Exact Post-Selection Inference for Sequential Regression Procedures

We propose new inference tools for forward stepwise regression, least angle regression, and the lasso. Assuming a Gaussian model for the observation vector y, we first describe a general scheme to perform valid inference after any selection event that can be characterized as y falling into a polyhedral set. This framework allows us to derive conditional (post-selection) hypothesis tests at any step of forward stepwise or least angle regression, or any step along the lasso regularization path, because, as it turns out, selection events for these procedures can be expressed as polyhedral constraints on y. The p-values associated with these tests are exactly uniform under the null distribution, in finite samples, yielding exact type I error control. The tests can also be inverted to produce confidence intervals for appropriate underlying regression parameters. The R package "selectiveInference", freely available on the CRAN repository, implements the new inference tools described in this paper.Comment: 26 pages, 5 figure

Self-determination theory and diminished functioning: the role of interpersonal control and psychological need thwarting

Drawing from self-determination theory (Ryan & Deci, 2002), three studies explored the social-environmental conditions that satisfy versus thwart psychological needs and, in turn, impact psychological functioning and well/ill-being. In cross-sectional Studies 1 and 2, structural equation modeling analyses supported latent factor models in which need satisfaction was predicted by athletes’ perceptions of autonomy support and need thwarting was better predicted by perceived coach control. Athletes’ perceptions of need satisfaction predicted positive outcomes associated with sport participation (vitality and positive affect) whereas perceptions of need thwarting more consistently predicted maladaptive outcomes (disordered eating, burnout, depression, negative affect, and physical symptoms). In addition, athletes’ perceptions of psychological need thwarting were significantly associated with perturbed physiological arousal (elevated levels of secretory immunoglobulin A) prior to training. The final study involved the completion of a diary and supported the relations observed in the cross-sectional studies at a daily level. These findings have important implications for the operationalization and measurement of interpersonal styles and psychological needs

Field Theory of the Fermi Function

The Fermi function $F(Z,E)$ accounts for QED corrections to beta decays that are enhanced at either small electron velocity $\beta$ or large nuclear charge $Z$. For precision applications, the Fermi function must be combined with other radiative corrections and with scale- and scheme-dependent hadronic matrix elements. We formulate the Fermi function as a field theory object and present a new factorization formula for QED radiative corrections to beta decays. We provide new results for the anomalous dimension of the corresponding effective operator complete through three loops, and resum perturbative logarithms and $\pi$-enhancements with renormalization group methods. Our results are important for tests of fundamental physics with precision beta decay and related processes

A Peptide Core Motif for Binding to Heterotrimeric G Protein α Subunits

Recently, in vitro selection using mRNA display was used to identify a novel peptide sequence that binds with high affinity to G{alpha}i1. The peptide was minimized to a 9-residue sequence (R6A-1) that retains high affinity and specificity for the GDP-bound state of G{alpha}i1 and acts as a guanine nucleotide dissociation inhibitor (GDI). Here we demonstrate that the R6A-1 peptide interacts with G{alpha} subunits representing all four G protein classes, acting as a core motif for G{alpha} interaction. This contrasts with the consensus G protein regulatory(GPR) sequence, a 28-mer peptide GDI derived from the GoLoco (G{alpha}i/0-Loco interaction)/GPR motif that shares no homology with R6A-1 and binds only to G{alpha}i1-3 in this assay. Binding of R6A-1 is generally specific to the GDP-bound state of the G{alpha} subunits and excludes association with G{beta}{gamma}. R6A-G{alpha}i1 complexes are resistant to trypsin digestion and exhibit distinct stability in the presence of Mg2+, suggesting that the R6A and GPR peptides exert their activities using different mechanisms. Studies using G{alpha}i1/G{alpha}s chimeras identify two regions of G{alpha}i1 (residues 1–35 and 57–88) as determinants for strong R6A-Gi{alpha}1 interaction. Residues flanking the R6A-1 peptide confer unique binding properties, indicating that the core motif could be used as a starting point for the development of peptides exhibiting novel activities and/or specificity for particular G protein subclasses or nucleotide-bound states

Prehypertensive blood pressures and regional cerebral blood flow independently relate to cognitive performance in midlife

Background High blood pressure is thought to contribute to dementia in late life, but our understanding of the relationship between individual differences in blood pressure ( BP ) and cognitive functioning is incomplete. In this study, cognitive performance in nonhypertensive midlife adults was examined as a function of resting BP and regional cerebral blood flow ( rCBF ) responses during cognitive testing. We hypothesized that BP would be negatively related to cognitive performance and that cognitive performance would also be related to rCBF responses within areas related to BP control. We explored whether deficits related to systolic BP might be explained by rCBF responses to mental challenge. Methods and Results Healthy midlife participants (n=227) received neuropsychological testing and performed cognitive tasks in a magnetic resonance imaging scanner. A pseudocontinuous arterial spin labeling sequence assessed rCBF in brain areas related to BP in prior studies. Systolic BP was negatively related to 4 of 5 neuropsychological factors (standardized β&gt;0.13): memory, working memory, executive function, and mental efficiency. The rCBF in 2 brain regions of interest was similarly related to memory, executive function, and working memory (standardized β&gt;0.17); however, rCBF responses did not explain the relationship between resting systolic BP and cognitive performance. Conclusions Relationships at midlife between prehypertensive levels of systolic BP and both cognitive and brain function were modest but suggested the possible value of midlife intervention. </jats:sec

Investigating intra-host and intra-herd sequence diversity of foot-and-mouth disease virus

Due to the poor-fidelity of the enzymes involved in RNA genome replication, foot-and-mouth disease (FMD) virus samples comprise of unique polymorphic populations. In this study, deep sequencing was utilised to characterise the diversity of FMD virus (FMDV) populations in 6 infected cattle present on a single farm during the series of outbreaks in the UK in 2007. A novel RT–PCR method was developed to amplify a 7.6 kb nucleotide fragment encompassing the polyprotein coding region of the FMDV genome. Illumina sequencing of each sample identified the fine polymorphic structures at each nucleotide position, from consensus level changes to variants present at a 0.24% frequency. These data were used to investigate population dynamics of FMDV at both herd and host levels, evaluate the impact of host on the viral swarm structure and to identify transmission links with viruses recovered from other farms in the same series of outbreaks. In 7 samples, from 6 different animals, a total of 5 consensus level variants were identified, in addition to 104 sub-consensus variants of which 22 were shared between 2 or more animals. Further analysis revealed differences in swarm structures from samples derived from the same animal suggesting the presence of distinct viral populations evolving independently at different lesion sites within the same infected animal