Are the Perseus-Pisces chain and the Pavo-Indus wall connected?

A significant empty region was found between the southern Pavo- Indus (PI) wall and the northern Perseus-Pisces (PP) chain. This survey tests the reality of this void which may simply reflect previous poor sampling of the galaxies in this region. Redshifts for a magnitude selected sample of 379 galaxies were obtained covering the four UKST/SERC survey fields with Bt <= 17.0. All redshifts were obtained with the FLAIR multi-object spectroscopy system on the 1.2 m U.K. Schmidt Telescope at Siding Spring, Australia. Two highly significant density enhancements were found in the galaxy distribution at 133 Mpc and 200 Mpc (Ho=75 km/s/Mpc). We claim that no connexion exists between PP and PI. However, a southern extension of PP was detected and makes the total length of this chain of more than 150 Mpc.Comment: 14 pages, postscript including tables and figures

Hawking radiation by Kerr black holes and conformal symmetry

The exponential blueshift associated with the event horizon of a black hole makes conformal symmetry play a fundamental role in accounting for its thermal properties. Using a derivation based on two-point functions, we show that the spectrum of thermal radiation of scalar particles by Kerr (and Schwarzschild) black holes can be explicitly derived on the basis of a $2$-dimensional conformal symmetry arising in the wave equation near the horizon. This result reinforces the recently conjectured relation between Kerr geometry and a $2$-dimensional conformal field theory.Comment: Version published in Phys. Rev. Let

Nonminimal Couplings in the Early Universe: Multifield Models of Inflation and the Latest Observations

Models of cosmic inflation suggest that our universe underwent an early phase of accelerated expansion, driven by the dynamics of one or more scalar fields. Inflationary models make specific, quantitative predictions for several observable quantities, including particular patterns of temperature anistropies in the cosmic microwave background radiation. Realistic models of high-energy physics include many scalar fields at high energies. Moreover, we may expect these fields to have nonminimal couplings to the spacetime curvature. Such couplings are quite generic, arising as renormalization counterterms when quantizing scalar fields in curved spacetime. In this chapter I review recent research on a general class of multifield inflationary models with nonminimal couplings. Models in this class exhibit a strong attractor behavior: across a wide range of couplings and initial conditions, the fields evolve along a single-field trajectory for most of inflation. Across large regions of phase space and parameter space, therefore, models in this general class yield robust predictions for observable quantities that fall squarely within the "sweet spot" of recent observations.Comment: 17pp, 2 figs. References added to match the published version. Published in {\it At the Frontier of Spacetime: Scalar-Tensor Theory, Bell's Inequality, Mach's Principle, Exotic Smoothness}, ed. T. Asselmeyer-Maluga (Springer, 2016), pp. 41-57, in honor of Carl Brans's 80th birthda

Identification of novel small molecule inhibitors of adenovirus gene transfer using a high throughput screening approach

Due to many favourable attributes adenoviruses (Ads) are the most extensively used vectors for clinical gene therapy applications. However, following intravascular administration, the safety and efficacy of Ad vectors are hampered by the strong hepatic tropism and induction of a potent immune response. Such effects are determined by a range of complex interactions including those with neutralising antibodies, blood cells and factors, as well as binding to native cellular receptors (coxsackie adenovirus receptor (CAR), integrins). Once in the bloodstream, coagulation factor X (FX) has a pivotal role in determining Ad liver transduction and viral immune recognition. Due to difficulties in generating a vector devoid of multiple receptor binding motifs, we hypothesised that a small molecule inhibitor would be of value. Here, a pharmacological approach was implemented to block adenovirus transduction pathways. We developed a high throughput screening (HTS) platform to identify the small molecule inhibitors of FX-mediated Ad5 gene transfer. Using an in vitro fluorescence and cell-based HTS, we evaluated 10,240 small molecules. Following sequential rounds of screening, three compounds, T5424837, T5550585 and T5660138 were identified that ablated FX-mediated Ad5 transduction with low micromolar potency. The candidate molecules possessed common structural features and formed part of the one pharmacophore model. Focused, mini-libraries were generated with structurally related molecules and in vitro screening revealed novel hits with similar or improved efficacy. The compounds did not interfere with Ad5:FX engagement but acted at a subsequent step by blocking efficient intracellular transport of the virus. In vivo, T5660138 and its closely related analogue T5660136 significantly reduced Ad5 liver transgene expression at 48 h post-intravenous administration of a high viral dose (1 × 10&lt;sup&gt;11&lt;/sup&gt; vp/mouse). Therefore, this study identifies novel and potent small molecule inhibitors of the Ad5 transduction which may have applications in the Ad gene therapy setting

Progestogens in singleton gestations with preterm prelabor rupture of membranes: a systematic review and metaanalysis of randomized controlled trials

OBJECTIVE DATA: Preterm prelabor rupture of membranes occurs in 3% of all pregnancies. Neonatal benefit is seen in uninfected women who do not deliver immediately after preterm prelabor rupture of membranes. The purpose of this study was to evaluate whether the administration of progestogens in singleton pregnancies prolongs pregnancy after preterm prelabor rupture of membranes. STUDY: Searches were performed in MEDLINE, OVID, Scopus, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials with the use of a combination of keywords and text words related to "progesterone," "progestogen," "prematurity," and "preterm premature rupture of membranes" from the inception of the databases until January 2018. We included all randomized controlled trials of singleton gestations after preterm prelabor rupture of membranes that were randomized to either progestogens or control (either placebo or no treatment). Exclusion criteria were trials that included women who had contraindications to expectant management after preterm prelabor rupture of membranes (ie, chorioamnionitis, severe preeclampsia, and nonreassuring fetal status) and trials on multiple gestations. We planned to include all progestogens, including but not limited to 17-α hydroxyprogesterone caproate, and natural progesterone. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcome was latency from randomization to delivery. Metaanalysis was performed with the use of the random effects model of DerSimonian and Laird to produce relative risk with 95% confidence interval. Analysis was performed for each mode of progestogen administration separately. RESULTS: Six randomized controlled trials (n=545 participants) were included. Four of the included trials assessed the efficacy of 17-α hydroxyprogesterone caproate; 1 trial assessed rectal progestogen, and 1 trial had 3 arms that compared 17-α hydroxyprogesterone caproate, rectal progestogen, and placebo. The mean gestational age at time randomization was 26.9 weeks in the 17-α hydroxyprogesterone caproate group and 27.3 weeks in the control group. 17-α Hydroxyprogesterone caproate administration was not found to prolong the latency period between randomization and delivery (mean difference, 0.11 days; 95% confidence interval, -3.30 to 3.53). There were no differences in mean gestational age at delivery, mode of delivery, or maternal or neonatal outcomes between the 2 groups. Similarly, there was no difference in latency for those women who received rectal progesterone (mean difference, 4.00 days; 95% confidence interval, -0.72 to 8.72). CONCLUSION: Progestogen administration does not prolong pregnancy in singleton gestations with preterm prelabor rupture of membranes

Text and Transmission

The modern reader may encounter the Greek text of Euripides' surviving plays in many forms: in print either in complete editions or in separate editions of single plays published with translations or commentaries or both, and in digital form at well-known sites on the internet. When Euripides composed his plays, he is most likely to have written on a papyrus roll, although for rough drafts of small sections he could have used wax tablets, loose papyrus sheets, or pottery sherds. Although the papyrus rolls and early codices give us intriguing glimpses of the text of the Euripides plays up the seventh century CE, the surviving complete plays depend on the medieval textual tradition. For Euripides as for Aeschylus and Sophocles, Alexandrian scholars collected texts of as many plays as they could, comparing their titles to those known from the didascalic records. About seventy plays of Euripides never reached the medieval manuscript tradition

Designing personalised cancer treatments

The concept of personalised medicine for cancer is not new. It arguably began with the attempts by Salmon and Hamburger to produce a viable cellular chemosensitivity assay in the 1970s, and continues to this day. While clonogenic assays soon fell out of favour due to their high failure rate, other cellular assays fared better and although they have not entered widespread clinical practice, they have proved to be very useful research tools. For instance, the ATP-based chemosensitivity assay was developed in the early 1990s and is highly standardised. It has proved useful for evaluating new drugs and combinations, and in recent years has been used to understand the molecular basis of drug resistance and sensitivity to anti-cancer drugs. Recent developments allow unparalleled genotyping and phenotyping of tumours, providing a plethora of targets for the development of new cancer treatments. However, validation of such targets and new agents to permit translation to the clinic remains difficult. There has been one major disappointment in that cell lines, though useful, do not often reflect the behaviour of their parent cancers with sufficient fidelity to be useful. Low passage cell lines — either in culture or xenografts are being used to overcome some of these issues, but have several problems of their own. Primary cell culture remains useful, but large tumours are likely to receive neo-adjuvant treatment before removal and that limits the tumour types that can be studied. The development of new treatments remains difficult and prediction of the clinical efficacy of new treatments from pre-clinical data is as hard as ever. One lesson has certainly been that one cannot buck the biology — and that understanding the genome alone is not sufficient to guarantee success. Nowhere has this been more evident than in the development of EGFR inhibitors. Despite overexpression of EGFR by many tumour types, only those with activating EGFR mutations and an inability to circumvent EGFR blockade have proved susceptible to treatment. The challenge is how to use advanced molecular understanding with limited cellular assay information to improve both drug development and the design of companion diagnostics to guide their use. This has the capacity to remove much of the guesswork from the process and should improve success rates

Designing personalised cancer treatments

The concept of personalised medicine for cancer is not new. It arguably began with the attempts by Salmon and Hamburger to produce a viable cellular chemosensitivity assay in the 1970s, and continues to this day. While clonogenic assays soon fell out of favour due to their high failure rate, other cellular assays fared better and although they have not entered widespread clinical practice, they have proved to be very useful research tools. For instance, the ATP-based chemosensitivity assay was developed in the early 1990s and is highly standardised. It has proved useful for evaluating new drugs and combinations, and in recent years has been used to understand the molecular basis of drug resistance and sensitivity to anti-cancer drugs. Recent developments allow unparalleled genotyping and phenotyping of tumours, providing a plethora of targets for the development of new cancer treatments. However, validation of such targets and new agents to permit translation to the clinic remains difficult. There has been one major disappointment in that cell lines, though useful, do not often reflect the behaviour of their parent cancers with sufficient fidelity to be useful. Low passage cell lines — either in culture or xenografts are being used to overcome some of these issues, but have several problems of their own. Primary cell culture remains useful, but large tumours are likely to receive neo-adjuvant treatment before removal and that limits the tumour types that can be studied. The development of new treatments remains difficult and prediction of the clinical efficacy of new treatments from pre-clinical data is as hard as ever. One lesson has certainly been that one cannot buck the biology — and that understanding the genome alone is not sufficient to guarantee success. Nowhere has this been more evident than in the development of EGFR inhibitors. Despite overexpression of EGFR by many tumour types, only those with activating EGFR mutations and an inability to circumvent EGFR blockade have proved susceptible to treatment. The challenge is how to use advanced molecular understanding with limited cellular assay information to improve both drug development and the design of companion diagnostics to guide their use. This has the capacity to remove much of the guesswork from the process and should improve success rates

Recombination in the Open-Ended Value Landscape of Digital Innovation

Digital innovation introduces a new open-ended value landscape to anyone seeking to generate or capture new value. To understand this landscape, we distinguish between design recombination and use recombination, explore how they play out together, and redirect the attention from products and services toward digital resources. Digital resources serve as building-blocks in digital innovation, and they hold the potential to simultaneously be part of multiple value paths, offered through design recombination and assembled through use recombination. Building on this perspective, we offer the value spaces framework as a tool for better understanding value creation and capture in digital innovation. We illustrate the framework and offer the early contours of a research agenda for information systems researchers

Microflares in accretion disks

We have investigated the phenomenon of explosive chromospheric evaporation from an accretion disk as a mechanism for fast variability in accreting sources such as low mass X-ray binaries and active galactic nuclei. This has been done in the context of advection dominated accretion flows, allowing both high and low states to be considered. This mechanism can in principle produce sub-millisecond timescales in binaries and sub-minute timescales in active galaxies. However, even considering the possibility that large numbers of these microflares may be present simultaneously, the power emitted from these microflares probably amounts to only a small fraction of the total X-ray luminosity.Comment: 5 pages, 1 figure, uses older A&A class file; accepted for publication in A&