Methylation alterations are not a major cause of PTTG1 missregulation

Background: On its physiological cellular context, PTTG1 controls sister chromatid segregation during mitosis. Within its crosstalk to the cellular arrest machinery, relies a checkpoint of integrity for which gained the over name of securin. PTTG1 was found to promote malignant transformation in 3T3 fibroblasts, and further found to be overexpressed in different tumor types. More recently, PTTG1 has been also related to different processes such as DNA repair and found to trans-activate different cellular pathways involving c-myc, bax or p53, among others. PTTG1 over-expression has been correlated to a worse prognosis in thyroid, lung, colorectal cancer patients, and it can not be excluded that this effect may also occur in other tumor types. Despite the clinical relevance and the increasing molecular characterization of PTTG1, the reason for its up-regulation remains unclear. Method: We analysed PTTG1 differential expression in PC-3, DU-145 and LNCaP tumor cell lines, cultured in the presence of the methyl-transferase inhibitor 5-Aza-2'-deoxycytidine. We also tested whether the CpG island mapping PTTG1 proximal promoter evidenced a differential methylation pattern in differentiated thyroid cancer biopsies concordant to their PTTG1 immunohistochemistry status. Finally, we performed whole-genome LOH studies using Affymetix 50 K microarray technology and FRET analysis to search for allelic imbalances comprising the PTTG1 locus. Conclusion: Our data suggest that neither methylation alterations nor LOH are involved in PTTG1 over-expression. These data, together with those previously reported, point towards a post-transcriptional level of missregulation associated to PTTG1 over-expression.This project was funded by The Fundación de Investigación Biomédica Mutua Madrileña Automovilista. Neocodex have been partially funded by the Ministerio de Educación y Ciencia of Spain (FIT-010000-2004-69, PTQ04-1-0006, PTQ2003-0549, PTQ2003-0546 and PTQ2003-0783). MAJ was also supported by SAF2005- 07713-C03-03 and CS by FIS 06/757

ALMA observations of Elias 2–24: a protoplanetary disk with multiple gaps in the Ophiuchus molecular cloud

We present ALMA 1.3 mm continuum observations at 0. 2 (25 au) resolution of Elias 2–24, one of the largest and brightest protoplanetary disks in the Ophiuchus Molecular Cloud, and we report the presence of three partially resolved concentric gaps located at ∼20, 52, and 87 au from the star. We perform radiative transfer modeling of the disk to constrain its surface density and temperature radial profile and place the disk structure in the context of mechanisms capable of forming narrow gaps such as condensation fronts and dynamical clearing by actively forming planets. In particular, we estimate the disk temperature at the locations of the gaps to be 23, 15, and 12 K (at 20, 52, and 87 au, respectively), very close to the expected snowlines of CO (23–28 K) and N2 (12–15 K). Similarly, by assuming that the widths of the gaps correspond to 4–8× the Hill radii of forming planets (as suggested by numerical simulations), we estimate planet masses in the range of 0.2 1.5 – MJup, 1.0 8.0 – MJup, and 0.02 0.15 – MJup for the inner, middle, and outer gap, respectively. Given the surface density profile of the disk, the amount of “missing mass” at the location of each one of these gaps (between 4 and 20 MJup) is more than sufficient to account for the formation of such planets.Fil: Cieza, Lucas A.. Universidad Diego Portales; ChileFil: Casassus, Simon. Universidad de Chile; ChileFil: Pérez, Sebastian. Universidad de Chile; ChileFil: Hales, Antonio. Alma Observatory; ChileFil: Cárcamo, Miguel. Universidad de Chile; ChileFil: Ansdell, Megan. University of California at Berkeley; Estados UnidosFil: Avenhaus, Henning. Universitat Zurich; SuizaFil: Bayo, Amelia. Universidad de Valparaiso; ChileFil: Bertrang, Gesa H.-M.. Universidad Diego Portales; ChileFil: Cánovas, Hector. Agencia Espacial Europea; EspañaFil: Christiaens, Valentin. Universidad de Chile; ChileFil: Dent, William. Alma Observatory; ChileFil: Ferrero, Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Gamen, Roberto Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Olofsson, Johan. Universidad de Valparaiso; ChileFil: Orcajo, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Osses, Axel. Universidad de Chile; ChileFil: Peña Ramirez, Karla. Universidad de Antofagasta; ChileFil: Principe, David. Massachusetts Institute of Technology; Estados UnidosFil: Ruíz Rodríguez, Dary. Rochester Institute Of Technology; Estados UnidosFil: Schreiber, Matthias R.. Universidad de Valparaiso; ChileFil: Plas, Gerrit van der. Univ. Grenoble Alpes; SuizaFil: Williams, Jonathan P.. Institute For Astronomy, University Of Hawaii; Estados UnidosFil: Zurlo, Alice. Universidad Diego Portales; Chil

On the consistency of the peculiar GRBs 060218 and 060614 with the Ep,i - Eiso correlation

We analyze and discuss the position of GRB 060218 and GRB 060614 in the Ep,i - Eiso plane. GRB 060218 is important because of its similarity with GRB 980425, the proto-type event of the GRB-SN connection. While GRB 980425 is an outlier of the Ep,i - Eiso correlation, we find that GRB 060218 is fully consistent with it. This evidence, combined with the `chromatic' behavior of the afterglow light curves, is at odds with the hypothesis that GRB 060218 was a `standard' GRB seen off-axis and supports the existence of a class of truly sub--energetic GRBs. GRB 060614 is a peculiar event not accompanied by a bright Supernova. Based on published spectral information, we find that also this event is consistent with the Ep,i - Eiso correlation. We discuss the implications of our results for the rate of sub--energetic GRBs, the GRB/SN connection and the properties of the newly discovered sub-class of long GRBs not associated with bright Supernovae. We have included in our analysis other recent GRBs with clear evidence (or clear no evidence) of associated SNe.Comment: 9 pages, 4 figures, FINAL REVISED VERSION (added Figure 4 and short GRBs in Figure 1; minor changes and style corrections applied; references updated), submitted to A&A on November 25, 200

The Optical SN 2012bz Associated with the Long GRB 120422A

The association of Type Ic SNe with long-duration GRBs is well established. We endeavor, through accurate ground-based observational campaigns, to characterize these SNe at increasingly high redshifts. We obtained a series of optical photometric and spectroscopic observations of the Type Ic SN2012bz associated with the Swift long-duration GRB120422A (z=0.283) using the 3.6-m TNG and the 8.2-m VLT telescopes. The peak times of the light curves of SN2012bz in various optical filters differ, with the B-band and i'-band light curves reaching maximum at ~9 and ~23 rest-frame days, respectively. The bolometric light curve has been derived from individual bands photometric measurements, but no correction for the unknown contribution in the near-infrared (probably around 10-15%) has been applied. Therefore, the present light curve should be considered as a lower limit to the actual UV-optical-IR bolometric light curve. This pseudo-bolometric curve reaches its maximum (Mbol = -18.56 +/- 0.06) at 13 +/- 1 rest-frame days; it is similar in shape and luminosity to the bolometric light curves of the SNe associated with z<0.2 GRBs and more luminous than those of SNe associated with XRFs. A comparison with the model generated for the bolometric light curve of SN2003dh suggests that SN2012bz produced only about 15% less 56Ni than SN2003dh, about 0.35 Msol. Similarly the VLT spectra of SN2012bz, after correction for Galactic extinction and for the contribution of the host galaxy, suggest comparable explosion parameters with those observed in SN2003dh (EK~3.5 x 10^52 erg, Mej~7 Msol) and a similar progenitor mass (~25-40 Msol). GRB120422A is consistent with the Epeak-Eiso and the EX,iso-Egamma,iso-E_peak relations. GRB120422A/SN2012bz shows the GRB-SN connection at the highest redshift so far accurately monitored both photometrically and spectroscopically.Comment: 7 pages, 6 figures, 2 tables, accepted for publication in Astronomy & Astrophysic

Freezing and large time scales induced by geometrical frustration

We investigate the properties of an effective Hamiltonian with competing interactions involving spin and chirality variables, relevant for the description of the {\it trimerized} version of the spin-1/2 {\it kagome} antiferromagnet. Using classical Monte Carlo simulations, we show that remarkable behaviors develop at very low temperatures. Through an {\it order by disorder} mechanism, the low-energy states are characterized by a dynamical freezing of the chiralities, which decouples the lattice into ``dimers'' and ``triangles'' of antiferromagnetically coupled spins. Under the presence of an external magnetic field, the particular topology of the chiralities induces a very slow spin dynamics, reminiscent of what happens in ordinary spin glasses.Comment: 12 pages, 13 figure

An optical supernova associated with the X-ray flash XRF 060218

Long-duration gamma-ray bursts (GRBs) are associated with type Ic supernovae that are more luminous than average and that eject material at very high velocities. Less-luminous supernovae were not hitherto known to be associated with GRBs, and therefore GRB-supernovae were thought to be rare events. Whether X-ray flashes - analogues of GRBs, but with lower luminosities and fewer gamma-rays - can also be associated with supernovae, and whether they are intrinsically 'weak' events or typical GRBs viewed off the axis of the burst, is unclear. Here we report the optical discovery and follow-up observations of the type Ic supernova SN 2006aj associated with X-ray flash XRF 060218. Supernova 2006aj is intrinsically less luminous than the GRB-supernovae, but more luminous than many supernovae not accompanied by a GRB. The ejecta velocities derived from our spectra are intermediate between these two groups, which is consistent with the weakness of both the GRB output and the supernova radio flux. Our data, combined with radio and X-ray observations, suggest that XRF 060218 is an intrinsically weak and soft event, rather than a classical GRB observed off-axis. This extends the GRB-supernova connection to X-ray flashes and fainter supernovae, implying a common origin. Events such as XRF 060218 are probably more numerous than GRB-supernovae.Comment: Final published versio

Challenging GRB models through the broadband dataset of GRB060908

Context: Multiwavelength observations of gamma-ray burst prompt and afterglow emission are a key tool to disentangle the various possible emission processes and scenarios proposed to interpret the complex gamma-ray burst phenomenology. Aims: We collected a large dataset on GRB060908 in order to carry out a comprehensive analysis of the prompt emission as well as the early and late afterglow. Methods: Data from Swift-BAT, -XRT and -UVOT together with data from a number of different ground-based optical/NIR and millimeter telescopes allowed us to follow the afterglow evolution from about a minute from the high-energy event down to the host galaxy limit. We discuss the physical parameters required to model these emissions. Results: The prompt emission of GRB060908 was characterized by two main periods of activity, spaced by a few seconds of low intensity, with a tight correlation between activity and spectral hardness. Observations of the afterglow began less than one minute after the high-energy event, when it was already in a decaying phase, and it was characterized by a rather flat optical/NIR spectrum which can be interpreted as due to a hard energy-distribution of the emitting electrons. On the other hand, the X-ray spectrum of the afterglow could be fit by a rather soft electron distribution. Conclusions: GRB060908 is a good example of a gamma-ray burst with a rich multi-wavelength set of observations. The availability of this dataset, built thanks to the joint efforts of many different teams, allowed us to carry out stringent tests for various interpretative scenarios showing that a satisfactorily modeling of this event is challenging. In the future, similar efforts will enable us to obtain optical/NIR coverage comparable in quality and quantity to the X-ray data for more events, therefore opening new avenues to progress gamma-ray burst research.Comment: A&A, in press. 11 pages, 5 figure

Transition from Fireball to Poynting-flux-dominated Outflow in Three-Episode GRB 160625B

The ejecta composition is an open question in gamma-ray bursts (GRB) physics. Some GRBs possess a quasi-thermal spectral component in the time-resolved spectral analysis, suggesting a hot fireball origin. Others show a featureless non-thermal spectrum known as the "Band" function, consistent with a synchrotron radiation origin and suggesting that the jet is Poynting-flux-dominated at the central engine and likely in the emission region as well. There are also bursts showing a sub-dominant thermal component and a dominant synchrotron component suggesting a likely hybrid jet composition. Here we report an extraordinarily bright GRB 160625B, simultaneously observed in gamma-rays and optical wavelengths, whose prompt emission consists of three isolated episodes separated by long quiescent intervals, with the durations of each "sub-burst" being $\sim$ 0.8 s, 35 s, and 212 s, respectively. Its high brightness (with isotropic peak luminosity L$_{\rm p, iso}\sim 4\times 10^{53}$ erg/s) allows us to conduct detailed time-resolved spectral analysis in each episode, from precursor to main burst and to extended emission. The spectral properties of the first two sub-bursts are distinctly different, allowing us to observe the transition from thermal to non-thermal radiation between well-separated emission episodes within a single GRB. Such a transition is a clear indication of the change of jet composition from a fireball to a Poynting-flux-dominated jet.Comment: Revised version reflecting the referees' comments. 27 pages, 11 figures, 5 tables. The final edited version will appear in Nature Astronom

A Novel Model of Mixed Vascular Dementia Incorporating Hypertension in a Rat Model of Alzheimer's Disease.

Alzheimer's disease (AD) and mixed dementia (MxD) comprise the majority of dementia cases in the growing global aging population. MxD describes the coexistence of AD pathology with vascular pathology, including cerebral small vessel disease (SVD). Cardiovascular disease increases risk for AD and MxD, but mechanistic synergisms between the coexisting pathologies affecting dementia risk, progression and the ultimate clinical manifestations remain elusive. To explore the additive or synergistic interactions between AD and chronic hypertension, we developed a rat model of MxD, produced by breeding APPswe/PS1ΔE9 transgenes into the stroke-prone spontaneously hypertensive rat (SHRSP) background, resulting in the SHRSP/FAD model and three control groups (FAD, SHRSP and non-hypertensive WKY rats, n = 8-11, both sexes, 16-18 months of age). After behavioral testing, rats were euthanized, and tissue assessed for vascular, neuroinflammatory and AD pathology. Hypertension was preserved in the SHRSP/FAD cross. Results showed that SHRSP increased FAD-dependent neuroinflammation (microglia and astrocytes) and tau pathology, but plaque pathology changes were subtle, including fewer plaques with compact cores and slightly reduced plaque burden. Evidence for vascular pathology included a change in the distribution of astrocytic end-foot protein aquaporin-4, normally distributed in microvessels, but in SHRSP/FAD rats largely dissociated from vessels, appearing disorganized or redistributed into neuropil. Other evidence of SVD-like pathology included increased collagen IV staining in cerebral vessels and PECAM1 levels. We identified a plasma biomarker in SHRSP/FAD rats that was the only group to show increased Aqp-4 in plasma exosomes. Evidence of neuron damage in SHRSP/FAD rats included increased caspase-cleaved actin, loss of myelin and reduced calbindin staining in neurons. Further, there were mitochondrial deficits specific to SHRSP/FAD, notably the loss of complex II, accompanying FAD-dependent loss of mitochondrial complex I. Cognitive deficits exhibited by FAD rats were not exacerbated by the introduction of the SHRSP phenotype, nor was the hyperactivity phenotype associated with SHRSP altered by the FAD transgene. This novel rat model of MxD, encompassing an amyloidogenic transgene with a hypertensive phenotype, exhibits several features associated with human vascular or "mixed" dementia and may be a useful tool in delineating the pathophysiology of MxD and development of therapeutics

Development methodology to share vehicles optimizing the variability of the mileage

A simulation is a tool used to visualize the behaviors of a system, which will later help make decisions regarding how to handle the variables involved in the system, as well as the specific changes that have to be made. This study shows a case of vehicle allocation for different people within a company, evaluating methodologies, vehicle rotation to reduce the variance of the mileage and eliminating penalties with rental agencies for exceeding the permitted mileage. The paper shows a literature review of allocation models and similar studies, and later displays a detailed description of the problem, the variables that was used, the composition of the simulation and the optimization model that were generated, the results of the simulation, and finally, the findings of the research