Design, synthesis and biological activity of selective hCAs inhibitors based on 2-(benzylsulfinyl)benzoic acid scaffold

A large library of derivatives based on the scaffold of 2-(benzylsulfinyl)benzoic acid were synthesised and tested as atypical inhibitors against four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). The exploration of the chemical space around the main functional groups led to the discovery of selective hCA IX inhibitors in the micromolar/nanomolar range, thus establishing robust structure-activity relationships within this versatile scaffold. HPLC separation of some selected chiral compounds and biological evaluation of the corresponding enantiomers was performed along with molecular modelling studies on the most active derivatives

Preferential expression of the transcription coactivator HTIF1alpha gene in acute myeloid leukemia and MDS-related AML

HTIF1α, a transcription coactivator which is able to mediate RARα activity and functionally interact with PML, is encoded by a gene on chromosome 7q32–34, which is a critical region in acute myeloid leukemias (AML). With the assumption that this gene may be related to AML, we investigated the HTIF1α DNA structure and RNA expression in leukemic cells from 36 M1–M5 AML patients (28 ‘de novo’ and eight ‘secondary’ to myelodysplastic syndrome (MDS)). Abnormal HTIF1α DNA fragments were never found, whereas loss of HTIF1α DNA was observed in the patients with chromosome 7q32 deletion and translocation, and in one case without detectable chromosome 7 abnormality. HTIF1α RNA was found in acute myelocytic leukemic blasts, and was almost undetectable in normal mononuclear cells. The expression varied among the patients: higher in M1 to M3 subtypes, with the highest values in M1; low levels were constantly observed in M4 and M5 AML. In addition, HTIF1α was significantly overexpressed in MDS-related AML (MDR-AML), but not in MDS. We also found that HTIF1α expression was high in myeloid cell lines. In myeloblastic HL60 and promyelocytic NB4 cells, induced to differentiate along the monocytic–macrophage pathway by TPA or vitamin D3, HTIF1α expression decreased, whereas it was maintained at high levels on induction to granulocytic differentiation by RA or DMSO. In K562 cells, HTIF1α RNA levels did not change after hemin-induced erythroid differentiation. These results suggest that HTIF1α could play a role in myeloid differentiation, being distinctly regulated in hematopoietic lineages

HST color-magnitude diagrams of 74 galactic globular clusters in the HST F439W and F555W bands

We present the complete photometric database and the color-magnitude diagrams for 74 Galactic globular clusters observed with the HST/WFPC2 camera in the F439W and F555W bands. A detailed discussion of the various reduction steps is also presented, and of the procedures to transform instrumental magnitudes into both the HST F439W and F555W flight system and the standard Johnson B and V systems. We also describe the artificial star experiments which have been performed to derive the star count completeness in all the relevant branches of the color magnitude diagram. The entire photometric database and the completeness function will be made available on the Web immediately after the publication of the present paper.Comment: 21 pages, 77 figures. High resolution version of this paper can be retrived at http://dipastro.pd.astro.it/globular

RubikAuth: Fast and Secure Authentication in Virtual Reality

There is a growing need for usable and secure authentication in virtual reality (VR). Established concepts (e.g., 2D graphical PINs) are vulnerable to observation attacks, and proposed alternatives are relatively slow. We present RubikAuth, a novel authentication scheme for VR where users authenticate quickly by selecting digits from a virtual 3Dcube that is manipulated with a handheld controller. We report two studies comparing how pointing using gaze, headpose, and controller tapping impacts RubikAuth’s usability and observation resistance under three realistic threat models. Entering a four-symbol RubikAuth password is fast:1.69 s to 3.5 s using controller tapping, 2.35 s to 4.68 s using head pose, and 2.39 s to 4.92 s using gaze and highly resilient to observations; 97.78% to 100% of observation attacks were unsuccessful. Our results suggest that providing attackers with support material contributes to more realistic security evaluations

Is Eriophyes mali Nalepa present in Italy?

In the last few years, blistering symptoms were observed on apple plants in commercial orchards. Blisters are commonly found on apple leaves as well as on small fruits. This symptom is compatible with that described for apple blister mites belonging to the genus Eriophyes (Eriophyidae). To assess the identity of the etiological agent, leaf blisters and buds of symptomatic apple and, as a control, pear plants were examined under the dissection microscope and eriophyoid mites were collected. Specimens were examined using both molecular and morphological approaches. The analysis of sequences confirmed that eriophyoid mites collected from symptomatic apple and pear plants are genetically different. Our analyses highlight a complex scenario inside the genus Eriophyes that is worth to be studied in more detai

Internal calibration of Gaia BP/RP low-resolution spectra

The full third Gaia data release will provide the calibrated spectra obtained with the blue and red Gaia slit-less spectrophotometers. The main challenge when facing Gaia spectral calibration is that no lamp spectra or flat fields are available during the mission. Also, the significant size of the line spread function with respect to the dispersion of the prisms produces alien photons contaminating neighbouring positions of the spectra. This makes the calibration special and different from standard approaches. This work gives a detailed description of the internal calibration model to obtain the spectrophotometric data in the Gaia catalogue. The main purpose of the internal calibration is to bring all the epoch spectra onto a common flux and pixel (pseudo-wavelength) scale, taking into account variations over the focal plane and with time, producing a mean spectrum from all the observations of the same source. In order to describe all observations in a common mean flux and pseudo-wavelength scale, we construct a suitable representation of the internally calibrated mean spectra via basis functions and we describe the transformation between non calibrated epoch spectra and calibrated mean spectra via a discrete convolution, parametrising the convolution kernel to recover the relevant coefficients. The model proposed here is able to combine all observations into a mean instrument to allow the comparison of different sources and observations obtained with different instrumental conditions along the mission and the generation of mean spectra from a number of observations of the same source. The output of this model provides the internal mean spectra, not as a sampled function (flux and wavelength), but as a linear combination of basis functions, although sampled spectra can easily be derived from them.Comment: 20 pages, 22 figure

Resolving Globular Cluster Formation within a Cosmological Context

We place constraints on the formation redshifts for blue globular clusters (BGCs), independent of the details of hydrodynamics and population III star formation. The observed radial distribution of BGCs in the Milky Way Galaxy suggests that they formed in biased dark matter halos at high redshift. As a result, simulations of a ~1 Mpc box up to z~10 must resolve BGC formation in LCDM. We find that most halo stars could be produced from destroyed BGCs and other low-mass clusters that formed at high redshift. We present a proof-of-concept simulation that captures the formation of globular-like star clusters.Comment: Accepted for publication in ApJ

Gaia data release 1: Principles of the photometric calibration of the G band

Context. Gaia is an ESA cornerstone mission launched on 19 December 2013 aiming to obtain the most complete and precise 3D map of our Galaxy by observing more than one billion sources. This paper is part of a series of documents explaining the data processing and its results for Gaia Data Release 1, focussing on the G band photometry. Aims. This paper describes the calibration model of the Gaia photometric passband for Gaia Data Release 1. Methods. The overall principle of splitting the process into internal and external calibrations is outlined. In the internal calibration, a self-consistent photometric system is generated. Then, the external calibration provides the link to the absolute photometric flux scales. Results. The Gaia photometric calibration pipeline explained here was applied to the first data release with good results. Details are given of the various calibration elements including the mathematical formulation of the models used and of the extraction and preparation of the required input parameters (e.g. colour terms). The external calibration in this first release provides the absolute zero point and photometric transformations from the Gaia G passband to other common photometric systems. Conclusions. This paper describes the photometric calibration implemented for the first Gaia data release and the instrumental effects taken into account. For this first release no aperture losses, radiation damage, and other second-order effects have not yet been implemented in the calibration.Comment: 15 pages, 16 figures, Gaia data release 1 documentation special volum