Anomalous Nematic States in High Half-Filled Landau Levels.

It is well established that the ground states of a two-dimensional electron gas with half-filled high (N≥2) Landau levels are compressible charge-ordered states, known as quantum Hall stripe (QHS) phases. The generic features of QHSs are a maximum (minimum) in a longitudinal resistance R_{xx} (R_{yy}) and a nonquantized Hall resistance R_{H}. Here, we report on emergent minima (maxima) in R_{xx} (R_{yy}) and plateaulike features in R_{H} in half-filled N≥3 Landau levels. Remarkably, these unexpected features develop at temperatures considerably lower than the onset temperature of QHSs, suggestive of a new ground state.

Electron-Hole Asymmetric Chiral Breakdown of Reentrant Quantum Hall States.

Reentrant integer quantum Hall (RIQH) states are believed to be correlated electron solid phases, although their microscopic description remains unclear. As bias current increases, longitudinal and Hall resistivities measured for these states exhibit multiple sharp breakdown transitions, a signature unique to RIQH states. A comparison of RIQH breakdown characteristics at multiple voltage probes indicates that these signatures can be ascribed to a phase boundary between broken-down and unbroken regions, spreading chirally from source and drain contacts as a function of bias current and passing voltage probes one by one. The chiral sense of the spreading is not set by the chirality of the edge state itself, instead depending on electron- or holelike character of the RIQH state.

Optical Emission Spectroscopy Study of Competing Phases of Electrons in the Second Landau Level.

Quantum phases of electrons in the filling factor range 2≤ν≤3 are probed by the weak optical emission from the partially populated second Landau level and spin wave measurements. Observations of optical emission include a multiplet of sharp peaks that exhibit a strong filling factor dependence. Spin wave measurements by resonant inelastic light scattering probe breaking of spin rotational invariance and are used to link this optical emission with collective phases of electrons. A remarkably rapid interplay between emission peak intensities manifests phase competition in the second Landau level.

708 Common and 2010 rare DISC1 locus variants identified in 1542 subjects: analysis for association with psychiatric disorder and cognitive traits.

A balanced t(1;11) translocation that transects the Disrupted in schizophrenia 1 (DISC1) gene shows genome-wide significant linkage for schizophrenia and recurrent major depressive disorder (rMDD) in a single large Scottish family, but genome-wide and exome sequencing-based association studies have not supported a role for DISC1 in psychiatric illness. To explore DISC1 in more detail, we sequenced 528 kb of the DISC1 locus in 653 cases and 889 controls. We report 2718 validated single-nucleotide polymorphisms (SNPs) of which 2010 have a minor allele frequency of <1%. Only 38% of these variants are reported in the 1000 Genomes Project European subset. This suggests that many DISC1 SNPs remain undiscovered and are essentially private. Rare coding variants identified exclusively in patients were found in likely functional protein domains. Significant region-wide association was observed between rs16856199 and rMDD (P=0.026, unadjusted P=6.3 × 10(-5), OR=3.48). This was not replicated in additional recurrent major depression samples (replication P=0.11). Combined analysis of both the original and replication set supported the original association (P=0.0058, OR=1.46). Evidence for segregation of this variant with disease in families was limited to those of rMDD individuals referred from primary care. Burden analysis for coding and non-coding variants gave nominal associations with diagnosis and measures of mood and cognition. Together, these observations are likely to generalise to other candidate genes for major mental illness and may thus provide guidelines for the design of future studies.

Successful treatment of cutaneous zygomycosis with extensive surgical debridement and oral posaconazole in an immunocompetent patient.

We describe a case of successful treatment of cutaneous zygomycosis using a combination of extensive surgical debridement and the oral antifungal agent, posaconazole.

Learning the hard way: the importance of accurate data.

AIM: The outcome of surgery for colorectal cancer in each unit in the UK is collated by the National Bowel Cancer Audit Project (NBOCAP). In 2008-2009 our unit had a raw 30-day postoperative mortality close to the national average, but when it was nationally adjusted it appeared to be an outlier. The purpose of this study was to identify reasons for this disparity. METHOD: All records were obtained for patients undergoing surgery for colorectal cancer over the 2 years. Data submitted to NBOCAP to determine adjusted rates were compared with actual data. RESULTS: There were major discordances between submitted and actual data for American Society of Anesthesiology grades and timing of surgery. This explained why the unit appeared to be an outlier. CONCLUSION: There is increasing emphasis on outcome of health service delivery, which has important implications. Submission of correct data is essential if objective comparison is to be made on which to base decisions on service delivery among units and within health regions.

Conserved features of cancer cells define their sensitivity to HAMLET-induced death; c-Myc and glycolysis.

HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here, we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small-hairpin RNA (shRNA) inhibition, proteomic and metabolomic technology, we identified the c-Myc oncogene as one essential determinant of HAMLET sensitivity. Increased c-Myc expression levels promoted sensitivity to HAMLET and shRNA knockdown of c-Myc suppressed the lethal response, suggesting that oncogenic transformation with c-Myc creates a HAMLET-sensitive phenotype. Furthermore, HAMLET sensitivity was modified by the glycolytic state of tumor cells. Glucose deprivation sensitized tumor cells to HAMLET-induced cell death and in the shRNA screen, hexokinase 1 (HK1), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 and hypoxia-inducible factor 1α modified HAMLET sensitivity. HK1 was shown to bind HAMLET in a protein array containing ∼8000 targets, and HK activity decreased within 15 min of HAMLET treatment, before morphological signs of tumor cell death. In parallel, HAMLET triggered rapid metabolic paralysis in carcinoma cells. Tumor cells were also shown to contain large amounts of oleic acid and its derivatives already after 15 min. The results identify HAMLET as a novel anti-cancer agent that kills tumor cells by exploiting unifying features of cancer cells such as oncogene addiction or the Warburg effect.

Can the use of a rapid polymerase chain screening method decrease the incidence of nosocomial meticillin-resistant Staphylococcus aureus?

Rapid detection of MRSA may be important for the control of MRSA spread in hospitals. The aim of this investigation was to compare the use of a rapid polymerase chain reaction (PCR) screening method with standard culture for the detection of meticillin-resistant Staphylococcus aureus (MRSA) colonisation and to determine its impact on the incidence of MRSA in two hospital wards. During the first phase of the investigation (four months), patients in a surgical ward were screened using the rapid PCR technique and patients in a medical/cardiology ward were screened with standard culture methods. During the second phase of the investigation (four months), MRSA screening methods were switched between the two wards. An audit of infection control practices on each ward was made at the end of each phase in order to check whether any changes had occurred that might influence the risks of MRSA transmission. Use of the rapid PCR method significantly reduced the median time between swabs being taken, to the results being telephoned to the wards (excluding weekends), from 47 to 21 h (P<0.001). However, comparison of MRSA incidence during use of PCR (20/1000 bed-days) and culture methods (22.1/1000 bed-days) revealed no significant difference in incidence on the surgical ward (P=0.69). Regarding the medical/cardiology ward, analysis of data was complicated by an increase in the detection of MRSA during the PCR phase (P<0.05). The study demonstrated that rapid PCR can significantly reduce the turnaround times but reducing the time between swabs being taken to results being telephoned to the ward is still not sufficient to limit the transmission of MRSA.

SPINE bioinformatics and data-management aspects of high-throughput structural biology.

SPINE (Structural Proteomics In Europe) was established in 2002 as an integrated research project to develop new methods and technologies for high-throughput structural biology. Development areas were broken down into workpackages and this article gives an overview of ongoing activity in the bioinformatics workpackage. Developments cover target selection, target registration, wet and dry laboratory data management and structure annotation as they pertain to high-throughput studies. Some individual projects and developments are discussed in detail, while those that are covered elsewhere in this issue are treated more briefly. In particular, this overview focuses on the infrastructure of the software that allows the experimentalist to move projects through different areas that are crucial to high-throughput studies, leading to the collation of large data sets which are managed and eventually archived and/or deposited.

Merkel cell carcinoma in South East Scotland, 1993-2003.

BACKGROUND AND AIMS: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy. The aims of this study were to look at the incidence and distribution of MCC in a predominantly skin type I Caucasian population, review overall management of the disease and assess patient outcomes. METHODS: Cases were identified through the regional pathology database. Twenty patients were diagnosed with MCC over a 10-year period (1993-2003) and managed at the Regional Plastic Surgery Unit at St John's Hospital, Livingston. RESULTS: The disease incidence was found to be 0.133 per 100,000 per annum. All patients were Caucasian, seven males and 13 females (1:1.9 ratio). The mean age at presentation was 77 years (range 58-93 years). The majority of lesions were found to be stage IA (80%), located in the head and neck region. There were two cases (10%) with stage II disease and two (10%) with stage III disease (both with liver metastases) at the time of diagnosis. All patients were managed operatively. Seventeen of the 20 had wide local excisions; of the remaining three, two were only suitable for debulking procedures and one patient (stage II) had only a diagnostic biopsy, refusing intervention thereafter. One patient received adjuvant chemoradiotherapy. CONCLUSION: Surgery remains the mainstay of treatment but adjuvant therapy, in particular chemotherapy, is problematic in a frail, elderly population.

Crystal structure of Bacillus subtilis YckF: structural and functional evolution.

The crystal structure of the YckF protein from Bacillus subtilis was determined with MAD phasing and refined at 1.95A resolution. YckF forms a tight tetramer both in crystals and in solution. Conservation of such oligomerization in other phosphate sugar isomerases indicates that the crystallographically observed tetramer is physiologically relevant. The structure of YckF was compared to with its ortholog from Methanococcus jannaschii, MJ1247. Both of these proteins have phosphate hexulose isomerase activity, although neither of the organisms can utilize methane or methanol as source of energy and/or carbon. Extensive sequence and structural similarities with MJ1247 and with the isomerase domain of glucosamine-6-phosphate synthase from Escherichia coli allowed us to group residues contributing to substrate binding or catalysis. Few notable differences among these structures suggest possible cooperativity of the four active sites of the tetramer. Phylogenetic relationships between obligatory and facultative methylotrophs along with B. subtilis and E. coli provide clues about the possible evolution of genes as they loose their physiological importance.