A functional motor unit in the culture dish : co-culture of spinal cord explants and muscle cells

Human primary muscle cells cultured aneurally in monolayer rarely contract spontaneously because, in the absence of a nerve component, cell differentiation is limited and motor neuron stimulation is missing(1). These limitations hamper the in vitro study of many neuromuscular diseases in cultured muscle cells. Importantly, the experimental constraints of monolayered, cultured muscle cells can be overcome by functional innervation of myofibers with spinal cord explants in co-cultures. Here, we show the different steps required to achieve an efficient, proper innervation of human primary muscle cells, leading to complete differentiation and fiber contraction according to the method developed by Askanas(2). To do so, muscle cells are co-cultured with spinal cord explants of rat embryos at ED 13.5, with the dorsal root ganglia still attached to the spinal cord slices. After a few days, the muscle fibers start to contract and eventually become cross-striated through innervation by functional neurites projecting from the spinal cord explants that connecting to the muscle cells. This structure can be maintained for many months, simply by regular exchange of the culture medium. The applications of this invaluable tool are numerous, as it represents a functional model for multidisciplinary analyses of human muscle development and innervation. In fact, a complete de novo neuromuscular junction installation occurs in a culture dish, allowing an easy measurement of many parameters at each step, in a fundamental and physiological context. Just to cite a few examples, genomic and/or proteomic studies can be performed directly on the co-cultures. Furthermore, pre- and post-synaptic effects can be specifically and separately assessed at the neuromuscular junction, because both components come from different species, rat and human, respectively. The nerve-muscle co-culture can also be performed with human muscle cells isolated from patients suffering from muscle or neuromuscu diseases(3), and thus can be used as a screening tool for candidate drugs. Finally, no special equipment but a regular BSL2 facility is needed to reproduce a functional motor unit in a culture dish. This method thus is valuable for both the muscle as well as the neuromuscular research communities for physiological and mechanistic studies of neuromuscular function, in a normal and disease context

Information-Geometric Optimization Algorithms: A Unifying Picture via Invariance Principles

We present a canonical way to turn any smooth parametric family of probability distributions on an arbitrary search space $X$ into a continuous-time black-box optimization method on $X$, the \emph{information-geometric optimization} (IGO) method. Invariance as a design principle minimizes the number of arbitrary choices. The resulting \emph{IGO flow} conducts the natural gradient ascent of an adaptive, time-dependent, quantile-based transformation of the objective function. It makes no assumptions on the objective function to be optimized. The IGO method produces explicit IGO algorithms through time discretization. It naturally recovers versions of known algorithms and offers a systematic way to derive new ones. The cross-entropy method is recovered in a particular case, and can be extended into a smoothed, parametrization-independent maximum likelihood update (IGO-ML). For Gaussian distributions on $\mathbb{R}^d$, IGO is related to natural evolution strategies (NES) and recovers a version of the CMA-ES algorithm. For Bernoulli distributions on $\{0,1\}^d$, we recover the PBIL algorithm. From restricted Boltzmann machines, we obtain a novel algorithm for optimization on $\{0,1\}^d$. All these algorithms are unified under a single information-geometric optimization framework. Thanks to its intrinsic formulation, the IGO method achieves invariance under reparametrization of the search space $X$, under a change of parameters of the probability distributions, and under increasing transformations of the objective function. Theory strongly suggests that IGO algorithms have minimal loss in diversity during optimization, provided the initial diversity is high. First experiments using restricted Boltzmann machines confirm this insight. Thus IGO seems to provide, from information theory, an elegant way to spontaneously explore several valleys of a fitness landscape in a single run.Comment: Final published versio

On the performance of massive and woodframe passivehouses in Belgium : a field study

In this paper we present the results of a field study in which the indoor climate and the energy use for space heating in 6 passive houses in Belgium were monitored. The test group consisted of 4 houses with a massive shell construction and 2 timber frame houses. 2 houses were inhabited and 4 were used for promotional activities by the builders. The results are compared to the performance predicted by the PHPP method. We can conclude that the results are in good agreement with the predictions and that no significant difference in performance is found between the massive and timber frame constructions

An algebraic characterization of transition system equivalences

AbstractI. Castellani (1987, J. Comput. System Sci. 34, 210–235) has shown that observation equivalence of transition systems could be characterized by particular reductions: systems are equivalent if, and only if, they can be reduced to the same form. Moreover, every transition system has a minimal reduced form. We extend these results to logical equivalence, by an algebraic interpretation of temporal logics: we characterize logical equivalence of transition systems by particular reductions (saturating quasi-homomorphisms) or their power algebras of sets of states and paths and prove that every power algebra has a minimal reduced form. We then offer alternative proofs for logical characterizations of observation equivalence: in particular we apply our method to prove M. Hennessy and C. Stirling's (1984, “Lecture Notes in Comput. Sci. Vol. 176,” pp. 301–311, Springer-Verlag, New York/Berlin) result that “Future Perfect” logic characterizes observation equivalence of generalized transition systems, i.e., systems whose infinite behaviours are restricted by arbitrary fairness constraints

401(k) Plan Expenses

Under a 401(k) plan, your benefit is your vested account balance. This account balance reflects the contributions you make to the plan, the contributions your employer makes to the plan on your behalf (if any), and investment gains and losses. Many 401(k) plan participants are responsible for choosing how to invest their account balances. If you direct the investment of your 401(k) plan account balance, it is important to understand that fees and expenses may substantially reduce the growth of your 401(k) plan account balance over the course of your working life. The Department of Labor (DOL) estimates that paying 1% in extraneous fees can reduce your 401(k) plan account balance by 28% over the course of 35 years. Accordingly, it is important to familiarize yourself with the various types of fees and expenses that can affect the growth of your 401(k) plan account balance. This fact sheet summarizes many of these common fees

ESTABLISHING IDENTITY OF NON-EU NATIONALS IN IRISH MIGRATION PROCESSES. ESRI RESEARCH SERIES NUMBER 69 DECEMBER 2017

Establishing the identity of non-EEA nationals1 entering the EU is often the first step in determining eligibility for visas, certain residence or visitor permissions and permissions associated with international protection statuses. Establishing identity is an EU-level policy priority as set out in both the European Agenda on Security (European Commission, 2015a) and the European Agenda on Migration (European Commission, 2015b). No legal or overarching definition of ‘identity’ in the context of migration procedures exists in the majority of Member States. For the purposes of migration, identity is generally established by documents such as birth certificates, passports or other identity papers. Biometric identification refers to physical characteristics including fingerprints and digital facial images. Any individual wishing to enter Ireland, whether visa required or not, is subject to immigration controls at ports of entry. All non-EEA (both visa required and non-visa required) nationals require permission to enter Ireland upon arrival.2 Visa required non-EEA nationals must apply for a visa to travel to Ireland. However, an Irish visa is a form of pre-entry clearance to travel to a point of entry to the State only (Quinn, 2011). In almost all cases a passport or travel document is required in order for a non-EEA national to be issued a visa, to register in the State and to access the territory at the border. Protection applicants are not required to have a passport or travel document to access the asylum procedure. This study looks at the processes in place for establishing the identities of applicants for: short- and long-stay visas; residence and visitor permissions; international protection and permission to remain; and in relation to persons subject to a deportation order who have exhausted the asylum process. This study also looks at the process of establishing applicants’ identities at the point of access to the national territory

Stochastic population dynamics in populations of western terrestrial garter snakes with divergent life histories

Comparative evaluations of population dynamics in species with temporal and spatial variation in life-history traits are rare because they require long-term demographic time series from multiple populations. We present such an analysis using demographic data collected during the interval 1978–1996 for six populations of western terrestrial garter snakes (Thamnophis elegans) from two evolutionarily divergent ecotypes. Three replicate populations from a slow-living ecotype, found in mountain meadows of northeastern California, were characterized by individuals that develop slowly, mature late, reproduce infrequently with small reproductive effort, and live longer than individuals of three populations of a fast-living ecotype found at lakeshore locales. We constructed matrix population models for each of the populations based on 8–13 years of data per population and analyzed both deterministic dynamics based on mean annual vital rates and stochastic dynamics incorporating annual variation in vital rates. (1) Contributions of highly variable vital rates to fitness (λs) were buffered against the negative effects of stochastic variation, and this relationship was consistent with differences between the meadow (M-slow) and lakeshore (L-fast) ecotypes. (2) Annual variation in the proportion of gravid females had the greatest negative effect among all vital rates on λs. The magnitude of variation in the proportion of gravid females and its effect on λs was greater in M-slow than L-fast populations. (3) Variation in the proportion of gravid females, in turn, depended on annual variation in prey availability, and its effect on λs was 4–23 times greater in M-slow than L-fast populations. In addition to differences in stochastic dynamics between ecotypes, we also found higher mean mortality rates across all age classes in the L-fast populations. Our results suggest that both deterministic and stochastic selective forces have affected the evolution of divergent life-history traits in the two ecotypes, which, in turn, affect population dynamics. M-slow populations have evolved life-history traits that buffer fitness against direct effects of variation in reproduction and that spread lifetime reproduction across a greater number of reproductive bouts. These results highlight the importance of long-term demographic and environmental monitoring and of incorporating temporal dynamics into empirical studies of life-history evolution