the two cobalt atoms with unprecedented precision. Electronic transport measurements on this two-impurity Kondo system reveal a rich physical scenario which is governed by a crossover from local Kondo screening to non-local singlet formation due to antiferromagnetic coupling as a function of separation of the cobalt atoms.Comment: 22 pages, 5 figure

The Formation and Evolution of the First Massive Black Holes

The first massive astrophysical black holes likely formed at high redshifts (z>10) at the centers of low mass (~10^6 Msun) dark matter concentrations. These black holes grow by mergers and gas accretion, evolve into the population of bright quasars observed at lower redshifts, and eventually leave the supermassive black hole remnants that are ubiquitous at the centers of galaxies in the nearby universe. The astrophysical processes responsible for the formation of the earliest seed black holes are poorly understood. The purpose of this review is threefold: (1) to describe theoretical expectations for the formation and growth of the earliest black holes within the general paradigm of hierarchical cold dark matter cosmologies, (2) to summarize several relevant recent observations that have implications for the formation of the earliest black holes, and (3) to look into the future and assess the power of forthcoming observations to probe the physics of the first active galactic nuclei.Comment: 39 pages, review for "Supermassive Black Holes in the Distant Universe", Ed. A. J. Barger, Kluwer Academic Publisher

Mycolactone-dependent depletion of endothelial cell thrombomodulin is strongly associated with fibrin deposition in Buruli ulcer lesions

A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM) expression on the surface of human dermal microvascular endothelial cells (HDMVEC) at doses as low as 2ng/ml and as early as 8hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques) was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this. Fibrin-driven tisischemia could contribute to the development of the tissue necrosis seen in BU lesions

Feasibility investigation of direct laser cutting process of metal foam with high pore density

To avoid damage to the pore structure of metal foam, a laser cutting process for efficiently and directly cutting metal foam into regular shapes is proposed. After analyzing the proposed laser cutting process, its effects when applied to three different types of metal material (copper, ferroalloy, and nickel) and two levels of pore density, namely 90 and 110 pores per inch (PPI), were investigated. The results show that metal foam with a good surface quality can be obtained without damaging the pore structure by using the proposed laser cutting process. Of the three metal types considered, the highest material removal rate (MRR) and material oxidation rate (MOR) were observed for ferroalloy foam. Of the two pore densities, metal foam of 90 PPI showed a larger material removal rate than metal foam of 110 PPI. The MRR and MOR increased with an increase in the laser output power and decrease in the scanning speed. Using a central composite experimental design method, optimized processing parameters of 26 W laser output power and 475 mm/s scanning speed were adopted to cut the metal foam with a high pore density

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

Background: An in-depth understanding of the fundamental principles that regulate thyroid hormone homeostasis is critical for the development of new diagnostic and treatment ap-proaches for patients with thyroid disease. Summary: Important clinical practices in use today for the treatment of patients with hypothy-roidism, hyperthyroidism, or thyroid cancer, are the result of laboratory discoveries made by scientists investigating the most basic aspects of thyroid structure and molecular biology. In this document, a panel of experts commissioned by the American Thyroid Association makes a se-ries of recommendations related to the study of thyroid hormone economy and action. These recommendations are intended to promote standardization of study design, which should in turn increase the comparability and reproducibility of experimental findings. Conclusions: It is expected that adherence to these recommendations by investigators in the field will facilitate progress towards a better understanding of the thyroid gland and thyroid hormone dependent processes

Shotgun Proteomics Identifies Serum Fibronectin as a Candidate Diagnostic Biomarker for Inclusion in Future Multiplex Tests for Ectopic Pregnancy

Ectopic pregnancy (EP) is difficult to diagnose early and accurately. Women often present at emergency departments in early pregnancy with a 'pregnancy of unknown location' (PUL), and diagnosis and exclusion of EP is challenging due to a lack of reliable biomarkers. The objective of this study was to identify novel diagnostic biomarkers for EP. Shotgun proteomics, incorporating combinatorial-ligand library pre-fractionation, was used to interrogate pooled sera (n = 40) from women undergoing surgery for EP, termination of viable intrauterine pregnancy and management of non-viable intrauterine pregnancy. Western blot was used to validate results in individual sera. ELISAs were developed to interrogate sera from women with PUL (n = 120). Sera were collected at time of first symptomatic presentation and categorized according to pregnancy outcome. The main outcome measures were differences between groups and area under the receiver operating curve (ROC). Proteomics identified six biomarker candidates. Western blot detected significant differences in levels of two of these candidates. ELISA of sera from second cohort revealed that these differences were only significant for one of these candidates, fibronectin. ROC analysis of ability of fibronectin to discriminate EP from other pregnancy outcomes suggested that fibronectin has diagnostic potential (ROC 0.6439; 95% CI 0.5090 to 0.7788; P>0.05), becoming significant when 'ambiguous' medically managed PUL excluded from analysis (ROC 0.6538; 95% CI 0.5158 to 0.7918; P<0.05). Fibronectin may make a useful adjunct to future multiplex EP diagnostic tests

Inhibition of Hypoxia-Inducible Factor-1α (HIF-1α) Protein Synthesis by DNA damage inducing agents

10.1371/journal.pone.0010522PLoS ONE55

Tests of chameleon gravity

Theories of modified gravity, where light scalars with non-trivial self-interactions and non-minimal couplings to matter—chameleon and symmetron theories—dynamically suppress deviations from general relativity in the solar system. On other scales, the environmental nature of the screening means that such scalars may be relevant. The highly-nonlinear nature of screening mechanisms means that they evade classical fifth-force searches, and there has been an intense effort towards designing new and novel tests to probe them, both in the laboratory and using astrophysical objects, and by reinterpreting existing datasets. The results of these searches are often presented using different parametrizations, which can make it difficult to compare constraints coming from different probes. The purpose of this review is to summarize the present state-of-the-art searches for screened scalars coupled to matter, and to translate the current bounds into a single parametrization to survey the state of the models. Presently, commonly studied chameleon models are well-constrained but less commonly studied models have large regions of parameter space that are still viable. Symmetron models are constrained well by astrophysical and laboratory tests, but there is a desert separating the two scales where the model is unconstrained. The coupling of chameleons to photons is tightly constrained but the symmetron coupling has yet to be explored. We also summarize the current bounds on f(R) models that exhibit the chameleon mechanism (Hu and Sawicki models). The simplest of these are well constrained by astrophysical probes, but there are currently few reported bounds for theories with higher powers of R. The review ends by discussing the future prospects for constraining screened modified gravity models further using upcoming and planned experiments

Acute posthypoxic myoclonus after cardiopulmonary resuscitation

<p>Abstract</p> <p>Background</p> <p>Acute posthypoxic myoclonus (PHM) can occur in patients admitted after cardiopulmonary resuscitation (CPR) and is considered to have a poor prognosis. The origin can be cortical and/or subcortical and this might be an important determinant for treatment options and prognosis. The aim of the study was to investigate whether acute PHM originates from cortical or subcortical structures, using somatosensory evoked potential (SEP) and electroencephalogram (EEG).</p> <p>Methods</p> <p>Patients with acute PHM (focal myoclonus or status myoclonus) within 72 hours after CPR were retrospectively selected from a multicenter cohort study. All patients were treated with hypothermia. Criteria for cortical origin of the myoclonus were: giant SEP potentials; or epileptic activity, status epilepticus, or generalized periodic discharges on the EEG (no back-averaging was used). Good outcome was defined as good recovery or moderate disability after 6 months.</p> <p>Results</p> <p>Acute PHM was reported in 79/391 patients (20%). SEPs were available in 51/79 patients and in 27 of them (53%) N20 potentials were present. Giant potentials were seen in 3 patients. EEGs were available in 36/79 patients with 23/36 (64%) patients fulfilling criteria for a cortical origin. Nine patients (12%) had a good outcome. A broad variety of drugs was used for treatment.</p> <p>Conclusions</p> <p>The results of this study show that acute PHM originates from subcortical, as well as cortical structures. Outcome of patients admitted after CPR who develop acute PHM in this cohort was better than previously reported in literature. The broad variety of drugs used for treatment shows the existing uncertainty about optimal treatment.</p