Electrical resistance of individual defects at a topological insulator surface

Three-dimensional topological insulators host surface states with linear dispersion, which manifest as a Dirac cone. Nanoscale transport measurements provide direct access to the transport properties of the Dirac cone in real space and allow the detailed investigation of charge carrier scattering. Here, we use scanning tunnelling potentiometry to analyse the resistance of different kinds of defects at the surface of a (Bi0.53Sb0.47)2Te3 topological insulator thin film. The largest localized voltage drop we find to be located at domain boundaries in the topological insulator film, with a resistivity about four times higher than that of a step edge. Furthermore, we resolve resistivity dipoles located around nanoscale voids in the sample surface. The influence of such defects on the resistance of the topological surface state is analysed by means of a resistor network model. The effect resulting from the voids is found to be small compared to the other defects

Treatment of melanoma cells with the synthetic retinoid CD437 induces apoptosis via activation of AP-1 in vitro, and causes growth inhibition in xenografts in vivo

Human malignant melanoma is notoriously resistant to pharmacological modulation. We describe here for the first time that the synthetic retinoid CD437 has a strong dose-dependent antiproliferative effect on human melanoma cells (IC50: 5 x 10(-6) M) via the induction of programmed cell death, as judged by analysis of cell morphology, electron microscopical features, and DNA fragmentation. Programmed cell death was preceded by a strong activation of the AP-1 complex in CD437-treated cells as demonstrated by gel retardation and chloramphenicol transferase (CAT) assays. Northern blot analysis showed a time-dependent increase in the expression of c-fos and c-jun encoding components of AP-1, whereas bcl-2 and p53 mRNA levels remained constant. CD437 also exhibited a strong growth inhibitory effect on MeWo melanoma cells in a xenograft model. In tissue sections of CD437-treated MeWo tumors from these animals, apoptotic melanoma cells and c-fos overexpressing cells were colocalized by TdT-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) staining and in situ hybridization. Taken together, this report identifies CD437 as a retinoid that activates and upregulates the transcription factor AP-1, leading eventually to programmed cell death of exposed human melanoma cells in vitro and in vivo. Further studies are needed to evaluate whether synthetic retinoids such as CD437 represent a new class of retinoids, which may open up new ways to a more effective therapy of malignant melanoma

Candida albicans Isolates from the Gut of Critically Ill Patients Respond to Phosphate Limitation by Expressing Filaments and a Lethal Phenotype

Candida albicans is an opportunistic pathogen that proliferates in the intestinal tract of critically ill patients where it continues to be a major cause of infectious-related mortality. The precise cues that shift intestinal C. albicans from its ubiquitous indolent colonizing yeast form to an invasive and lethal filamentous form remain unknown. We have previously shown that severe phosphate depletion develops in the intestinal tract during extreme physiologic stress and plays a major role in shifting intestinal Pseudomonas aeruginosa to express a lethal phenotype via conserved phosphosensory-phosphoregulatory systems. Here we studied whether phosphate dependent virulence expression could be similarly demonstrated for C. albicans. C. albicans isolates from the stool of critically ill patients and laboratory prototype strains (SC5314, BWP17, SN152) were evaluated for morphotype transformation and lethality against C. elegans and mice during exposure to phosphate limitation. Isolates ICU1 and ICU12 were able to filament and kill C. elegans in a phosphate dependent manner. In a mouse model of intestinal phosphate depletion (30% hepatectomy), direct intestinal inoculation of C. albicans caused mortality that was prevented by oral phosphate supplementation. Prototype strains displayed limited responses to phosphate limitation; however, the pho4Δ mutant displayed extensive filamentation during low phosphate conditions compared to its isogenic parent strain SN152, suggesting that mutation in the transcriptional factor Pho4p may sensitize C. albicans to phosphate limitation. Extensive filamentation was also observed in strain ICU12 suggesting that this strain is also sensitized to phosphate limitation. Analysis of the sequence of PHO4 in strain ICU12, its transcriptional response to phosphate limitation, and phosphatase assays confirmed that ICU12 demonstrates a profound response to phosphate limitation. The emergence of strains of C. albicans with marked responsiveness to phosphate limitation may represent a fitness adaptation to the complex and nutrient scarce environment typical of the gut of a critically ill patient

What has changed in canine pyoderma? A narrative review

Canine pyoderma is a common presentation in small animal practice and frequently leads to prescription of systemic antimicrobial agents. A good foundation of knowledge on pyoderma was established during the 1970s and 1980s, when treatment of infection provided relatively few challenges. However, the ability to treat canine pyoderma effectively is now limited substantially by the emergence of multidrug-resistant, methicillin-resistant staphylococci (MRS) and, in some countries, by restrictions on antimicrobial prescribing for pets. The threat from rising antimicrobial resistance and the zoonotic potential of MRS add a new dimension of public health implications to the management of canine pyoderma and necessitate a revisit and the search for new best management strategies. This narrative review focusses on the impact of MRS on how canine pyoderma is managed and how traditional treatment recommendations need to be updated in the interest of good antimicrobial stewardship. Background information on clinical characteristics, pathogens, and appropriate clinical and microbiological diagnostic techniques, are reviewed in so far as they can support early identification of multidrug-resistant pathogens. The potential of new approaches for the control and treatment of bacterial skin infections is examined and the role of owner education and hygiene is highlighted. Dogs with pyoderma offer opportunities for good antimicrobial stewardship by making use of the unique accessibility of the skin through cytology, bacterial culture and topical therapy. In order to achieve long term success and to limit the spread of multidrug resistance, there is a need to focus on identification and correction of underlying diseases that trigger pyoderma in order to avoid repeated treatment

new/s/leak - Information Extraction and Visualization for Investigative Data Journalists

We present new/s/leak, a novel tool developed for and with the help of journalists, which enables the automatic analysis and discovery of newsworthy stories from large textual datasets. We rely on different NLP preprocessing steps such named entity tagging, extraction of time expressions, entity networks, relations and metadata. The system features an intuitive web-based user interface based on network visualization combined with data exploring methods and various search and faceting mechanisms. We report the current state of the software and exemplify it with the WikiLeaks PlusD (Cablegate) data

Guidance for Multi-Type Entity Graphs from Text Collections

The visual exploration of graphs encoding relationships between entities of multiple types (e.g., persons, locations,...) supports journalists in finding newsworthy information in large text collections. Journalists may have interest in certain entity types or their relations such as locations or person-person relations. This interest may change during the exploration process. The exploration of such large graphs is often supported by guidance using a degree-of-interest (DOI) function. Although many DOIs exist, they do not differentiate entity types, rely on additional data, or require complex settings overburding the journalists. We present a novel DOI for graphs with multiple types of entities. We show the interesting subgraph around the focal node and offer information about possible further steps. The user can interactively set her interest in entity types and entity relations. We apply our approach to a graph extracted from WikiLeaks PlusD Cablegate documents and report on journalists' feedback

new/s/leak – Information Extraction and Visualization for Investigative Data Journalists

We present new/s/leak, a novel tool developed for and with the help of journalists, which enables the automatic analysis and discovery of newsworthy stories from large textual datasets. We rely on different NLP preprocessing steps such named entity tagging, extraction of time expressions, entity networks, relations and metadata. The system features an intuitive web-based user interface based on network visualization combined with data exploring methods and various search and faceting mechanisms. We report the current state of the software and exemplify it with the WikiLeaks PlusD (Cablegate) data