A hopeful therapy for Niemann-Pick C diseases

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Scanning Probe Microscopy on heterogeneous CaCu3Ti4O12 thin films

The conductive atomic force microscopy provided a local characterization of the dielectric heterogeneities in CaCu3Ti4O12 (CCTO) thin films deposited by MOCVD on IrO2 bottom electrode. In particular, both techniques have been employed to clarify the role of the inter- and sub-granular features in terms of conductive and insulating regions. The microstructure and the dielectric properties of CCTO thin films have been studied and the evidence of internal barriers in CCTO thin films has been provided. The role of internal barriers and the possible explanation for the extrinsic origin of the giant dielectric response in CCTO has been evaluated

Kodaira-Spencer formality of products of complex manifolds

We shall say that a complex manifold $X$ is emph{Kodaira-Spencer formal} if its Kodaira-Spencer differential graded Lie algebra $A^{0,*}_X(Theta_X)$ is formal; if this happen, then the deformation theory of $X$ is completely determined by the graded Lie algebra $H^*(X,Theta_X)$ and the base space of the semiuniversal deformation is a quadratic singularity.. Determine when a complex manifold is Kodaira-Spencer formal is generally difficult and we actually know only a limited class of cases where this happen. Among such examples we have Riemann surfaces, projective spaces, holomorphic Poisson manifolds with surjective anchor map $H^*(X,Omega^1_X) o H^*(X,Theta_X)$ and every compact K"{a}hler manifold with trivial or torsion canonical bundle. In this short note we investigate the behavior of this property under finite products. Let $X,Y$ be compact complex manifolds; we prove that whenever $X$ and $Y$ are K"{a}hler, then $X imes Y$ is Kodaira-Spencer formal if and only if the same holds for $X$ and $Y$. A revisit of a classical example by Douady shows that the above result fails if the K"{a}hler assumption is droppe

L∞L_\infty-Algebras of Classical Field Theories and the Batalin-Vilkovisky Formalism

We review in detail the Batalin-Vilkovisky formalism for Lagrangian field theories and its mathematical foundations with an emphasis on higher algebraic structures and classical field theories. In particular, we show how a field theory gives rise to an $L_\infty$-algebra and how quasi-isomorphisms between $L_\infty$-algebras correspond to classical equivalences of field theories. A few experts may be familiar with parts of our discussion, however, the material is presented from the perspective of a very general notion of a gauge theory. We also make a number of new observations and present some new results. Most importantly, we discuss in great detail higher (categorified) Chern-Simons theories and give some useful shortcuts in usually rather involved computations.Comment: v3: 131 pages, minor improvements, published versio

Quantum Degenerate Systems

Degenerate dynamical systems are characterized by symplectic structures whose rank is not constant throughout phase space. Their phase spaces are divided into causally disconnected, nonoverlapping regions such that there are no classical orbits connecting two different regions. Here the question of whether this classical disconnectedness survives quantization is addressed. Our conclusion is that in irreducible degenerate systems --in which the degeneracy cannot be eliminated by redefining variables in the action--, the disconnectedness is maintained in the quantum theory: there is no quantum tunnelling across degeneracy surfaces. This shows that the degeneracy surfaces are boundaries separating distinct physical systems, not only classically, but in the quantum realm as well. The relevance of this feature for gravitation and Chern-Simons theories in higher dimensions cannot be overstated.Comment: 18 pages, no figure

Shortened primary cilium length and dysregulated Sonic hedgehog signaling in Niemann-Pick C1 disease

The Niemann-Pick type C1 (NPC1) disease is a neurodegenerative lysosomal storage disorder due to mutations in the NPC1 gene, encoding a transmembrane protein related to the Sonic hedgehog receptor, Patched, and involved in intracellular trafficking of cholesterol. We have recently found that the proliferation of cerebellar granule neuron precursors is significantly reduced in Npc1-/- mice due to the downregulation of Shh expression. This finding prompted us to analyze the formation of the primary cilium, a non-motile organelle that is specialized for Shh signal transduction and responsible, when defective, for several human genetic disorders. In this study, we show that the expression and subcellular localization of Shh effectors and ciliary proteins are severely disturbed in Npc1-deficient mice. The dysregulation of Shh signaling is associated with a shortening of the primary cilium length and with a reduction of the fraction of ciliated cells in Npc1-deficient mouse brains and the human fibroblasts of NPC1 patients. These defects are prevented by treatment with 2-hydroxypropyl-β-cyclodextrin, a promising therapy currently under clinical investigation. Our findings indicate that defective Shh signaling is responsible for abnormal morphogenesis of the cerebellum of Npc1-deficient mice and show, for the first time, that the formation of the primary cilium is altered in NPC1 disease

Marine reserves help preserve genetic diversity after impacts derived from climate variability: Lessons from the pink abalone in Baja California

Genetic diversity is crucial for the adaptation of exploited species like the pink abalone (Haliotis corrugata), faced with threats from climate change, overfishing and impacts associated with aquaculture production. While marine reserves are commonly used to mitigate risks to marine populations, the duration, size, location and larval connectivity needed for a reserve to help conserve genetic resources is still poorly understood. Here, we examine the effects of fishing, reserves, and restocking on the genetic diversity of 10 populations from central Baja California, Mexico, and Southern California, USA. We demonstrate that each population shows characteristic genetic signatures according to recent management decisions. We found high allelic diversity, particularly rare alleles, a larger effective population size and a lack of a recent genetic bottleneck in pink abalones within a small (0.8 km2), recently established (5 years) reserve in Baja California, compared to other fished sites after a climatic bottleneck. Higher diversity may result from the presence of older animals in the reserve. Due to its location, the reserve may also act as an important hub connecting distant populations via larval dispersal. In contrast, a population from California showed genetic isolation, loss of allelic diversity and high relatedness, consistent with the collapse of fisheries in the 1990s and their lack of recovery thereafter. In addition, a fished area in Baja California with a history of restocking for over a decade showed an increase in frequency of related individuals and high genetic differentiation from nearby sites that were consistent with the production of larvae from a few adults in the laboratory. A network of strategically placed small marine reserves that considers ocean circulation patterns could help to maintain genetic diversity and connectivity of exploited populations