Human in vitro models for understanding mechanisms of autism spectrum disorder.

Early brain development is a critical epoch for the development of autism spectrum disorder (ASD). In vivo animal models have, until recently, been the principal tool used to study early brain development and the changes occurring in neurodevelopmental disorders such as ASD. In vitro models of brain development represent a significant advance in the field. Here, we review the main methods available to study human brain development in vitro and the applications of these models for studying ASD and other psychiatric disorders. We discuss the main findings from stem cell models to date focusing on cell cycle and proliferation, cell death, cell differentiation and maturation, and neuronal signaling and synaptic stimuli. To be able to generalize the results from these studies, we propose a framework of experimental design and power considerations for using in vitro models to study ASD. These include both technical issues such as reproducibility and power analysis and conceptual issues such as the brain region and cell types being modeled

Eurocentric Archival Knowledge Production and Decolonizing Archival Theory

This dissertation is interested in how archival theory—the theoretical work of archiving produced by archivists and, to a lesser extent, the modes of doing archival research deployed by researchers—tackles the colonial roots and routes of archives, archivists and archival theories and practices. At the base of this examination of archival theory is the assumption that theory produces the object it evaluates. Thus, as opposed to interrogating a pre-existing archive, archival theory produces imaginative and material archival spaces in which archivists and researchers labour. In this dissertation, then, I examine the ways in which Eurocentric intellectual frameworks continue to frame archival theory and, thus, delimit how archivists and researchers produce knowledge about and through archives. In particular, this dissertation is interested in how the Eurocentrism underwriting archival theory as much shapes archivists’ understanding of colonialism and colonial archives by establishing the archive’s and archival theory’s geography, history and future trajectory as covers over the archives’ and archival theory’s colonial history. With an eye to the work of contemporary archivists and theorists who critically interrogate the ways archives and archivists reproduce unequal social relations of power, the following chapters negotiate the tension within these critiques between developing more democratic, socially just and postcolonial archives and archival theory, and the Eurocentric intellectual frameworks that reiterate the divisions between West and non-West, modern societies and traditional communities, literate and oral, and between reason and feeling. The works of Canadian archivists and scholars figure prominently in my dissertation as they both shape my analyses of the effects of Eurocentrism and continuing settler colonial relations on archives, archiving and archival research, and also become objects of analysis through which I trace out the discourses that work to secure and trouble settler title and entitlement to Aboriginal land by erasing or nullifying Indigenous sovereignty in and through Canada’s archives. The aim of my dissertation is to propose modes of archival knowledge production that trouble, if not displace, these Eurocentric and settler frameworks to decolonize archives and archival theory

A Schmidt-Nochka Theorem for closed subschemes in subgeneral position

In previous work, the authors established a generalized version of Schmidt's subspace theorem for closed subschemes in general position in terms of Seshadri constants. We extend our theorem to weighted sums involving closed subschemes in subgeneral position, providing a joint generalization of Schmidt's theorem with seminal inequalities of Nochka. A key aspect of the proof is the use of a lower bound for Seshadri constants of intersections from algebraic geometry, as well as a generalized Chebyshev inequality. As an application, we extend inequalities of Nochka and Ru-Wong from hyperplanes in $m$-subgeneral position to hypersurfaces in $m$-subgeneral position in projective space, proving a sharp result in dimensions $2$ and $3$, and coming within a factor of $3/2$ of a sharp inequality in all dimensions. We state analogous results in Nevanlinna theory generalizing the Second Main Theorem and Nochka's theorem (Cartan's conjecture)

DIGITAL INNOVATION AND CRAFTSMANSHIP: THE CASE OF C. F. MARTIN & COMPANY

Craftsmanship is a concept often left unaddressed in the IT innovation literature. Further, this literature often fails to consider innovation that involves human labor on the shop floor. With the sheer volume of organizations that operate in craft-based industries, placing a strident focus upon craftsmanship and predominantly innovating on the shop floor, this is particularly concerning. This work therefore examines the influence of considered craftsmanship on the nature and consequences of digital innovation in the guitar manufacturing process at C. F. Martin & Company. We propose a model of innovation that incorporates the concept of the activity system, drawn from the field of activity theory. Individual innovations cause disturbances in actor-tooltask relationships (activity systems). This drives a series of reconfigurations, in an effort to eliminate said disturbances. Preliminary qualitative evidence is provided, supporting the proposed model, in the form of a series of semi-structured interviews

A Comprehensive Analysis of Molecule-Intrinsic Quasi-Atomic, Bonding, and Correlating Orbitals. I. Hartree-Fock Wave Functions

Through a basis-set-independent web of localizing orbital-transformations, the electronic wave function of a molecule is expressed in terms of a set of orbitals that reveal the atomic structure and the bonding pattern of a molecule. The analysis is based on resolving the valence orbital space in terms of an internal space, which has minimal basis set dimensions, and an external space. In the internal space, oriented quasi-atomic orbitals and split-localized molecular orbitals are determined by new, fast localization methods. The density matrix between the oriented quasi-atomic orbitals as well as the locations of the split-localized orbitals exhibit atomic populations and inter-atomic bonding patterns. A correlation-adapted quasi-atomic basis is determined in the external orbital space. The general formulations are specified in detail for Hartree-Fock wave functions. Applications to specific molecules exemplify the general scheme

A Comprehensive Analysis in Terms of Molecule-Intrinsic Quasi- Atomic Orbitals. IV. Bond Breaking and Bond Forming along the Dissociative Reaction Path of Dioxetane

The quantitative analysis of molecular density matrices in terms of oriented quasi-atomic orbitals (QUAOs) is shown to yield detailed conceptual insight into the dissociation of dioxetane on the basis of ab initio wave functions. The QUAOs persist and can be followed throughout the reaction path. The kinetic bond orders and the orbital populations of the QUAOs quantitatively reveal the changes of the bonding interactions along the reaction path. At the transition state the OO bond is broken, and the molecule becomes a biradical. After the transition state the reaction path bifurcates. The minimum energy path gently descends from the transition state via a valley–ridge inflection point to a second saddle point, from which two new minimum energy paths lead to two equivalent formaldehyde dimers. The CC bond breaks, and the π-bonds of the formaldehyde fragments form in close vicinity of the second saddle point. The changes of the interactions in this region are elucidated by the analysis of the rearrangements of the QUAOs

Is the PAMELA Positron Excess Winos?

Recently the PAMELA satellite-based experiment reported an excess of galactic positrons that could be a signal of annihilating dark matter. The PAMELA data may admit an interpretation as a signal from a wino-like LSP of mass about 200 GeV, normalized to the local relic density, and annihilating mainly into W-bosons. This possibility requires the current conventional estimate for the energy loss rate of positrons be too large by roughly a factor of five. Data from anti-protons and gamma rays also provide tension with this interpretation, but there are significant astrophysical uncertainties associated with their propagation. It is not unreasonable to take this well-motivated candidate seriously, at present, in part because it can be tested in several ways soon. The forthcoming PAMELA data on higher energy positrons and the FGST (formerly GLAST) data, should provide important clues as to whether this scenario is correct. If correct, the wino interpretation implies a cosmological history in which the dark matter does not originate in thermal equilibrium.Comment: 7 pages, 4 figue