WASP-34b: a near-grazing transiting sub-Jupiter-mass exoplanet in a hierarchical triple system

We report the discovery of WASP-34b, a sub-Jupiter-mass exoplanet transiting its 10.4-magnitude solar-type host star (1SWASP J110135.89-235138.4; TYC 6636-540-1) every 4.3177 days in a slightly eccentric orbit (e = 0.038±0.012). We find a planetary mass of 0.59±0.01 MJup and radius of 1.22-0.08+0.11 RJup. There is a linear trend in the radial velocities of 55±4 m s-1 y-1 indicating the presence of a long-period third body in the system with a mass ?0.45 MJup at a distance of ?1.2 AU from the host star. This third-body is either a low-mass star, a white dwarf, or another planet. The transit depth ((RP/Rstar)2 = 0.0126) and high impact parameter (b = 0.90) suggest that this could be the first known transiting exoplanet expected to undergo grazing transits, but with a confidence of only 80%. Radial velocity and photometric data are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/526/A130

Ultracam - An Ultra-Fast Triple-Beam CCD Camera

ULTRACAM is a high-speed three-colour CCD camera designed to provide imaging photometry at high temporal resolutions. The instrument is highly portable and will be used at a number of large telescopes around the world. ULTRACAM was successfully commissioned on the 4.2-m William Herschel Telescope on La Palma on 16 May 2002 over 3 months ahead of schedule and within budget. The instrument was funded by PPARC and designed and built by a consortium involving the Universities of Sheffield Southampton and the UKATC Edinburgh. We present an overview of the design and performance characteristics of ULTRACAM and highlight some of its most recent scientific results.

Optimised extraction of heterocyclic aromatic amines from blood using hollow fibre membrane liquid-phase microextraction and triple quadrupole mass spectrometry

Heterocyclic aromatic amines (HCA) are carcinogenic mutagens formed during cooking of proteinaceous foods, particularly meat. To assist in the ongoing search for biomarkers of HCA exposure in blood, a method is described for the extraction from human plasma of the most abundant HCAs: 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) (and its isomer 7,8-DiMeIQx), using Hollow Fibre Membrane Liquid-Phase Microextraction. This technique employs 2.5 cm lengths of porous polypropylene fibres impregnated with organic solvent to facilitate simultaneous extraction from an alkaline aqueous sample into a low volume acidic acceptor phase. This low cost protocol is extensively optimised for fibre length, extraction time, sample pH and volume. Detection is by UPLC-MS/MS using positive mode electrospray ionisation with a 3.4 min runtime, with optimum peak shape, sensitivity and baseline separation being achieved at pH 9.5. To our knowledge this is the first description of HCA chromatography under alkaline conditions. Application of fixed ion ratio tolerances for confirmation of analyte identity is discussed. Assay precision is between 4.5 and 8.8% while lower limits of detection between 2 and 5 pg/mL are below the concentrations postulated for acid-labile HCA-protein adducts in blood.

Enantioselective Assembly of a Ruthenium(II) Polypyridyl Complex into a Double Helix

Evolution can increase the complexity of matter by self-organization into helical architectures, the best example being the DNA double helix. One common aspect, apparently shared by most of these architectures, is the presence of covalent bonds within the helix backbone. Here, we report the unprecedented crystal structures of a metal complex that self-organizes into a continuous double helical structure, assembled by non-covalent building blocks. Built up solely by weak stacking interactions, this alternating tread stairs-like double helical assembly mimics the DNA double helix structure. Starting from a racemic mixture in aqueous solution, the ruthenium(II) polypyridyl complex forms two polymorphic structures of a left-handed double helical assembly of only the Λ-enantiomer. The stacking of the helices is different in both polymorphs: a crossed woodpile structure versus a parallel columnar stacking.

The fate of chemoresistance in triple negative breast cancer (TNBC)

Background: Treatment options for women presenting with triple negative breast cancer (TNBC) are limited due to the lack of a therapeutic target and as a result, are managed with standard chemotherapy such as paclitaxel (Taxol®). Following chemotherapy, the ideal tumour response is apoptotic cell death. Post-chemotherapy, cells can maintain viability by undergoing viable cellular responses such as cellular senescence, generating secretomes which can directly enhance the malignant phenotype. 
Scope of Review: How tumour cells retain viability in response to chemotherapeutic engagement is discussed. In addition we discuss the implications of this retained tumour cell viability in the context of the development of recurrent and metastatic TNBC disease. Current adjuvant and neo-adjuvant treatments available and the novel potential therapies that are being researched are also reviewed. 
Major conclusions: Cellular senescence and cytoprotective autophagy are potential mechanisms of chemoresistance in TNBC. These two non-apoptotic outcomes in response to chemotherapy are inextricably linked and are neglected outcomes of investigation in the chemotherapeutic arena. Cellular fate assessments may therefore have the potential to predict TNBC patient outcome. 
General Significance: Focusing on the fact that cancer cells can bypass the desired cellular apoptotic response to chemotherapy through cellular senescence and cytoprotective autophagy will highlight the importance of targeting non-apoptotic survival pathways to enhance chemotherapeutic efficacy

Hydrophilic Interaction Ultra-High Performance Liquid Chromatography Coupled with Triple-Quadrupole Mass Spectrometry for Determination of Nucleosides and Nucleobases in Animal Horns

Traditional Chinese Medicines (TCMs) derived from animal horns are one of the most important types of Chinese medicine. In the present study, a fast and sensitive analytical method was established for qualitative and quantitative determination of 14 nucleosides and nucleobases in animal horns using hydrophilic interaction ultra-high performance liquid chromatography coupled with triple-quadruple tandem mass spectrometry (HILIC-UPLC-QQQ-MS/MS) in selective reaction monitoring (SRM) mode. The method was optimized and validated, and showed good linearity, precision, repeatability, and accuracy. The method was successfully used to determine contents of the 14 nucleosides and nucleobases in 25 animal horn samples. Hierarchical clustering analysis (HCA) and principal component analysis (PCA) were performed and the 25 samples were thereby divided into two groups, which agreed with taxonomy. The method may enable quick and effective search of substitutes for precious horns.

Knowledge Transfer in Quadruple Helix Ecosystems: An Absorptive Capacity Perspective

Increased understanding of knowledge transfer (KT) from universities to the wider regional knowledge ecosystem offers opportunities for increased regional innovation and commercialisation. The aim of this article is to improve the understanding of the KT phenomena in an open innovation context where multiple diverse quadruple helix stakeholders are interacting. An absorptive capacity-based conceptual framework is proposed, using a priori constructs which portrays the multidimensional process of KT between universities and its constituent stakeholders in pursuit of open innovation and commercialisation. Given the lack of overarching theory in the field, an exploratory, inductive theory building methodology was adopted using semi-structured interviews, document analysis and longitudinal observation data over a three-year period. The findings identify five factors, namely human centric factors, organisational factors, knowledge characteristics, power relationships and network characteristics, which mediate both the ability of stakeholders to engage in KT and the effectiveness of knowledge acquisition, assimilation, transformation and exploitation. This research has implications for policy makers and practitioners by identifying the need to implement interventions to overcome the barriers to KT effectiveness between regional quadruple helix stakeholders within an open innovation ecosystem.

On the triple peaks of SNHunt248 in NGC 5806

We present our findings on a supernova (SN) impostor, SNHunt248, based on optical and near-IR data spanning ~15 yr before discovery, to ~1 yr post-discovery. The light curve displays three distinct peaks, the brightest of which is at MR ~ −15.0 mag. The post-discovery evolution is consistent with the ejecta from the outburst interacting with two distinct regions of circumstellar material. The 0.5–2.2 μm spectral energy distribution at −740 d is well-matched by a single 6700 K blackbody with log (L/L⊙) ~ 6.1. This temperature and luminosity support previous suggestions of a yellow hypergiant progenitor; however, we find it to be brighter than the brightest and most massive Galactic late-F to early-G spectral type hypergiants. Overall the historical light curve displays variability of up to ~ ± 1 mag. At current epochs (~1 yr post-outburst), the absolute magnitude (MR ~ − 9 mag) is just below the faintest observed historical absolute magnitude ~10 yr before discovery.

A BRCA1 deficient, NFκB driven immune signal predicts good outcome in triple negative breast cancer

Triple negative (TNBCs) and the closely related Basal-like (BLBCs) breast cancers are a loosely defined collection of cancers with poor clinical outcomes. Both show strong similarities with BRCA1-mutant breast cancers and BRCA1 dysfunction, or 'BRCAness', is observed in a large proportion of sporadic BLBCs. BRCA1 expression and function has been shown in vitro to modulate responses to radiation and chemotherapy. Exploitation of this knowledge in the treatment of BRCA1-mutant patients has had varying degrees of success. This reflects the significant problem of accurately detecting those patients with BRCA1 dysfunction. Moreover, not all BRCA1 mutations/loss of function result in the same histology/pathology or indeed have similar effects in modulating therapeutic responses. Given the poor clinical outcomes and lack of targeted therapy for these subtypes, a better understanding of the biology underlying these diseases is required in order to develop novel therapeutic strategies.We have discovered a consistent NFκB hyperactivity associated with BRCA1 dysfunction as a consequence of increased Reactive Oxygen Species (ROS). This biology is found in a subset of BRCA1-mutant and triple negative breast cancer cases and confers good outcome. The increased NFκB signalling results in an anti-tumour microenvironment which may allow CD8+ cytotoxic T cells to suppress tumour progression. However, tumours lacking this NFκB-driven biology have a more tumour-promoting environment and so are associated with poorer prognosis. Tumour-derived gene expression data and cell line models imply that these tumours may benefit from alternative treatment strategies such as reprogramming the microenvironment and targeting the IGF and AR signalling pathways.

The value of adjuvant radiotherapy on survival and recurrence in triple-negative breast cancer: a systematic review and meta-analysis of 5,507 patients

BACKGROUND: The value of adjuvant radiotherapy in triple negative breast cancer (TNBC) remains unclear. A systematic review and meta-analysis was conducted in TNBC patients to assess survival and recurrence outcomes associated with radiotherapy following either breast conserving therapy (BCT) or post-mastectomy radiotherapy (PMRT). METHODS: Four electronic databases were searched from January 2000 to November 2015 (PubMed, MEDLINE, EMBASE and Web of Science). Studies investigating overall survival and/or recurrence in TNBC patients according to radiotherapy administration were included. A random effects meta-analysis was conducted using mastectomy only patients as the reference.  RESULTS: Twelve studies were included. The pooled hazard ratio (HR) for locoregional recurrence comparing BCT and PMRT to mastectomy only was 0.61 (95% confidence interval [CI] 0.41-0.90) and 0.62 (95% CI 0.44-0.86), respectively. Adjuvant radiotherapy was not significantly associated with distant recurrence. The pooled HR for overall survival comparing BCT and PMRT to mastectomy only was 0.57 (95% CI 0.36-0.88) and HR 1.12 (95% CI 0.75, 1.69). Comparing PMRT to mastectomy only, tests for interaction were not significant for stage (p=0.98) or age at diagnosis (p=0.85). However, overall survival was improved in patients with late-stage disease (T3-4, N2-3) pooled HR 0.53 (95% CI 0.32-0.86), and women <40 years, pooled HR 0.30 (95% CI 0.11-0.82). CONCLUSIONS: Adjuvant radiotherapy was associated with a significantly lower risk of locoregional recurrence in TNBC patients, irrespective of the type of surgery. While radiotherapy was not consistently associated with an overall survival gain, benefits may be obtained in women with late-stage disease and younger patients. 

Understanding Quadruple Helix Relationships of University Technology Commercialisation: A Micro Level Approach

Given recent demands for more co-creational university technology commercialisation
processes involving industry and end users, this paper adopts a micro level approach to explore
the challenges faced by universities when managing quadruple helix stakeholders within the
technology commercialisation processes. To explore this research question, a qualitative
research methodology which relies upon comparative case analysis was adopted to explore the
technology commercialisation process in two universities within a UK region. The findings
revealed that university type impacts Quadruple Helix stakeholder salience and engagement
and consequently university technology commercialisation activities and process. This is
important as recent European regional policy fails to account for contextual influences when
promoting Quadruple Helix stakeholder relationships in co-creational university technology
commercialisation.

ARB: Phase II window of opportunity study of short-term preoperative treatment with enzalutamide in ER-positive and triple-negative breast cancer

The androgen receptor (AR) is expressed in 60-80% of breast cancers (BC) across all molecular phenotypes, with a higher incidence in oestrogen receptor positive (ER+) BC compared to ER negative tumours. In ER+ disease, AR-expression has been linked to endocrine resistance which might be reversed with combined treatment targeting ER and AR. In triple negative BCs (TNBC), preclinical and clinical investigations have described a subset of patients that express the AR and are sensitive to androgen blockade, providing a novel therapeutic target. Enzalutamide, a potent 2nd generation anti-androgen, has demonstrated substantial preclinical and clinical anti-tumour activity in AR+ breast cancer. Short-term preoperative window of opportunity studies are a validated strategy for novel treatments to provide proof-of-concept and define the most appropriate patient population by directly assessing treatment effects in tumour tissue before and after treatment. The ARB study aims to assess the anti-tumour effects of enzalutamide in early ER+ breast cancer and TNBC, to identify the optimal target population for further studies and to directly explore the biologic effects of enzalutamide on BC and stromal cells. Methods: ARB is an international, investigator sponsored WOO phase II study in women with newly diagnosed primary ER+ BC or AR+ TNBC of ≥ 1cm. The study has two cohorts. In the ER+ cohort, postmenopausal patients will be randomised 2:1 to receive either enzalutamide (160mg OD) plus exemestane (50mg OD) or exemestane (25mg OD). In the TNBC cohort, AR+ will receive single agent treatment with enzalutamide (160mg OD). Study treatment is planned for 15–29 days, followed by surgery or neo-adjuvant therapy. Tissue and blood samples are collected before treatment and on the last day of study treatment. The primary endpoint is inhibition of tumour-cell proliferation, as measured by change in Ki67 expression, determined centrally by 2 investigators. Secondary endpoints include induction of apoptosis (Caspase3), circulating hormone levels and safety. ARB aims to recruit ≈235 patients from ≈40 sites in the UK, Germany, Spain and USA. The study is open to recruitment.