4,030 research outputs found
Gender-Specific Fine Motor Skill Learning Is Impaired by Myelin-Targeted Neurofibromatosis Type 1 Gene Mutation
Simple Summary
Most neurofibromatosis type 1 (NF1) patients present with neurological issues in parallel with abnormal brain white matter and myelin. Although links for NF1 neuropathophysiology and abnormal myelin were proposed long ago, no current data can openly support or refute this idea. Various studies suggest that Nf1 mutations affect myelin biology and function, but any impact on learning/memory remains unclear. Here, we show that mice with an Nf1 mutation induced in adult myelinating cells present learning, but not memory, issues in a voluntary fine motor skill test, the complex wheel (CW). The specific parameters shaping CW learning curves are differentially impacted in an Nf1 mutation dose- and gender-dependent manner and are responsive to nitric oxide modulation. Fate analyses of Nf1 mutant cells support links between defective myelin and fine motor learning issues. Our results diversify the potential therapeutic targets and windows of time for NF1 treatments that restore or improve myelin function. Abstract
Neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene. The clinical presentation of NF1 includes diverse neurological issues in pediatric and adult patients, ranging from learning disabilities, motor skill issues, and attention deficit disorder, to increased risk of depression and dementia. Preclinical research suggests that abnormal neuronal signaling mediates spatial learning and attention issues in NF1; however, drugs that improve phenotypes in models show inconclusive results in clinical trials, highlighting the need for a better understanding of NF1 pathophysiology and broader therapeutic options. Most NF1 patients show abnormalities in their brain white matter (WM) and myelin, and links with NF1 neuropathophysiology have been suggested; however, no current data can clearly support or refute this idea. We reported that myelin-targeted Nf1 mutation impacts oligodendrocyte signaling, myelin ultrastructure, WM connectivity, and sensory–motor behaviors in mice; however, any impact on learning and memory remains unknown. Here, we adapted a voluntary running test—the complex wheel (CW; a wheel with unevenly spaced rungs)—to delineate fine motor skill learning curves following induction of an Nf1 mutation in pre-existing myelinating cells (pNf1 mice). We found that pNf1 mutant females experience delayed or impaired learning in the CW, while proper learning in pNf1 males is predominantly disrupted; these phenotypes add complexity to the gender-dependent learning differences in the mouse strain used. No broad differences in memory of acquired CW skills were detected in any gender, but gene-dose effects were observed at the studied time points. Finally, nitric oxide signaling regulation differentially impacted learning in wild type (WT)/pNf1, male/female mice. Our results provide evidence for fine motor skill learning issues upon induction of an Nf1 mutation in mature myelinating cells. Together with previous connectivity, cellular, and molecular analyses, these results diversify the potential treatments for neurological issues in NF1
Matching microscopic and macroscopic responses in glasses
We first reproduce on the Janus and Janus II computers a milestone experiment
that measures the spin-glass coherence length through the lowering of
free-energy barriers induced by the Zeeman effect. Secondly we determine the
scaling behavior that allows a quantitative analysis of a new experiment
reported in the companion Letter [S. Guchhait and R. Orbach, Phys. Rev. Lett.
118, 157203 (2017)]. The value of the coherence length estimated through the
analysis of microscopic correlation functions turns out to be quantitatively
consistent with its measurement through macroscopic response functions.
Further, non-linear susceptibilities, recently measured in glass-forming
liquids, scale as powers of the same microscopic length.Comment: 6 pages, 4 figure
Nature of the spin-glass phase at experimental length scales
We present a massive equilibrium simulation of the three-dimensional Ising
spin glass at low temperatures. The Janus special-purpose computer has allowed
us to equilibrate, using parallel tempering, L=32 lattices down to T=0.64 Tc.
We demonstrate the relevance of equilibrium finite-size simulations to
understand experimental non-equilibrium spin glasses in the thermodynamical
limit by establishing a time-length dictionary. We conclude that
non-equilibrium experiments performed on a time scale of one hour can be
matched with equilibrium results on L=110 lattices. A detailed investigation of
the probability distribution functions of the spin and link overlap, as well as
of their correlation functions, shows that Replica Symmetry Breaking is the
appropriate theoretical framework for the physically relevant length scales.
Besides, we improve over existing methodologies to ensure equilibration in
parallel tempering simulations.Comment: 48 pages, 19 postscript figures, 9 tables. Version accepted for
publication in the Journal of Statistical Mechanic
Janus II: a new generation application-driven computer for spin-system simulations
This paper describes the architecture, the development and the implementation
of Janus II, a new generation application-driven number cruncher optimized for
Monte Carlo simulations of spin systems (mainly spin glasses). This domain of
computational physics is a recognized grand challenge of high-performance
computing: the resources necessary to study in detail theoretical models that
can make contact with experimental data are by far beyond those available using
commodity computer systems. On the other hand, several specific features of the
associated algorithms suggest that unconventional computer architectures, which
can be implemented with available electronics technologies, may lead to order
of magnitude increases in performance, reducing to acceptable values on human
scales the time needed to carry out simulation campaigns that would take
centuries on commercially available machines. Janus II is one such machine,
recently developed and commissioned, that builds upon and improves on the
successful JANUS machine, which has been used for physics since 2008 and is
still in operation today. This paper describes in detail the motivations behind
the project, the computational requirements, the architecture and the
implementation of this new machine and compares its expected performances with
those of currently available commercial systems.Comment: 28 pages, 6 figure
The three dimensional Ising spin glass in an external magnetic field: the role of the silent majority
We perform equilibrium parallel-tempering simulations of the 3D Ising
Edwards-Anderson spin glass in a field. A traditional analysis shows no signs
of a phase transition. Yet, we encounter dramatic fluctuations in the behaviour
of the model: Averages over all the data only describe the behaviour of a small
fraction of it. Therefore we develop a new approach to study the equilibrium
behaviour of the system, by classifying the measurements as a function of a
conditioning variate. We propose a finite-size scaling analysis based on the
probability distribution function of the conditioning variate, which may
accelerate the convergence to the thermodynamic limit. In this way, we find a
non-trivial spectrum of behaviours, where a part of the measurements behaves as
the average, while the majority of them shows signs of scale invariance. As a
result, we can estimate the temperature interval where the phase transition in
a field ought to lie, if it exists. Although this would-be critical regime is
unreachable with present resources, the numerical challenge is finally well
posed.Comment: 42 pages, 19 figures. Minor changes and added figure (results
unchanged
Critical parameters of the three-dimensional Ising spin glass
We report a high-precision finite-size scaling study of the critical behavior
of the three-dimensional Ising Edwards-Anderson model (the Ising spin glass).
We have thermalized lattices up to L=40 using the Janus dedicated computer. Our
analysis takes into account leading-order corrections to scaling. We obtain Tc
= 1.1019(29) for the critical temperature, \nu = 2.562(42) for the thermal
exponent, \eta = -0.3900(36) for the anomalous dimension and \omega = 1.12(10)
for the exponent of the leading corrections to scaling. Standard (hyper)scaling
relations yield \alpha = -5.69(13), \beta = 0.782(10) and \gamma = 6.13(11). We
also compute several universal quantities at Tc.Comment: 9 pages, 5 figure
Thermodynamic glass transition in a spin glass without time-reversal symmetry
Spin glasses are a longstanding model for the sluggish dynamics that appears
at the glass transition. However, spin glasses differ from structural glasses
for a crucial feature: they enjoy a time reversal symmetry. This symmetry can
be broken by applying an external magnetic field, but embarrassingly little is
known about the critical behaviour of a spin glass in a field. In this context,
the space dimension is crucial. Simulations are easier to interpret in a large
number of dimensions, but one must work below the upper critical dimension
(i.e., in d<6) in order for results to have relevance for experiments. Here we
show conclusive evidence for the presence of a phase transition in a
four-dimensional spin glass in a field. Two ingredients were crucial for this
achievement: massive numerical simulations were carried out on the Janus
special-purpose computer, and a new and powerful finite-size scaling method.Comment: 10 pages, 6 figure
Critical Behavior of Three-Dimensional Disordered Potts Models with Many States
We study the 3D Disordered Potts Model with p=5 and p=6. Our numerical
simulations (that severely slow down for increasing p) detect a very clear spin
glass phase transition. We evaluate the critical exponents and the critical
value of the temperature, and we use known results at lower values to
discuss how they evolve for increasing p. We do not find any sign of the
presence of a transition to a ferromagnetic regime.Comment: 9 pages and 9 Postscript figures. Final version published in J. Stat.
Mec
A multi-voiced account of family entrepreneuring research: expanding the agenda of family entrepreneurship
Purpose This conceptual, multi-voiced paper aims to collectively explore and theorize family entrepreneuring, which is a research stream dedicated to investigating the emergence and becoming of entrepreneurial phenomena in business families and family firms. Design/methodology/approach Because of the novelty of this research stream, the authors asked 20 scholars in entrepreneurship and family business to reflect on topics, methods and issues that should be addressed to move this field forward. Findings Authors highlight key challenges and point to new research directions for understanding family entrepreneuring in relation to issues such as agency, processualism and context. Originality/value This study offers a compilation of multiple perspectives and leverage recent developments in the fields of entrepreneurship and family business to advance research on family entrepreneuring
Investigación en matemáticas, economÃa y ciencias sociales
El resultado de este libro que reune inquietudes académicas en torno a temas tan estudiados como los que están alrededor del maÃz, del frijol o del café; y tan contemporáneos como las aplicaciones concretas de las ciencias ya citadas, al estudio de la adopción del comercio electrónico en empresas del sector agroindustrial o, el caso de la generación de biogas o energÃa eléctrica por medio de biodigestores. Al editar este texto e incorporarlo a la bibliografÃa de los temas de referencia, se enriquecen opciones de consulta para los estudiosos de esos temas en general; pero también para interesados en aspectos tan especÃficos como la cadena de suministro del mercado hortofrutÃcola en Texcoco
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