How an organization controls its actions. Governance describes the mechanisms an organization uses to ensure that its constituents follow its established processes and policies. It is the primary means of maintaining oversight and accountability in a loosely coupled organizational structure. A proper governance strategy implements systems to monitor and record what is going on, takes steps to ensure compliance with agreed policies, and provides for corrective action in cases where the rules have been ignored or misconstrued.

Xin Bing, Florentina Bunea, Marten Wegkamp.

Source: Bernoulli, Volume 26, Number 3, 1765--1796.

Abstract:
Topic models have become popular for the analysis of data that consists in a collection of n independent multinomial observations, with parameters $N_{i}inmathbb{N}$ and $Pi_{i}in[0,1]^{p}$ for $i=1,ldots,n$. The model links all cell probabilities, collected in a $p imes n$ matrix $Pi$, via the assumption that $Pi$ can be factorized as the product of two nonnegative matrices $Ain[0,1]^{p imes K}$ and $Win[0,1]^{K imes n}$. Topic models have been originally developed in text mining, when one browses through $n$ documents, based on a dictionary of $p$ words, and covering $K$ topics. In this terminology, the matrix $A$ is called the word-topic matrix, and is the main target of estimation. It can be viewed as a matrix of conditional probabilities, and it is uniquely defined, under appropriate separability assumptions, discussed in detail in this work. Notably, the unique $A$ is required to satisfy what is commonly known as the anchor word assumption, under which $A$ has an unknown number of rows respectively proportional to the canonical basis vectors in $mathbb{R}^{K}$. The indices of such rows are referred to as anchor words. Recent computationally feasible algorithms, with theoretical guarantees, utilize constructively this assumption by linking the estimation of the set of anchor words with that of estimating the $K$ vertices of a simplex. This crucial step in the estimation of $A$ requires $K$ to be known, and cannot be easily extended to the more realistic set-up when $K$ is unknown. This work takes a different view on anchor word estimation, and on the estimation of $A$. We propose a new method of estimation in topic models, that is not a variation on the existing simplex finding algorithms, and that estimates $K$ from the observed data. We derive new finite sample minimax lower bounds for the estimation of $A$, as well as new upper bounds for our proposed estimator. We describe the scenarios where our estimator is minimax adaptive. Our finite sample analysis is valid for any $n,N_{i},p$ and $K$, and both $p$ and $K$ are allowed to increase with $n$, a situation not handled well by previous analyses. We complement our theoretical results with a detailed simulation study. We illustrate that the new algorithm is faster and more accurate than the current ones, although we start out with a computational and theoretical disadvantage of not knowing the correct number of topics $K$, while we provide the competing methods with the correct value in our simulations.

Michael Jauch, Peter D. Hoff, David B. Dunson.

Source: Bernoulli, Volume 26, Number 2, 1560--1586.

Abstract:
Random orthogonal matrices play an important role in probability and statistics, arising in multivariate analysis, directional statistics, and models of physical systems, among other areas. Calculations involving random orthogonal matrices are complicated by their constrained support. Accordingly, we parametrize the Stiefel and Grassmann manifolds, represented as subsets of orthogonal matrices, in terms of Euclidean parameters using the Cayley transform. We derive the necessary Jacobian terms for change of variables formulas. Given a density defined on the Stiefel or Grassmann manifold, these allow us to specify the corresponding density for the Euclidean parameters, and vice versa. As an application, we present a Markov chain Monte Carlo approach to simulating from distributions on the Stiefel and Grassmann manifolds. Finally, we establish that the Euclidean parameters corresponding to a uniform orthogonal matrix can be approximated asymptotically by independent normals. This result contributes to the growing literature on normal approximations to the entries of random orthogonal matrices or transformations thereof.

Kamran Kalbasi, Thomas Mountford.

Source: Bernoulli, Volume 26, Number 2, 1504--1534.

Abstract:
In this paper, we study the local times of vector-valued Gaussian fields that are ‘diagonally operator-self-similar’ and whose increments are stationary. Denoting the local time of such a Gaussian field around the spatial origin and over the temporal unit hypercube by $Z$, we show that there exists $lambdain(0,1)$ such that under some quite weak conditions, $lim_{n ightarrow+infty}frac{sqrt[n]{mathbb{E}(Z^{n})}}{n^{lambda}}$ and $lim_{x ightarrow+infty}frac{-logmathbb{P}(Z>x)}{x^{frac{1}{lambda}}}$ both exist and are strictly positive (possibly $+infty$). Moreover, we show that if the underlying Gaussian field is ‘strongly locally nondeterministic’, the above limits will be finite as well. These results are then applied to establish similar statements for the intersection local times of diagonally operator-self-similar Gaussian fields with stationary increments.

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.

Chenlu Shi, Boxin Tang.

Source: Bernoulli, Volume 26, Number 1, 418--431.

Abstract:
Strong orthogonal arrays were recently introduced as a class of space-filling designs for computer experiments. The most attractive are those of strength three for their economical run sizes. Although the existence of strong orthogonal arrays of strength three has been completely characterized, the construction of these arrays has not been explored. In this paper, we provide a systematic and comprehensive study on the construction of these arrays, with the aim at better space-filling properties. Besides various characterizing results, three families of strength-three strong orthogonal arrays are presented. One of these families deserves special mention, as the arrays in this family enjoy almost all of the space-filling properties of strength-four strong orthogonal arrays, and do so with much more economical run sizes than the latter. The theory of maximal designs and their doubling constructions plays a crucial role in many of theoretical developments.

South Australia -- Genealogy.

Penney, Anna -- Travels.

Klemm (Family)

Vice President Pence’s trip to Iowa shows how the Trump administration’s aims to move past coronavirus are sometimes complicated by the virus itself.

Aliaksandr Hubin, Geir Storvik, Florian Frommlet.

Source: Bayesian Analysis, Volume 15, Number 1, 263--333.

Abstract:
Logic regression was developed more than a decade ago as a tool to construct predictors from Boolean combinations of binary covariates. It has been mainly used to model epistatic effects in genetic association studies, which is very appealing due to the intuitive interpretation of logic expressions to describe the interaction between genetic variations. Nevertheless logic regression has (partly due to computational challenges) remained less well known than other approaches to epistatic association mapping. Here we will adapt an advanced evolutionary algorithm called GMJMCMC (Genetically modified Mode Jumping Markov Chain Monte Carlo) to perform Bayesian model selection in the space of logic regression models. After describing the algorithmic details of GMJMCMC we perform a comprehensive simulation study that illustrates its performance given logic regression terms of various complexity. Specifically GMJMCMC is shown to be able to identify three-way and even four-way interactions with relatively large power, a level of complexity which has not been achieved by previous implementations of logic regression. We apply GMJMCMC to reanalyze QTL (quantitative trait locus) mapping data for Recombinant Inbred Lines in Arabidopsis thaliana and from a backcross population in Drosophila where we identify several interesting epistatic effects. The method is implemented in an R package which is available on github.

Quan Zhou, Yongtao Guan.

Source: Bayesian Analysis, Volume 14, Number 2, 573--594.

Abstract:
Bayesian variable selection regression (BVSR) is able to jointly analyze genome-wide genetic datasets, but the slow computation via Markov chain Monte Carlo (MCMC) hampered its wide-spread usage. Here we present a novel iterative method to solve a special class of linear systems, which can increase the speed of the BVSR model-fitting tenfold. The iterative method hinges on the complex factorization of the sum of two matrices and the solution path resides in the complex domain (instead of the real domain). Compared to the Gauss-Seidel method, the complex factorization converges almost instantaneously and its error is several magnitude smaller than that of the Gauss-Seidel method. More importantly, the error is always within the pre-specified precision while the Gauss-Seidel method is not. For large problems with thousands of covariates, the complex factorization is 10–100 times faster than either the Gauss-Seidel method or the direct method via the Cholesky decomposition. In BVSR, one needs to repetitively solve large penalized regression systems whose design matrices only change slightly between adjacent MCMC steps. This slight change in design matrix enables the adaptation of the iterative complex factorization method. The computational innovation will facilitate the wide-spread use of BVSR in reanalyzing genome-wide association datasets.

Daniela Pauger, Helga Wagner.

Source: Bayesian Analysis, Volume 14, Number 2, 341--369.

Abstract:
We propose a Bayesian approach to obtain a sparse representation of the effect of a categorical predictor in regression type models. As this effect is captured by a group of level effects, sparsity cannot only be achieved by excluding single irrelevant level effects or the whole group of effects associated to this predictor but also by fusing levels which have essentially the same effect on the response. To achieve this goal, we propose a prior which allows for almost perfect as well as almost zero dependence between level effects a priori. This prior can alternatively be obtained by specifying spike and slab prior distributions on all effect differences associated to this categorical predictor. We show how restricted fusion can be implemented and develop an efficient MCMC (Markov chain Monte Carlo) method for posterior computation. The performance of the proposed method is investigated on simulated data and we illustrate its application on real data from EU-SILC (European Union Statistics on Income and Living Conditions).

And they're on sale for Black Friday. 

Irune Diaz-Aparicio
Feb 12, 2020; 40:1453-1482
Development Plasticity Repair

Sibylle Béchet
Apr 8, 2020; 40:3104-3118
Neurobiology of Disease

John D. Cahoy
Jan 2, 2008; 28:264-278
Cellular

Michele Bellesi
May 24, 2017; 37:5263-5273
Cellular

Niko A. Busch
Jun 17, 2009; 29:7869-7876
BehavioralSystemsCognitive

John D. Cahoy
Jan 2, 2008; 28:264-278
Cellular

Spanish translation of the BIS press release about the BIS Quarterly Review, March 2018

Spanish version of Press release about CPMI and the Markets Committee issuing a report on "Central bank digital currencies" (12 March 2018)

Spanish version of Press release about new members joining the Committee on Payments and Market Infrastructures (19 March 2018)

Spanish translation of "Frequently asked questions on market risk capital requirements" by the Basel Committee, March 2018.

Spanish version of BIS Press Release - Big tech in finance: opportunities and risks, 23 June 2019

The UK's plans to launch a smartphone application to track potential COVID-19 infections won't include Apple and Google. The country's National Health Service has designed its own mobile software to do contact tracing of people exposed to the coronavirus. The NHS reportedly found that its own tech works "sufficiently well." The NHS chose a centralized model for its data collection and storage.

Merchants soon will be able to sell products on Google Shopping at no charge. Previously, they had to pay per click, but the cost was not fixed. There was no minimum, but they had to set a maximum for ad spend and Google would stop displaying their ads once the maximum was reached. Starting next week, search results on the Google Shopping tab will consist primarily of free product listings.

Speech by Mr Fernando Restoy, Chairman, Financial Stability Institute, Bank for International Settlements, at the ASBA-BID-FELABAN XVI Banking public-private sector regional policy dialogue "Challenges and opportunities in the new financial ecosystem", Washington DC, 16 October 2019.

Krabbe's disease is an infantile neurodegenerative disease, which is affected by mutations in the lysosomal enzyme galactocerebrosidase, leading to the accumulation of its metabolite psychosine. We have shown previously that the S1P receptor agonist fingolimod (FTY720) attenuates psychosine-induced glial cell death and demyelination both in vitro and ex vivo models. These data, together with a lack of therapies for Krabbe's disease, prompted the current preclinical study examining the effects of fingolimod in twitcher mice, a murine model of Krabbe's disease. Twitcher mice, both male and female, carrying a natural mutation in the galc gene were given fingolimod via drinking water (1 mg/kg/d). The direct impact of fingolimod administration was assessed via histochemical and biochemical analysis using markers of myelin, astrocytes, microglia, neurons, globoid cells, and immune cells. The effects of fingolimod on twitching behavior and life span were also demonstrated. Our results show that treatment of twitcher mice with fingolimod significantly rescued myelin levels compared with vehicle-treated animals and also regulated astrocyte and microglial reactivity. Furthermore, nonphosphorylated neurofilament levels were decreased, indicating neuroprotective and neurorestorative processes. These protective effects of fingolimod on twitcher mice brain pathology was reflected by an increased life span of fingolimod-treated twitcher mice. These in vivo findings corroborate initial in vitro studies and highlight the potential use of S1P receptors as drug targets for treatment of Krabbe's disease.

SIGNIFICANCE STATEMENT This study demonstrates that the administration of the therapy known as fingolimod in a mouse model of Krabbe's disease (namely, the twitcher mouse model) significantly rescues myelin levels. Further, the drug fingolimod also regulates the reactivity of glial cells, astrocytes and microglia, in this mouse model. These protective effects of fingolimod result in an increased life span of twitcher mice.

Human ventral temporal cortex (VTC) is critical for visual recognition. It is thought that this ability is supported by large-scale patterns of activity across VTC that contain information about visual categories. However, it is unknown how category representations in VTC are organized at the submillimeter scale and across cortical depths. To fill this gap in knowledge, we measured BOLD responses in medial and lateral VTC to images spanning 10 categories from five domains (written characters, bodies, faces, places, and objects) at an ultra-high spatial resolution of 0.8 mm using 7 Tesla fMRI in both male and female participants. Representations in lateral VTC were organized most strongly at the general level of domains (e.g., places), whereas medial VTC was also organized at the level of specific categories (e.g., corridors and houses within the domain of places). In both lateral and medial VTC, domain-level and category-level structure decreased with cortical depth, and downsampling our data to standard resolution (2.4 mm) did not reverse differences in representations between lateral and medial VTC. The functional diversity of representations across VTC partitions may allow downstream regions to read out information in a flexible manner according to task demands. These results bridge an important gap between electrophysiological recordings in single neurons at the micron scale in nonhuman primates and standard-resolution fMRI in humans by elucidating distributed responses at the submillimeter scale with ultra-high-resolution fMRI in humans.

SIGNIFICANCE STATEMENT Visual recognition is a fundamental ability supported by human ventral temporal cortex (VTC). However, the nature of fine-scale, submillimeter distributed representations in VTC is unknown. Using ultra-high-resolution fMRI of human VTC, we found differential distributed visual representations across lateral and medial VTC. Domain representations (e.g., faces, bodies, places, characters) were most salient in lateral VTC, whereas category representations (e.g., corridors/houses within the domain of places) were equally salient in medial VTC. These results bridge an important gap between electrophysiological recordings in single neurons at a micron scale and fMRI measurements at a millimeter scale.

During differentiation, oligodendrocyte precursor cells (OPCs) extend a network of processes that make contact with axons and initiate myelination. Recent studies revealed that actin polymerization is required for initiation of myelination whereas actin depolymerization promotes myelin wrapping. Here, we used primary OPCs in culture isolated from neonatal rat cortices of both sexes and young male and female mice with oligodendrocyte-specific deletion of mechanistic target of rapamycin (mTOR) to demonstrate that mTOR regulates expression of specific cytoskeletal targets and actin reorganization in oligodendrocytes during developmental myelination. Loss or inhibition of mTOR reduced expression of profilin2 and ARPC3, actin polymerizing factors, and elevated levels of active cofilin, which mediates actin depolymerization. The deficits in actin polymerization were revealed in reduced phalloidin and deficits in oligodendrocyte cellular branching complexity at the peak of morphologic differentiation and a delay in initiation of myelination. We further show a critical role for mTOR in expression and localization of myelin basic protein (Mbp) mRNA and MBP protein to the cellular processes where it is necessary at the myelin membrane for axon wrapping. Mbp mRNA transport deficits were confirmed by single molecule RNA FISH. Moreover, expression of the kinesin family member 1B, an Mbp mRNA transport protein, was reduced in CC1+ cells in the mTOR cKO and in mTOR inhibited oligodendrocytes undergoing differentiation in vitro. These data support the conclusion that mTOR regulates both initiation of myelination and axon wrapping by targeting cytoskeletal reorganization and MBP localization to oligodendrocyte processes.

SIGNIFICANCE STATEMENT Myelination is essential for normal CNS development and adult axon preservation and function. The mechanistic target of rapamycin (mTOR) signaling pathway has been implicated in promoting CNS myelination; however, there is a gap in our understanding of the mechanisms by which mTOR promotes developmental myelination through regulating specific downstream targets. Here, we present evidence that mTOR promotes the initiation of myelination through regulating specific cytoskeletal targets and cellular process expansion by oligodendrocyte precursor cells as well as expression and cellular localization of myelin basic protein.

Microglial cells are considered as sensors of brain pathology by detecting any sign of brain lesions, infections, or dysfunction and can influence the onset and progression of neurological diseases. They are capable of sensing their neuronal environment via many different signaling molecules, such as neurotransmitters, neurohormones and neuropeptides. The neuropeptide VGF has been associated with many metabolic and neurological disorders. TLQP21 is a VGF-derived peptide and has been shown to signal via C3aR1 and C1qBP receptors. The effect of TLQP21 on microglial functions in health or disease is not known. Studying microglial cells in acute brain slices, we found that TLQP21 impaired metabotropic purinergic signaling. Specifically, it attenuated the ATP-induced activation of a K⁺ conductance, the UDP-stimulated phagocytic activity, and the ATP-dependent laser lesion-induced process outgrowth. These impairments were reversed by blocking C1qBP, but not C3aR1 receptors. While microglia in brain slices from male mice lack C3aR1 receptors, both receptors are expressed in primary cultured microglia. In addition to the negative impact on purinergic signaling, we found stimulating effects of TLQP21 in cultured microglia, which were mediated by C3aR1 receptors: it directly evoked membrane currents, stimulated basal phagocytic activity, evoked intracellular Ca²⁺ transient elevations, and served as a chemotactic signal. We conclude that TLQP21 has differential effects on microglia depending on C3aR1 activation or C1qBP-dependent attenuation of purinergic signaling. Thus, TLQP21 can modulate the functional phenotype of microglia, which may have an impact on their function in health and disease.

SIGNIFICANCE STATEMENT The neuropeptide VGF and its peptides have been associated with many metabolic and neurological disorders. TLQP21 is a VGF-derived peptide that activates C1qBP receptors, which are expressed by microglia. We show here, for the first time, that TLQP21 impairs P2Y-mediated purinergic signaling and related functions. These include modulation of phagocytic activity and responses to injury. As purinergic signaling is central for microglial actions in the brain, this TLQP21-mediated mechanism might regulate microglial activity in health and disease. We furthermore show that, in addition to C1qBP, functional C3aR1 responses contribute to TLQP21 action on microglia. However, C3aR1 responses were only present in primary cultures but not in situ, suggesting that the expression of these receptors might vary between different microglial activation states.

Have you ever wondered if you are getting adequate nutrients from the food you eat? It is a common misconception that malnutrition means not getting enough food. This is, however, incorrect! People who take in insufficient food can be malnourished, but also those who consume too much face the same risks. Malnutrition is defined as “An abnormal physiological condition caused by [...]