Identification of HMX1 target genes: a predictive promoter model approach.

PURPOSE: A homozygous mutation in the H6 family homeobox 1 (HMX1) gene is responsible for a new oculoauricular defect leading to eye and auricular developmental abnormalities as well as early retinal degeneration (MIM 612109). However, the HMX1 pathway remains poorly understood, and in the first approach to better understand the pathway's function, we sought to identify the target genes. METHODS: We developed a predictive promoter model (PPM) approach using a comparative transcriptomic analysis in the retina at P15 of a mouse model lacking functional Hmx1 (dmbo mouse) and its respective wild-type. This PPM was based on the hypothesis that HMX1 binding site (HMX1-BS) clusters should be more represented in promoters of HMX1 target genes. The most differentially expressed genes in the microarray experiment that contained HMX1-BS clusters were used to generate the PPM, which was then statistically validated. Finally, we developed two genome-wide target prediction methods: one that focused on conserving PPM features in human and mouse and one that was based on the co-occurrence of HMX1-BS pairs fitting the PPM, in human or in mouse, independently. RESULTS: The PPM construction revealed that sarcoglycan, gamma (35kDa dystrophin-associated glycoprotein) (Sgcg), teashirt zinc finger homeobox 2 (Tshz2), and solute carrier family 6 (neurotransmitter transporter, glycine) (Slc6a9) genes represented Hmx1 targets in the mouse retina at P15. Moreover, the genome-wide target prediction revealed that mouse genes belonging to the retinal axon guidance pathway were targeted by Hmx1. Expression of these three genes was experimentally validated using a quantitative reverse transcription PCR approach. The inhibitory activity of Hmx1 on Sgcg, as well as protein tyrosine phosphatase, receptor type, O (Ptpro) and Sema3f, two targets identified by the PPM, were validated with luciferase assay. CONCLUSIONS: Gene expression analysis between wild-type and dmbo mice allowed us to develop a PPM that identified the first target genes of Hmx1.

Update on the non-prewhitening model observer in computed tomography for the assessment of the adaptive statistical and model-based iterative reconstruction algorithms.

The state of the art to describe image quality in medical imaging is to assess the performance of an observer conducting a task of clinical interest. This can be done by using a model observer leading to a figure of merit such as the signal-to-noise ratio (SNR). Using the non-prewhitening (NPW) model observer, we objectively characterised the evolution of its figure of merit in various acquisition conditions. The NPW model observer usually requires the use of the modulation transfer function (MTF) as well as noise power spectra. However, although the computation of the MTF poses no problem when dealing with the traditional filtered back-projection (FBP) algorithm, this is not the case when using iterative reconstruction (IR) algorithms, such as adaptive statistical iterative reconstruction (ASIR) or model-based iterative reconstruction (MBIR). Given that the target transfer function (TTF) had already shown it could accurately express the system resolution even with non-linear algorithms, we decided to tune the NPW model observer, replacing the standard MTF by the TTF. It was estimated using a custom-made phantom containing cylindrical inserts surrounded by water. The contrast differences between the inserts and water were plotted for each acquisition condition. Then, mathematical transformations were performed leading to the TTF. As expected, the first results showed a dependency of the image contrast and noise levels on the TTF for both ASIR and MBIR. Moreover, FBP also proved to be dependent of the contrast and noise when using the lung kernel. Those results were then introduced in the NPW model observer. We observed an enhancement of SNR every time we switched from FBP to ASIR to MBIR. IR algorithms greatly improve image quality, especially in low-dose conditions. Based on our results, the use of MBIR could lead to further dose reduction in several clinical applications.

Analysis of Earnings, Stock Prices and Bond Yields: The Fed Model Approach

Prediction of the stock market valuation is a common interest to all market participants. Theoretically sound market valuation can be achieved by discounting future earnings of equities to present. Competing valuation models seek to find variables that affect the equity market valuation in a way that the market valuation can be explained and also variables that could be used to predict market valuation. In this paper we test the contemporaneous relationship between stock prices, forward looking earnings and long-term government bond yields. We test this so-called Fed model in a long- and short-term time series analysis. In order to test the dynamics of the relationship, we use the cointegration framework. The data used in this study spans over four decades of various market conditions between 1964-2007, using data from United States. The empirical results of our analysis do not give support for the Fed model. We are able to show that the long-term government bonds do not play statistically significant role in this relationship. The effect of forward earnings yield on the stock market prices is significant and thus we suggest the use of standard valuation ratios when trying to predict the future paths of equity prices. Also, changes in the long-term government bond yields do not have significant short-term impact on stock prices.

Developing Life Skills through Physical Activity: A Teaching Personal and Social Responsibility Model Approach

Ethnographic methods were used to study a weekly after-school physical activity program over an eight-month period. Based on Hellison’s Teaching Personal and Social Responsibility (TPSR) model, the program sought to foster positive life skills amongst youth. The study investigated how the developed program influenced this life skills education experience. Several themes were identified from the data revolving around culture, life skills, pedagogy, and lessons learned. Data suggests that the positive environment developed within the program positively influenced youths’ life skill education experience. The topic of ethnicity as it relates to the experience of marginalized youth in physical activity settings is also discussed. This study supports TPSR literature and suggests that effort to establish caring relationships and empower youth contribute to the establishment of a positive atmosphere where life skills education can occur. Beyond this, practical tools were developed through this study to help others deliver life skill education.

Simple general method of generating non-oxo, non-amavadine model octacoordinated vanadium(IV) complexes of some tetradentate ONNO chelating ligands from various oxovanadium(IV/V) compounds and structural characterization of one of them

A simple general route of obtaining very stable octacoordinated non-oxovanadium( IV) complexes of the general formula VL2 (where H2L is a tetradentate ONNO donor) is presented. Six such complexes (1-6) are adequately characterized by elemental analysis, mass spectrometry, and various spectroscopic techniques. One of these compounds (1) has been structurally characterized. The molecule has crystallographic 4 symmetry and has a dodecahedral structure existing in a tetragonal space group P4n2. The non-oxo character and VL2 stoichiometry for all of the complexes are established from analytical and mass spectrometric data. In addition, the non-oxo character is clearly indicated by the complete absence of the strong nu(v=o) band in the 925-1025 cm(-1) region, which is a signature of all oxovanadium species. The complexes are quite stable in open air in the solid state and in solution, a phenomenon rarely observed in non-oxovanadium(IV) or bare vanadium(IV) complexes.

Risk taking for oneself and others: a structural model approach

Economic theory makes no predictions about social factors affecting decisions under risk. We examine situations in which a decision maker decides for herself and another person under conditions of payoff equality, and compare them to individual decisions. By estimating a structural model, we find that responsibility leaves utility curvature unaffected, but accentuates the subjective distortion of very small and very large probabilities for both gains and losses. We also find that responsibility reduces loss aversion, but that these results only obtain under some specific definitions of the latter. These results serve to generalize and reconcile some of the still largely contradictory findings in the literature. They also have implications for financial agency, which we discuss.

Comparison of terrain following and cut cell grids using a non-hydrostatic model

Terrain following coordinates are widely used in operational models but the cut cell method has been proposed as an alternative that can more accurately represent atmospheric dynamics over steep orography. Because the type of grid is usually chosen during model implementation, it becomes necessary to use different models to compare the accuracy of different grids. In contrast, here a C-grid finite volume model enables a like-for-like comparison of terrain following and cut cell grids. A series of standard two-dimensional tests using idealised terrain are performed: tracer advection in a prescribed horizontal velocity field, a test starting from resting initial conditions, and orographically induced gravity waves described by nonhydrostatic dynamics. In addition, three new tests are formulated: a more challenging resting atmosphere case, and two new advection tests having a velocity field that is everywhere tangential to the terrain following coordinate surfaces. These new tests present a challenge on cut cell grids. The results of the advection tests demonstrate that accuracy depends primarily upon alignment of the flow with the grid rather than grid orthogonality. A resting atmosphere is well-maintained on all grids. In the gravity waves test, results on all grids are in good agreement with existing results from the literature, although terrain following velocity fields lead to errors on cut cell grids. Due to semi-implicit timestepping and an upwind-biased, explicit advection scheme, there are no timestep restrictions associated with small cut cells. We do not find the significant advantages of cut cells or smoothed coordinates that other authors find.

Practice location of physicians: a discrete choice model approach

Economists and policymakers have long been concerned with increasing the supply of health professionals in rural and remote areas. This work seeks to understand which factors influence physicians’ choice of practice location right after completing residency. Differently from previous papers, we analyse the Brazilian missalocation and assess the particularities of developing countries. We use a discrete choice model approach with a multinomial logit specification. Two rich databases are employed containing the location and wage of formally employed physicians as well as details from their post-graduation. Our main findings are that amenities matter, physicians have a strong tendency to remain in the region they completed residency and salaries are significant in the choice of urban, but not rural, communities. We conjecture this is due to attachments built during training and infrastructure concerns.

Bank networks and firm credit: an agent based model approach

Starting from the idea that economic systems fall into complexity theory, where its many agents interact with each other without a central control and that these interactions are able to change the future behavior of the agents and the entire system, similar to a chaotic system we increase the model of Russo et al. (2014) to carry out three experiments focusing on the interaction between Banks and Firms in an artificial economy. The first experiment is relative to Relationship Banking where, according to the literature, the interaction over time between Banks and Firms are able to produce mutual benefits, mainly due to reduction of the information asymmetry between them. The following experiment is related to information heterogeneity in the credit market, where the larger the bank, the higher their visibility in the credit market, increasing the number of consult for new loans. Finally, the third experiment is about the effects on the credit market of the heterogeneity of prices that Firms faces in the goods market.

A simple and non-destructive model for individual leaf area estimation in citrus

Introduction. Leaf area is often related to plant growth, development, physiology and yield. Many non-destructive models have been proposed for leaf area estimation of several plant genotypes, demonstrating that leaf length, leaf width and leaf area are closely correlated. Thus, the objective of our study was to develop a reliable model for leaf area estimation from linear measurements of leaf dimensions for citrus genotypes. Materials and methods. Leaves of citrus genotypes were harvested, and their dimensions (length, width and area) were measured. Values of leaf area were regressed against length, width, the square of length, the square of width and the product (length x width). The most accurate equations, either linear or second-order polynomial, were regressed again with a new data set; then the most reliable equation was defined. Results and discussion. The first analysis showed that the variables length, width and the square of length gave better results in second-order polynomial equations, while the linear equations were more suitable and accurate when the width and the product (length x width) were used. When these equations were regressed with the new data set, the coefficient of determination (R(2)) and the agreement index 'd' were higher for the one that used the variable product (length x width), while the Mean Absolute Percentage Error was lower. Conclusion. The product of the simple leaf dimensions (length x width) can provide a reliable and simple non-destructive model for leaf area estimation across citrus genotypes.

Ghost poles in the nucleon propagator in the linear sigma model approach and its role in pi N low-energy theorems

Complex mass poles, or ghost poles, are present in the Hartree-Fock solution of the Schwinger-Dyson equation for the nucleon propagator in renormalizable models with Yukawa-type meson-nucleon couplings, as shown many years ago by Brown, Puff and Wilets (BPW), These ghosts violate basic theorems of quantum field theory and their origin is related to the ultraviolet behavior of the model interactions, Recently, Krein et.al, proved that the ghosts disappear when vertex corrections are included in a self-consistent way, softening the interaction sufficiently in the ultraviolet region. In previous studies of pi N scattering using ''dressed'' nucleon propagator and bare vertices, did by Nutt and Wilets in the 70's (NW), it was found that if these poles are explicitly included, the value of the isospin-even amplitude A((+)) is satisfied within 20% at threshold. The absence of a theoretical explanation for the ghosts and the lack of chiral symmetry in these previous studies led us to re-investigate the subject using the approach of the linear sigma-model and study the interplay of low-energy theorems for pi N scattering and ghost poles. For bare interaction vertices we find that ghosts are present in this model as well and that the A((+)) value is badly described, As a first approach to remove these complex poles, we dress the vertices with phenomenological form factors and a reasonable agreement with experiment is achieved, In order to fix the two cutoff parameters, we use the A((+)) value for the chiral limit (m(pi) --> 0) and the experimental value of the isoscalar scattering length, Finally, we test our model by calculating the phase shifts for the S waves and we find a good agreement at threshold. (C) 1997 Elsevier B.V. B.V.

The non-adiabatic hyperspherical approach to the two-dimensional D- ion in the presence of a magnetic field

We have used the adiabatic hyperspherical approach to determine the energies and wave functions of the ground state and first excited states of a two-dimensional D- ion in the presence of a magnetic field. Using a modified hyperspherical angular variable, potential energy curves are analytically obtained, allowing an accurate determination of the energy levels of this system. Upper and lower bounds for the ground-state energy have been determined by a non-adiabatic procedure, as the purpose is to improve the accuracy of method. The results are shown to be comparable to the best variational calculations reported in the literature.