The Dark UNiverse Explorer (DUNE): Proposal to ESA's Cosmic Vision

The Dark UNiverse Explorer (DUNE) is a wide-field space imager whose primary goal is the study of dark energy and dark matter with unprecedented precision. For this purpose, DUNE is optimised for the measurement of weak gravitational lensing but will also provide complementary measurements of baryonic accoustic oscillations, cluster counts and the Integrated Sachs Wolfe effect. Immediate auxiliary goals concern the evolution of galaxies, to be studied with unequalled statistical power, the detailed structure of the Milky Way and nearby galaxies, and the demographics of Earth-mass planets. DUNE is an Medium-class mission which makes use of readily available components, heritage from other missions, and synergy with ground based facilities to minimise cost and risks. The payload consists of a 1.2m telescope with a combined visible/NIR field-of-view of 1 deg^2. DUNE will carry out an all-sky survey, ranging from 550 to 1600nm, in one visible and three NIR bands which will form a unique legacy for astronomy. DUNE will yield major advances in a broad range of fields in astrophysics including fundamental cosmology, galaxy evolution, and extrasolar planet search. DUNE was recently selected by ESA as one of the mission concepts to be studied in its Cosmic Vision programme.Comment: Accepted in Experimental Astronom

Increasing the Reliability of Adaptive Quadrature Using Explicit Interpolants

We present two new adaptive quadrature routines. Both routines differ from previously published algorithms in many aspects, most significantly in how they represent the integrand, how they treat non-numerical values of the integrand, how they deal with improper divergent integrals and how they estimate the integration error. The main focus of these improvements is to increase the reliability of the algorithms without significantly impacting their efficiency. Both algorithms are implemented in Matlab and tested using both the "families" suggested by Lyness and Kaganove and the battery test used by Gander and Gautschi and Kahaner. They are shown to be more reliable, albeit in some cases less efficient, than other commonly-used adaptive integrators.Comment: 32 pages, submitted to ACM Transactions on Mathematical Softwar

First microlensing candidate towards M31 from the Nainital Microlensing Survey

We report our first microlensing candidate NMS-E1 towards M31 from the data accumulated during the four years of Nainital Microlensing Survey. Cousin R and I band observations of ~13'x13' field in the direction of M31 have been carried out since 1998 and data is analysed using the pixel technique proposed by the AGAPE collaboration. NMS-E1 lies in the disk of M31 at \alpha = 0:43:33.3 and \delta = +41:06:44, about 15.5 arcmin to the South-East direction of the center of M31. The degenerate Paczy\'{n}ski fit gives a half intensity duration of ~59 days. The photometric analysis of the candidate shows that it reached R~20.1 mag at the time of maximum brightness and the colour of the source star was estimated to be (R-I)_0 ~ 1.1 mag. The microlensing candidate is blended by red variable stars; consequently the light curves do not strictly follow the characteristic Paczy\'{n}ski shape and achromatic nature. However its long period monitoring and similar behaviour in R and I bands supports its microlensing nature.Comment: no changes except typos corrected, to appear in A&

Interleukin-2 and histamine in combination inhibit tumour growth and angiogenesis in malignant glioma

Biotherapy including interleukin-2 (IL-2) treatment seems to be more effective outside the central nervous system when compared to the effects obtained when the same tumour is located intracerebrally. Recently published studies suggest that reduced activity of NK cells in tumour tissue can be increased by histamine. The present study was designed to determine whether IL-2 and histamine, alone or in combination, can induce anti-tumour effects in an orthotopic rat glioma model. One group of rats was treated with histamine alone (4 mg kg–1s.c. as daily injections from day 6 after intracranial tumour implantation), another group with IL-2 alone as a continuous subcutaneous infusion and a third group with both histamine and IL-2. The animals were sacrificed at day 24 after tumour implantation. IL-2 and histamine in combination significantly reduced tumour growth. The microvessel density was significantly reduced, an effect mainly affecting the small vessels. No obvious alteration in the pattern of VEGF mRNA expression was evident and no significant changes in apoptosis were observed. Neither IL-2 nor histamine alone caused any detectable effects on tumour growth. Histamine caused an early and pronounced decline in tumour blood flow compared to normal brain. The results indicate that the novel combination of IL-2 and histamine can be of value in reducing intracerebral tumour growth and, thus, it might be of interest to re-evaluate the therapeutic potential of biotherapy in malignant glioma. © 2000 Cancer Research Campaig

Perception and Processing of Faces in the Human Brain Is Tuned to Typical Feature Locations.

UNLABELLED: Faces are salient social stimuli whose features attract a stereotypical pattern of fixations. The implications of this gaze behavior for perception and brain activity are largely unknown. Here, we characterize and quantify a retinotopic bias implied by typical gaze behavior toward faces, which leads to eyes and mouth appearing most often in the upper and lower visual field, respectively. We found that the adult human visual system is tuned to these contingencies. In two recognition experiments, recognition performance for isolated face parts was better when they were presented at typical, rather than reversed, visual field locations. The recognition cost of reversed locations was equal to ∼60% of that for whole face inversion in the same sample. Similarly, an fMRI experiment showed that patterns of activity evoked by eye and mouth stimuli in the right inferior occipital gyrus could be separated with significantly higher accuracy when these features were presented at typical, rather than reversed, visual field locations. Our findings demonstrate that human face perception is determined not only by the local position of features within a face context, but by whether features appear at the typical retinotopic location given normal gaze behavior. Such location sensitivity may reflect fine-tuning of category-specific visual processing to retinal input statistics. Our findings further suggest that retinotopic heterogeneity might play a role for face inversion effects and for the understanding of conditions affecting gaze behavior toward faces, such as autism spectrum disorders and congenital prosopagnosia. SIGNIFICANCE STATEMENT: Faces attract our attention and trigger stereotypical patterns of visual fixations, concentrating on inner features, like eyes and mouth. Here we show that the visual system represents face features better when they are shown at retinal positions where they typically fall during natural vision. When facial features were shown at typical (rather than reversed) visual field locations, they were discriminated better by humans and could be decoded with higher accuracy from brain activity patterns in the right occipital face area. This suggests that brain representations of face features do not cover the visual field uniformly. It may help us understand the well-known face-inversion effect and conditions affecting gaze behavior toward faces, such as prosopagnosia and autism spectrum disorders

Tau Be or not Tau Be? - A Perspective on Service Compatibility and Substitutability

One of the main open research issues in Service Oriented Computing is to propose automated techniques to analyse service interfaces. A first problem, called compatibility, aims at determining whether a set of services (two in this paper) can be composed together and interact with each other as expected. Another related problem is to check the substitutability of one service with another. These problems are especially difficult when behavioural descriptions (i.e., message calls and their ordering) are taken into account in service interfaces. Interfaces should capture as faithfully as possible the service behaviour to make their automated analysis possible while not exhibiting implementation details. In this position paper, we choose Labelled Transition Systems to specify the behavioural part of service interfaces. In particular, we show that internal behaviours (tau transitions) are necessary in these transition systems in order to detect subtle errors that may occur when composing a set of services together. We also show that tau transitions should be handled differently in the compatibility and substitutability problem: the former problem requires to check if the compatibility is preserved every time a tau transition is traversed in one interface, whereas the latter requires a precise analysis of tau branchings in order to make the substitution preserve the properties (e.g., a compatibility notion) which were ensured before replacement.Comment: In Proceedings WCSI 2010, arXiv:1010.233

The antimalarial drug amodiaquine stabilizes p53 through ribosome biogenesis stress, independently of its autophagy-inhibitory activity

Pharmacological inhibition of ribosome biogenesis is a promising avenue for cancer therapy. Herein, we report a novel activity of the FDA-approved antimalarial drug amodiaquine which inhibits rRNA transcription, a rate-limiting step for ribosome biogenesis, in a dose-dependent manner. Amodiaquine triggers degradation of the catalytic subunit of RNA polymerase I (Pol I), with ensuing RPL5/RPL11-dependent stabilization of p53. Pol I shutdown occurs in the absence of DNA damage and without the subsequent ATM-dependent inhibition of rRNA transcription. RNAseq analysis revealed mechanistic similarities of amodiaquine with BMH-21, the first-in-class Pol I inhibitor, and with chloroquine, the antimalarial analog of amodiaquine, with well-established autophagy-inhibitory activity. Interestingly, autophagy inhibition caused by amodiaquine is not involved in the inhibition of rRNA transcription, suggesting two independent anticancer mechanisms. In vitro, amodiaquine is more efficient than chloroquine in restraining the proliferation of human cell lines derived from colorectal carcinomas, a cancer type with predicted susceptibility to ribosome biogenesis stress. Taken together, our data reveal an unsuspected activity of a drug approved and used in the clinics for over 30 years, and provide rationale for repurposing amodiaquine in cancer therapy

Proinsulin C-peptide elicits disaggregation of insulin resulting in enhanced physiological insulin effects

Using surface plasmon resonance (SPR) and electrospray mass spectrometry (ESI-MS), proinsulin C-peptide was found to influence insulin-insulin interactions. In SPR with chip-bound insulin, C-peptide mixed with analyte insulin increased the binding, while alone C-peptide did not. A control peptide with the same residues in random sequence had little effect. In ESI-MS, C-peptide lowered the presence of insulin hexamer. The data suggest that C-peptide promotes insulin disaggregation. Insulin/insulin oligomer μM dissociation constants were determined. Compatible with these findings, type 1 diabetic patients receiving insulin and C-peptide developed 66% more stimulation of glucose metabolism than when given insulin alone. A role of C-peptide in promoting insulin disaggregation may be important physiologically during exocytosis of pancreatic β-cell secretory granulae and pharmacologically at insulin injection sites. It is compatible with the normal co-release of C-peptide and insulin and may contribute to the beneficial effect of C-peptide and insulin replacement in type 1 diabetics