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London : Scribe, 2019.

Stuttgart : In Kommission: Wissenschaftliche Verlagsgesellschaft, 2019.

Michael P. Fay, Michael A. Proschan

Source: Statist. Surv., Volume 4, 1--39.

Abstract:
In a mathematical approach to hypothesis tests, we start with a clearly defined set of hypotheses and choose the test with the best properties for those hypotheses. In practice, we often start with less precise hypotheses. For example, often a researcher wants to know which of two groups generally has the larger responses, and either a t-test or a Wilcoxon-Mann-Whitney (WMW) test could be acceptable. Although both t-tests and WMW tests are usually associated with quite different hypotheses, the decision rule and p-value from either test could be associated with many different sets of assumptions, which we call perspectives. It is useful to have many of the different perspectives to which a decision rule may be applied collected in one place, since each perspective allows a different interpretation of the associated p-value. Here we collect many such perspectives for the two-sample t-test, the WMW test and other related tests. We discuss validity and consistency under each perspective and discuss recommendations between the tests in light of these many different perspectives. Finally, we briefly discuss a decision rule for testing genetic neutrality where knowledge of the many perspectives is vital to the proper interpretation of the decision rule.

Restricted Boltzmann Machine (RBM) is an energy based, undirected graphical model. It is commonly used for unsupervised and supervised machine learning. Typically, RBM is trained using contrastive divergence (CD). However, training with CD is slow and does not estimate exact gradient of log-likelihood cost function. In this work, the model expectation of gradient learning for RBM has been calculated using a quantum annealer (D-Wave 2000Q), which is much faster than Markov chain Monte Carlo (MCMC) used in CD. Training and classification results are compared with CD. The classification accuracy results indicate similar performance of both methods. Image reconstruction as well as log-likelihood calculations are used to compare the performance of quantum and classical algorithms for RBM training. It is shown that the samples obtained from quantum annealer can be used to train a RBM on a 64-bit `bars and stripes' data set with classification performance similar to a RBM trained with CD. Though training based on CD showed improved learning performance, training using a quantum annealer eliminates computationally expensive MCMC steps of CD.

Manifold optimization appears in a wide variety of computational problems in the applied sciences. In recent statistical methodologies such as sufficient dimension reduction and regression envelopes, estimation relies on the optimization of likelihood functions over spaces of matrices such as the Stiefel or Grassmann manifolds. Recently, Huang, Absil, Gallivan, and Hand (2016) have introduced the library ROPTLIB, which provides a framework and state of the art algorithms to optimize real-valued objective functions over commonly used matrix-valued Riemannian manifolds. This article presents ManifoldOptim, an R package that wraps the C++ library ROPTLIB. ManifoldOptim enables users to access functionality in ROPTLIB through R so that optimization problems can easily be constructed, solved, and integrated into larger R codes. Computationally intensive problems can be programmed with Rcpp and RcppArmadillo, and otherwise accessed through R. We illustrate the practical use of ManifoldOptim through several motivating examples involving dimension reduction and envelope methods in regression.

Zhenhua Lin, Fang Yao.

Source: The Annals of Statistics, Volume 47, Number 6, 3533--3577.

Abstract:
In this work we develop a novel and foundational framework for analyzing general Riemannian functional data, in particular a new development of tensor Hilbert spaces along curves on a manifold. Such spaces enable us to derive Karhunen–Loève expansion for Riemannian random processes. This framework also features an approach to compare objects from different tensor Hilbert spaces, which paves the way for asymptotic analysis in Riemannian functional data analysis. Built upon intrinsic geometric concepts such as vector field, Levi-Civita connection and parallel transport on Riemannian manifolds, the developed framework applies to not only Euclidean submanifolds but also manifolds without a natural ambient space. As applications of this framework, we develop intrinsic Riemannian functional principal component analysis (iRFPCA) and intrinsic Riemannian functional linear regression (iRFLR) that are distinct from their traditional and ambient counterparts. We also provide estimation procedures for iRFPCA and iRFLR, and investigate their asymptotic properties within the intrinsic geometry. Numerical performance is illustrated by simulated and real examples.

Anton Thalmaier, James Thompson.

Source: Bernoulli, Volume 26, Number 3, 2202--2225.

Abstract:
In this article, we derive moment estimates, exponential integrability, concentration inequalities and exit times estimates for canonical diffusions firstly on sub-Riemannian limits of Riemannian foliations and secondly in the nonsmooth setting of $operatorname{RCD}^{*}(K,N)$ spaces. In each case, the necessary ingredients are Itô’s formula and a comparison theorem for the Laplacian, for which we refer to the recent literature. As an application, we derive pointwise Carmona-type estimates on eigenfunctions of Schrödinger operators.

Tom Alberts, Firas Rassoul-Agha, Mackenzie Simper.

Source: Bernoulli, Volume 26, Number 3, 1927--1955.

Abstract:
We prove that given any fixed asymptotic velocity, the finite length O’Connell–Yor polymer has an infinite length limit satisfying the law of large numbers with this velocity. By a Markovian property of the quenched polymer this reduces to showing the existence of Busemann functions : almost sure limits of ratios of random point-to-point partition functions. The key ingredients are the Burke property of the O’Connell–Yor polymer and a comparison lemma for the ratios of partition functions. We also show the existence of infinite length limits in the Brownian last passage percolation model.

Siekmann, Francis Heinrich Ernst, 1830-1917.

Traeger, Ernst Wilhelm, 1805-1874.

Stress alters brain function by modifying the structure and function of neurons and astrocytes. The fine processes of astrocytes are critical for the clearance of neurotransmitters during synaptic transmission. Thus, experience-dependent remodeling of glial processes is anticipated to alter the output of neural circuits. However, the molecular mechanisms that underlie glial structural plasticity are not known. Here we show that a single exposure of male and female mice to an acute stress produced a long-lasting retraction of the lateral processes of cerebellar Bergmann glial cells. These cells express the GluA1 subunit of AMPA-type glutamate receptors, and GluA1 knockdown is known to shorten the length of glial processes. We found that stress reduced the level of GluA1 protein and AMPA receptor-mediated currents in Bergmann glial cells, and these effects were absent in mice devoid of CPEB3, a protein that binds to GluA1 mRNA and regulates GluA1 protein synthesis. Administration of a β-adrenergic receptor blocker attenuated the reduction in GluA1, and deletion of adenylate cyclase 5 prevented GluA1 suppression. Therefore, stress suppresses GluA1 protein synthesis via an adrenergic/adenylyl cyclase/CPEB3 pathway, and reduces the length of astrocyte lateral processes. Our results identify a novel mechanism for GluA1 subunit plasticity in non-neuronal cells and suggest a previously unappreciated role for AMPA receptors in stress-induced astrocytic remodeling.

SIGNIFICANCE STATEMENT Astrocytes play important roles in synaptic transmission by extending fine processes around synapses. In this study, we showed that a single exposure to an acute stress triggered a retraction of lateral/fine processes in mouse cerebellar astrocytes. These astrocytes express GluA1, a glutamate receptor subunit known to lengthen astrocyte processes. We showed that astrocytic structural changes are associated with a reduction of GluA1 protein levels. This requires activation of β-adrenergic receptors and is triggered by noradrenaline released during stress. We identified adenylyl cyclase 5, an enzyme that elevates cAMP levels, as a downstream effector and found that lowering GluA1 levels depends on CPEB3 proteins that bind to GluA1 mRNA. Therefore, stress regulates GluA1 protein synthesis via an adrenergic/adenylyl cyclase/CPEB3 pathway in astrocytes and remodels their fine processes.

Neonatal stroke is as frequent as stroke in the elderly, but many pathophysiological injury aspects are distinct in neonates, including immune signaling. While myeloid cells can traffic into the brain via multiple routes, the choroid plexus (CP) has been identified as a uniquely educated gate for immune cell traffic during health and disease. To understand the mechanisms of myeloid cell trafficking via the CP and their influence on neonatal stroke, we characterized the phenotypes of CP-infiltrating myeloid cells after transient middle cerebral artery occlusion (tMCAO) in neonatal mice of both sexes in relation to blood-brain barrier permeability, injury, microglial activation, and CX3CR1-CCR2 signaling, focusing on the dynamics early after reperfusion. We demonstrate rapid recruitment of multiple myeloid phenotypes in the CP ipsilateral to the injury, including inflammatory CD45⁺CD11b⁺Ly6c^highCD86⁺, beneficial CD45⁺CD11b⁺Ly6c^lowCD206⁺, and CD45⁺CD11b⁺Ly6c^lowLy6g^high cells, but only minor leukocyte infiltration into acutely ischemic-reperfused cortex and negligible vascular albumin leakage. We report that CX3CR1-CCR2-mediated myeloid cell recruitment contributes to stroke injury. Considering the complexity of inflammatory cascades triggered by stroke and a role for TLR2 in injury, we also used direct TLR2 stimulation as an independent injury model. TLR2 agonist rapidly recruited myeloid cells to the CP, increased leukocytosis in the CSF and blood, but infiltration into the cortex remained low over time. While the magnitude and the phenotypes of myeloid cells diverged between tMCAO and TLR2 stimulation, in both models, disruption of CX3CR1-CCR2 signaling attenuated both monocyte and neutrophil trafficking to the CP and cortex.

SIGNIFICANCE STATEMENT Stroke during the neonatal period leads to long-term disabilities. The mechanisms of ischemic injury and inflammatory response differ greatly between the immature and adult brain. We examined leukocyte trafficking via the choroid plexus (CP) following neonatal stroke in relation to blood-brain barrier integrity, injury, microglial activation, and signaling via CX3CR1 and CCR2 receptors, or following direct TLR2 stimulation. Ischemia-reperfusion triggered marked unilateral CX3CR1-CCR2 dependent accumulation of diverse leukocyte subpopulations in the CP without inducing extravascular albumin leakage or major leukocyte infiltration into the brain. Disrupted CX3CR1-CCR2 signaling was neuroprotective in part by attenuating monocyte and neutrophil trafficking. Understanding the migratory patterns of CP-infiltrating myeloid cells with intact and disrupted CX3CR1-CCR2 signaling could identify novel therapeutic targets to protect the neonatal brain.

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As editor Wilhelm Crous puts it, "We haven't seen this movie before."

QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor that demonstrates inhibition of key serine and metallo beta-lactamases at a nano molar range in biochemical assays with purified enzymes. The broad-spectrum inhibitory activity of QPX7728 observed in biochemical experiments translates into enhancement of the potency of many beta-lactams against strains of target pathogens producing beta-lactamases. The impact of bacterial efflux and permeability on inhibitory potency were determined using isogenic panels of KPC-3 producing isogenic strains of K. pneumoniae and P. aeruginosa and OXA-23-producing strains of A. baumannii with various combinations of efflux and porin mutations. QPX7728 was minimally affected by multi-drug resistance efflux pumps in either Enterobacteriaceae, or in non-fermenters such as P. aeruginosa or A. baumannii. In P. aeruginosa, the potency of QPX7728 was further enhanced when the outer membrane is permeabilized. The potency of QPX7728 in P. aeruginosa is not affected by inactivation of the carbapenem porin OprD. While changes in OmpK36 (but not OmpK35) reduced the potency of QPX7728 (8-16-fold), QPX7728 (4 μg/ml) nevertheless completely reversed KPC-mediated meropenem resistance in strains with porin mutations, consistent with a lesser effect of these mutations on the potency of QPX7728 compared to other agents. The ultra-broad-spectrum beta-lactamase inhibition profile combined with enhancement of the activity of multiple beta-lactam antibiotics with varying sensitivity to the intrinsic resistance mechanisms of efflux and permeability indicate QPX7728 is a useful inhibitor for use with multiple beta-lactam antibiotics.

Michael Mann, distinguished professor of atmospheric sciences and director of Penn State's Earth System Science Center at Penn State, has been elected to the National Academy of Sciences, recognizing distinguished and continuing achievements in original research. Membership in the NAS is one of the highest honors given to a scientist or engineer in the United States.

France forward Antoine Griezmann has been named as the UEFA EURO 2016 Player of the Tournament by UEFA's technical observers after finishing with six goals and two assists.

France forward Antoine Griezmann has received his award as the Player of the Tournament for UEFA EURO 2016 in the run-up to Les Bleus' European Qualifier against Bulgaria.

Agency: GSS Closing Date: 5/28/2020

The number of registrations before PM Modi's mention was hovering at only 74,000 which jumped to 1,53,000 after PM's mention.