Selective constraints on the activation domain of transcription factor Pit-1.

The POU transcription factor Pit-1 activates members of the prolactin/growth hormone gene family in specific endocrine cell types of the pituitary gland. Although Pit-1 is structurally conserved among vertebrate species, evolutionary changes in the pattern of Pit-1 RNA splicing have led to a notable "contraction" of the transactivation domain in the mammalian lineage, relative to Pit-1 in salmonid fish. By site-directed mutagenesis we demonstrate that two splice insertions in salmon Pit-1, called beta (29 aa) and gamma (33 aa), are critical for cooperative activation of the salmon prolactin gene. Paradoxically, Pit-1-dependent activation of the prolactin gene in rat is enhanced in the absence of the homologous beta-insert sequence. This apparent divergence in the mechanism of activation of prolactin genes by Pit-1 is target gene specific, as activation of rat and salmon growth hormone genes by Pit-1 splice variants is entirely conserved. Our data suggest that efficient activation of the prolactin gene in the vertebrate pituitary has significantly constrained the pattern of splicing within the Pit-1 transactivation domain. Rapid evolutionary divergence of prolactin gene function may have demanded changes in Pit-1/protein interactions to accommodate new patterns of transcriptional control by developmental or physiological factors.

Bioenergetic scaling: metabolic design and body-size constraints in mammals.

The cytosolic phosphorylation ratio ([ATP]/[ADP][P(i)]) in the mammalian heart was found to be inversely related to body mass with an exponent of -0.30 (r = 0.999). This exponent is similar to -0.25 calculated for the mass-specific O2 consumption. The inverse of cytosolic free [ADP], the Gibbs energy of ATP hydrolysis (delta G'ATP), and the efficiency of ATP production (energy captured in forming 3 mol of ATP per cycle along the mitochondrial respiratory chain from NADH to 1/2 O2) were all found to scale with body mass with a negative exponent. On the basis of scaling of the phosphorylation ratio and free cytosolic [ADP], we propose that the myocardium and other tissues of small mammals represent a metabolic system with a higher driving potential (a higher delta G'ATP from the higher [ATP]/[ADP][P(i)]) and a higher kinetic gain [(delta V/Vmax)/delta [ADP]] where small changes in free [ADP] produce large changes in steady-state rates of O2 consumption. From the inverse relationship between mitochondrial efficiency and body size we calculate that tissues of small mammals are more efficient than those of large mammals in converting energy from the oxidation of foodstuffs to the bond energy of ATP. A higher efficiency also indicates that mitochondrial electron transport is not the major site for higher heat production in small mammals. We further propose that the lower limit of about 2 g for adult endotherm body size (bumblebee-bat, Estrucan shrew, and hummingbird) may be set by the thermodynamics of the electron transport chain. The upper limit for body size (100,000-kg adult blue whale) may relate to a minimum delta G'ATP of approximately 55 kJ/mol for a cytoplasmic phosphorylation ratio of 12,000 M-1.

Tectono-sedimentary evolution of the ’Numidian Formation’ and Lateral Facies (southern branch of the western Tethys): constraints for central-western Mediterranean geodynamics

The origin of the Numidian Formation (latest Oligocene to middle Miocene), characterized by ultra-mature quartzose arenites with abundant well-rounded frosted quartz grains, remains controversial. This formation, sedimented in the external domain of the Maghrebian Flysch Basin, displays three characteristic stratigraphic members with marked longitudinal (proximal–distal) and transverse (along-chain) variations with palaeogeographical importance. The origin of the Numidian supply is related to the outward tectogenetic propagation when a forebulge evolved in the African foreland, leading to the erosion of African cratonic areas rich in quartzose arenites (Nubian Sandstone-like). The ages of the Numidian Formation checked by Betic, Maghrebian and Southern Apennine data suggest a timing for the accretionary orogenic wedge, earlier in the Betic-Rifian Arc (after middle Burdigalian), later in the Algerian-Tunisian Tell (after late Burdigalian) and afterwards in Sicily and the Southern Apennines (after Langhian). A geodynamic evolutionary model for the central-western Mediterranean is proposed.

The European Citizens‘ Initiative – Chances, Constraints and Limits. IHS Political Science Series No. 134, April 2013

In order to celebrate the 20th anniversary of the establishment of European Union citizenship under the Maastricht Treaty in 1993, the year 2013 has been designated by the European Commission as the ‘European Year of Citizens’. The European Citizen’s Initiative (ECI) – labelled by the Commission as a ‘direct gateway through which citizens can make their voices heard in Brussels’ - may emerge in the European awareness as a new appealing platform for policy-shaping and communication. The ECI, through its transnational vox civilis character, figures among the most important novelties in the Lisbon Treaty and in the long run may facilitate and accelerate the bottom-up building of a European demos. The question is, however, whether the mechanism of pan-European signature collection is strong enough to face the democratic challenges present in the EU, especially during the ongoing financial crisis.

Exports and Capacity Constraints: A smooth transition regression model for six euro-area countries. CEPS Working Document No. 395/May 2014

The significant gains in export market shares made in a number of vulnerable euro-area crisis countries have not been accompanied by an appropriate improvement in price competitiveness. This paper argues that, under certain conditions, firms consider export activity as a substitute for serving domestic demand. The strength of the link between domestic demand and exports is dependent on capacity constraints. Our econometric model for six euro-area countries suggests domestic demand pressure and capacity-constraint restrictions as additional variables of a properly specified export equation. As an innovation to the literature, we assess the empirical significance through the logistic and the exponential variant of the non-linear smooth transition regression model. We find that domestic demand developments are relevant for the short-run dynamics of exports in particular during more extreme stages of the business cycle. A strong substitutive relationship between domestic and foreign sales can most clearly be found for Spain, Portugal and Italy, providing evidence of the importance of sunk costs and hysteresis in international trade.

Productivity and Credit Constraints: Firm-Level Evidence from Propensity Score Matching. Factor Markets Working Paper No. 3, September 2011

Drawing on a unique, farm-level panel dataset with 37,409 observations and employing a matching estimator, this paper analyses how farm access to credit affects farm input allocation and farm efficiency in the Central and Eastern European transition countries. We find that farms are asymmetrically credit constrained with respect to inputs. Farm use of variable inputs and capital investment increases up to 2.3% and 29%, respectively, per €1,000 of additional credit. Our estimates also suggest that farm access to credit increases total factor productivity up to 1.9% per €1,000 of additional credit, indicating that an improvement in access to credit results in an adjustment in the relative input intensities on farms. This finding is further supported by a negative effect of better access to credit on labour, suggesting that these two are substitutes. Interestingly, farms are found not to be credit constrained with respect to land.

Commonalities and Differences in Labour Market Developments and Constraints in Different EU Regions. Factor Markets Working Paper No. 22, February 2012

This paper provides a detailed overview of the differences across EU member states’ labour markets, through the extensive use of descriptive statistics. The objective is two-fold: firstly, it identifies the commonalities and differences in rural labour markets across EU regions and their developments, with special regard to agriculture, and secondly it emphasises the constraints that may hinder the efficient functioning of labour markets. Therefore, the paper starts with a description of the main indicators in the general labour market theory, such as the structure of the population in terms of age and gender distribution, unemployment and activity rates, employment levels, quality of human capital, migration patterns, and so forth. Secondly, we focus on the differences among rural and urban areas to then look closely at the agricultural sector. The institutional framework in which labour market institutions operate is also included. Lastly, as an attempt to summarise the analysis and to classify the EU member states according to certain rural and specific agricultural indicators, cluster analysis is also employed. Policy implications include investment in human capital and vocational training, support to young farmers, promoting economic diversification and upgrading infrastructure, with special regard to the new member states and to the Southern parts of Europe.

Primary sex determination of placental mammals: a modelling study uncovers dynamical developmental constraints in the formation of Sertoli and granulosa cells

Primary sex determination in placental mammals is a very well studied developmental process. Here, we aim to investigate the currently established scenario and to assess its adequacy to fully recover the observed phenotypes, in the wild type and perturbed situations. Computational modelling allows clarifying network dynamics, elucidating crucial temporal constrains as well as interplay between core regulatory modules.

A Unified Approach to Automatic Testing of Architectural Constraints

Architectural decisions are often encoded in the form of constraints and guidelines. Non-functional requirements can be ensured by checking the conformance of the implementation against this kind of invariant. Conformance checking is often a costly and error-prone process that involves the use of multiple tools, differing in effectiveness, complexity and scope of applicability. To reduce the overall effort entailed by this activity, we propose a novel approach that supports verification of human- readable declarative rules through the use of adapted off-the-shelf tools. Our approach consists of a rule specification DSL, called Dicto, and a tool coordination framework, called Probo. The approach has been implemented in a soon to be evaluated prototype.

Age constraints on the tectonic evolution of the Itremo region in Central Madagascar

The Itremo region in Central Madagascar comprises a deformed metasedimentary sequence (Itremo Group) that has undergone greenschist to lower amphibolite facies metamorphism. During a first phase of deformation (D1) Itremo Group sediments were deformed into a fold-and-thrust belt and transported toward the E to NE on top of migmatitic gneisses rocks of Anatananarivo block. A second phase of deformation (D2) affected both the fold-and-thrust belt and structurally underlying units, and formed large-scale N-S trending folds with steeply dipping axial planes. A Late Neoproterozoic Th–U–Pb XRF monazite age (565±17 Ma) dates the emplacement of a granite that truncates first-phase structures in the Itremo Group, and indicates that the fold-and-thrust belt formed prior to ≈565 Ma. Th–U–Pb electron microprobe dating was applied to elongated monazites that lie within the first-phase foliation of Itremo Group metapelites. The detrital cores of zoned monazites reveal two distinct age populations at ∼2000 and 1700 Ma, the latter age giving a maximum depositional age for the Itremo Group. Statistical analysis of ages determined from the rims of zoned monazites and from unzoned monazites indicates three Late Proterozoic–Early Paleozoic monazite growth events at about 565–540, 500 and 430 Ma. The oldest age population is contemporaneous within error, with the intrusion of the dated granite. The two younger age populations are found both in the Th–U–Pb and Ar–Ar data; together with the perturbation of the Rb–Sr system we interpret both ages as due to alteration related to fluid circulation events, possibly connected to the emplacement of pegmatite fields in Central Madagascar. Syn-D1 tectonic growth of contact metamorphism minerals such as andalusite has been observed locally in metapelites along the margin of Middle Neoproterozoic (≈800 Ma) granites, suggesting that D1 in the Itremo Group is contemporaneous with the intrusion of granites at ≈800 Ma. The N-S trending D2 folds are associated with ≈E-W shortening during the final assembly of Gondwana in Late Neoproterozoic–Early Cambrian times.