Methodology for urban rail and construction technology research and development planning

A series of transit system visits, organized by the American Public Transit Association (APTA), was conducted in which the system operators identified the most pressing development needs. These varied by property and were reformulated into a series of potential projects. To assist in the evaluation, a data base useful for estimating the present capital and operating costs of various transit system elements was generated from published data. An evaluation model was developed which considered the rate of deployment of the research and development project, potential benefits, development time and cost. An outline of an evaluation methodology that considered benefits other than capital and operating cost savings was also presented. During the course of the study, five candidate projects were selected for detailed investigation; (1) air comfort systems; (2) solid state auxiliary power conditioners; (3) door systems; (4) escalators; and (5) fare collection systems. Application of the evaluation model to these five examples showed the usefulness of modeling deployment rates and indicated a need to increase the scope of the model to quantitatively consider reliability impacts

Patterning of the basal telencephalon and hypothalamus is essential for guidance of cortical projections

PMID: 11830575We have investigated the mechanisms that control the guidance of corticofugal projections as they extend along different subdivisions of the forebrain. To this aim, we analyzed the development of cortical projections in mice that lack Nkx2-1, a homeobox gene whose expression is restricted to two domains within the forebrain: the basal telencephalon and the hypothalamus. Molecular respecification of the basal telencephalon and hypothalamus in Nkx2-1-deficient mice causes a severe defect in the guidance of layer 5 cortical projections and ascending fibers of the cerebral peduncle. These axon tracts take an abnormal path when coursing through both the basal telencephalon and hypothalamus. By contrast, loss of Nkx2-1 function does not impair guidance of corticothalamic or thalamocortical axons. In vitro experiments demonstrate that the basal telencephalon and the hypothalamus contain an activity that repels the growth of cortical axons, suggesting that loss of this activity is the cause of the defects observed in Nkx2-1 mutants. Furthermore, analysis of the expression of candidate molecules in the basal telencephalon and hypothalamus of Nkx2-1 mutants suggests that Slit2 contributes to this activity.This work was supported by the research grants to J. L. R. R. from Nina Ireland, NARSAD, NIDA (R01DA12462) and NIMH (RO1 MH49428-01, RO1 MH51561-01A1 and K02 MH01046-01). O. M. is a NARSAD Young Investigator Award recipient and a UC Davis MIND Institute Scholar.Peer reviewe

Single-cell RNA sequencing identifies distinct mouse medial ganglionic eminence cell types.

Many subtypes of cortical interneurons (CINs) are found in adult mouse cortices, but the mechanism generating their diversity remains elusive. We performed single-cell RNA sequencing on the mouse embryonic medial ganglionic eminence (MGE), the major birthplace for CINs, and on MGE-like cells differentiated from embryonic stem cells. Two distinct cell types were identified as proliferating neural progenitors and immature neurons, both of which comprised sub-populations. Although lineage development of MGE progenitors was reconstructed and immature neurons were characterized as GABAergic, cells that might correspond to precursors of different CINs were not identified. A few non-neuronal cell types were detected, including microglia. In vitro MGE-like cells resembled bona fide MGE cells but expressed lower levels of Foxg1 and Epha4. Together, our data provide detailed understanding of the embryonic MGE developmental program and suggest how CINs are specified

The mechanical response of semiflexible networks to localized perturbations

Previous research on semiflexible polymers including cytoskeletal networks in cells has suggested the existence of distinct regimes of elastic response, in which the strain field is either uniform (affine) or non-uniform (non-affine) under external stress. Associated with these regimes, it has been further suggested that a new fundamental length scale emerges, which characterizes the scale for the crossover from non-affine to affine deformations. Here, we extend these studies by probing the response to localized forces and force dipoles. We show that the previously identified nonaffinity length [D.A. Head et al. PRE 68, 061907 (2003).] controls the mesoscopic response to point forces and the crossover to continuum elastic behavior at large distances.Comment: 16 pages, 18 figures; substantial changes to text and figures to clarify the crossover to continuum elasticity and the role of finite-size effect

Critical Reflections on Building a Community of Conversation about Water Governance in Australia

Water governance has emerged as a field of research endeavour in response to failures of current and historical management approaches to adequately address persistent decline in ecological health of many river catchments and pressures on associated communities. Attention to situational framing is a key aspect of emerging approaches to water governance research, including innovations that build capacity and confidence to experiment with approaches capable of transforming situations usefully framed as ‘wicked’. Despite international investment in water governance research, a national research agenda on water governance was lacking in Australia in the late 2000s as were mechanisms to build the capacity of interdisciplinary and transdisciplinary research and collaborative policy practice. Through a two-year Water Governance Research Initiative (WGRI), we designed and facilitated the development of a community of conversation between researchers concerned with the dynamics of human-ecological systems from the natural sciences, humanities, social sciences, policy, economics, law and philosophy. The WGRI was designed as a learning system, with the intention that it would provide opportunities for conversations, learning and reflection to emerge. In this paper we outline the starting conditions and design of the WGRI, critically reflect on new narratives that arose from this initiative, and evaluate its effectiveness as a boundary organisation that contributed to knowledge co-production in water governance. Our findings point to the importance of investment in institutions that can act as integrative and facilitative governance mechanisms, to build capacity to work with and between research, policy, local stakeholders and practitioners

Multiple conserved regulatory domains promote Fezf2 expression in the developing cerebral cortex.

BackgroundThe genetic programs required for development of the cerebral cortex are under intense investigation. However, non-coding DNA elements that control the expression of developmentally important genes remain poorly defined. Here we investigate the regulation of Fezf2, a transcription factor that is necessary for the generation of deep-layer cortical projection neurons.ResultsUsing a combination of chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) we mapped the binding of four deep-layer-enriched transcription factors previously shown to be important for cortical development. Building upon this we characterized the activity of three regulatory regions around the Fezf2 locus at multiple stages throughout corticogenesis. We identified a promoter that was sufficient for expression in the cerebral cortex, and enhancers that drove reporter gene expression in distinct forebrain domains, including progenitor cells and cortical projection neurons.ConclusionsThese results provide insight into the regulatory logic controlling Fezf2 expression and further the understanding of how multiple non-coding regulatory domains can collaborate to control gene expression in vivo

Unfolding cross-linkers as rheology regulators in F-actin networks

We report on the nonlinear mechanical properties of a statistically homogeneous, isotropic semiflexible network cross-linked by polymers containing numerous small unfolding domains, such as the ubiquitous F-actin cross-linker Filamin. We show that the inclusion of such proteins has a dramatic effect on the large strain behavior of the network. Beyond a strain threshold, which depends on network density, the unfolding of protein domains leads to bulk shear softening. Past this critical strain, the network spontaneously organizes itself so that an appreciable fraction of the Filamin cross-linkers are at the threshold of domain unfolding. We discuss via a simple mean-field model the cause of this network organization and suggest that it may be the source of power-law relaxation observed in in vitro and in intracellular microrheology experiments. We present data which fully justifies our model for a simplified network architecture.Comment: 11 pages, 4 figures. to appear in Physical Review

Comparative Monte Carlo Efficiency by Monte Carlo Analysis

We propose a modified power method for computing the subdominant eigenvalue $\lambda_2$ of a matrix or continuous operator. Here we focus on defining simple Monte Carlo methods for its application. The methods presented use random walkers of mixed signs to represent the subdominant eigenfuction. Accordingly, the methods must cancel these signs properly in order to sample this eigenfunction faithfully. We present a simple procedure to solve this sign problem and then test our Monte Carlo methods by computing the $\lambda_2$ of various Markov chain transition matrices. We first computed ${\lambda_2}$ for several one and two dimensional Ising models, which have a discrete phase space, and compared the relative efficiencies of the Metropolis and heat-bath algorithms as a function of temperature and applied magnetic field. Next, we computed $\lambda_2$ for a model of an interacting gas trapped by a harmonic potential, which has a mutidimensional continuous phase space, and studied the efficiency of the Metropolis algorithm as a function of temperature and the maximum allowable step size $\Delta$. Based on the $\lambda_2$ criterion, we found for the Ising models that small lattices appear to give an adequate picture of comparative efficiency and that the heat-bath algorithm is more efficient than the Metropolis algorithm only at low temperatures where both algorithms are inefficient. For the harmonic trap problem, we found that the traditional rule-of-thumb of adjusting $\Delta$ so the Metropolis acceptance rate is around 50% range is often sub-optimal. In general, as a function of temperature or $\Delta$, $\lambda_2$ for this model displayed trends defining optimal efficiency that the acceptance ratio does not. The cases studied also suggested that Monte Carlo simulations for a continuum model are likely more efficient than those for a discretized version of the model.Comment: 23 pages, 8 figure

Soluble Guanylate Cyclase Generation of cGMP Regulates Migration of MGE Neurons

Here we have provided evidence that nitric oxide-cyclic GMP (NO-cGMP) signaling regulates neurite length and migration of immature neurons derived from the medial ganglionic eminence (MGE). Dlx1/2(-/-) and Lhx6(-/-) mouse mutants, which exhibit MGE interneuron migration defects, have reduced expression of the gene encoding the alpha subunit of a soluble guanylate cyclase (Gucy1A3). Furthermore, Dlx1/2(-/-) mouse mutants have reduced expression of NO synthase 1 (NOS1). Gucy1A3(-/-) mice have a transient reduction in cortical interneuron number. Pharmacological inhibition of soluble guanylate cyclase and NOS activity rapidly induces neurite retraction of MGE cells in vitro and in slice culture and robustly inhibits cell migration from the MGE and caudal ganglionic eminence. We provide evidence that these cellular phenotypes are mediated by activation of the Rho signaling pathway and inhibition of myosin light chain phosphatase activity