188 research outputs found
Giant vesicles at the prolate-oblate transition: A macroscopic bistable system
Giant phospholipid vesicles are shown to exhibit thermally activated
transitions between a prolate and an oblate shape on a time scale of several
seconds. From the fluctuating contour of such a vesicle we extract ellipticity
as an effective reaction coordinate whose temporal probability distribution is
bimodal. We then reconstruct the effective potential from which we derive an
activation energy of the order of in agreement with theoretical
calculations. The dynamics of this transition is well described within a
Kramers model of overdamped diffusion in a bistable potential. Thus, this
system can serve as a model for macroscopic bistability.Comment: 10 pages, LaTeX, epsfig, 4 eps figures included, to appear in
Europhys. Let
How to determine local elastic properties of lipid bilayer membranes from atomic-force-microscope measurements: A theoretical analysis
Measurements with an atomic force microscope (AFM) offer a direct way to
probe elastic properties of lipid bilayer membranes locally: provided the
underlying stress-strain relation is known, material parameters such as surface
tension or bending rigidity may be deduced. In a recent experiment a
pore-spanning membrane was poked with an AFM tip, yielding a linear behavior of
the force-indentation curves. A theoretical model for this case is presented
here which describes these curves in the framework of Helfrich theory. The
linear behavior of the measurements is reproduced if one neglects the influence
of adhesion between tip and membrane. Including it via an adhesion balance
changes the situation significantly: force-distance curves cease to be linear,
hysteresis and nonzero detachment forces can show up. The characteristics of
this rich scenario are discussed in detail in this article.Comment: 14 pages, 9 figures, REVTeX4 style. New version corresponds to the
one accepted by PRE. The result section is restructured: a comparison to
experimental findings is included; the discussion on the influence of
adhesion between AFM tip and membrane is extende
Recherche de reproductibilité dans les relations inter structures durant les crises d'épilepsie
Cet article s'inscrit dans le cadre de l'étude des signaux stéréoélectroencéphalographiques (EEG de profondeur) enregistrés lors de crises d'épilepsie. Il propose une méthode de mise en correspondance capable de quantifier, d'une crise à l'autre, les reproductibilités des relations inter-canaux estimées par la fonction de cohérence. Le travail est illustré sur des signaux construits à partir de différents scénarios décrivant un sous-type d'épilepsie (origine temporale). Les perspectives de ce travail sont liées, d'une part, à l'extraction de similarités dans l'évolution des relations qui s'établissent entre les structures cérébrales durant les crises et, d'autre part, à la mise en évidence de scénarios récurrents dans l'organisation de ces crises
Effective Area-Elasticity and Tension of Micro-manipulated Membranes
We evaluate the effective Hamiltonian governing, at the optically resolved
scale, the elastic properties of micro-manipulated membranes. We identify
floppy, entropic-tense and stretched-tense regimes, representing different
behaviors of the effective area-elasticity of the membrane. The corresponding
effective tension depends on the microscopic parameters (total area, bending
rigidity) and on the optically visible area, which is controlled by the imposed
external constraints. We successfully compare our predictions with recent data
on micropipette experiments.Comment: To be published in Phys. Rev. Let
Active Membrane Fluctuations Studied by Micropipet Aspiration
We present a detailed analysis of the micropipet experiments recently
reported in J-B. Manneville et al., Phys. Rev. Lett. 82, 4356--4359 (1999),
including a derivation of the expected behaviour of the membrane tension as a
function of the areal strain in the case of an active membrane, i.e.,
containing a nonequilibrium noise source. We give a general expression, which
takes into account the effect of active centers both directly on the membrane,
and on the embedding fluid dynamics, keeping track of the coupling between the
density of active centers and the membrane curvature. The data of the
micropipet experiments are well reproduced by the new expressions. In
particular, we show that a natural choice of the parameters quantifying the
strength of the active noise explains both the large amplitude of the observed
effects and its remarkable insensitivity to the active-center density in the
investigated range. [Submitted to Phys Rev E, 22 March 2001]Comment: 14 pages, 5 encapsulated Postscript figure
Generalized Structural Description of Calcium–Sodium Aluminosilicate Hydrate Gels: The Cross-Linked Substituted Tobermorite Model
Structural models for the primary strength and durability-giving reaction product in modern cements, a calcium (alumino)silicate hydrate gel, have previously been based solely on non-cross-linked tobermorite structures. However, recent experimental studies of laboratory-synthesized and alkali-activated slag (AAS) binders have indicated that the calcium–sodium aluminosilicate hydrate [C-(N)-A-S-H] gel formed in these systems can be significantly cross-linked. Here, we propose a model that describes the C-(N)-A-S-H gel as a mixture of cross-linked and non-cross-linked tobermorite-based structures (the cross-linked substituted tobermorite model, CSTM), which can more appropriately describe the spectroscopic and density information available for this material. Analysis of the phase assemblage and Al coordination environments of AAS binders shows that it is not possible to fully account for the chemistry of AAS by use of the assumption that all of the tetrahedral Al is present in a tobermorite-type C-(N)-A-S-H gel, due to the structural constraints of the gel. Application of the CSTM can for the first time reconcile this information, indicating the presence of an additional activation product that contains highly connected four-coordinated silicate and aluminate species. The CSTM therefore provides a more advanced description of the chemistry and structure of calcium–sodium aluminosilicate gel structures than that previously established in the literature
Maintaining RNA integrity in a homogeneous population of mammary epithelial cells isolated by Laser Capture Microdissection
Background: Laser-capture microdissection (LCM) that enables the isolation of specific cell populations from complex tissues under morphological control is increasingly used for subsequent gene expression studies in cell biology by methods such as real-time quantitative PCR (qPCR), microarrays and most recently by RNA-sequencing. Challenges are i) to select precisely and efficiently cells of interest and ii) to maintain RNA integrity. The mammary gland which is a complex and heterogeneous tissue, consists of multiple cell types, changing in relative proportion during its development and thus hampering gene expression profiling comparison on whole tissue between physiological stages. During lactation, mammary epithelial cells (MEC) are predominant. However several other cell types, including myoepithelial (MMC) and immune cells are present, making it difficult to precisely determine the specificity of gene expression to the cell type of origin. In this work, an optimized reliable procedure for producing RNA from alveolar epithelial cells isolated from frozen histological sections of lactating goat, sheep and cow mammary glands using an infrared-laser based Arcturus Veritas LCM (Applied Biosystems®) system has been developed. The following steps of the microdissection workflow: cryosectioning, staining, dehydration and harvesting of microdissected cells have been carefully considered and designed to ensure cell capture efficiency without compromising RNA integrity.[br/] Results: The best results were obtained when staining 8 μm-thick sections with Cresyl violet® (Ambion, Applied Biosystems®) and capturing microdissected cells during less than 2 hours before RNA extraction. In addition, particular attention was paid to animal preparation before biopsies or slaughtering (milking) and freezing of tissue blocks which were embedded in a cryoprotective compound before being immersed in isopentane. The amount of RNA thus obtained from ca.150 to 250 acini (300,000 to 600,000 μm2) ranges between 5 to 10 ng. RNA integrity number (RIN) was ca. 8.0 and selectivity of this LCM protocol was demonstrated through qPCR analyses for several alveolar cell specific genes, including LALBA (α-lactalbumin) and CSN1S2 (αs2-casein), as well as Krt14 (cytokeratin 14), CD3e and CD68 which are specific markers of MMC, lymphocytes and macrophages, respectively.[br/] Conclusions: RNAs isolated from MEC in this manner were of very good quality for subsequent linear amplification, thus making it possible to establish a referential gene expression profile of the healthy MEC, a useful platform for tumor biomarker discovery
GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture
Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment
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