A measure on the set of compact Friedmann-Lemaitre-Robertson-Walker models

Compact, flat Friedmann-Lemaitre-Robertson-Walker (FLRW) models have recently regained interest as a good fit to the observed cosmic microwave background temperature fluctuations. However, it is generally thought that a globally, exactly-flat FLRW model is theoretically improbable. Here, in order to obtain a probability space on the set F of compact, comoving, 3-spatial sections of FLRW models, a physically motivated hypothesis is proposed, using the density parameter Omega as a derived rather than fundamental parameter. We assume that the processes that select the 3-manifold also select a global mass-energy and a Hubble parameter. The inferred range in Omega consists of a single real value for any 3-manifold. Thus, the obvious measure over F is the discrete measure. Hence, if the global mass-energy and Hubble parameter are a function of 3-manifold choice among compact FLRW models, then probability spaces parametrised by Omega do not, in general, give a zero probability of a flat model. Alternatively, parametrisation by the injectivity radius r_inj ("size") suggests the Lebesgue measure. In this case, the probability space over the injectivity radius implies that flat models occur almost surely (a.s.), in the sense of probability theory, and non-flat models a.s. do not occur.Comment: 19 pages, 4 figures; v2: minor language improvements; v3: generalisation: m, H functions of

BrainScope: interactive visual exploration of the spatial and temporal human brain transcriptome

Spatial and temporal brain transcriptomics has recently emerged as an invaluable data source for molecular neuroscience. The complexity of such data poses considerable challenges for analysis and visualization. We present BrainScope: a web portal for fast, interactive visual exploration of the Allen Atlases of the adult and developing human brain transcriptome. Through a novel methodology to explore high-dimensional data (dual t-SNE), BrainScope enables the linked, all-in-one visualization of genes and samples across the whole brain and genome, and across developmental stages. We show that densities in t-SNE scatter plots of the spatial samples coincide with anatomical regions, and that densities in t-SNE scatter plots of the genes represent gene co-expression modules that are significantly enriched for biological functions. We also show that the topography of the gene t-SNE maps reflect brain region-specific gene functions, enabling hypothesis and data driven research. We demonstrate the discovery potential of BrainScope through three examples: (i) analysis of cell type specific gene sets, (ii) analysis of a set of stable gene co-expression modules across the adult human donors and (iii) analysis of the evolution of co-expression of oligodendrocyte specific genes over developmental stages. BrainScope is publicly accessible at www.brainscope.nl.FSW – Publicaties zonder aanstelling Universiteit Leide

JOYS+: mid-infrared detection of gas-phase SO2_2 emission in a low-mass protostar. The case of NGC 1333 IRAS2A: hot core or accretion shock?

JWST/MIRI has sharpened our infrared eyes toward the star formation process. This paper presents the first mid-infrared detection of gaseous SO$_2$ emission in an embedded low-mass protostellar system. MIRI-MRS observations of the low-mass protostellar binary NGC 1333 IRAS2A are presented from the JWST Observations of Young protoStars (JOYS+) program, revealing emission from the SO$_2~\nu_3$ asymmetric stretching mode at 7.35 micron. The results are compared to those derived from high-angular resolution SO$_2$ data obtained with ALMA. The SO$_2$ emission from the $\nu_3$ band is predominantly located on $\sim50-100$ au scales around the main component of the binary, IRAS2A1. A rotational temperature of $92\pm8$ K is derived from the $\nu_3$ lines. This is in good agreement with the rotational temperature derived from pure rotational lines in the vibrational ground state (i.e., $\nu=0$) with ALMA ($104\pm5$ K). However, the emission of the $\nu_3$ lines is not in LTE given that the total number of molecules predicted by a LTE model is found to be a factor $2\times10^4$ higher than what is derived for the $\nu=0$ state. This difference can be explained by a vibrational temperature that is $\sim100$ K higher than the derived rotational temperature of the $\nu=0$ state. The brightness temperature derived from the continuum around the $\nu_3$ band of SO$_2$ is $\sim180$ K, which confirms that the $\nu_3=1$ level is not collisionally populated but rather infrared pumped by scattered radiation. This is also consistent with the non-detection of the $\nu_2$ bending mode at 18-20 micron. Given the rotational temperature, the extent of the emission ($\sim100$ au in radius), and the narrow line widths in the ALMA data (3.5 km/s), the SO$_2$ in IRAS2A likely originates from ice sublimation in the central hot core around the protostar rather than from an accretion shock at the disk-envelope boundary.Comment: 19 pages, 17 figures, accepted for publication in A&A, abstract abbreviate

Hippocampal atrophy in people with memory deficits: results from the population-based IPREA study

ABSTRACT Background: Clinical studies have shown that hippocampal atrophy is present before dementia in people with memory deficits and can predict dementia development. The question remains whether this association holds in the general population. This is of interest for the possible use of hippocampal atrophy to screen population for preventive interventions. The aim of this study was to assess hippocampal volume and shape abnormalities in elderly adults with memory deficits in a cross-sectional population-based study. Methods: We included individuals participating in the Italian Project on the Epidemiology of Alzheimer Disease (IPREA) study: 75 cognitively normal individuals (HC), 31 individuals with memory deficits (MEM), and 31 individuals with memory deficits not otherwise specified (MEMnos). Hippocampal volumes and shape were extracted through manual tracing and the growing and adaptive meshes (GAMEs) shape-modeling algorithm. We investigated between-group differences in hippocampal volume and shape, and correlations with memory deficits. Results: In MEM participants, hippocampal volumes were significantly smaller than in HC and were mildly associated with worse memory scores. Memory-associated shape changes mapped to the anterior hippocampus. Shape-based analysis detected no significant difference between MEM and HC, while MEMnos showed shape changes in the posterior hippocampus compared with HC and MEM groups. Conclusions: These findings support the discriminant validity of hippocampal volumetry as a biomarker of memory impairment in the general population. The detection of shape changes in MEMnos but not in MEM participants suggests that shape-based biomarkers might lack sensitivity to detect Alzheimer's-like pathology in the general populatio

The distributed ASCI supercomputer project

The Distributed ASCI Supercomputer (DAS) is a homogeneous wide-area distributed system consisting of four cluster computers at different locations. DAS has been used for research on communication software, parallel languages and programming systems, schedulers, parallel applications, and distributed applications. The paper gives a preview of the most interesting research results obtained so far in the DAS project

A New Minimal-Stress Freely-Moving Rat Model for Preclinical Studies on Intranasal Administration of CNS Drugs

Purpose. To develop a new minimal-stress model for intranasal administration in freely moving rats and to evaluate in this model the brain distribution of acetaminophen following intranasal versus intravenous administration. Methods. Male Wistar rats received one intranasal cannula, an intra-cerebral microdialysis probe, and two blood cannulas for drug administration and serial blood sampling respectively. To evaluate this novel model, the following experiments were conducted. 1) Evans Blue was administered to verify the selectivity of intranasal exposure. 2) During a 1 min infusion 10, 20, or 40 μl saline was administered intranasally or 250 µl intravenously. Corticosterone plasma concentrations over time were compared as biomarkers for stress. 3) 200 µg of the model drug acetaminophen was given in identical setup and plasma, and brain pharmacokinetics were determined. Results. In 96 % of the rats, only the targeted nasal cavity was deeply colored. Corticosterone plasma concentrations were not influenced, neither by route nor volume of administration. Pharmacokinetics of acetaminophen were identical after intravenous and intranasal administration, although the Cmax in microdialysates was reached a little earlier following intravenous administration. Conclusion. A new minimal-stress model for intranasal administration in freely moving rats has been successfully developed and allows direct comparison with intravenous administration. KEY WORDS: acetaminophen; brain; intranasal infusion; microdialysis; pharmacokinetics

Prediction of setup times for an advanced upper limb functional electrical stimulation system

Introduction: Rehabilitation devices take time to don, and longer or unpredictable setup time impacts on usage. This paper reports on the development of a model to predict setup time for upper limb functional electrical stimulation. Methods: Participants’ level of impairment (Fugl Meyer-Upper Extremity Scale), function (Action Research Arm Test) and mental status (Mini Mental Scale) were measured. Setup times for each stage of the setup process and total setup times were recorded. A predictive model of setup time was devised using upper limb impairment and task complexity. Results: Six participants with stroke were recruited, mean age 60 (�17) years and mean time since stroke 9.8 (�9.6) years. Mean Fugl Meyer-Upper Extremity score was 31.1 (�6), Action Research Arm Test 10.4 (�7.9) and Mini Mental Scale 26.1 (�2.7). Linear regression analysis showed that upper limb impairment and task complexity most effectively predicted setup time (51% as compared with 39%) (F(2,21) ¼ 12.782, adjusted R2 ¼ 0.506; p<.05). Conclusions: A model to predict setup time based on upper limb impairment and task complexity accounted for 51% of the variation in setup time. Further studies are required to test the model in real-world settings and to identify other contributing factors

In-depth study of moderately young but extremely red, very dusty substellar companion HD206893B

Accepted for publication in Astronomy & Astrophysics. Reproduced with permission from Astronomy & Astrophysics. © 2018 ESO.The substellar companion HD206893b has recently been discovered by direct imaging of its disc-bearing host star with the SPHERE instrument. We investigate the atypical properties of the companion, which has the reddest near-infrared colours among all known substellar objects, either orbiting a star or isolated, and we provide a comprehensive characterisation of the host star-disc-companion system. We conducted a follow-up of the companion with adaptive optics imaging and spectro-imaging with SPHERE, and a multiinstrument follow-up of its host star. We obtain a R=30 spectrum from 0.95 to 1.64 micron of the companion and additional photometry at 2.11 and 2.25 micron. We carried out extensive atmosphere model fitting for the companions and the host star in order to derive their age, mass, and metallicity. We found no additional companion in the system in spite of exquisite observing conditions resulting in sensitivity to 6MJup (2MJup) at 0.5" for an age of 300 Myr (50 Myr). We detect orbital motion over more than one year and characterise the possible Keplerian orbits. We constrain the age of the system to a minimum of 50 Myr and a maximum of 700 Myr, and determine that the host-star metallicity is nearly solar. The comparison of the companion spectrum and photometry to model atmospheres indicates that the companion is an extremely dusty late L dwarf, with an intermediate gravity (log g 4.5-5.0) which is compatible with the independent age estimate of the system. Though our best fit corresponds to a brown dwarf of 15-30 MJup aged 100-300 Myr, our analysis is also compatible with a range of masses and ages going from a 50 Myr 12MJup planetary-mass object to a 50 MJup Hyades-age brown dwarf...Peer reviewedFinal Accepted Versio

Biomechanics of single cortical neurons

This study presents experimental results and computational analysis of the large strain dynamic behavior of single neurons in vitro with the objective of formulating a novel quantitative framework for the biomechanics of cortical neurons. Relying on the atomic force microscopy (AFM) technique, novel testing protocols are developed to enable the characterization of neural soma deformability over a range of indentation rates spanning three orders of magnitude, 10, 1, and 0.1 μm s[superscript −1]. Modified spherical AFM probes were utilized to compress the cell bodies of neonatal rat cortical neurons in load, unload, reload and relaxation conditions. The cell response showed marked hysteretic features, strong non-linearities, and substantial time/rate dependencies. The rheological data were complemented with geometrical measurements of cell body morphology, i.e. cross-diameter and height estimates. A constitutive model, validated by the present experiments, is proposed to quantify the mechanical behavior of cortical neurons. The model aimed to correlate empirical findings with measurable degrees of (hyper)elastic resilience and viscosity at the cell level. The proposed formulation, predicated upon previous constitutive model developments undertaken at the cortical tissue level, was implemented in a three-dimensional finite element framework. The simulated cell response was calibrated to the experimental measurements under the selected test conditions, providing a novel single cell model that could form the basis for further refinements.Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (DAAD-19-02-D-002)Joint Improvised Explosive Device Defeat Organization (U.S.) (W911NF-07-1-0035)National Science Foundation (U.S.). Graduate Research FellowshipNational Institutes of Health (U.S.) (Molecular, Cell, and Tissue Biomechanics Training Grant)Ecole des ponts et chaussees (France)Computation and Systems Biology Programme of Singapore--Massachusetts Institute of Technology Allianc

A catalogue of Triticum monococcum genes encoding toxic and immunogenic peptides for celiac disease patients

The celiac disease (CD) is an inflammatory condition characterized by injury to the lining of the small-intestine on exposure to the gluten of wheat, barley and rye. The involvement of gluten in the CD syndrome has been studied in detail in bread wheat, where a set of “toxic” and “immunogenic” peptides has been defined. For wheat diploid species, information on CD epitopes is poor. In the present paper, we have adopted a genomic approach in order to understand the potential CD danger represented by storage proteins in diploid wheat and sequenced a sufficiently large number of cDNA clones related to storage protein genes of Triticum monococcum. Four bona fide toxic peptides and 13 immunogenic peptides were found. All the classes of storage proteins were shown to contain harmful sequences. The major conclusion is that einkorn has the full potential to induce the CD syndrome, as already evident for polyploid wheats. In addition, a complete overview of the storage protein gene arsenal in T. monococcum is provided, including a full-length HMW x-type sequence and two partial HMW y-type sequences