Multiepoch Mulitwavelength Spectra and Models for Blazar 3C 279

Peer reviewe

How Ligands Illuminate GPCR Molecular Pharmacology

G protein-coupled receptors (GPCRs), which are modulated by a variety of endogenous and synthetic ligands, represent the largest family of druggable targets in the human genome. Recent structural and molecular studies have both transformed and expanded classical concepts of receptor pharmacology and have begun to illuminate the distinct mechanisms by which structurally, chemically, and functionally diverse ligands modulate GPCR function. These molecular insights into ligand engagement and action have enabled new computational methods and accelerated the discovery of novel ligands and tool compounds, especially for understudied and orphan GPCRs. These advances promise to streamline the development of GPCR-targeted medications. © 2017 Elsevier Inc

Stationary strings near a higher-dimensional rotating black hole

We study stationary string configurations in a space-time of a higher-dimensional rotating black hole. We demonstrate that the Nambu-Goto equations for a stationary string in the 5D Myers-Perry metric allow a separation of variables. We present these equations in the first-order form and study their properties. We prove that the only stationary string configuration which crosses the infinite red-shift surface and remains regular there is a principal Killing string. A worldsheet of such a string is generated by a principal null geodesic and a timelike at infinity Killing vector field. We obtain principal Killing string solutions in the Myers-Perry metrics with an arbitrary number of dimensions. It is shown that due to the interaction of a string with a rotating black hole there is an angular momentum transfer from the black hole to the string. We calculate the rate of this transfer in a spacetime with an arbitrary number of dimensions. This effect slows down the rotation of the black hole. We discuss possible final stationary configurations of a rotating black hole interacting with a string.Comment: 13 pages, contains additianal material at the end of Section 8, also small misprints are correcte

On the multiplicity of the O-star Cyg OB2 #8A and its contribution to the gamma-ray source 3EG J2033+4118

We present the results of an intensive spectroscopic campaign in the optical waveband revealing that Cyg OB2 #8A is an O6 + O5.5 binary system with a period of about 21.9 d. Cyg OB2 #8A is a bright X-ray source, as well as a non-thermal radio emitter. We discuss the binarity of this star in the framework of a campaign devoted to the study of non-thermal emitters, from the radio waveband to gamma-rays. In this context, we attribute the non-thermal radio emission from this star to a population of relativistic electrons, accelerated by the shock of the wind-wind collision. These relativistic electrons could also be responsible for a putative gamma-ray emission through inverse Compton scattering of photospheric UV photons, thus contributing to the yet unidentified EGRET source 3EG J2033+4118.Comment: 8 pages, 4 figures, conference on "The Multiwavelength Approach to Gamma-Ray Sources", to appear in Ap&S

Dynamical mean-field theory of spiking neuron ensembles: response to a single spike with independent noises

Dynamics of an ensemble of $N$-unit FitzHugh-Nagumo (FN) neurons subject to white noises has been studied by using a semi-analytical dynamical mean-field (DMF) theory in which the original $2 N$-dimensional {\it stochastic} differential equations are replaced by 8-dimensional {\it deterministic} differential equations expressed in terms of moments of local and global variables. Our DMF theory, which assumes weak noises and the Gaussian distribution of state variables, goes beyond weak couplings among constituent neurons. By using the expression for the firing probability due to an applied single spike, we have discussed effects of noises, synaptic couplings and the size of the ensemble on the spike timing precision, which is shown to be improved by increasing the size of the neuron ensemble, even when there are no couplings among neurons. When the coupling is introduced, neurons in ensembles respond to an input spike with a partial synchronization. DMF theory is extended to a large cluster which can be divided into multiple sub-clusters according to their functions. A model calculation has shown that when the noise intensity is moderate, the spike propagation with a fairly precise timing is possible among noisy sub-clusters with feed-forward couplings, as in the synfire chain. Results calculated by our DMF theory are nicely compared to those obtained by direct simulations. A comparison of DMF theory with the conventional moment method is also discussed.Comment: 29 pages, 2 figures; augmented the text and added Appendice

"That's the world standard": a critical ethnography of "Universal" knowledge

This paper analyzes how knowledge is reproduced as "universal" in contemporary higher education and how this production of universality influences the application of knowledge. Using a case study of clinical psychology, it describes the results of over two years of ethnographic fieldwork in a university and professional settings in Singapore with short comparative field studies in Australia and the Netherlands. The results provide critical insights into the cultural effects and knowledge contestations within transnational higher education

Hyperbaric oxygen therapy to treat acute sport-related traumatic brain injuries: A case series

We report on hyperbaric oxygen (HBO2) therapy used to improve postinjury outcomes in eight acutely concussed high school student-athletes (5 males, 3 females, mean age = 16.0 ± 1.2 years). Patients were randomly assigned into one of three intervention groups: (a) HBO2 therapy; (b) hyperbaric therapy with compressed medical-grade air (HBA); or (c) normobaric 100% O2 therapy. All patients completed five 1-hr treatments within the first 10 days following his or her concussion. Main outcome measures included mental status examination, symptom burden, and the number of days from injury until the physician permitted the student-athlete to return to activity. Patients receiving HBO2 treatment experienced the greatest absolute symptom reduction over the five treatment sessions. No meaningful differences were found in mental status examination. All participants returned to activity in a similar timeframe. HBO2 therapy may be an effective option for the acute treatment of postconcussion symptoms, particularly in young athletes presenting with a high symptom burden

Comparison of s- and d-wave gap symmetry in nonequilibrium superconductivity

Recent application of ultrafast pump/probe optical techniques to superconductors has renewed interest in nonequilibrium superconductivity and the predictions that would be available for novel superconductors, such as the high-Tc cuprates. We have reexamined two of the classical models which have been used in the past to interpret nonequilibrium experiments with some success: the mu* model of Owen and Scalapino and the T* model of Parker. Predictions depend on pairing symmetry. For instance, the gap suppression due to excess quasiparticle density n in the mu* model, varies as n^{3/2} in d-wave as opposed to n for s-wave. Finally, we consider these models in the context of S-I-N tunneling and optical excitation experiments. While we confirm that recent pump/probe experiments in YBCO, as presently interpreted, are in conflict with d-wave pairing, we refute the further claim that they agree with s-wave.Comment: 14 pages, 11 figure

Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer: a systematic review and economic analysis

Background Breast cancer and its treatment can have an impact on health-related quality of life and survival. Tumour profiling tests aim to identify whether or not women need chemotherapy owing to their risk of relapse. Objectives To conduct a systematic review of the effectiveness and cost-effectiveness of the tumour profiling tests oncotype DX® (Genomic Health, Inc., Redwood City, CA, USA), MammaPrint® (Agendia, Inc., Amsterdam, the Netherlands), Prosigna® (NanoString Technologies, Inc., Seattle, WA, USA), EndoPredict® (Myriad Genetics Ltd, London, UK) and immunohistochemistry 4 (IHC4). To develop a health economic model to assess the cost-effectiveness of these tests compared with clinical tools to guide the use of adjuvant chemotherapy in early-stage breast cancer from the perspective of the NHS and Personal Social Services. Design A systematic review and health economic analysis were conducted. Review methods The systematic review was partially an update of a 2013 review. Nine databases were searched in February 2017. The review included studies assessing clinical effectiveness in people with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative, stage I or II cancer with zero to three positive lymph nodes. The economic analysis included a review of existing analyses and the development of a de novo model. Results A total of 153 studies were identified. Only one completed randomised controlled trial (RCT) using a tumour profiling test in clinical practice was identified: Microarray In Node-negative Disease may Avoid ChemoTherapy (MINDACT) for MammaPrint. Other studies suggest that all the tests can provide information on the risk of relapse; however, results were more varied in lymph node-positive (LN+) patients than in lymph node-negative (LN0) patients. There is limited and varying evidence that oncotype DX and MammaPrint can predict benefit from chemotherapy. The net change in the percentage of patients with a chemotherapy recommendation or decision pre/post test ranged from an increase of 1% to a decrease of 23% among UK studies and a decrease of 0% to 64% across European studies. The health economic analysis suggests that the incremental cost-effectiveness ratios for the tests versus current practice are broadly favourable for the following scenarios: (1) oncotype DX, for the LN0 subgroup with a Nottingham Prognostic Index (NPI) of > 3.4 and the one to three positive lymph nodes (LN1–3) subgroup (if a predictive benefit is assumed); (2) IHC4 plus clinical factors (IHC4+C), for all patient subgroups; (3) Prosigna, for the LN0 subgroup with a NPI of > 3.4 and the LN1–3 subgroup; (4) EndoPredict Clinical, for the LN1–3 subgroup only; and (5) MammaPrint, for no subgroups. Limitations There was only one completed RCT using a tumour profiling test in clinical practice. Except for oncotype DX in the LN0 group with a NPI score of > 3.4 (clinical intermediate risk), evidence surrounding pre- and post-test chemotherapy probabilities is subject to considerable uncertainty. There is uncertainty regarding whether or not oncotype DX and MammaPrint are predictive of chemotherapy benefit. The MammaPrint analysis uses a different data source to the other four tests. The Translational substudy of the Arimidex, Tamoxifen, Alone or in Combination (TransATAC) study (used in the economic modelling) has a number of limitations. Conclusions The review suggests that all the tests can provide prognostic information on the risk of relapse; results were more varied in LN+ patients than in LN0 patients. There is limited and varying evidence that oncotype DX and MammaPrint are predictive of chemotherapy benefit. Health economic analyses indicate that some tests may have a favourable cost-effectiveness profile for certain patient subgroups; all estimates are subject to uncertainty. More evidence is needed on the prediction of chemotherapy benefit, long-term impacts and changes in UK pre-/post-chemotherapy decisions. Study registration This study is registered as PROSPERO CRD42017059561. Funding The National Institute for Health Research Health Technology Assessment programme