A parametric study of vestibular stimulation during centrifugation

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2006.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections."February 2006."Includes bibliographical references (p. 155-160).Artificial Gravity (AG) provided by short-radius centrifugation is a promising countermeasure to the health problems associated with long duration human spaceflight. Head-turns performed during centrifugation, however, trigger a disturbing vestibular response that is only qualitatively understood. In order to design an efficient incremental adaptation procedure, the present study investigates the quantitative aspect of the vestibular side effects associated with AG, in particular, the relationship among crosscoupled stimulation, vestibular response, and adaptation. We tested 20 young adults with supine right-quadrant yaw head-turns performed in a dark environment during short-radius centrifugation. We studied the changes in vestibular response and adaptation to head-turns at different levels of cross-coupled stimulation. Nine combinations of head-turn angle (20°, 40° or 80°) with centrifugevelocity (12, 19 or 30 rpm) were tested over two consecutive days.(cont.) There were four key findings: 1. All measures, except the slow-phase velocity (SPV) peak amplitude of the vestibulo-ocular reflex, decrease significantly between the two experimental days, which demonstrates that significant adaptation is achieved. 2. Large head-angles lead to longer vertical vestibulo-ocular reflex time-constants than smaller angles do, but do not lead to greater adaptation. 3. In the nose-up position, the perceived body-tilt is highly correlated with the true tilt of the gravito-inertial force at mid-chest level. 4. The SPV-peak amplitude and all subjective ratings except body-tilt show significant correlation with the intensity of the cross-coupled stimulus (CCS): the larger the CCS, the stronger the vestibular response.by Jeremie M. Pouly.S.M

USP2-45 Is a Circadian Clock Output Effector Regulating Calcium Absorption at the Post-Translational Level.

The mammalian circadian clock influences most aspects of physiology and behavior through the transcriptional control of a wide variety of genes, mostly in a tissue-specific manner. About 20 clock-controlled genes (CCGs) oscillate in virtually all mammalian tissues and are generally considered as core clock components. One of them is Ubiquitin-Specific Protease 2 (Usp2), whose status remains controversial, as it may be a cogwheel regulating the stability or activity of core cogwheels or an output effector. We report here that Usp2 is a clock output effector related to bodily Ca2+ homeostasis, a feature that is conserved across evolution. Drosophila with a whole-body knockdown of the orthologue of Usp2, CG14619 (dUsp2-kd), predominantly die during pupation but are rescued by dietary Ca2+ supplementation. Usp2-KO mice show hyperabsorption of dietary Ca2+ in small intestine, likely due to strong overexpression of the membrane scaffold protein NHERF4, a regulator of the Ca2+ channel TRPV6 mediating dietary Ca2+ uptake. In this tissue, USP2-45 is found in membrane fractions and negatively regulates NHERF4 protein abundance in a rhythmic manner at the protein level. In clock mutant animals (Cry1/Cry2-dKO), rhythmic USP2-45 expression is lost, as well as the one of NHERF4, confirming the inverse relationship between USP2-45 and NHERF4 protein levels. Finally, USP2-45 interacts in vitro with NHERF4 and endogenous Clathrin Heavy Chain. Taken together these data prompt us to define USP2-45 as the first clock output effector acting at the post-translational level at cell membranes and possibly regulating membrane permeability of Ca2+

Accelerated Axonal Loss Following Acute CNS Demyelination in Mice Lacking Protein Tyrosine Phosphatase Receptor Type Z

Protein tyrosine phosphatase receptor type Z (Ptprz) is widely expressed in the mammalian central nervous system and has been suggested to regulate oligodendrocyte survival and differentiation. We investigated the role of Ptprz in oligodendrocyte remyelination after acute, toxin-induced demyelination in Ptprz null mice. We found neither obvious impairment in the recruitment of oligodendrocyte precursor cells, astrocytes, or reactive microglia/macrophage to lesions nor a failure for oligodendrocyte precursor cells to differentiate and remyelinate axons at the lesions. However, we observed an unexpected increase in the number of dystrophic axons by 3 days after demyelination, followed by prominent Wallerian degeneration by 21 days in the Ptprz-deficient mice. Moreover, quantitative gait analysis revealed a deficit of locomotor behavior in the mutant mice, suggesting increased vulnerability to axonal injury. We propose that Ptprz is necessary to maintain central nervous system axonal integrity in a demyelinating environment and may be an important target of axonal protection in inflammatory demyelinating diseases, such as multiple sclerosis and periventricular leukomalacia. (Am J Pathol 2012, 181:1518-1523; http://dx.doi.org/10.1016/j.ajpath.2012.07.011)UK Multiple Sclerosis SocietyMultiple Sclerosis International FederationUniv Cambridge, Dept Vet Med, Cambridge CB3 0ES, EnglandUniv Cambridge, Wellcome Trust & MRC Cambridge Stem Cell Inst, Cambridge CB3 0ES, EnglandUniversidade Federal de São Paulo, Dept Biosci, Santos, BrazilMerck Serono Int, Geneva Res Ctr, Geneva, SwitzerlandUniversidade Federal de São Paulo, Dept Biosci, Santos, BrazilWeb of Scienc

Globally increased ultraconserved noncoding RNA expression in pancreatic adenocarcinoma

This is the final version of the article. Available from the publisher via the DOI in this record.Transcribed ultraconserved regions (T-UCRs) are a class of non-coding RNAs with 100% sequence conservation among human, rat and mouse genomes. T-UCRs are differentially expressed in several cancers, however their expression in pancreatic adenocarcinoma (PDAC) has not been studied. We used a qPCR array to profile all 481 T-UCRs in pancreatic cancer specimens, pancreatic cancer cell lines, during experimental pancreatic desmoplasia and in the pancreases of P48Cre/wt; KrasLSL-G12D/wt mice. Fourteen, 57 and 29% of the detectable T-UCRs were differentially expressed in the cell lines, human tumors and transgenic mouse pancreases, respectively. The vast majority of the differentially expressed T-UCRs had increased expression in the cancer. T-UCRs were monitored using an in vitro model of the desmoplastic reaction. Twenty-five % of the expressed T-UCRs were increased in the HPDE cells cultured on PANC-1 cellular matrix. UC.190, UC.233 and UC.270 were increased in all three human data sets. siRNA knockdown of each of these three T-UCRs reduced the proliferation of MIA PaCa-2 cells up to 60%. The expression pattern among many T-UCRs in the human and mouse pancreases closely correlated with one another, suggesting that groups of T-UCRs are co-activated in PDAC. Successful knockout of the transcription factor EGR1 in PANC-1 cells caused a reduction in the expression of a subset of T-UCRs suggesting that EGR1 may control T-UCR expression in PDAC. We report a global increase in expression of T-UCRs in both human and mouse PDAC. Commonalties in their expression pattern suggest a similar mechanism of transcriptional upregulation for T-UCRs in PDAC.Supported by grants R21/R33CA114304 and U01CA111294. G.A.C. is supported as a Fellow at The University of Texas MD Anderson Research Trust, as a University of Texas System Regents Research Scholar and by the CLL Global Research Foundation. Work in Dr. Calin’s laboratory is supported in part by a 2009 Seena Magowitz–Pancreatic Cancer Action Network AACR Pilot Grant, the Laura and John Arnold Foundation, the RGK Foundation and the Estate of C. G. Johnson, Jr. A.C.P.A.P. was supported by NIH fellowship 5F31CA142238

A Probabilistic Framework for Security Scenarios with Dependent Actions

This work addresses the growing need of performing meaningful probabilistic analysis of security. We propose a framework that integrates the graphical security modeling technique of attack–defense trees with probabilistic information expressed in terms of Bayesian networks. This allows us to perform probabilistic evaluation of attack–defense scenarios involving dependent actions. To improve the efficiency of our computations, we make use of inference algorithms from Bayesian networks and encoding techniques from constraint reasoning. We discuss the algebraic theory underlying our framework and point out several generalizations which are possible thanks to the use of semiring theory

Improved diagnosis by automated macro‐ and micro‐anatomical region mapping of skin photographs

Background: The exact location of skin lesions is key in clinical dermatology. On one hand, it supports differential diagnosis (DD) since most skin conditions have specific predilection sites. On the other hand, location matters for dermatosurgical interventions. In practice, lesion evaluation is not well standardized and anatomical descriptions vary or lack altogether. Automated determination of anatomical location could benefit both situations. Objective: Establish an automated method to determine anatomical regions in clinical patient pictures and evaluate the gain in DD performance of a deep learning model (DLM) when trained with lesion locations and images. Methods: Retrospective study based on three datasets: macro-anatomy for the main body regions with 6000 patient pictures partially labelled by a student, micro-anatomy for the ear region with 182 pictures labelled by a student and DD with 3347 pictures of 16 diseases determined by dermatologists in clinical settings. For each dataset, a DLM was trained and evaluated on an independent test set. The primary outcome measures were the precision and sensitivity with 95% CI. For DD, we compared the performance of a DLM trained with lesion pictures only with a DLM trained with both pictures and locations. Results: The average precision and sensitivity were 85% (CI 84-86), 84% (CI 83-85) for macro-anatomy, 81% (CI 80-83), 80% (CI 77-83) for micro-anatomy and 82% (CI 78-85), 81% (CI 77-84) for DD. We observed an improvement in DD performance of 6% (McNemar test P-value 0.0009) for both average precision and sensitivity when training with both lesion pictures and locations. Conclusion: Including location can be beneficial for DD DLM performance. The proposed method can generate body region maps from patient pictures and even reach surgery relevant anatomical precision, e.g. the ear region. Our method enables automated search of large clinical databases and make targeted anatomical image retrieval possible

An Algebraic Theory for Data Linkage

There are countless sources of data available to governments, companies, and citizens, which can be combined for good or evil. We analyse the concepts of combining data from common sources and linking data from different sources. We model the data and its information content to be found in a single source by an ordered partial monoid, and the transfer of information between sources by different types of morphisms. To capture the linkage between a family of sources, we use a form of Grothendieck construction to create an ordered partial monoid that brings together the global data of the family in a single structure. We apply our approach to database theory and axiomatic structures in approximate reasoning. Thus, ordered partial monoids provide a foundation for the algebraic study for information gathering in its most primitive form

Computability of ordinary differential equations

In this paper we provide a brief review of several results about the computability of initial-value problems (IVPs) defined with ordinary differential equations (ODEs). We will consider a variety of settings and analyze how the computability of the IVP will be affected. Computational complexity results will also be presented, as well as computable versions of some classical theorems about the asymptotic behavior of ODEs.info:eu-repo/semantics/publishedVersio

Stratégie de réduction des micropolluants à l'échelle d'une agglomération : comparaison entre les effluents d’exutoires pluviaux et d’une station d'épuration

Colloque avec actes et comité de lecture. Internationale.International audienc

BMJ Open

INTRODUCTION: The prevalence of postnatal depression (PND) is significant: reaching up to 20% in the general population. In mechanistic terms, the risk of PND lies in an interaction between a maternal psychophysiological vulnerability and a chronic environmental context of stress. On the one hand, repetition of stressor during pregnancy mimics a chronic stress model that is relevant to the study of the allostatic load and the adaptive mechanisms. On the other hand, vulnerability factors reflect a psychological profile mirroring mindfulness functioning (psychological quality that involves bringing one's complete and non-judgemental attention to the present experience on a moment-to-moment basis). This psychological resource is linked to protective and resilient psychic functioning. Thus, PND appears to be a relevant model for studying the mechanisms of chronic stress and vulnerability to psychopathologies.In this article, we present the protocol of an ongoing study (started in May 2017). METHODS AND ANALYSIS: The study is being carried out in five maternities and will involve 260 women. We aim to determine the predictive psychobiological factors for PND emergence and to provide a better insight into the mechanisms involved in chronic stress during pregnancy. We use a multidisciplinary approach that encompasses psychological resources and biophysiological and genetic profiles in order to detect relevant vulnerability biomarkers for chronic stress and the development of PND. To do so, each woman will be involved in the study from her first trimester of pregnancy until 12 months postdelivery. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ile de France III Ethics Committee, France (2016-A00887-44). We aim to disseminate the findings through international conferences and international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03088319; Pre-results