Integration of Oscillatory and Subanalytic Functions

We prove the stability under integration and under Fourier transform of a concrete class of functions containing all globally subanalytic functions and their complex exponentials. This paper extends the investigation started in [J.-M. Lion, J.-P. Rolin: "Volumes, feuilles de Rolle de feuilletages analytiques et th\'eor\`eme de Wilkie" Ann. Fac. Sci. Toulouse Math. (6) 7 (1998), no. 1, 93-112] and [R. Cluckers, D. J. Miller: "Stability under integration of sums of products of real globally subanalytic functions and their logarithms" Duke Math. J. 156 (2011), no. 2, 311-348] to an enriched framework including oscillatory functions. It provides a new example of fruitful interaction between analysis and singularity theory.Comment: Final version. Accepted for publication in Duke Math. Journal. Changes in proofs: from Section 6 to the end, we now use the theory of continuously uniformly distributed modulo 1 functions that provides a uniform technical point of view in the proofs of limit statement

MicroRNA profiling reveals marker of motor neuron disease in ALS models

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. microRNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining thein vivomiRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents.SIGNIFICANCE STATEMENTAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons (MNs) in the brain and spinal cord are selectively lost. To develop tools to aid in our understanding of the distinct expression profiles of MNs and, ultimately, to monitor MN disease progression, we identified small regulatory microRNAs (miRNAs) that were highly enriched or exclusive in MNs. The signal for one of these MN-enriched miRNAs is detectable in spinal tap biofluid from an ALS rat model, where its levels change as disease progresses, suggesting that it may be a clinically useful marker of disease status. Furthermore, rats treated with ALS therapy have restored expression of this MN RNA marker, making it an MN-specific and drug-responsive marker for ALS rodents.</jats:p

Structure and stability of two polymorphs of creatine and its monohydrate

An experimental search for crystalline forms of creatine including a variable temperature X-ray powder diffraction study has produced three polymorphs and a formic acid solvate. The crystal structures of creatine forms I and II were determined from X-ray powder diffraction data plus the creatine formic acid (1 : 1) solvate structure was obtained by single crystal X-ray diffraction methods. Evidence of a third polymorphic form of creatine obtained by rapid desolvation of creatine monohydrate is also presented. The results highlight the role of automated parallel crystallisation, slurry experiments and VT-XRPD as powerful techniques for effective physical form screening. They also highlight the importance of various complementary analytical techniques in structural characterisation and in achieving better understanding of the relationship between various solid-state forms. The structural relationships between various solid-state forms of creatine using the XPac method provided a rationale for the different relative stabilities of forms I and II of creatine with respect to the monohydrate form

Scaling laws and vortex profiles in 2D decaying turbulence

We use high resolution numerical simulations over several hundred of turnover times to study the influence of small scale dissipation onto vortex statistics in 2D decaying turbulence. A self-similar scaling regime is detected when the scaling laws are expressed in units of mean vorticity and integral scale, as predicted by Carnevale et al., and it is observed that viscous effects spoil this scaling regime. This scaling regime shows some trends toward that of the Kirchhoff model, for which a recent theory predicts a decay exponent $\xi=1$. In terms of scaled variables, the vortices have a similar profile close to a Fermi-Dirac distribution.Comment: 4 Latex pages and 4 figures. Submitted to Phys. Rev. Let

The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic β-cell line

A previously uncharacterized putative ion channel, NALCN (sodium leak channel, non-selective), has been recently shown to be responsible for the tetrodotoxin (TTX)-resistant sodium leak current implicated in the regulation of neuronal excitability. Here, we show that NALCN encodes a current that is activated by M3 muscarinic receptors (M3R) in a pancreatic β-cell line. This current is primarily permeant to sodium ions, independent of intracellular calcium stores and G proteins but dependent on Src activation, and resistant to TTX. The current is recapitulated by co-expression of NALCN and M3R in human embryonic kidney-293 cells and in Xenopus oocytes. We also show that NALCN and M3R belong to the same protein complex, involving the intracellular I–II loop of NALCN and the intracellular i3 loop of M3R. Taken together, our data show the molecular basis of a muscarinic-activated inward sodium current that is independent of G-protein activation, and provide new insights into the properties of NALCN channels

From here and now to there and then : practical recommendations for extrapolating cetacean density surface models to novel conditions

Density surface models (DSMs) are clearly established as a method of choice for the analysis of cetacean line transect survey data, and are increasingly used to inform risk assessments in remote marine areas subject to rising anthropogenic impacts (e.g. the high seas). However, despite persistent skepticism about the validity of extrapolated models, more and more DSMs are being applied well beyond the boundaries of the study regions where field sampling originally took place. This leads to potentially uncertain and error-prone model predictions that may mislead on-the-ground management interventions and undermine conservation decision-making. In addition, no consensus currently exists on the best way to define and measure extrapolation when it occurs, leaving users without the tools they require to audit models projected into novel conditions. Consequently, a transparent and consistent protocol for identifying scenarios under which extrapolation may be appropriate (or conversely, ill-advised) is urgently needed to better gauge how models behave outside the boundaries of sample data and to know how much faith can be placed in their outputs. This report aims to address this gap by synthesising recent advances in extrapolation detection, and presenting recommendations for a minimum standard for measuring extrapolation in novel environmental space. Such guidelines are essential to promoting transparency, replicability, and quality control, and will help marine scientists, managers and policy agencies to (i) better interpret density surfaces and their associated uncertainty; (ii) refine model development and selection approaches; and (iii) optimise the allocation of future survey effort by identifying priority knowledge gaps, e.g. by delineating areas where model predictions are the least supported by data. Our review is accompanied by supplementary R code offering a user-friendly framework for quantifying, summarising and visualising various forms of extrapolation in multivariate environmental space a priori (ahead of model fitting). We illustrate its application with case studies designed to revisit previously published predictions of sperm whale (Physeter macrocephalus) and beaked whale (Ziphiidae spp.) densities in the Northwest Atlantic, and evaluate them in light of several extrapolation metrics. Very early in their training, ecologists are given strong warnings against extrapolating, as model predictions made in data-deficient contexts rely heavily on assumptions that may not hold outside the range of sampled conditions. Navigating the ‘uncharted waters’ of extrapolation, however, is critical to scientific progress, and will be best achieved with a clear understanding of the mechanics, benefits, and limitations of extrapolated models.Publisher PD