A Computational Approach to Estimating Nondisjunction Frequency in Saccharomyces cerevisiae.

Errors segregating homologous chromosomes during meiosis result in aneuploid gametes and are the largest contributing factor to birth defects and spontaneous abortions in humans. Saccharomyces cerevisiae has long served as a model organism for studying the gene network supporting normal chromosome segregation. Measuring homolog nondisjunction frequencies is laborious, and involves dissecting thousands of tetrads to detect missegregation of individually marked chromosomes. Here we describe a computational method (TetFit) to estimate the relative contributions of meiosis I nondisjunction and random-spore death to spore inviability in wild type and mutant strains. These values are based on finding the best-fit distribution of 4, 3, 2, 1, and 0 viable-spore tetrads to an observed distribution. Using TetFit, we found that meiosis I nondisjunction is an intrinsic component of spore inviability in wild-type strains. We show proof-of-principle that the calculated average meiosis I nondisjunction frequency determined by TetFit closely matches empirically determined values in mutant strains. Using these published data sets, TetFit uncovered two classes of mutants: Class A mutants skew toward increased nondisjunction death, and include those with known defects in establishing pairing, recombination, and/or synapsis of homologous chromosomes. Class B mutants skew toward random spore death, and include those with defects in sister-chromatid cohesion and centromere function. Epistasis analysis using TetFit is facilitated by the low numbers of tetrads (as few as 200) required to compare the contributions to spore death in different mutant backgrounds. TetFit analysis does not require any special strain construction, and can be applied to previously observed tetrad distributions

Using Grid Cells for Navigation

SummaryMammals are able to navigate to hidden goal locations by direct routes that may traverse previously unvisited terrain. Empirical evidence suggests that this “vector navigation” relies on an internal representation of space provided by the hippocampal formation. The periodic spatial firing patterns of grid cells in the hippocampal formation offer a compact combinatorial code for location within large-scale space. Here, we consider the computational problem of how to determine the vector between start and goal locations encoded by the firing of grid cells when this vector may be much longer than the largest grid scale. First, we present an algorithmic solution to the problem, inspired by the Fourier shift theorem. Second, we describe several potential neural network implementations of this solution that combine efficiency of search and biological plausibility. Finally, we discuss the empirical predictions of these implementations and their relationship to the anatomy and electrophysiology of the hippocampal formation

Gauge Boson Exchange in AdSd+1AdS_{d+1}

We study the amplitude for exchange of massless gauge bosons between pairs of massive scalar fields in Anti-de Sitter space. In the AdS/CFT correspondence this amplitude describes the contribution of conserved flavor symmetry currents to 4-point functions of scalar operators in the boundary conformal theory. A concise, covariant (Y2K-compatible) derivation of the gauge boson propagator in \AdS_{d+1} is given. Techniques are developed to calculate the two bulk integrals over AdS space leading to explicit expressions or convenient, simple integral representations for the amplitude. The amplitude contains leading power and sub-leading logarithmic singularities in the gauge boson channel and leading logarithms in the crossed channel. The new methods of this paper are expected to have other applications in the study of the Maldacena conjecture.Comment: Corrections in (3.17) and (4.23); version to be published in Nuclear Physics B; 22 pages, 1 figure, using Plain TeX and BoxedEPS macros; email to [email protected]

Playing poker with a committee : assessing the viability of coalitional coercive diplomacy

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Political Science, 2007.Includes bibliographical references.Since the end of the Cold War, 'coercive diplomacy', that is the strategic use of threats aimed at convincing an adversary to stop or undo 'hostile' actions, has become a principle crisis management tool of the Western powers. Yet as a strategy it has a relatively poor track record of success; a record that theorists have struggled to explain. Despite the fact that the majority of such engagements have been undertaken multilaterally, little work to date has focused on the impact that employing a coalitional 'coercing agent' has on the ability to craft a potent package of threats. This study aims to contribute to the debate by testing empirically the impact of coalitional dynamics on the ability of Western powers to employ coercive diplomacy. More specifically, it explores the theoretical tension between the anecdotal assumptions held by certain theorists regarding coalitional action problems (CAP) on the one hand and Jakobsen's four-point ideal policy of coercive diplomacy on the other. I explore this tension through two case studies: the employment of coercive diplomacy by NATO and the Contact Group aimed at halting Serbian aggression in Bosnia between 1992 and 1995 and the Western coalition's attempt to roll back the Iraqi invasion of Kuwait in 1990. The study finds that although CAP do arise as predicted, coalitions have effective mechanisms for overcoming them and thus are able to effectively implement coercive threat packages that approximate to Jakobsen's ideal policy.by Daniel Peter Burgess.S.M

Nurture corners in pre-school settings:Involving and nurturing children and parents

This article draws on the findings from a small qualitative study which focused on gathering perspectives and accounts of experiences from nursery practitioners, health and third sector professionals and parents. It explored the ways in which parents/carers and practitioners experienced the nurture approach developed in preschool settings in Glasgow, Scotland and their perspectives on the impact that this provision has had on the development and well-being of young children and family engagement in learning. The findings provided some insights into the specific ways in which settings involved parents and worked towards developing a nurturing ethos towards parents themselves, underpinned by the following three elements: a welcoming setting, sensitive and empathic staff and creative practice. The study identified challenges for some nurseries in achieving this, such as the limited scope for nurture corner practitioners in some of the settings to fully utilise their skills with parents due to accommodation constraints

The state of child neglect in the UK - An Annual Review by Action for Children in Partnership with the University of Stirling

First paragraph: Over the last decade awareness of the extent of child neglect has grown and there is now a significant evidence base about the severe impact of neglect upon children's well-being and development (Farmer and Lutman, 2012; Stevenson, 2007). There is emerging evidence about the factors associated with effective early intervention and the difference that therapeutic support for children and their families can make (Long et al. 2012)

Reduced grid-like theta modulation in schizophrenia

The hippocampal formation has been implicated in the pathophysiology of schizophrenia, with patients showing impairments in spatial and relational cognition, structural changes in entorhinal cortex, and reduced theta coherence with medial prefrontal cortex. Both the entorhinal cortex and medial prefrontal cortex exhibit a six-fold (or 'hexadirectional') modulation of neural activity during virtual navigation that is indicative of grid cell populations and associated with accurate spatial navigation. Here, we examined whether these grid-like patterns are disrupted in schizophrenia. We asked 17 participants with diagnoses of schizophrenia and 23 controls (matched for age, sex and IQ) to perform a virtual reality spatial navigation task during magnetoencephalography. The control group showed stronger 4-10 Hz theta power during movement onset, as well as hexadirectional modulation of theta band oscillatory activity in the right entorhinal cortex whose directional stability across trials correlated with navigational accuracy. This hexadirectional modulation was absent in patients, with a significant difference between groups. These results suggest that impairments in spatial and relational cognition associated with schizophrenia may arise from disrupted grid firing patterns in entorhinal cortex