Designing a regional cabinet: How the economic context, political fragmentation and polarization shape cabinet size

This article aims at studying the effect of the state of the economy and the characteristics of the party supply in Parliament on regional cabinet size. We complement previous literature on the characteristics of governments and analyse whether the magnitude of the cabinet varies as a function of the state of the economy, the number of opposition parties and the level of party polarization for the opposition parties. Results show that better economic conditions and a larger number of opposition political parties in parliament are associated with a larger number of portfolios. Ideological polarization of the parties in the legislature does not seem to have an influence when designing the cabinet structure. Findings also show that the effect of the economic conditions is not equal for all cabinets: cabinets with less political constraints (majority status or fewer opposition parties) will be more sensitive to economic vicissitudes. This article, therefore, highlights how the parliamentary scenario and the economic context significantly influence the decisions on how to form or reshuffle a cabinet

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Pharmacokinetic (Pk) Activity of Cabazitaxel (Cbz) in Patients (Pts) with Renal Impairment (Ri)

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Herschel Observations of the W43 "mini-starburst"

Aims: To explore the infrared and radio properties of one of the closest Galactic starburst regions. Methods: Images obtained with the Herschel Space Observatory at wavelengths of 70, 160, 250, 350, and 500 microns using the PACS and SPIRE arrays are analyzed and compared with radio continuum VLA data and 8 micron images from the Spitzer Space Telescope. The morphology of the far-infrared emission is combined with radial velocity measurements of millimeter and centimeter wavelength transitions to identify features likely to be associated with the W43 complex. Results: The W43 star-forming complex is resolved into a dense cluster of protostars, infrared dark clouds, and ridges of warm dust heated by massive stars. The 4 brightest compact sources with L > 1.5 x 10^4 Lsun embedded within the Z-shaped ridge of bright dust emission in W43 remain single at 4" (0.1 pc) resolution. These objects, likely to be massive protostars or compact clusters in early stages of evolution are embedded in clumps with masses of 10^3 to 10^4 Msun, but contribute only 2% to the 3.6 x 10^6 Lsun far-IR luminosity of W43 measured in a 16 by 16 pc box. The total mass of gas derived from the far-IR dust emission inside this region is ~10^6 Msun. Cometary dust clouds, compact 6 cm radio sources, and warm dust mark the locations of older populations of massive stars. Energy release has created a cavity blowing-out below the Galactic plane. Compression of molecular gas in the plane by the older HII region near G30.684-0.260 and the bipolar structure of the resulting younger W43 HII region may have triggered the current mini-star burst.Comment: 5 pages, 3 figures, accepted for A&A Special Issu

Linking pre- and proto-stellar objects in the intermediate-/high-mass star forming region IRAS 05345+3157

To better understand the initial conditions of the high-mass star formation process, it is crucial to study at high-angular resolution the morphology, the kinematics, and eventually the interactions of the coldest condensations associated with intermediate-/high-mass star forming regions. The paper studies the cold condensations in the intermediate-/high-mass proto-cluster IRAS 05345+3157, focusing the attention on the interaction with the other objects in the cluster. We have performed millimeter high-angular resolution observations, both in the continuum and several molecular lines, with the PdBI and the SMA. In a recent paper, we have already published part of these data. The main finding of that work was the detection of two cold and dense gaseous condensations, called N and S (masses ~2 and ~9 M_sun), characterised by high values of the deuterium fractionation (~0.1 in both cores). In this paper, we present a full report of the observations, and a complete analysis of the data obtained. The millimeter maps reveal the presence of 3 cores inside the interferometers primary beam, called C1-a, C1-b and C2. None of them are associated with cores N and S. C1-b is very likely associated with a newly formed early-B ZAMS star embedded inside a hot-core, while C1-a is more likely associated with a class 0 intermediate-mass protostar. The nature of C2 is unclear. Both C1-a and C1-b are good candidates as driving sources of a powerful CO outflow, which strongly interacts with N and S, as demonstrated by the velocity gradient across both condensations. Our major conclusion is that the chemical properties of these pre-stellar cores are similar to those observed in low-mass isolated ones, while the kinematics is dominated by the turbulence triggered by the CO outflow and can influece their evolution.Comment: 16 pages, 13 figures, accepted for publication in Astronomy & Astrophysic

Efficacy of Futibatinib, an Irreversible Fibroblast Growth Factor Receptor Inhibitor, in FGFR-Altered Breast Cancer

Several alterations in fibroblast growth factor receptor (FGFR) genes have been found in breast cancer; however, they have not been well characterized as therapeutic targets. Futibatinib (TAS-120; Taiho) is a novel, selective, pan-FGFR inhibitor that inhibits FGFR1-4 at nanomolar concentrations. We sought to determine futibatinib\u27s efficacy in breast cancer models. Nine breast cancer patient-derived xenografts (PDXs) with various FGFR1-4 alterations and expression levels were treated with futibatinib. Antitumor efficacy was evaluated by change in tumor volume and time to tumor doubling. Alterations indicating sensitization to futibatinib in vivo were further characterized in vitro. FGFR gene expression between patient tumors and matching PDXs was significantly correlated; however, overall PDXs had higher FGFR3-4 expression. Futibatinib inhibited tumor growth in 3 of 9 PDXs, with tumor stabilization in an FGFR2-amplified model and prolonged regression (\u3e 110 days) in an FGFR2 Y375C mutant/amplified model. FGFR2 overexpression and, to a greater extent, FGFR2 Y375C expression in MCF10A cells enhanced cell growth and sensitivity to futibatinib. Per institutional and public databases, FGFR2 mutations and amplifications had a population frequency of 1.1%-2.6% and 1.5%-2.5%, respectively, in breast cancer patients. FGFR2 alterations in breast cancer may represent infrequent but highly promising targets for futibatinib

Efficacy of futibatinib, an irreversible fibroblast growth factor receptor inhibitor, in FGFR-altered breast cancer.

Several alterations in fibroblast growth factor receptor (FGFR) genes have been found in breast cancer; however, they have not been well characterized as therapeutic targets. Futibatinib (TAS-120; Taiho) is a novel, selective, pan-FGFR inhibitor that inhibits FGFR1-4 at nanomolar concentrations. We sought to determine futibatinib\u27s efficacy in breast cancer models. Nine breast cancer patient-derived xenografts (PDXs) with various FGFR1-4 alterations and expression levels were treated with futibatinib. Antitumor efficacy was evaluated by change in tumor volume and time to tumor doubling. Alterations indicating sensitization to futibatinib in vivo were further characterized in vitro. FGFR gene expression between patient tumors and matching PDXs was significantly correlated; however, overall PDXs had higher FGFR3-4 expression. Futibatinib inhibited tumor growth in 3 of 9 PDXs, with tumor stabilization in an FGFR2-amplified model and prolonged regression (\u3e 110 days) in an FGFR2 Y375C mutant/amplified model. FGFR2 overexpression and, to a greater extent, FGFR2 Y375C expression in MCF10A cells enhanced cell growth and sensitivity to futibatinib. Per institutional and public databases, FGFR2 mutations and amplifications had a population frequency of 1.1%-2.6% and 1.5%-2.5%, respectively, in breast cancer patients. FGFR2 alterations in breast cancer may represent infrequent but highly promising targets for futibatinib

A Phase I Study of Tak-659 and Paclitaxel in Patients With Taxane-Refractory Advanced Solid Tumors

BACKGROUND: Paclitaxel resistance limits durability of response in patients with initial clinical benefit. Overexpression of spleen tyrosine kinase (SYK) has been proposed as a possible resistance mechanism. This phase I trial evaluated the safety and preliminary activity of the SYK inhibitor TAK-659 combined with paclitaxel in patients with advanced taxane-refractory solid tumors. PATIENTS AND METHODS: Patients with advanced solid tumors and prior progression on taxane-based therapy received intravenous infusion of paclitaxel on days 1, 8, and 15 plus oral TAK-659 daily in 28-day cycles. The dose-escalation phase included six cohorts treated at different dose levels; the dose-expansion phase included patients with ovarian cancer treated at the highest dose level. Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Efficacy was evaluated using Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: Our study included 49 patients. Maximum tolerated dose was not reached, but higher rates of adverse events were observed at higher dose levels. There were no treatment-related deaths. The most common treatment-related adverse events of any grade were increased aspartate aminotransferase (n = 31; 63%), increased alanine aminotransferase (n = 26; 53%), decreased neutrophil count (n = 26; 53%), and decreased white blood cell count (n = 26; 53%). Most adverse events were either grade 1 or 2. In the 44 patients with evaluable disease, 12 (27%) had stable disease as the best overall response, including three patients with prolonged stable disease, and 4 patients (9%) achieved a partial response. CONCLUSIONS: The combination of paclitaxel and TAK-659 showed preliminary activity possibly overcoming resistance to taxane-based therapy as well as a tolerable safety profile in patients with advanced solid tumors

ALMA Observations of Asteroid 3 Juno at 60 Kilometer Resolution

We present Atacama Large Millimeter/submillimeter Array (ALMA) 1.3 mm continuum images of the asteroid 3 Juno obtained with an angular resolution of 0.042 arcseconds (60 km at 1.97 AU). The data were obtained over a single 4.4 hr interval, which covers 60% of the 7.2 hr rotation period, approximately centered on local transit. A sequence of ten consecutive images reveals continuous changes in the asteroid's profile and apparent shape, in good agreement with the sky projection of the three-dimensional model of the Database of Asteroid Models from Inversion Techniques. We measure a geometric mean diameter of 259pm4 km, in good agreement with past estimates from a variety of techniques and wavelengths. Due to the viewing angle and inclination of the rotational pole, the southern hemisphere dominates all of the images. The median peak brightness temperature is 215pm13 K, while the median over the whole surface is 197pm15 K. With the unprecedented resolution of ALMA, we find that the brightness temperature varies across the surface with higher values correlated to the subsolar point and afternoon areas, and lower values beyond the evening terminator. The dominance of the subsolar point is accentuated in the final four images, suggesting a reduction in the thermal inertia of the regolith at the corresponding longitudes, which are possibly correlated to the location of the putative large impact crater. These results demonstrate ALMA's potential to resolve thermal emission from the surface of main belt asteroids, and to measure accurately their position, geometric shape, rotational period, and soil characteristics.Comment: 8 pages, 3 figures, 2 tables, accepted for publication in the Astrophysical Journal Letter

First Results from High Angular Resolution ALMA Observations Toward the HL Tau Region

We present Atacama Large Millimeter/submillimeter Array (ALMA) observations from the 2014 Long Baseline Campaign in dust continuum and spectral line emission from the HL Tau region. The continuum images at wavelengths of 2.9, 1.3, and 0.87 mm have unprecedented angular resolutions of 0.075 arcseconds (10 AU) to 0.025 arcseconds (3.5 AU), revealing an astonishing level of detail in the circumstellar disk surrounding the young solar analogue HL Tau, with a pattern of bright and dark rings observed at all wavelengths. By fitting ellipses to the most distinct rings, we measure precise values for the disk inclination (46.72pm0.05 degrees) and position angle (+138.02pm0.07 degrees). We obtain a high-fidelity image of the 1.0 mm spectral index ($\alpha$), which ranges from $\alpha\sim2.0$ in the optically-thick central peak and two brightest rings, increasing to 2.3-3.0 in the dark rings. The dark rings are not devoid of emission, we estimate a grain emissivity index of 0.8 for the innermost dark ring and lower for subsequent dark rings, consistent with some degree of grain growth and evolution. Additional clues that the rings arise from planet formation include an increase in their central offsets with radius and the presence of numerous orbital resonances. At a resolution of 35 AU, we resolve the molecular component of the disk in HCO+ (1-0) which exhibits a pattern over LSR velocities from 2-12 km/s consistent with Keplerian motion around a ~1.3 solar mass star, although complicated by absorption at low blue-shifted velocities. We also serendipitously detect and resolve the nearby protostars XZ Tau (A/B) and LkHa358 at 2.9 mm.Comment: 11 pages, 5 figures, 2 tables, accepted for publication in the Astrophysical Journal Letter