Javier Cárcamo, Antonio Cuevas, Luis-Alberto Rodríguez.

Source: Bernoulli, Volume 26, Number 3, 2143--2175.

Abstract:
We show that various functionals related to the supremum of a real function defined on an arbitrary set or a measure space are Hadamard directionally differentiable. We specifically consider the supremum norm, the supremum, the infimum, and the amplitude of a function. The (usually non-linear) derivatives of these maps adopt simple expressions under suitable assumptions on the underlying space. As an application, we improve and extend to the multidimensional case the results in Raghavachari ( Ann. Statist. 1 (1973) 67–73) regarding the limiting distributions of Kolmogorov–Smirnov type statistics under the alternative hypothesis. Similar results are obtained for analogous statistics associated with copulas. We additionally solve an open problem about the Berk–Jones statistic proposed by Jager and Wellner (In A Festschrift for Herman Rubin (2004) 319–331 IMS). Finally, the asymptotic distribution of maximum mean discrepancies over Donsker classes of functions is derived.

Akio Fujiwara, Koichi Yamagata.

Source: Bernoulli, Volume 26, Number 3, 2105--2142.

Abstract:
We herein develop a theory of contiguity in the quantum domain based upon a novel quantum analogue of the Lebesgue decomposition. The theory thus formulated is pertinent to the weak quantum local asymptotic normality introduced in the previous paper [Yamagata, Fujiwara, and Gill, Ann. Statist. 41 (2013) 2197–2217], yielding substantial enlargement of the scope of quantum statistics.

Sarat B. Moka, Dirk P. Kroese.

Source: Bernoulli, Volume 26, Number 3, 2082--2104.

Abstract:
We present a perfect sampling algorithm for Gibbs point processes, based on the partial rejection sampling of Guo, Jerrum and Liu (In STOC’17 – Proceedings of the 49th Annual ACM SIGACT Symposium on Theory of Computing (2017) 342–355 ACM). Our particular focus is on pairwise interaction processes, penetrable spheres mixture models and area-interaction processes, with a finite interaction range. For an interaction range $2r$ of the target process, the proposed algorithm can generate a perfect sample with $O(log(1/r))$ expected running time complexity, provided that the intensity of the points is not too high and $Theta(1/r^{d})$ parallel processor units are available.

Arnak S. Dalalyan, Lionel Riou-Durand.

Source: Bernoulli, Volume 26, Number 3, 1956--1988.

Abstract:
Langevin diffusion processes and their discretizations are often used for sampling from a target density. The most convenient framework for assessing the quality of such a sampling scheme corresponds to smooth and strongly log-concave densities defined on $mathbb{R}^{p}$. The present work focuses on this framework and studies the behavior of the Monte Carlo algorithm based on discretizations of the kinetic Langevin diffusion. We first prove the geometric mixing property of the kinetic Langevin diffusion with a mixing rate that is optimal in terms of its dependence on the condition number. We then use this result for obtaining improved guarantees of sampling using the kinetic Langevin Monte Carlo method, when the quality of sampling is measured by the Wasserstein distance. We also consider the situation where the Hessian of the log-density of the target distribution is Lipschitz-continuous. In this case, we introduce a new discretization of the kinetic Langevin diffusion and prove that this leads to a substantial improvement of the upper bound on the sampling error measured in Wasserstein distance.

Ulrike Mayer, Henryk Zähle, Zhou Zhou.

Source: Bernoulli, Volume 26, Number 3, 1891--1911.

Abstract:
We derive a functional weak limit theorem for a local empirical process of a wide class of piece-wise locally stationary (PLS) time series. The latter result is applied to derive the asymptotics of weighted empirical quantiles and weighted V-statistics of non-stationary time series. The class of admissible underlying time series is illustrated by means of PLS linear processes and PLS ARCH processes.

Holger Sambale, Arthur Sinulis.

Source: Bernoulli, Volume 26, Number 3, 1863--1890.

Abstract:
We derive sufficient conditions for a probability measure on a finite product space (a spin system ) to satisfy a (modified) logarithmic Sobolev inequality. We establish these conditions for various examples, such as the (vertex-weighted) exponential random graph model, the random coloring and the hard-core model with fugacity. This leads to two separate branches of applications. The first branch is given by mixing time estimates of the Glauber dynamics. The proofs do not rely on coupling arguments, but instead use functional inequalities. As a byproduct, this also yields exponential decay of the relative entropy along the Glauber semigroup. Secondly, we investigate the concentration of measure phenomenon (particularly of higher order) for these spin systems. We show the effect of better concentration properties by centering not around the mean, but around a stochastic term in the exponential random graph model. From there, one can deduce a central limit theorem for the number of triangles from the CLT of the edge count. In the Erdős–Rényi model the first-order approximation leads to a quantification and a proof of a central limit theorem for subgraph counts.

Jason M. Klusowski, Yihong Wu.

Source: Bernoulli, Volume 26, Number 3, 1635--1664.

Abstract:
Learning properties of large graphs from samples has been an important problem in statistical network analysis since the early work of Goodman ( Ann. Math. Stat. 20 (1949) 572–579) and Frank ( Scand. J. Stat. 5 (1978) 177–188). We revisit a problem formulated by Frank ( Scand. J. Stat. 5 (1978) 177–188) of estimating the number of connected components in a large graph based on the subgraph sampling model, in which we randomly sample a subset of the vertices and observe the induced subgraph. The key question is whether accurate estimation is achievable in the sublinear regime where only a vanishing fraction of the vertices are sampled. We show that it is impossible if the parent graph is allowed to contain high-degree vertices or long induced cycles. For the class of chordal graphs, where induced cycles of length four or above are forbidden, we characterize the optimal sample complexity within constant factors and construct linear-time estimators that provably achieve these bounds. This significantly expands the scope of previous results which have focused on unbiased estimators and special classes of graphs such as forests or cliques. Both the construction and the analysis of the proposed methodology rely on combinatorial properties of chordal graphs and identities of induced subgraph counts. They, in turn, also play a key role in proving minimax lower bounds based on construction of random instances of graphs with matching structures of small subgraphs.

Arun K. Kuchibhotla, Rohit K. Patra.

Source: Bernoulli, Volume 26, Number 2, 1587--1618.

Abstract:
We consider estimation and inference in a single index regression model with an unknown but smooth link function. In contrast to the standard approach of using kernels or regression splines, we use smoothing splines to estimate the smooth link function. We develop a method to compute the penalized least squares estimators (PLSEs) of the parametric and the nonparametric components given independent and identically distributed (i.i.d.) data. We prove the consistency and find the rates of convergence of the estimators. We establish asymptotic normality under mild assumption and prove asymptotic efficiency of the parametric component under homoscedastic errors. A finite sample simulation corroborates our asymptotic theory. We also analyze a car mileage data set and a Ozone concentration data set. The identifiability and existence of the PLSEs are also investigated.

Pier Luigi Conti, Daniela Marella, Fulvia Mecatti, Federico Andreis.

Source: Bernoulli, Volume 26, Number 2, 1044--1069.

Abstract:
In this paper, a class of resampling techniques for finite populations under $pi $ps sampling design is introduced. The basic idea on which they rest is a two-step procedure consisting in: (i) constructing a “pseudo-population” on the basis of sample data; (ii) drawing a sample from the predicted population according to an appropriate resampling design. From a logical point of view, this approach is essentially based on the plug-in principle by Efron, at the “sampling design level”. Theoretical justifications based on large sample theory are provided. New approaches to construct pseudo populations based on various forms of calibrations are proposed. Finally, a simulation study is performed.

Stanislav Minsker, Xiaohan Wei.

Source: Bernoulli, Volume 26, Number 1, 694--727.

Abstract:
Let $Y$ be a $d$-dimensional random vector with unknown mean $mu $ and covariance matrix $Sigma $. This paper is motivated by the problem of designing an estimator of $Sigma $ that admits exponential deviation bounds in the operator norm under minimal assumptions on the underlying distribution, such as existence of only 4th moments of the coordinates of $Y$. To address this problem, we propose robust modifications of the operator-valued U-statistics, obtain non-asymptotic guarantees for their performance, and demonstrate the implications of these results to the covariance estimation problem under various structural assumptions.

Mingjie Liang, René L. Schilling, Jian Wang.

Source: Bernoulli, Volume 26, Number 1, 664--693.

Abstract:
We present a general method to construct couplings of stochastic differential equations driven by Lévy noise in terms of coupling operators. This approach covers both coupling by reflection and refined basic coupling which are often discussed in the literature. As applications, we prove regularity results for the transition semigroups and obtain successful couplings for the solutions to stochastic differential equations driven by additive Lévy noise.

Nicolas Privault, Grzegorz Serafin.

Source: Bernoulli, Volume 26, Number 1, 587--615.

Abstract:
We derive normal approximation bounds in the Kolmogorov distance for sums of discrete multiple integrals and weighted $U$-statistics made of independent Bernoulli random variables. Such bounds are applied to normal approximation for the renormalized subgraph counts in the Erdős–Rényi random graph. This approach completely solves a long-standing conjecture in the general setting of arbitrary graph counting, while recovering recent results obtained for triangles and improving other bounds in the Wasserstein distance.

Eric Beutner, Laurent Bordes, Laurent Doyen.

Source: Bernoulli, Volume 26, Number 1, 557--586.

Abstract:
Virtual age models are very useful to analyse recurrent events. Among the strengths of these models is their ability to account for treatment (or intervention) effects after an event occurrence. Despite their flexibility for modeling recurrent events, the number of applications is limited. This seems to be a result of the fact that in the semiparametric setting all the existing results assume the virtual age function that describes the treatment (or intervention) effects to be known. This shortcoming can be overcome by considering semiparametric virtual age models with parametrically specified virtual age functions. Yet, fitting such a model is a difficult task. Indeed, it has recently been shown that for these models the standard profile likelihood method fails to lead to consistent estimators. Here we show that consistent estimators can be constructed by smoothing the profile log-likelihood function appropriately. We show that our general result can be applied to most of the relevant virtual age models of the literature. Our approach shows that empirical process techniques may be a worthwhile alternative to martingale methods for studying asymptotic properties of these inference methods. A simulation study is provided to illustrate our consistency results together with an application to real data.

Xiucai Ding.

Source: Bernoulli, Volume 26, Number 1, 387--417.

Abstract:
We consider the recovery of a low rank $M imes N$ matrix $S$ from its noisy observation $ ilde{S}$ in the high dimensional framework when $M$ is comparable to $N$. We propose two efficient estimators for $S$ under two different regimes. Our analysis relies on the local asymptotics of the eigenstructure of large dimensional rectangular matrices with finite rank perturbation. We derive the convergent limits and rates for the singular values and vectors for such matrices.

Fangzheng Xie, Yanxun Xu.

Source: Bayesian Analysis, Volume 15, Number 1, 159--186.

Abstract:
We propose a kernel mixture of polynomials prior for Bayesian nonparametric regression. The regression function is modeled by local averages of polynomials with kernel mixture weights. We obtain the minimax-optimal contraction rate of the full posterior distribution up to a logarithmic factor by estimating metric entropies of certain function classes. Under the assumption that the degree of the polynomials is larger than the unknown smoothness level of the true function, the posterior contraction behavior can adapt to this smoothness level provided an upper bound is known. We also provide a frequentist sieve maximum likelihood estimator with a near-optimal convergence rate. We further investigate the application of the kernel mixture of polynomials to partial linear models and obtain both the near-optimal rate of contraction for the nonparametric component and the Bernstein-von Mises limit (i.e., asymptotic normality) of the parametric component. The proposed method is illustrated with numerical examples and shows superior performance in terms of computational efficiency, accuracy, and uncertainty quantification compared to the local polynomial regression, DiceKriging, and the robust Gaussian stochastic process.

Matthew R. Williams, Terrance D. Savitsky.

Source: Bayesian Analysis, Volume 15, Number 1, 57--77.

Abstract:
An informative sampling design leads to unit inclusion probabilities that are correlated with the response variable of interest. However, multistage sampling designs may also induce higher order dependencies, which are ignored in the literature when establishing consistency of estimators for survey data under a condition requiring asymptotic independence among the unit inclusion probabilities. This paper constructs new theoretical conditions that guarantee that the pseudo-posterior, which uses sampling weights based on first order inclusion probabilities to exponentiate the likelihood, is consistent not only for survey designs which have asymptotic factorization, but also for survey designs that induce residual or unattenuated dependence among sampled units. The use of the survey-weighted pseudo-posterior, together with our relaxed requirements for the survey design, establish a wide variety of analysis models that can be applied to a broad class of survey data sets. Using the complex sampling design of the National Survey on Drug Use and Health, we demonstrate our new theoretical result on multistage designs characterized by a cluster sampling step that expresses within-cluster dependence. We explore the impact of multistage designs and order based sampling.

Nadja Klein, Michael Stanley Smith.

Source: Bayesian Analysis, Volume 14, Number 4, 1143--1171.

Abstract:
We show how to extract the implicit copula of a response vector from a Bayesian regularized regression smoother with Gaussian disturbances. The copula can be used to compare smoothers that employ different shrinkage priors and function bases. We illustrate with three popular choices of shrinkage priors—a pairwise prior, the horseshoe prior and a g prior augmented with a point mass as employed for Bayesian variable selection—and both univariate and multivariate function bases. The implicit copulas are high-dimensional, have flexible dependence structures that are far from that of a Gaussian copula, and are unavailable in closed form. However, we show how they can be evaluated by first constructing a Gaussian copula conditional on the regularization parameters, and then integrating over these. Combined with non-parametric margins the regularized smoothers can be used to model the distribution of non-Gaussian univariate responses conditional on the covariates. Efficient Markov chain Monte Carlo schemes for evaluating the copula are given for this case. Using both simulated and real data, we show how such copula smoothing models can improve the quality of resulting function estimates and predictive distributions.

Peter D. Hoff

Source: Bayesian Anal., Volume 6, Number 2, 179--196.

Abstract:
Modern datasets are often in the form of matrices or arrays, potentially having correlations along each set of data indices. For example, data involving repeated measurements of several variables over time may exhibit temporal correlation as well as correlation among the variables. A possible model for matrix-valued data is the class of matrix normal distributions, which is parametrized by two covariance matrices, one for each index set of the data. In this article we discuss an extension of the matrix normal model to accommodate multidimensional data arrays, or tensors. We show how a particular array-matrix product can be used to generate the class of array normal distributions having separable covariance structure. We derive some properties of these covariance structures and the corresponding array normal distributions, and show how the array-matrix product can be used to define a semi-conjugate prior distribution and calculate the corresponding posterior distribution. We illustrate the methodology in an analysis of multivariate longitudinal network data which take the form of a four-way array.

Ruosi Guo, Chunming Zhang, Zhengjun Zhang.

Source: Statistical Science, Volume 35, Number 1, 145--157.

Abstract:
In many scientific disciplines, finding hidden influential factors behind observational data is essential but challenging. The majority of existing approaches, such as the independent component analysis (${mathrm{ICA}}$), rely on linear transformation, that is, true signals are linear combinations of hidden components. Motivated from analyzing nonlinear temporal signals in neuroscience, genetics, and finance, this paper proposes the “maximum independent component analysis” (${mathrm{MaxICA}}$), based on max-linear combinations of components. In contrast to existing methods, ${mathrm{MaxICA}}$ benefits from focusing on significant major components while filtering out ignorable components. A major tool for parameter learning of ${mathrm{MaxICA}}$ is an augmented genetic algorithm, consisting of three schemes for the elite weighted sum selection, randomly combined crossover, and dynamic mutation. Extensive empirical evaluations demonstrate the effectiveness of ${mathrm{MaxICA}}$ in either extracting max-linearly combined essential sources in many applications or supplying a better approximation for nonlinearly combined source signals, such as $mathrm{EEG}$ recordings analyzed in this paper.

Gregorio Quintana-Ortí, Amelia Simó.

Source: Statistical Science, Volume 34, Number 2, 236--252.

Abstract:
This paper is focused on kernel regression when the response variable is the shape of a 3D object represented by a configuration matrix of landmarks. Regression methods on this shape space are not trivial because this space has a complex finite-dimensional Riemannian manifold structure (non-Euclidean). Papers about it are scarce in the literature, the majority of them are restricted to the case of a single explanatory variable, and many of them are based on the approximated tangent space. In this paper, there are several methodological innovations. The first one is the adaptation of the general method for kernel regression analysis in manifold-valued data to the three-dimensional case of Kendall’s shape space. The second one is its generalization to the multivariate case and the addressing of the curse-of-dimensionality problem. Finally, we propose bootstrap confidence intervals for prediction. A simulation study is carried out to check the goodness of the procedure, and a comparison with a current approach is performed. Then, it is applied to a 3D database obtained from an anthropometric survey of the Spanish child population with a potential application to online sales of children’s wear.

Víctor Elvira, Luca Martino, David Luengo, Mónica F. Bugallo.

Source: Statistical Science, Volume 34, Number 1, 129--155.

Abstract:
Importance sampling (IS) methods are broadly used to approximate posterior distributions or their moments. In the standard IS approach, samples are drawn from a single proposal distribution and weighted adequately. However, since the performance in IS depends on the mismatch between the targeted and the proposal distributions, several proposal densities are often employed for the generation of samples. Under this multiple importance sampling (MIS) scenario, extensive literature has addressed the selection and adaptation of the proposal distributions, interpreting the sampling and weighting steps in different ways. In this paper, we establish a novel general framework with sampling and weighting procedures when more than one proposal is available. The new framework encompasses most relevant MIS schemes in the literature, and novel valid schemes appear naturally. All the MIS schemes are compared and ranked in terms of the variance of the associated estimators. Finally, we provide illustrative examples revealing that, even with a good choice of the proposal densities, a careful interpretation of the sampling and weighting procedures can make a significant difference in the performance of the method.

Brian Zingg
Apr 15, 2020; 40:3250-3267
Systems/Circuits

Ye Zhang
Sep 3, 2014; 34:11929-11947
Cellular

Jozsef Csicsvari
Jan 1, 1999; 19:274-287
Articles

KM Harris
Jul 1, 1992; 12:2685-2705
Articles

Michael N. Shadlen
May 15, 1998; 18:3870-3896
Articles

Ye Zhang
Sep 3, 2014; 34:11929-11947
Cellular

Italian translation of the BIS press release about the BIS Quarterly Review, September 2018

French translation of the Basel Committee is publishing "Sound Practices: implications of fintech developments for banks and bank supervisors", February 2018.

French translation of the BIS press release about the BIS Quarterly Review, March 2019

Based on remarks by Mr Luiz Awazu Pereira da Silva, Deputy General Manager of the BIS, with Jon Frost and Leonardo Gambacorta at the Santander International Banking Conference on "Banking on trust: Building confidence in the future", Madrid, 5 November 2019.

Revealing the organization and function of neural circuits is greatly facilitated by viral tools that spread transsynaptically. Adeno-associated virus (AAV) exhibits anterograde transneuronal transport, however, the synaptic specificity of this spread and its broad application within a diverse set of circuits remains to be explored. Here, using anatomic, functional, and molecular approaches, we provide evidence for the preferential transport of AAV1 to postsynaptically connected neurons and reveal its spread is strongly dependent on synaptic transmitter release. In addition to glutamatergic pathways, AAV1 also spreads through GABAergic synapses to both excitatory and inhibitory cell types. We observed little or no transport, however, through neuromodulatory projections (e.g., serotonergic, cholinergic, and noradrenergic). In addition, we found that AAV1 can be transported through long-distance descending projections from various brain regions to effectively transduce spinal cord neurons. Combined with newly designed intersectional and sparse labeling strategies, AAV1 can be applied within a wide variety of pathways to categorize neurons according to their input sources, morphology, and molecular identities. These properties make AAV1 a promising anterograde transsynaptic tool for establishing a comprehensive cell-atlas of the brain, although its capacity for retrograde transport currently limits its use to unidirectional circuits.

SIGNIFICANCE STATEMENT The discovery of anterograde transneuronal spread of AAV1 generates great promise for its application as a unique tool for manipulating input-defined cell populations and mapping their outputs. However, several outstanding questions remain for anterograde transsynaptic approaches in the field: (1) whether AAV1 spreads exclusively or specifically to synaptically connected neurons, and (2) how broad its application could be in various types of neural circuits in the brain. This study provides several lines of evidence in terms of anatomy, functional innervation, and underlying mechanisms, to strongly support that AAV1 anterograde transneuronal spread is highly synapse specific. In addition, several potentially important applications of transsynaptic AAV1 in probing neural circuits are described.

One of the first signs of viral infection is body-wide aches and pain. Although this type of pain usually subsides, at the extreme, viral infections can induce painful neuropathies that can last for decades. Neither of these types of pain sensitization is well understood. A key part of the response to viral infection is production of interferons (IFNs), which then activate their specific receptors (IFNRs) resulting in downstream activation of cellular signaling and a variety of physiological responses. We sought to understand how type I IFNs (IFN-α and IFN-β) might act directly on nociceptors in the dorsal root ganglion (DRG) to cause pain sensitization. We demonstrate that type I IFNRs are expressed in small/medium DRG neurons and that their activation produces neuronal hyper-excitability and mechanical pain in mice. Type I IFNs stimulate JAK/STAT signaling in DRG neurons but this does not apparently result in PKR-eIF2α activation that normally induces an anti-viral response by limiting mRNA translation. Rather, type I IFNs stimulate MNK-mediated eIF4E phosphorylation in DRG neurons to promote pain hypersensitivity. Endogenous release of type I IFNs with the double-stranded RNA mimetic poly(I:C) likewise produces pain hypersensitivity that is blunted in mice lacking MNK-eIF4E signaling. Our findings reveal mechanisms through which type I IFNs cause nociceptor sensitization with implications for understanding how viral infections promote pain and can lead to neuropathies.

SIGNIFICANCE STATEMENT It is increasingly understood that pathogens interact with nociceptors to alert organisms to infection as well as to mount early host defenses. Although specific mechanisms have been discovered for diverse bacterial and fungal pathogens, mechanisms engaged by viruses have remained elusive. Here we show that type I interferons, one of the first mediators produced by viral infection, act directly on nociceptors to produce pain sensitization. Type I interferons act via a specific signaling pathway (MNK-eIF4E signaling), which is known to produce nociceptor sensitization in inflammatory and neuropathic pain conditions. Our work reveals a mechanism through which viral infections cause heightened pain sensitivity

Autism spectrum disorder (ASD) is characterized partly by atypical attentional engagement, reflected in exaggerated and variable responses to sensory stimuli. Attentional engagement is known to be regulated by the locus ceruleus (LC). Moderate baseline LC activity globally dampens neural responsivity and is associated with adaptive deployment and narrowing of attention to task-relevant stimuli. In contrast, increased baseline LC activity enhances neural responsivity across cortex and widening of attention to environmental stimuli regardless of their task relevance. Given attentional atypicalities in ASD, this study is the first to evaluate whether, under different attentional task demands, individuals with ASD exhibit a different profile of LC activity compared with typically developing controls. Males and females with ASD and age- and gender-matched controls participated in a one-back letter detection test while task-evoked pupillary responses, an established correlate for LC activity, were recorded. Participants completed this task in two conditions, either in the absence or presence of distractor auditory tones. Compared with controls, individuals with ASD evinced atypical pupillary responses in the presence versus absence of distractors. Notably, this atypical pupillary profile was evident despite the fact that both groups exhibited equivalent task performance. Moreover, between-group differences in pupillary responses were observed specifically in response to task-relevant events, providing confirmation that the group differences most likely were specifically associated with distinctions in LC activity. These findings suggest that individuals with ASD show atypical modulation of LC activity with changes in attentional demands, offering a possible mechanistic and neurobiological account for attentional atypicalities in ASD.

SIGNIFICANCE STATEMENT Individuals with autism spectrum disorder (ASD) exhibit atypical attentional behaviors, including altered sensory responses and atypical fixedness, but the neural mechanism underlying these behaviors remains elusive. One candidate mechanism is atypical locus ceruleus (LC) activity, as the LC plays a critical role in attentional modulation. Specifically, LC activity is involved in regulating the trade-off between environmental exploration and focused attention. This study shows that, under tightly controlled conditions, task-evoked pupil responses, an LC activity proxy, are lower in individuals with ASD than in controls, but only in the presence of task-irrelevant stimuli. This suggests that individuals with ASD evince atypical modulation of LC activity in accordance with changes in attentional demands, offering a mechanistic account for attentional atypicalities in ASD.

MECP2 gain-of-function and loss-of-function in genetically engineered monkeys recapitulates typical phenotypes in patients with autism, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remain unknown. Here we report a combination of gene–circuit–behavior analyses including MECP2 coexpression network, locomotive and cognitive behaviors, and EEG and fMRI findings in 5 MECP2 overexpressed monkeys (Macaca fascicularis; 3 females) and 20 wild-type monkeys (Macaca fascicularis; 11 females). Whole-genome expression analysis revealed MECP2 coexpressed genes significantly enriched in GABA-related signaling pathways, whereby reduced β-synchronization within fronto-parieto-occipital networks was associated with abnormal locomotive behaviors. Meanwhile, MECP2-induced hyperconnectivity in prefrontal and cingulate networks accounted for regressive deficits in reversal learning tasks. Furthermore, we stratified a cohort of 49 patients with autism and 72 healthy controls of 1112 subjects using functional connectivity patterns, and identified dysconnectivity profiles similar to those in monkeys. By establishing a circuit-based construct link between genetically defined models and stratified patients, these results pave new avenues to deconstruct clinical heterogeneity and advance accurate diagnosis in psychiatric disorders.

SIGNIFICANCE STATEMENT Autism spectrum disorder (ASD) is a complex disorder with co-occurring symptoms caused by multiple genetic variations and brain circuit abnormalities. To dissect the gene–circuit–behavior causal chain underlying ASD, animal models are established by manipulating causative genes such as MECP2. However, it is unknown whether such models have captured any circuit-level pathology in ASD patients, as demonstrated by human brain imaging studies. Here, we use transgenic macaques to examine the causal effect of MECP2 overexpression on gene coexpression, brain circuits, and behaviors. For the first time, we demonstrate that the circuit abnormalities linked to MECP2 and autism-like traits in the monkeys can be mapped to a homogeneous ASD subgroup, thereby offering a new strategy to deconstruct clinical heterogeneity in ASD.

By building a new broch, the project aims to better understand how and why the original structures were constructed

Henry Ford spent the majority of the war as a pacifist. By 1917, however, his state-of-the-art assembly line was churning out vital engine parts to feed the war machine.

Hadrian’s Wall was a 73 mile barrier stretching from coast to coast, splitting the warlike north of Britain from the more docile south. It was the Roman Empire’s way of imposing peace in a hostile land

It's been more than a week since there were any new or active cases of COVID-19 in the catchment area for the Northwestern Health Unit (NWHU), and staff can not focus increasing testing.

The new service will join others at the existing 811 HealthLine, helping connect people with their local food services and offering answers for those without access to online services.

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Bank of Spain Working Papers by Henrique S. Basso and Juan F. Jimeno

Need for Surface Surface Modelling is a method used to create and represent complex shapes with high curvature controls. Generally, surfaces are used as an alternative where a particular feature is difficult to create using solid modeling. It is helpful

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A Special Purpose Machine, which is intended to perform a specific task, have a wide range of scope in the Industrial Applications like quantity packaging and bottle filling. It includes limit switches, sensors, logic controls where the process can be

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An adolescent girl with a history of frequent electronic cigarette use of nicotine was hospitalized with severe necrotizing pneumonia. Blood cultures obtained before the administration of empirical broad-spectrum intravenous antibiotics had positive results for the growth of Fusobacterium necrophorum. The pathogen is an uncommon but well-known cause of anaerobic pneumonia with unique features that are collectively referred to as Lemierre syndrome or postanginal sepsis. The syndrome begins as a pharyngeal infection. Untreated, the infection progresses to involve the ipsilateral internal jugular vein, resulting in septic thrombophlebitis with direct spread from the neck to the lungs causing multifocal necrotizing pneumonia. The teenager we present in this report had neither a preceding pharyngeal infection nor Doppler ultrasonographic evidence for the presence of deep neck vein thrombi, leading us to explore alternative mechanisms for her pneumonia. We propose the possibility that her behavior of frequent vaping led to sufficient pharyngeal irritation such that F necrophorum colonizing her oropharynx was inhaled directly into her lungs during electronic cigarette use. Preexisting, but not yet recognized, vaping-related lung injury may have also contributed to her risk of developing the infection. The patient was hospitalized for 10 days. At follow-up one month later, she still became short of breath with minimal exertion.

Within just a few weeks, the corona crisis has led to a collapse of over 90 percent of flight operations in the capital region. In light of this dramatic situation, the Flughafen Berlin Brandenburg GmbH (FBB) Executive Board concluded a works agreement ...