Genetic Dissection of a QTL Affecting Bone Geometry.

Parameters of bone geometry such as width, length, and cross-sectional area are major determinants of bone strength. Although these traits are highly heritable, few genes influencing bone geometry have been identified. Here, we dissect a major quantitative trait locus (QTL) influencing femur size. This QTL was originally identified in an F2 cross between the C57BL/6J-hg/hg (HG) and CAST/EiJ strains and was referred to as femur length in high growth mice 2 (Feml2). Feml2 was located on chromosome (Chr.) 9 at ∼20 cM. Here, we show that the HG.CAST-(D9Mit249-D9Mit133)/Ucd congenic strain captures Feml2 In an F2 congenic cross, we fine-mapped the location of Feml2 to an ∼6 Mbp region extending from 57.3 to 63.3 Mbp on Chr. 9. We have identified candidates by mining the complete genome sequence of CAST/EiJ and through allele-specific expression (ASE) analysis of growth plates in C57BL/6J × CAST/EiJ F1 hybrids. Interestingly, we also find that the refined location of Feml2 overlaps a cluster of six independent genome-wide associations for human height. This work provides the foundation for the identification of novel genes affecting bone geometry

Torsion-Adding and Asymptotic Winding Number for Periodic Window Sequences

In parameter space of nonlinear dynamical systems, windows of periodic states are aligned following routes of period-adding configuring periodic window sequences. In state space of driven nonlinear oscillators, we determine the torsion associated with the periodic states and identify regions of uniform torsion in the window sequences. Moreover, we find that the measured of torsion differs by a constant between successive windows in periodic window sequences. We call this phenomenon as torsion-adding. Finally, combining the torsion and the period adding rules, we deduce a general rule to obtain the asymptotic winding number in the accumulation limit of such periodic window sequences

Economical comparison of CHP systems for industrial user with large steam demand

In this paper cogeneration benefits applied to a user with a high steam demand are analyzed. The methodology for the feasibility study and the economical analysis of the investment is presented under the Italian legislative framework. The methodology is applied to an actual case and a detailed description and discussion of all data input is provided. Especially this last key point will be faced using starting data usually available in these kind of studies (i.e., not very detailed for thermal consumption). Finally a comparison of different CHP technologies and a sensitivity analysis is done

Organization of production and the distribution of labor income in Spain

This paper examines evidences of market labor income inequality in Spain, as if they were the outcome of the market equilibrium from occupational choices of individuals with different general skills. We find that the parameters of the distribution of skills, production technology, and internal organization of firms that match the observed organization of production (number of persons occupied as employees, entrepreneurs-managers and solo self-employed, distribution of firm sizes) in Spain, also explain reasonably well the distribution of market labor income, within groups and for all occupied individuals together. The proposed model can be of use in evaluating the potential consequences for labor income inequality of changes in the organization of production

Substituted Anthraquinones Represent a Potential Scaffold for DNA Methyltransferase 1-Specific Inhibitors

In humans, the most common epigenetic DNA modification is methylation of the 5-carbon of cytosines, predominantly in CpG dinucleotides. DNA methylation is an important epigenetic mark associated with gene repression. Disruption of the normal DNA methylation pattern is known to play a role in the initiation and progression of many cancers. DNA methyltransferase 1 (DNMT1), the most abundant DNA methyltransferase in humans, is primarily responsible for maintenance of the DNA methylation pattern and is considered an important cancer drug target. Recently, laccaic acid A (LCA), a highly substituted anthraquinone natural product, was identified as a direct, DNA-competitive inhibitor of DNMT1. Here, we have successfully screened a small library of simplified anthraquinone compounds for DNMT1 inhibition. Using an endonuclease-coupled DNA methylation assay, we identified two anthraquinone compounds, each containing an aromatic substituent, that act as direct DNMT1 inhibitors. These simplified anthraquinone compounds retain the DNA-competitive mechanism of action of LCA and exhibit some selectivity for DNMT1 over DNMT3a. The newly identified compounds are at least 40-fold less potent than LCA, but have significantly less complex structures. Collectively, this data indicates that substituted anthraquinone compounds could serve as a novel scaffold for developing DNMT1-specific inhibitors

Firm size and productivity from occupational choices

We model the distributions of firm sizes and of firms’ total factor productivity (TFP) as outcomes of a market equilibrium from the occupational decisions of individuals with different entrepreneurial skills, of working as employees, employers, or solo entrepreneurs. The model explains empirical regularities such as (i) the positive cross-section correlation between average size of firms and average labor productivity of countries, (ii) the positive association between size and TFP of firms in an economy, and (iii) the power law distribution of firm sizes. Two parameters of the model, one that measures the organizational size diseconomies and other related to the dispersion of the distribution of entrepreneurial skills in the population, appear as main determinants of the differences in firm sizes and in productivity, across economies and among firms within an economy. The results of the paper should be of interest for the design and evaluation of firm-size-dependent policies