Crystal structure of the breakpoint cluster region-homology domain from phosphoinositide 3-kinase p85α subunit

Proteins such as the product of the breakpoint cluster region, chimaerin, and the Src homology 3-binding protein 3BP1, are GTPase activating proteins (GAPs) for members of the Rho subfamily of small GTP-binding proteins (G proteins or GTPases). A 200-residue region, named the breakpoint cluster region-homology (BH) domain, is responsible for the GAP activity. We describe here the crystal structure of the BH domain from the p85 subunit of phosphatidylinositol 3-kinase at 2.0 Å resolution. The domain is composed of seven helices, having a previously unobserved arrangement. A core of four helices contains most residues that are conserved in the BH family. Their packing suggests the location of a G-protein binding site. This structure of a GAP-like domain for small GTP-binding proteins provides a framework for analyzing the function of this class of molecules.

Globular cluster ages

We review two new methods to determine the age of globular clusters (GCs). These two methods are more accurate than the classical isochrone fitting technique. The first method is based on the morphology of the horizontal branch and is independent of the distance modulus of the globular cluster. The second method uses a careful binning of the stellar luminosity function and determines simultaneously the distance and age of the GC. We find that the oldest galactic GCs have an age of 13.5 ± 2 gigayears (Gyr). The absolute minimum age for the oldest GCs is 10.5 Gyr (with 99% confidence) and the maximum 16.0 Gyr (with 99% confidence). Therefore, an Einstein–De Sitter Universe (Ω = 1) is not totally ruled out if the Hubble constant is about 65 ± 10 Km s−1 Mpc−1.

Oxidation states of the manganese cluster during the flash-induced S-state cycle of the photosynthetic oxygen-evolving complex.

The Mn K-edge x-ray absorption spectra for the pure S states of the tetranuclear Mn cluster of the oxygen-evolving complex of photosystem II during flash-induced S-state cycling have been determined. The relative S-state populations in samples given 0, 1, 2, 3, 4, or 5 flashes were determined from fitting the flash-induced electron paramagnetic resonance (EPR) multiline signal oscillation pattern to the Kok model. The edge spectra of samples given 0, 1, 2, or 3 flashes were combined with EPR information to calculate the pure S-state edge spectra. The edge positions (defined as the zero-crossing of the second derivatives) are 6550.1, 6551.7, 6553.5, and 6553.8 eV for S0, S1, S2, and S3, respectively. In addition to the shift in edge position, the S0--> S1 and S1--> S2 transitions are accompanied by characteristic changes in the shape of the edge, both indicative of Mn oxidation. The edge position shifts very little (0.3 eV) for the S2--> S3 transition, and the edge shape shows only subtle changes. We conclude that probably no direct Mn oxidation is involved in this transition. The proposed Mn oxidation state assignments are as follows: S0 (II, III, IV, IV) or (III, III, III, IV), S1 (III, III, IV, IV), S2 (III, IV, IV, IV), S3 (III, IV, IV, IV).

Twenty-five coregulated transcripts define a sterigmatocystin gene cluster in Aspergillus nidulans.

Sterigmatocystin (ST) and the aflatoxins (AFs), related fungal secondary metabolites, are among the most toxic, mutagenic, and carcinogenic natural products known. The ST biosynthetic pathway in Aspergillus nidulans is estimated to involve at least 15 enzymatic activities, while certain Aspergillus parasiticus, Aspergillus flavus, and Aspergillus nomius strains contain additional activities that convert ST to AF. We have characterized a 60-kb region in the A. nidulans genome and find it contains many, if not all, of the genes needed for ST biosynthesis. This region includes verA, a structural gene previously shown to be required for ST biosynthesis, and 24 additional closely spaced transcripts ranging in size from 0.6 to 7.2 kb that are coordinately induced only under ST-producing conditions. Each end of this gene cluster is demarcated by transcripts that are expressed under both ST-inducing and non-ST-inducing conditions. Deduced polypeptide sequences of regions within this cluster had a high percentage of identity with enzymes that have activities predicted for ST/AF biosynthesis, including a polyketide synthase, a fatty acid synthase (alpha and beta subunits), five monooxygenases, four dehydrogenases, an esterase, an 0-methyltransferase, a reductase, an oxidase, and a zinc cluster DNA binding protein. A revised system for naming the genes of the ST pathway is presented.

Construction of a 2.8-megabase yeast artificial chromosome contig and cloning of the human methylthioadenosine phosphorylase gene from the tumor suppressor region on 9p21.

Many human malignant cells lack methylthioadenosine phosphorylase (MTAP) enzyme activity. The gene (MTAP) encoding this enzyme was previously mapped to the short arm of chromosome 9, band p21-22, a region that is frequently deleted in multiple tumor types. To clone candidate tumor suppressor genes from the deleted region on 9p21-22, we have constructed a long-range physical map of 2.8 megabases for 9p21 by using overlapping yeast artificial chromosome and cosmid clones. This map includes the type IIFN gene cluster, the recently identified candidate tumor suppressor genes CDKN2 (p16INK4A) and CDKN2B (p15INK4B), and several CpG islands. In addition, we have identified other transcription units within the yeast artificial chromosome contig. Sequence analysis of a 2.5-kb cDNA clone isolated from a CpG island that maps between the IFN genes and CDKN2 reveals a predicted open reading frame of 283 amino acids followed by 1302 nucleotides of 3' untranslated sequence. This gene is evolutionarily conserved and shows significant amino acid homologies to mouse and human purine nucleoside phosphorylases and to a hypothetical 25.8-kDa protein in the pet gene (coding for cytochrome bc1 complex) region of Rhodospirillum rubrum. The location, expression pattern, and nucleotide sequence of this gene suggest that it codes for the MTAP enzyme.

Deep observation of the NGC1275 region with MAGIC: search of diffuse gamma-ray emission from cosmic rays in the Perseus cluster

Clusters of galaxies are expected to be reservoirs of cosmic rays (CRs) that should produce diffuse γ-ray emission due to their hadronic interactions with the intra-cluster medium. The nearby Perseus cool-core cluster, identified as the most promising target to search for such an emission, has been observed with the MAGIC telescopes at very-high energies (VHE, E ≥ 100 GeV) for a total of 253 hr from 2009 to 2014. The active nuclei of NGC 1275, the central dominant galaxy of the cluster, and IC 310, lying at about 0.6º from the centre, have been detected as point-like VHE γ-ray emitters during the first phase of this campaign. We report an updated measurement of the NGC 1275 spectrum, which is described well by a power law with a photon index Γ = 3.6 ± 0.2_(stat) ± 0.2_(syst) between 90 GeV and 1200 GeV. We do not detect any diffuse γ-ray emission from the cluster and so set stringent constraints on its CR population. To bracket the uncertainties over the CR spatial and spectral distributions, we adopt different spatial templates and power-law spectral indexes α. For α = 2.2, the CR-to-thermal pressure within the cluster virial radius is constrained to be ≤ 1 − 2%, except if CRs can propagate out of the cluster core, generating a flatter radial distribution and releasing the CR-to-thermal pressure constraint to ≤ 20%. Assuming that the observed radio mini-halo of Perseus is generated by secondary electrons from CR hadronic interactions, we can derive lower limits on the central magnetic field, B_(0), that depend on the CR distribution. For α = 2.2, B_(0) ≥ 5 − 8 µG, which is below the ∼25 µG inferred from Faraday rotation measurements, whereas for α ≤ 2.1, the hadronic interpretation of the diffuse radio emission contrasts with our γ-ray flux upper limits independently of the magnetic field strength.

Análisis del modelo RFM según el método convencional y el método de las 2-Tuplas

En el siguiente Trabajo de Fin de Máster se pone en práctica la Minería de Datos (Data Mining), llevando a cabo una investigación de CRM (Customer Relationship Management) en la cual se analizan los comportamientos de compra de los clientes de una empresa que comercializa solo por internet (online). Este negocio es de origen español y mediante estos análisis podremos saber principalmente cuántos tipos de clientes posee y cómo son sus hábitos de compra para poder clasificarlos. Para ello, utilizaremos la segmentación RFM (Recency, Frequency, Monetary) que la calcularemos mediante dos metodologías muy importantes que son el Método Convencional y el Método de las 2-Tuplas. En el primer método realizaremos una clasificación numérica mediante quintiles que se numerarán de 1 a 5 tanto para la Recencia, la Frecuencia y el Valor Monetario, con los que podremos determinar el comportamiento de compra de cada cliente. En el segundo método veremos otra clasificación de los clientes más precisa, más detallada y con la ventaja que ofrece un valor lingüístico para poder entender mejor a que cluster pertenece cada cliente. Finalmente, realizaremos unos análisis de clusters con el método de “K-medias” con diferentes segmentos (entre 5 y 7 segmentos) que nos permitirán distinguir cuántos tipos de clientes tiene este negocio y cómo son con respecto a su hábito de compra. Todo esto con el fin de dar respuesta a este negocio sobre cómo es el comportamiento de compra de cada cliente, cuáles son los más importantes, cuáles son los menos importantes, cuántos han dejado de comprar, etc.

The young open cluster Berkeley 55

We present UBV photometry of the highly reddened and poorly studied open cluster Berkeley 55, revealing an important population of B-type stars and several evolved stars of high luminosity. Intermediate-resolution far-red spectra of several candidate members confirm the presence of one F-type supergiant and six late supergiants or bright giants. The brightest blue stars are mid-B giants. Spectroscopic and photometric analyses indicate an age 50 ± 10 Myr. The cluster is located at a distance d ≈ 4 kpc, consistent with other tracers of the Perseus Arm in this direction. Berkeley 55 is thus a moderately young open cluster with a sizable population of candidate red (super)giant members, which can provide valuable information about the evolution of intermediate-mass stars.

A massive association around the obscured open cluster RSGC3

Context. Four clusters of red supergiants have been discovered in a region of the Milky Way close to base of the Scutum-Crux Arm and the tip of the Long Bar. Population synthesis models indicate that they must be very massive to harbour so many supergiants. If the clusters are physically connected, this Scutum Complex would be the largest and most massive star-forming region ever identified in the Milky Way. Aims. The spatial extent of one of these clusters, RSGC3, has not been investigated. In this paper we explore the possibility that a population of red supergiants could be located in its vicinity. Methods. We utilised 2MASS JHKS photometry to identify candidate obscured luminous red stars in the vicinity of RSGC3. We observed a sample of candidates with the TWIN spectrograph on the 3.5-m telescope at Calar Alto, obtaining intermediate-resolution spectroscopy in the 8000−9000 Å range. We re-evaluated a number of classification criteria proposed in the literature for this spectral range and found that we could use our spectra to derive spectral types and luminosity classes. Results. We measured the radial velocity of five members of RSGC3, finding velocities similar to the average for members of Stephenson 2. Among the candidates observed outside the cluster, our spectra revealed eight M-type supergiants at distances <18′ from the centre of RSGC3, distributed in two clumps. The southern clump is most likely another cluster of red supergiants, with reddening and age identical to RSGC3. From 2MASS photometry, we identified four likely supergiant members of the cluster in addition to the five spectroscopically observed. The northern clump may be a small cluster with similar parameters. Photometric analysis of the area around RSGC3 suggests the presence of a large (>30) population of red supergiants with similar colours. Conclusions. Our data suggest that the massive cluster RSGC3 is surrounded by an extended association, which may be very massive ( ≳ 105 M⊙). We also show that supergiants in the Scutum Complex may be characterised via a combination of 2MASS photometry and intermediate-to-high-resolution spectroscopy in the Z band.

A third cluster of red supergiants in the vicinity of the massive cluster RSGC3

Context. Recent studies have shown that the area around the massive, obscured cluster RSGC3 may harbour several clusters of red supergiants. Aims. We analyse a clump of photometrically selected red supergiant candidates 20′ south of RSGC3 in order to confirm the existence of another of these clusters. Methods. Using medium-resolution infrared spectroscopy around 2.27 μm, we derived spectral types and velocities along the line of sight for the selected candidates, confirming their nature and possible association. Results. We find a compact clump of eight red supergiants and four other candidates at some distance, all of them spectroscopically confirmed red supergiants. The majority of these objects must form an open cluster, which we name Alicante 10. Because of the high reddening and strong field contamination, the cluster sequence is not clearly seen in 2MASS or GPS-UKIDSS. From the observed sources, we derive E(J − KS) = 2.6 and d ≈ 6 kpc. Conclusions. Although the cluster is smaller than RSGC3, it has an initial mass in excess of 10 000 M⊙, and it seems to be part of the RSGC3 complex. With the new members this association already has 35 spectroscopically confirmed red supergiants, confirming its place as one of the most active sites of recent stellar formation in the Galaxy.

Massive open star clusters using the VVV survey III. A young massive cluster at the far edge of the Galactic bar

Context. Young massive clusters are key to map the Milky Way’s structure, and near-infrared large area sky surveys have contributed strongly to the discovery of new obscured massive stellar clusters. Aims. We present the third article in a series of papers focused on young and massive clusters discovered in the VVV survey. This article is dedicated to the physical characterization of VVV CL086, using part of its OB-stellar population. Methods. We physically characterized the cluster using JHKS near-infrared photometry from ESO public survey VVV images, using the VVV-SkZ pipeline, and near-infrared K-band spectroscopy, following the methodology presented in the first article of the series. Results. Individual distances for two observed stars indicate that the cluster is located at the far edge of the Galactic bar. These stars, which are probable cluster members from the statistically field-star decontaminated CMD, have spectral types between O9 and B0 V. According to our analysis, this young cluster (1.0 Myr < age < 5.0 Myr) is located at a distance of 11+5-6 kpc, and we estimate a lower limit for the cluster total mass of (2.8+1.6-1.4) · 103 M⊙. It is likely that the cluster contains even earlier and more massive stars.

VdBH 222: a starburst cluster in the inner Milky Way

Context. It has been suggested that the compact open cluster VdBH 222 is a young massive distant object. Aims. We set out to characterise VdBH 222 using a comprehensive set of multi-wavelength observations. Methods. We obtained multi-band optical (UBVR) and near-infrared (JHKS) photometry of the cluster field, as well as multi-object and long-slit optical spectroscopy for a large sample of stars in the field. We applied classical photometric analysis, as well as more sophisticated methods using the CHORIZOS code, to determine the reddening to the cluster. We then plotted dereddened HR diagrams and determined cluster parameters via isochrone fitting. Results. We have identified a large population of luminous supergiants confirmed as cluster members via radial velocity measurements. We find nine red supergiants (plus one other candidate) and two yellow supergiants. We also identify a large population of OB stars. Ten of them are bright enough to be blue supergiants. The cluster lies behind ≈7.5 mag of extinction for the preferred value of RV = 2.9. Isochrone fitting allows for a narrow range of ages between 12 and 16 Ma. The cluster radial velocity is compatible with distances of ~6 and ~10 kpc. The shorter distance is inconsistent with the age range and Galactic structure. The longer distance implies an age ≈ 12 Ma and a location not far from the position where some Galactic models place the far end of the Galactic bar. Conclusions. VdBH 222 is a young massive cluster with a likely mass >20 000 M⊙. Its population of massive evolved stars is comparable to that of large associations, such as Per OB1. Its location in the inner Galaxy, presumably close to the end of the Galactic bar, adds to the increasing evidence for vigorous star formation in the inner regions of the Milky Way.

The little-studied cluster Berkeley 90 I. LS III +46 11: a very massive O3.5 If* + O3.5 If* binary

Context. It appears that most (if not all) massive stars are born in multiple systems. At the same time, the most massive binaries are hard to find owing to their low numbers throughout the Galaxy and the implied large distances and extinctions. Aims. We want to study LS III +46 11, identified in this paper as a very massive binary; another nearby massive system, LS III +46 12; and the surrounding stellar cluster, Berkeley 90. Methods. Most of the data used in this paper are multi-epoch high S/N optical spectra, although we also use Lucky Imaging and archival photometry. The spectra are reduced with dedicated pipelines and processed with our own software, such as a spectroscopic-orbit code, CHORIZOS, and MGB. Results. LS III +46 11 is identified as a new very early O-type spectroscopic binary [O3.5 If* + O3.5 If*] and LS III +46 12 as another early O-type system [O4.5 V((f))]. We measure a 97.2-day period for LS III +46 11 and derive minimum masses of 38.80 ± 0.83 M⊙ and 35.60 ± 0.77 M⊙ for its two stars. We measure the extinction to both stars, estimate the distance, search for optical companions, and study the surrounding cluster. In doing so, a variable extinction is found as well as discrepant results for the distance. We discuss possible explanations and suggest that LS III +46 12 may be a hidden binary system where the companion is currently undetected.

GU Monocerotis: A high-mass eclipsing overcontact binary in the young open cluster Dolidze 25

Context. The eclipsing binary GU Mon is located in the star-forming cluster Dolidze 25, which has the lowest metallicity measured in a Milky Way young cluster. Aims. GU Mon has been identified as a short-period eclipsing binary with two early B-type components. We set out to derive its orbital and stellar parameters. Methods. We present a comprehensive analysis, including B and V light curves and 11 high-resolution spectra, to verify the orbital period and determine parameters. We used the stellar atmosphere code FASTWIND to obtain stellar parameters and create templates for cross-correlation. We obtained a model to fit the light and radial-velocity curves using the Wilson-Devinney code iteratively and simultaneously. Results. The two components of GU Mon are identical stars of spectral type B1 V with the same mass and temperature. The light curves are typical of an EW-type binary. The spectroscopic and photometric analyses agree on a period of 0.896640 ± 0.000007 d. We determine a mass of 9.0 ± 0.6 M⊙ for each component and for temperatures of 28 000 ± 2000 K. Both values are consistent with the spectral type. The two stars are overfilling their respective Roche lobes, sharing a common envelope and, therefore the orbit is synchronised and circularised. Conclusions. The GU Mon system has a fill-out factor above 0.8, containing two dwarf B-type stars on the main sequence. The two stars are in a very advanced stage of interaction, with their extreme physical similarity likely due to the common envelope. The expected evolution of such a system very probably leads to a merger while still on the main sequence.

EU Policies and Cluster Developments of Hydrogen Communities. Bruges European Economic Research (BEER) Papers 14/December 2008

This study takes on the issue of political and socio-economic conditions for the hydrogen economy as part of a future low carbon society in Europe. It is subdivided into two parts. A first part reviews the current EU policy framework in view of its impact on hydrogen and fuel cell development. In the second part an analysis of the regional dynamics and possible hydrogen and fuel cell clusters is carried out. The current EU policy framework does not hinder hydrogen development. Yet it does not constitute a strong push factor either. EU energy policies have the strongest impact on hydrogen and fuel cell development even though their potential is still underexploited. Regulatory policies have a weak but positive impact on hydrogen. EU spending policies show some inconsistencies. Regions with a high activity level in HFC also are generally innovative regions. Moreover, the article points out certain industrial clusters that favours some regions' conditions for taking part in the HFC development. However, existing hydrogen infrastructure seems to play a minor role for region's engagement. An overall well-functioning regional innovation system is important in the formative phase of an HFC innovation system, but that further research is needed before qualified policy implications can be drawn. Looking ahead the current policy framework at EU level does not set clear long term signals and lacks incentives that are strong enough to facilitate high investment in and deployment of sustainable energy technologies. The likely overall effect thus seems to be too weak to enable the EU hydrogen and fuel cell deployment strategy. According to our analysis an enhanced EU policy framework pushing for sustainability in general and the development of hydrogen and fuel cells in particular requires the following: 1) A strong EU energy policy with credible long term targets; 2) better coordination of EU policies: Europe needs a common understanding of key taxation concepts (green taxation, internalisation of externalities) and a common approach for the market introduction of new energy technologies; 3) an EU cluster policy as an attempt to better coordinate and support of European regions in their efforts to further develop HFC and to set up the respective infrastructure.