Eunji Lim.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 2053--2097.

Abstract:
We study the asymptotic behavior of the least squares estimators when the model is possibly misspecified. We consider the setting where we wish to estimate an unknown function $f_{*}:(0,1)^{d} ightarrow mathbb{R}$ from observations $(X,Y),(X_{1},Y_{1}),cdots ,(X_{n},Y_{n})$; our estimator $hat{g}_{n}$ is the minimizer of $sum _{i=1}^{n}(Y_{i}-g(X_{i}))^{2}/n$ over $gin mathcal{G}$ for some set of functions $mathcal{G}$. We provide sufficient conditions on the metric entropy of $mathcal{G}$, under which $hat{g}_{n}$ converges to $g_{*}$ as $n ightarrow infty $, where $g_{*}$ is the minimizer of $|g-f_{*}| riangleq mathbb{E}(g(X)-f_{*}(X))^{2}$ over $gin mathcal{G}$. As corollaries of our theorem, we establish $|hat{g}_{n}-g_{*}| ightarrow 0$ as $n ightarrow infty $ when $mathcal{G}$ is the set of monotone functions or the set of convex functions. We also make a connection between the convergence rate of $|hat{g}_{n}-g_{*}|$ and the metric entropy of $mathcal{G}$. As special cases of our finding, we compute the convergence rate of $|hat{g}_{n}-g_{*}|^{2}$ when $mathcal{G}$ is the set of bounded monotone functions or the set of bounded convex functions.

Alexandre Mösching, Lutz Dümbgen.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 24--49.

Abstract:
We consider bivariate observations $(X_{1},Y_{1}),ldots,(X_{n},Y_{n})$ such that, conditional on the $X_{i}$, the $Y_{i}$ are independent random variables. Precisely, the conditional distribution function of $Y_{i}$ equals $F_{X_{i}}$, where $(F_{x})_{x}$ is an unknown family of distribution functions. Under the sole assumption that $xmapsto F_{x}$ is isotonic with respect to stochastic order, one can estimate $(F_{x})_{x}$ in two ways: (i) For any fixed $y$ one estimates the antitonic function $xmapsto F_{x}(y)$ via nonparametric monotone least squares, replacing the responses $Y_{i}$ with the indicators $1_{[Y_{i}le y]}$. (ii) For any fixed $eta in (0,1)$ one estimates the isotonic quantile function $xmapsto F_{x}^{-1}(eta)$ via a nonparametric version of regression quantiles. We show that these two approaches are closely related, with (i) being more flexible than (ii). Then, under mild regularity conditions, we establish rates of convergence for the resulting estimators $hat{F}_{x}(y)$ and $hat{F}_{x}^{-1}(eta)$, uniformly over $(x,y)$ and $(x,eta)$ in certain rectangles as well as uniformly in $y$ or $eta$ for a fixed $x$.

Ran Dai, Hyebin Song, Rina Foygel Barber, Garvesh Raskutti.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 801--834.

Abstract:
We study the bias of the isotonic regression estimator. While there is extensive work characterizing the mean squared error of the isotonic regression estimator, relatively little is known about the bias. In this paper, we provide a sharp characterization, proving that the bias scales as $O(n^{-eta /3})$ up to log factors, where $1leq eta leq 2$ is the exponent corresponding to Hölder smoothness of the underlying mean. Importantly, this result only requires a strictly monotone mean and that the noise distribution has subexponential tails, without relying on symmetric noise or other restrictive assumptions.

Achillefs Tzioufas.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 3, 674--684.

Abstract:
The epidemic process on a graph is considered for which infectious contacts occur at rate which depends on whether a susceptible is infected for the first time or not. We show that the Vasershtein coupling extends if and only if secondary infections occur at rate which is greater than that of initial ones. Nonetheless we show that, with respect to the probability of occurrence of an infinite epidemic, the said proviso may be dropped regarding the totally asymmetric process in one dimension, thus settling in the affirmative this special case of the conjecture for arbitrary graphs due to [ Ann. Appl. Probab. 13 (2003) 669–690].

Davide Gabrielli, Ida Germana Minelli.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 3, 558--585.

Abstract:
Stochastic monotonicity is a well-known partial order relation between probability measures defined on the same partially ordered set. Strassen theorem establishes equivalence between stochastic monotonicity and the existence of a coupling compatible with respect to the partial order. We consider the case of a countable set and introduce the class of finitely decomposable flows on a directed acyclic graph associated to the partial order. We show that a probability measure stochastically dominates another probability measure if and only if there exists a finitely decomposable flow having divergence given by the difference of the two measures. We illustrate the result with some examples.

Qiyang Han, Tengyao Wang, Sabyasachi Chatterjee, Richard J. Samworth.

Source: The Annals of Statistics, Volume 47, Number 5, 2440--2471.

Abstract:
We study the least squares regression function estimator over the class of real-valued functions on $[0,1]^{d}$ that are increasing in each coordinate. For uniformly bounded signals and with a fixed, cubic lattice design, we establish that the estimator achieves the minimax rate of order $n^{-min{2/(d+2),1/d}}$ in the empirical $L_{2}$ loss, up to polylogarithmic factors. Further, we prove a sharp oracle inequality, which reveals in particular that when the true regression function is piecewise constant on $k$ hyperrectangles, the least squares estimator enjoys a faster, adaptive rate of convergence of $(k/n)^{min(1,2/d)}$, again up to polylogarithmic factors. Previous results are confined to the case $dleq2$. Finally, we establish corresponding bounds (which are new even in the case $d=2$) in the more challenging random design setting. There are two surprising features of these results: first, they demonstrate that it is possible for a global empirical risk minimisation procedure to be rate optimal up to polylogarithmic factors even when the corresponding entropy integral for the function class diverges rapidly; second, they indicate that the adaptation rate for shape-constrained estimators can be strictly worse than the parametric rate.

Calcineurin inhibitors, such as tacrolimus (FK506) and cyclosporine, are widely used as standard immunosuppressants in organ transplantation recipients. However, these drugs can cause severe pain in patients, commonly referred to as calcineurin inhibitor-induced pain syndrome (CIPS). Although calcineurin inhibition increases NMDAR activity in the spinal cord, the underlying mechanism remains enigmatic. Using an animal model of CIPS, we found that systemic administration of FK506 in male and female mice significantly increased the amount of α2-1–GluN1 complexes in the spinal cord and the level of α2-1–bound GluN1 proteins in spinal synaptosomes. Treatment with FK506 significantly increased the frequency of mEPSCs and the amplitudes of monosynaptic EPSCs evoked from the dorsal root and puff NMDAR currents in spinal dorsal horn neurons. Inhibiting α2-1 with gabapentin or disrupting the α2-1–NMDAR interaction with α2-1Tat peptide completely reversed the effects of FK506. In α2-1 gene KO mice, treatment with FK506 failed to increase the frequency of NMDAR-mediated mEPSCs and the amplitudes of evoked EPSCs and puff NMDAR currents in spinal dorsal horn neurons. Furthermore, systemic administration of gabapentin or intrathecal injection of α2-1Tat peptide reversed thermal and mechanical hypersensitivity in FK506-treated mice. In addition, genetically deleting GluN1 in dorsal root ganglion neurons or α2-1 genetic KO similarly attenuated FK506-induced thermal and mechanical hypersensitivity. Together, our findings indicate that α2-1–bound NMDARs mediate calcineurin inhibitor-induced tonic activation of presynaptic and postsynaptic NMDARs at the spinal cord level and that presynaptic NMDARs play a prominent role in the development of CIPS.

SIGNIFICANCE STATEMENT Calcineurin inhibitors are immunosuppressants used to prevent rejection of transplanted organs and tissues. However, these drugs can cause severe, unexplained pain. We showed that calcineurin inhibition enhances physical interaction between α2-1 and NMDARs and their synaptic trafficking in the spinal cord. α2-1 is essential for calcineurin inhibitor-induced aberrant activation of presynaptic and postsynaptic NMDARs in the spinal cord. Furthermore, inhibiting α2-1 or disrupting α2-1–NMDAR interaction reduces calcineurin inhibitor-induced pain hypersensitivity. Eliminating NMDARs in primary sensory neurons or α2-1 KO also attenuates calcineurin inhibitor-induced pain hypersensitivity. This new information extends our mechanistic understanding of the role of endogenous calcineurin in regulating synaptic plasticity and nociceptive transmission and suggests new strategies for treating this painful condition.

Most acute wheezing episodes in preschool children are associated with rhinovirus, which decreases extracellular adenosine triphosphate levels, leading to airway surface liquid dehydration and submucosal edema, which cause failure of mucus clearance. These children respond poorly to available treatments.

Hypertonic saline inhalation, a pro–airway surface liquid hydration therapy, significantly decreases both length of stay by 33% (1 day) and the absolute risk of hospitalization by 30% in preschool children presenting with acute wheezing episode to the emergency department. (Read the full article)

Hypertonic saline (3% and 5%), has been shown to improve clinical severity scores and reduce inpatient length of stay, and was associated with a trend toward lower admission rate in acute bronchiolitis.

We are not aware of any previous data using 7% hypertonic saline in bronchiolitis. Our results suggest that 7% saline does not lower clinical severity of illness, admission rate, or length of stay, when compared with normal saline. (Read the full article)

Wilmington, DE – Highlighting ongoing efforts to revitalize Delaware’s downtowns, Governor Jack Markell and Delaware State Housing Authority Director Anas Ben Addi presented a grant check on Monday to the owners of Tonic Bar and Grille, money that helped Tonic fund extensive renovations throughout the restaurant. Tonic’s grant rebate was funded by Delaware’s Downtown Development […]

The campaign applauds mothers for their unwavering energy at all hours of the day

The African Union (AU) said it has held discussions with officials from Madagascar to find out more about a herbal drink recently touted by the island nation’s president as a possible treatment for Covid-19.According to a statement issued on Tuesday, AU Commissioner for Social Affairs Amira El Fadil held a meeting with the chargé d’affaires of Madagascar’s embassy in the Ethiopian capital Addis Ababa on April 30, at which it was agreed that more information would be provided about the…

Earth’s continents may have been shifting for 2.5 billion years, according to a study of ancient rocks that finds plate tectonics evolved far earlier than we thought

Rocks from a 3.2-billion-year-old formation in Australia show changes in the direction of their magnetism over time that suggest plate tectonics started earlier than we thought

The story of how gin and tonic came together fizzes with adventure, discovery, imperial ambition, biopiracy and a generous splash of fake news

Rocks from a 3.2-billion-year-old formation in Australia show changes in the direction of their magnetism over time that suggest plate tectonics started earlier than we thought

ABSTRACT

Clostridium saccharoperbutylacetonicum is a mesophilic, anaerobic, butanol-producing bacterium, originally isolated from soil. It was recently reported that C. saccharoperbutylacetonicum possesses multiple cellulosomal elements and would potentially form the smallest cellulosome known in nature. Its genome contains only eight dockerin-bearing enzymes, and its unique scaffoldin bears two cohesins (Cohs), three X2 modules, and two carbohydrate-binding modules (CBMs). In this study, all of the cellulosome-related modules were cloned, expressed, and purified. The recombinant cohesins, dockerins, and CBMs were tested for binding activity using enzyme-linked immunosorbent assay (ELISA)-based techniques. All the enzymes were tested for their comparative enzymatic activity on seven different cellulosic and hemicellulosic substrates, thus revealing four cellulases, a xylanase, a mannanase, a xyloglucanase, and a lichenase. All dockerin-containing enzymes interacted similarly with the second cohesin (Coh2) module, whereas Coh1 was more restricted in its interaction pattern. In addition, the polysaccharide-binding properties of the CBMs within the scaffoldin were examined by two complementary assays, affinity electrophoresis and affinity pulldown. The scaffoldin of C. saccharoperbutylacetonicum exhibited high affinity for cellulosic and hemicellulosic substrates, specifically to microcrystalline cellulose and xyloglucan. Evidence that supports substrate-dependent in vivo secretion of cellulosomes is presented. The results of our analyses contribute to a better understanding of simple cellulosome systems by identifying the key players in this minimalistic system and the binding pattern of its cohesin-dockerin interaction. The knowledge gained by our study will assist further exploration of similar minimalistic cellulosomes and will contribute to the significance of specific sets of defined cellulosomal enzymes in the degradation of cellulosic biomass.

IMPORTANCE Cellulosome-producing bacteria are considered among the most important bacteria in both mesophilic and thermophilic environments, owing to their capacity to deconstruct recalcitrant plant-derived polysaccharides (and notably cellulose) into soluble saccharides for subsequent processing. In many ecosystems, the cellulosome-producing bacteria are particularly effective "first responders." The massive amounts of sugars produced are potentially amenable in industrial settings to further fermentation by appropriate microbes to biofuels, notably ethanol and butanol. Among the solvent-producing bacteria, Clostridium saccharoperbutylacetonicum has the smallest cellulosome system known thus far. The importance of investigating the building blocks of such a small, multifunctional nanomachine is crucial to understanding the fundamental activities of this efficient enzymatic complex.

Objective

To specifically report on ataxic-hypotonic cerebral palsy (CP) using registry data and to directly compare its features with other CP subtypes.

Discovery of the Breagh gas field in the Southern North Sea (SNS) has demonstrated the potential that the Lower Carboniferous (Visean, 346.7–330.9 Ma) Farne Group reservoirs have to contribute to the UK's future energy mix. New biostratigraphic correlations provide a basis to compare Asbian and Brigantian sedimentary cores from the Breagh Field and age-equivalent sediments exposed on the Northumberland Coast, which has proved critical in gaining an understanding of exploration and development opportunities. Thirteen facies associations characterize the mixed carbonate–siliciclastic system, grouped into: marine, delta front, delta shoreface, lower delta plain and upper delta plain gross depositional environments. The facies associations are interpreted as depositing in a mixed carbonate and siliciclastic fluvio-deltaic environment, and are arranged into coarsening- and cleaning-upward cycles (parasequences) bounded by flooding surfaces. Most cycles are characterized by mouth bars, distributary channels, interdistributary bays and common braided rivers, interpreted as river-dominated deltaic deposits. Some cycles include rare shoreface and tidally-influenced deposits, interpreted as river-dominated and wave- or tide-influenced deltaic deposits. The depositional processes that formed each cycle have important implications for the reservoir net/gross ratio (where this ratio indicates the proportion of sandstone beds in a cycle), thickness and lateral extent. The deltaic deposits were controlled by a combination of tectonic and eustatic (allocyclic) events and delta avulsion (autocyclic) processes, and are likely to reflect a changing tectonic regime, from extension within elongate fault-bounded basins (synrift) to passive regional thermal subsidence (post-rift). Deep incision by the Base Permian Unconformity across the Breagh Field has removed the Westphalian, Namurian and upper Visean, to leave the more prospective thicker clastic reservoirs within closure.

Thematic collection: This article is part of the Under-explored plays and frontier basins of the UK continental shelf collection available at: https://www.lyellcollection.org/cc/under-explored-plays-and-frontier-basins-of-the-uk-continental-shelf

Upper Lutetian–Bartonian sedimentary mélanges, corresponding to ancient mud-rich submarine mass transport deposits, are widely distributed over an area c. 300 km long and tens of kilometres wide along the exhumed outer part of the External Ligurian accretionary wedge in the Northern Apennines. The occurrence of methane-derived carbonate concretions (septarians) in a specific tectonostratigraphic position below these sedimentary mélanges allows us to document the relationships among a significant period of regional-scale slope failure, climate change (the Early and Mid-Eocene Optimum stages), the dissociation of gas hydrates and accretionary tectonics during the Ligurian Tectonic Phase (early–mid-Lutetian). The distribution of septarians at the core of thrust-related anticlines suggests that the dissociation of gas hydrates was triggered by accretionary tectonics rather than climate change. The different ages of slope failure emplacement and the formation of the septarians support the view that the dissociation of gas hydrates was not the most important trigger for slope failure. The latter occurred during a tectonic quiescence stage associated with a regressive depositional trend, and probably minor residual tectonic pulses, which followed the Ligurian Tectonic Phase, favouring the dynamic re-equilibrium of the External Ligurian accretionary wedge. Our findings provide useful information for a better understanding of the factors controlling giant slope failure events in modern accretionary settings, where they may cause tsunamis.

A significant part of mélanges recognized in exhumed convergent margins around the world has been recently documented to have chiefly originated from masse transport and subsurface remobilization and disruption (i.e. mélanges, from sedimentary and mud–serpentinite diapiric processes and from in situ fluidification–disruption). Tectonic and/or sedimentary processes occurring during subsequent multiple deformational events of convergent margin evolution commonly overprint and significantly rework the primary (sedimentary or diapiric) mélange fabric, forming polygenetic mélanges. This ultimately complicates their distinction from true tectonic mélanges, masking part of the recorded tectono-sedimentary evolution of the associated convergent margin. The contributions gathered in this thematic collection explore with different approaches (from field structural and stratigraphic observations to geophysical analyses) different types of polygenetic mélange, at various scales, around the world. These studies conclude that the understanding of this type of mélange may provide crucial insights for a more detailed interpretation of the evolution of ancient and modern convergent margins, and of processes and mechanisms triggering potential natural hazards (earthquakes and tsunamis). Case studies include the Apennines in the Central Mediterranean region, the Carpathians in Central Europe and the Nankai Prism in Japan.

Thematic collection: This article is part of the ‘Polygenetic mélanges: a glimpse on tectonic sedimentary and diapiric recycling in convergent margins’ collection available at https://www.lyellcollection.org/cc/polygenetic-melanges

In the Central Western Carpathians (CWC), most published paleomagnetic results from Permo-Mesozoic rocks document extensive remagnetizations and come from thin-skinned thrust units that have undergone multistage deformation. We present results from lower Triassic redbeds from the autochthonous cover overlying the basement that carry a primary magnetization. Petromagnetic results indicate that the dominant ferromagnetic carrier is hematite, while magnetic susceptibility and its anisotropy are controlled by both ferromagnetic and paramagnetic minerals. Magnetic fabrics document weak deformation related to Late Cretaceous shortening. The directions of the high unblocking temperature remanence components pass both reversal and fold tests, attesting to their primary nature. Paleomagnetic inclinations are flatter than expected from reference datasets, suggesting small latitudinal separation between the CWC and stable Europe. Paleomagnetic declinations are mostly clustered within individual mountain massifs, implying their tectonic coherence. They show only minor differences between the massifs, indicating a lack of significant vertical-axis tectonic rotations within the studied central parts of the CWC. The paleomagnetic declinations are therefore representative of the whole of the CWC in terms of regional paleogeographic interpretations, and imply moderate counterclockwise rotations (c. 26°) of the region with respect to stable Europe since the Early Triassic.

Recent advances in cough research suggest a more widespread use of cough-provocation tests to demonstrate the hypersensitivity of the cough reflex arc. Cough-provocation tests with capsaicin or acidic aerosols have been used for decades in scientific studies. Several factors have hindered their use in everyday clinical work: i.e. lack of standardisation, the need for special equipment and the limited clinical importance of the response. Cough-provocation tests with hypertonic aerosols (CPTHAs) involve provocations with hypertonic saline, hypertonic histamine, mannitol and hyperpnoea. They probably act via different mechanisms than capsaicin and acidic aerosols. They are safe and well tolerated and the response is repeatable. CPTHAs can assess not only the sensitivity of the cough reflex arc but also the tendency of the airway smooth muscles to constrict (airway hyper-responsiveness). They can differentiate between subjects with asthma or chronic cough and healthy subjects. The responsiveness to CPTHAs correlates with the cough-related quality of life among asthmatic subjects. Furthermore, the responsiveness to them decreases during treatment of chronic cough. A severe response to CPTHAs may indicate poor long-term prognosis in chronic cough. The mannitol test has been stringently standardised, is easy to administer with simple equipment, and has regulatory approval for the assessment of airway hyper-responsiveness. Manual counting of coughs during a mannitol challenge would allow the measurement of the function of the cough reflex arc as a part of clinical routine.

The Henry Buckley Collection of Planktonic Foraminifera at the Natural History Museum in London (NHMUK) consists of 1665 single-taxon slides housing 23 897 individuals from 203 sites in all the major ocean basins, as well as a vast research library of Scanning Electron Microscope (SEM) photomicrographs. Buckley picked the material from the NHMUK Ocean-Bottom Deposit Collection and also from fresh tow samples. However, his collection remains largely unused as he was discouraged by his managers in the Mineralogy Department from working on or publicizing the collection. Nevertheless, Buckley published pioneering papers on isotopic interpretation of oceanographic and climatic change and was one of the first workers to investigate foraminiferal wall structure using the SEM technique. Details of the collection and images of each slide are available via the NHMUK Data Portal (http://dx.doi.org/10.5519/0035055). The Buckley Collection and its associated Ocean-Bottom Deposit Collection have great potential for taxon-specific studies as well as geochemical work, and both collections are available on request.

Planktonic foraminifera are a source of important geochemical, palaeoceanographic, and palaeontological data. However, many aspects of their ecology remain poorly understood, including whether or not gross morphology has an ecological function. Here, we measure the force needed to crush multiple planktonic foraminiferal morphotypes from modern core top and tow samples. We find significant differences in the resistance of different morphotypes to compressional force. Three species, Globorotalia tumida (biconvex, keeled), Menardella menardii (discoidal, keeled), Truncorotalia truncatulinoides (conical, keeled), require on average 59% more force (1.07 v. 0.47 N) to crush than the least resistant species (Orbulina universa and Trilobatus sacculifer) in core-top samples. Towed samples of pre-gametogenic individuals also show significant differences of the same magnitude (0.693 v. 0.53 N) between the conical (T. truncatulinoides) and globular/spherical morphologies (Globoconella inflata and O. universa). We hypothesize that the greater compressional strength of certain shapes confers a fitness advantage against predators and could contribute to the repeated, convergent evolution of keeled, conical and bi-convex forms in planktonic foraminifer lineages.

Supplementary material: Raw data for all crushing experiments, wall thickness measurements, and results for all pair-wise Kolmogorov-Smirnov Tests are available at https://doi.org/10.6084/m9.figshare.c.3725236.v1

Thanks to its unique three-dimensional manufacturing capacity, ultrafast laser writing is a prime candidate to meet the growing demand for the miniaturization of photonic circuitry, e.g., for scaling up optical quantum computers capacity. Towards this goal, scientists from Canada discovered a phenomenon related to the material electronic resonance that allows a much greater miniaturization of the laser written devices. Surprisingly, the new phenomenon allows other intriguing applications such as a new concept of invisibility.

This just pushes every TreeHugger button.