Type I Error Of Four Pairwise Mean Comparison Procedures Conducted As Protected And Unprotected Tests

Type I error control accuracy of four commonly used pairwise mean comparison procedures, conducted as protected or unprotected tests, is examined. If error control philosophy is experimentwise, Tukey’s HSD, as an unprotected test, is most accurate and if philosophy is per-experiment, Dunn-Bonferroni, conducted as an unprotected test, is most accurate

PKCγ Regulates Syndecan-2 Inside-Out Signaling during Xenopus Left-Right Development

AbstractThe transmembrane proteoglycan syndecan-2 cell nonautonomously regulates left-right (LR) development in migrating mesoderm by an unknown mechanism, leading to LR asymmetric gene expression and LR orientation of the heart and gut. Here, we demonstrate that protein kinase C γ (PKCγ) mediates phosphorylation of the cytoplasmic domain of syndecan-2 in right, but not left, animal cap ectodermal cells. Notably, both phosphorylation states of syndecan-2 are obligatory for normal LR development, with PKCγ-dependent phosphorylated syndecan-2 in right ectodermal cells and nonphosphorylated syndecan-2 in left cells. The ectodermal cells contact migrating mesodermal cells during early gastrulation, concurrent with the transmission of LR information. This precedes the appearance of monocilia and is one of the earliest steps of LR development. These results demonstrate that PKCγ regulates the cytoplasmic phosphorylation of syndecan-2 and, consequently, syndecan-2-mediated inside-out signaling to adjacent cells

Irreducible triangulations of surfaces with boundary

A triangulation of a surface is irreducible if no edge can be contracted to produce a triangulation of the same surface. In this paper, we investigate irreducible triangulations of surfaces with boundary. We prove that the number of vertices of an irreducible triangulation of a (possibly non-orientable) surface of genus g>=0 with b>=0 boundaries is O(g+b). So far, the result was known only for surfaces without boundary (b=0). While our technique yields a worse constant in the O(.) notation, the present proof is elementary, and simpler than the previous ones in the case of surfaces without boundary

The lower and upper bound problems for cubical polytopes

We construct a family of cubical polytypes which shows that the upper bound on the number of facets of a cubical polytope (given a fixed number of vertices) is higher than previously suspected. We also formulate a lower bound conjecture for cubical polytopes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41359/1/454_2005_Article_BF02189315.pd

Polytopality and Cartesian products of graphs

We study the question of polytopality of graphs: when is a given graph the graph of a polytope? We first review the known necessary conditions for a graph to be polytopal, and we provide several families of graphs which satisfy all these conditions, but which nonetheless are not graphs of polytopes. Our main contribution concerns the polytopality of Cartesian products of non-polytopal graphs. On the one hand, we show that products of simple polytopes are the only simple polytopes whose graph is a product. On the other hand, we provide a general method to construct (non-simple) polytopal products whose factors are not polytopal.Comment: 21 pages, 10 figure

Pregnancy and neonatal outcomes of COVID-19: co-reporting of common outcomes from PAN-COVID and AAP SONPM registries

OBJECTIVE: Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with SARS-CoV-2 infection in pregnancy. We report the outcome of infected pregnancies from a collaboration formed early during the pandemic between the investigators of two registries, the UK and global Pregnancy and Neonatal outcomes in COVID-19 (PAN-COVID) study and the US American Academy of Pediatrics Section on Neonatal Perinatal Medicine (AAP SONPM) National Perinatal COVID-19 Registry. METHODS: This was an analysis of data from the PAN-COVID registry (January 1st to July 25th 2020), which includes pregnancies with suspected or confirmed maternal SARS-CoV-2 infection at any stage in pregnancy, and the AAP SONPM National Perinatal COVID-19 registry (April 4th to August 8th 2020), which includes pregnancies with positive maternal testing for SARS-CoV-2 from 14 days before delivery to 3 days after delivery. The registries collected data on maternal, fetal, perinatal and neonatal outcomes. The PAN-COVID results are presented both overall for pregnancies with suspected or confirmed SARS-CoV-2 infection and separately in those with confirmed infection. RESULTS: We report on 4005 pregnant women with suspected or confirmed SARS-CoV-2 infection (1606 from PAN-COVID and 2399 from AAP SONPM). For obstetric outcomes, in PAN-COVID overall, those with confirmed infection in PAN-COVID and AAP SONPM, respectively, maternal death occurred in 0.5%, 0.5% and 0.2% of cases, early neonatal death in 0.2%, 0.3% and 0.3% of cases and stillbirth in 0.5%, 0.6% and 0.4% of cases. Delivery was pre-term (<37 weeks' gestation) in 12.0% of all women in PAN-COVID, in 16.2% of those women with confirmed infection in PAN-COVID and in 15.7% of women in AAP SONPM. Extremely preterm delivery (< 27 weeks' gestation) occurred in 0.5% of cases in PAN-COVID and 0.3% in AAP SONPM. Neonatal SARS-CoV-2 infection was reported in 0.8% of all deliveries in PAN-COVID, in 2.0% in those with confirmed infection in PAN-COVID and in 1.8% in AAP SONPM; the proportions of neonates tested were 9.5%, 20.7% and 87.2%, respectively. The rates of a SGA neonate were 8.2% in PAN-COVID overall, 9.7% in those with confirmed infection and 9.6% in AAP SONPM. Mean gestational age adjusted birth-weight z-scores were -0.03 in PAN-COVID and -0.18 in AAP SONPM. CONCLUSIONS: The findings from the UK and US registries of pregnancies with SARS-CoV-2 infection were remarkably concordant. Preterm delivery affected a higher proportion of women than expected based on historical and contemporaneous national data. The proportions of pregnancies affected by stillbirth, a small for gestational age infant or early neonatal death were comparable to those in historical and contemporaneous UK and US data. Although maternal death was uncommon, the rate was higher than expected based on UK and US population data, which is likely explained by under-ascertainment of women affected by milder or asymptomatic infection in pregnancy in the PAN-COVID study although not in the AAP SONPM study. The data presented support strong guidance for enhanced precautions to prevent SARS-CoV-2 infection in pregnancy, particularly in the context of increased risks of preterm delivery and maternal mortality, and for priority vaccination of women planning pregnancy. This article is protected by copyright. All rights reserved

Phagocytosis by an HIV antibody is associated with reduced viremia irrespective of enhanced complement lysis

Increasingly, antibodies are being used to treat and prevent viral infections. In the context of HIV, efficacy is primarily attributed to dose-dependent neutralization potency and to a lesser extent Fc-mediated effector functions. It remains unclear whether augmenting effector functions of broadly neutralizing antibodies (bNAbs) may improve their clinical potential. Here, we use bNAb 10E8v4 targeting the membrane external proximal region (MPER) to examine the role of antibody-mediated effector and complement (C’) activity when administered prophylactically against SHIV challenge in rhesus macaques. With sub-protective dosing, we find a 78–88% reduction in post-acute viremia that is associated with 10E8v4-mediated phagocytosis acting at the time of challenge. Neither plasma nor tissue viremic outcomes in vivo is improved with an Fc-modified variant of 10E8v4 enhanced for C’ functions as determined in vitro. These results suggest that effector functions inherent to unmodified 10E8v4 contribute to efficacy against SHIVSF162P3 in the absence of plasma neutralizing titers, while C’ functions are dispensable in this setting, informing design of bNAb modifications for improving protective efficacy

An update on the Hirsch conjecture

The Hirsch conjecture was posed in 1957 in a letter from Warren M. Hirsch to George Dantzig. It states that the graph of a d-dimensional polytope with n facets cannot have diameter greater than n - d. Despite being one of the most fundamental, basic and old problems in polytope theory, what we know is quite scarce. Most notably, no polynomial upper bound is known for the diameters that are conjectured to be linear. In contrast, very few polytopes are known where the bound $n-d$ is attained. This paper collects known results and remarks both on the positive and on the negative side of the conjecture. Some proofs are included, but only those that we hope are accessible to a general mathematical audience without introducing too many technicalities.Comment: 28 pages, 6 figures. Many proofs have been taken out from version 2 and put into the appendix arXiv:0912.423

BRG1-SWI/SNF-dependent regulation of the Wt1 transcriptional landscape mediates epicardial activity during heart development and disease

Epicardium-derived cells (EPDCs) contribute cardiovascular cell types during development and in adulthood respond to Thymosin \u3b24 (T\u3b24) and myocardial infarction (MI) by reactivating a fetal gene programme to promote neovascularization and cardiomyogenesis. The mechanism for epicardial gene (re-)activation remains elusive. Here we reveal that BRG1, the essential ATPase subunit of the SWI/SNF chromatin-remodelling complex, is required for expression of Wilms' tumour 1 (Wt1), fetal EPDC activation and subsequent differentiation into coronary smooth muscle, and restores Wt1 activity upon MI. BRG1 physically interacts with T\u3b24 and is recruited by CCAAT/enhancer-binding protein \u3b2 (C/EBP\u3b2) to discrete regulatory elements in the Wt1 locus. BRG1-T\u3b24 co-operative binding promotes optimal transcription of Wt1 as the master regulator of embryonic EPDCs. Moreover, chromatin immunoprecipitation-sequencing reveals BRG1 binding at further key loci suggesting SWI/SNF activity across the fetal epicardial gene programme. These findings reveal essential functions for chromatin-remodelling in the activation of EPDCs during cardiovascular development and repair