Estimating the distribution of the demand for workers by GED/SVP classification

Thesis (PhD) — Boston College, 1975.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Economics

PLK1 inhibitors as a new targeted treatment for adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is an aggressive malignancy with limited treatment options. Polo-like kinase 1 (PLK1) is a promising drug target; PLK1 inhibitors (PLK1i) have been investigated in solid cancers and are more effective in TP53-mutated cases. We evaluated PLK1 expression in ACC samples and the efficacy of two PLK1i in ACC cell lines with different genetic backgrounds. PLK1 protein expression was investigated by immunohistochemistry in tissue samples and correlated with clinical data. The efficacy of rigosertib (RGS), targeting RAS/PI3K, CDKs and PLKs, and poloxin (Pol), specifically targeting the PLK1 polo-box domain, was tested in TP53-mutated NCI-H295R, MUC-1, and CU-ACC2 cells and in TP53 wild-type CU-ACC1. Effects on proliferation, apoptosis, and viability were determined. PLK1 immunostaining was stronger in TP53-mutated ACC samples vs wild-type (P = 0.0017). High PLK1 expression together with TP53 mutations correlated with shorter progression-free survival (P= 0.041). NCI-H295R showed a time- and dose-dependent reduction in proliferation with both PLK1i (P< 0.05at 100 nM RGS and 30 µM Pol). In MUC-1, a less pronounced decrease was observed (P< 0.05at 1000 nM RGS and 100 µM Pol). 100 nM RGS increased apoptosis in NCI-H295R (P< 0.001), with no effect on MUC-1. CU-ACC2 apoptosis was induced only at high concentrations (P < 0.05 at 3000 nM RGS and 100 µM Pol), while proliferation decreased at 1000 nM RGS and 30 µM Pol. CU-ACC1 proliferation reduced, and apoptosis increased, only at 100 µM Pol. TP53-mutated ACC cell lines demonstrated better response to PLK1i than wild-type CU-ACC1. These data suggest PLK1i may be a promising targeted treatment of a subset of ACC patients, pre-selected according to tumour genetic signature

ALMA 1.3 mm Survey of Lensed Submillimeter Galaxies Selected by Herschel: Discovery of Spatially Extended SMGs and Implications

We present an ALMA 1.3 mm (Band 6) continuum survey of lensed submillimeter galaxies (SMGs) at z = 1.0 to ∼3.2 with an angular resolution of ∼0farcs2. These galaxies were uncovered by the Herschel Lensing Survey and feature exceptionally bright far-infrared continuum emission (Speak ≳ 90 mJy) owing to their lensing magnification. We detect 29 sources in 20 fields of massive galaxy clusters with ALMA. Using both the Spitzer/IRAC (3.6/4.5 μm) and ALMA data, we have successfully modeled the surface brightness profiles of 26 sources in the rest-frame near- and far-infrared. Similar to previous studies, we find the median dust-to-stellar continuum size ratio to be small (Re,dust/Re,star = 0.38 ± 0.14) for the observed SMGs, indicating that star formation is centrally concentrated. This is, however, not the case for two spatially extended main-sequence SMGs with a low surface brightness at 1.3 mm (≲0.1 mJy arcsec−2), in which the star formation is distributed over the entire galaxy (Re,dust/Re,star > 1). As a whole, our SMG sample shows a tight anticorrelation between (Re,dust/Re,star) and far-infrared surface brightness (ΣIR) over a factor of ≃1000 in ΣIR. This indicates that SMGs with less vigorous star formation (i.e., lower ΣIR) lack central starburst and are likely to retain a broader spatial distribution of star formation over the whole galaxies (i.e., larger Re,dust/Re,star). The same trend can be reproduced with cosmological simulations as a result of central starburst and potentially subsequent "inside-out" quenching, which likely accounts for the emergence of compact quiescent galaxies at z ∼ 2

Cluster Lenses

Clusters of galaxies are the most recently assembled, massive, bound structures in the Universe. As predicted by General Relativity, given their masses, clusters strongly deform space-time in their vicinity. Clusters act as some of the most powerful gravitational lenses in the Universe. Light rays traversing through clusters from distant sources are hence deflected, and the resulting images of these distant objects therefore appear distorted and magnified. Lensing by clusters occurs in two regimes, each with unique observational signatures. The strong lensing regime is characterized by effects readily seen by eye, namely, the production of giant arcs, multiple-images, and arclets. The weak lensing regime is characterized by small deformations in the shapes of background galaxies only detectable statistically. Cluster lenses have been exploited successfully to address several important current questions in cosmology: (i) the study of the lens(es) - understanding cluster mass distributions and issues pertaining to cluster formation and evolution, as well as constraining the nature of dark matter; (ii) the study of the lensed objects - probing the properties of the background lensed galaxy population - which is statistically at higher redshifts and of lower intrinsic luminosity thus enabling the probing of galaxy formation at the earliest times right up to the Dark Ages; and (iii) the study of the geometry of the Universe - as the strength of lensing depends on the ratios of angular diameter distances between the lens, source and observer, lens deflections are sensitive to the value of cosmological parameters and offer a powerful geometric tool to probe Dark Energy. In this review, we present the basics of cluster lensing and provide a current status report of the field.Comment: About 120 pages - Published in Open Access at: http://www.springerlink.com/content/j183018170485723/ . arXiv admin note: text overlap with arXiv:astro-ph/0504478 and arXiv:1003.3674 by other author

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Yield and Economic Performance of Organic and Conventional Cotton-Based Farming Systems – Results from a Field Trial in India

The debate on the relative benefits of conventional and organic farming systems has in recent time gained significant interest. So far, global agricultural development has focused on increased productivity rather than on a holistic natural resource management for food security. Thus, developing more sustainable farming practices on a large scale is of utmost importance. However, information concerning the performance of farming systems under organic and conventional management in tropical and subtropical regions is scarce. This study presents agronomic and economic data from the conversion phase (2007–2010) of a farming systems comparison trial on a Vertisol soil in Madhya Pradesh, central India. A cotton-soybean-wheat crop rotation under biodynamic, organic and conventional (with and without Bt cotton) management was investigated. We observed a significant yield gap between organic and conventional farming systems in the 1st crop cycle (cycle 1: 2007–2008) for cotton (229%) and wheat (227%), whereas in the 2nd crop cycle (cycle 2: 2009–2010) cotton and wheat yields were similar in all farming systems due to lower yields in the conventional systems. In contrast, organic soybean (a nitrogen fixing leguminous plant) yields were marginally lower than conventional yields (21% in cycle 1, 211% in cycle 2). Averaged across all crops, conventional farming systems achieved significantly higher gross margins in cycle 1 (+29%), whereas in cycle 2 gross margins in organic farming systems were significantly higher (+25%) due to lower variable production costs but similar yields. Soybean gross margin was significantly higher in the organic system (+11%) across the four harvest years compared to the conventional systems. Our results suggest that organic soybean production is a viable option for smallholder farmers under the prevailing semi-arid conditions in India. Future research needs to elucidate the long-term productivity and profitability, particularly of cotton and wheat, and the ecological impact of the different farming systems

Resistance to HSP90 inhibition involving loss of MCL1 addiction

YesInhibition of the chaperone heat-shock protein 90 (HSP90) induces apoptosis, and it is a promising anti-cancer strategy. The mechanisms underpinning apoptosis activation following HSP90 inhibition and how they are modified during acquired drug resistance are unknown. We show for the first time that, to induce apoptosis, HSP90 inhibition requires the cooperation of multi BH3-only proteins (BID, BIK, PUMA) and the reciprocal suppression of the pro-survival BCL-2 family member MCL1, which occurs via inhibition of STAT5A. A subset of tumour cell lines exhibit dependence on MCL1 expression for survival and this dependence is also associated with tumour response to HSP90 inhibition. In the acquired resistance setting, MCL1 suppression in response to HSP90 inhibitors is maintained; however, a switch in MCL1 dependence occurs. This can be exploited by the BH3 peptidomimetic ABT737, through non-BCL-2-dependent synthetic lethality