25 research outputs found
Detecting the direction of a signal on high-dimensional spheres: Non-null and Le Cam optimality results
We consider one of the most important problems in directional statistics,
namely the problem of testing the null hypothesis that the spike direction
of a Fisher-von Mises-Langevin distribution on the -dimensional
unit hypersphere is equal to a given direction . After a reduction
through invariance arguments, we derive local asymptotic normality (LAN)
results in a general high-dimensional framework where the dimension goes
to infinity at an arbitrary rate with the sample size , and where the
concentration behaves in a completely free way with , which
offers a spectrum of problems ranging from arbitrarily easy to arbitrarily
challenging ones. We identify various asymptotic regimes, depending on the
convergence/divergence properties of , that yield different
contiguity rates and different limiting experiments. In each regime, we derive
Le Cam optimal tests under specified and we compute, from the Le Cam
third lemma, asymptotic powers of the classical Watson test under contiguous
alternatives. We further establish LAN results with respect to both spike
direction and concentration, which allows us to discuss optimality also under
unspecified . To investigate the non-null behavior of the Watson test
outside the parametric framework above, we derive its local asymptotic powers
through martingale CLTs in the broader, semiparametric, model of rotationally
symmetric distributions. A Monte Carlo study shows that the finite-sample
behaviors of the various tests remarkably agree with our asymptotic results.Comment: 47 pages, 4 figure
Structure of HsdS Subunit from Thermoanaerobacter tengcongensis Sheds Lights on Mechanism of Dynamic Opening and Closing of Type I Methyltransferase
Type I DNA methyltransferases contain one specificity subunit (HsdS) and two modification subunits (HsdM). The electron microscopy model of M.EcoKI-M2S1 methyltransferase shows a reasonable closed state of this clamp-like enzyme, but the structure of the open state is still unclear. The 1.95 Å crystal structure of the specificity subunit from Thermoanaerobacter tengcongensis (TTE-HsdS) shows an unreported open form inter-domain orientation of this subunit. Based on the crystal structure of TTE-HsdS and the closed state model of M.EcoKI-M2S1, we constructed a potential open state model of type I methyltransferase. Mutational studies indicated that two α-helices (aa30-59 and aa466-495) of the TTE-HsdM subunit are important inter-subunit interaction sites in the TTE-M2S1 complex. DNA binding assays also highlighted the importance of the C-terminal region of TTE-HsdM for DNA binding by the TTE-M2S1 complex. On the basis of structural analysis, biochemical experiments and previous studies, we propose a dynamic opening and closing mechanism for type I methyltransferase
Blood pressure and cholesterol level checks as dynamic interrelated screening examinations
This study analysed the determinants of screening uptake for blood pressure and cholesterol level checks. Furthermore, it investigated the presence of possible spillover effects from one type of cardiovascular screening to another type of cardiovascular screening. A dynamic random effects bivariate panel probit model with initial conditions (Wooldridge-type estimator) was adopted for the estimation. The outcome variables were the participation in blood pressure and cholesterol level checks by individuals in a given year. The balanced panel sample of 21,138 observations was constructed from 1,626 individuals from the British Household Panel Survey (BHPS) between 1996 and 2008. The analysis showed the significance of past screening behaviour for both cardiovascular screening examinations. For both cardiovascular screening examinations state dependence exist. The study also shows a significant spillover effect of the cholesterol level check on the blood pressure check and vice versa. Also a poorer health status led to a higher uptake for both types of screening examinations. Changes in recommendations have to consider the fact that taking part in one type of cardiovascular screening examination can influence the decision to take part in the other type of cardiovascular screening examination
Eucapnic Voluntary Hyperpnea: Gold Standard for Diagnosing Exercise-Induced Bronchoconstriction in Athletes?
In athletes, a secure diagnos is of exercise-induced bronchoconstriction (EIB) is dependent on objective testing. Evaluating spirometric indices of airflow before and following an exercise bout is intuitively the optimal means for the diagnosis; however, this approach is recognized as having several key limitations. Accordingly, alternative indirect bronchoprovocation tests have been recommended as surrogate means for obtaining a diagnosis of EIB. Of these tests, it is often argued that the eucapnic voluntary hyperpnea (EVH) challenge represents the ‘gold standard’. This article provides a state-of-the-art review of EVH, including an overview of the test methodology and its interpretation. We also address the performance of EVH against the other functional and clinical approaches commonly adopted for the diagnosis of EIB. The published evidence supports a key role for EVH in the diagnostic algorithm for EIB testing in athletes. However, its wide sensitivity and specificity and poor repeatability preclude EVH from being termed a ‘gold standard’ test for EIB
Towards a Processual Microbial Ontology
types: ArticleStandard microbial evolutionary ontology is organized according to a
nested hierarchy of entities at various levels of biological organization. It typically
detects and defines these entities in relation to the most stable aspects of evolutionary
processes, by identifying lineages evolving by a process of vertical inheritance
from an ancestral entity. However, recent advances in microbiology indicate
that such an ontology has important limitations. The various dynamics detected
within microbiological systems reveal that a focus on the most stable entities (or
features of entities) over time inevitably underestimates the extent and nature of
microbial diversity. These dynamics are not the outcome of the process of vertical
descent alone. Other processes, often involving causal interactions between entities
from distinct levels of biological organisation, or operating at different time scales,
are responsible not only for the destabilisation of pre-existing entities, but also for
the emergence and stabilisation of novel entities in the microbial world. In this
article we consider microbial entities as more or less stabilised functional wholes,
and sketch a network-based ontology that can represent a diverse set of processes
including, for example, as well as phylogenetic relations, interactions that stabilise
or destabilise the interacting entities, spatial relations, ecological connections, and
genetic exchanges. We use this pluralistic framework for evaluating (i) the existing
ontological assumptions in evolution (e.g. whether currently recognized entities are
adequate for understanding the causes of change and stabilisation in the microbial
world), and (ii) for identifying hidden ontological kinds, essentially invisible from
within a more limited perspective. We propose to recognize additional classes of
entities that provide new insights into the structure of the microbial world, namely ‘‘processually equivalent’’ entities, ‘‘processually versatile’’ entities, and ‘‘stabilized’’
entities.Economic and Social Research Council, U
Mutations of the domain forming the dimeric interface of the ArdA protein affect dimerization and antimodification activity but not antirestriction activity
ArdA antirestriction proteins are encoded by genes present in many conjugative plasmids and transposons within bacterial genomes. Antirestriction is the ability to prevent cleavage of foreign incoming DNA by restrictionmodification (RM) systems. Antimodification, the ability to inhibit modification by the RM system, can also be observed with some antirestriction proteins. As these mobile genetic elements can transfer antibiotic resistance genes, the ArdA proteins assist their spread. The consequence of antirestriction is therefore the enhanced dissemination of mobile genetic elements. ArdA proteins cause antirestriction by mimicking the DNA structure bound by Type I RM enzymes. The crystal structure of ArdA showed it to be a dimeric protein with a highly elongated curved cylindrical shape [McMahon SA et al. (2009) Nucleic Acids Res 37, 4887–4897]. Each monomer has three domains covered with negatively charged side chains and a very small interface with the other monomer. We investigated the role of the domain forming the dimer interface for ArdA activity via sitedirected mutagenesis. The antirestriction activity of ArdA was maintained when up to seven mutations per monomer were made or the interface was disrupted such that the protein could only exist as a monomer. The antimodification activity of ArdA was lost upon mutation of this domain. The ability of the monomeric form of ArdA to function in antirestriction suggests, first, that it can bind independently to the restriction subunit or the modification subunits of the RM enzyme, and second, that the many ArdA homologues with long amino acid extensions, present in sequence databases, may be active in antirestriction