Molecular mechanism of neuritogenesis driven by prion protein

The cellular form of prion protein (PrPC) is a ubiquitous component of both the central and peripheral nervous systems from early stages of development to adulthood. Its misfolded isoform PrPSc is the pathological agent of prion diseases, a group of fatal neurodegenerative diseases. PrPC has been suggested to play different roles in neuroprotection, synaptic activities, neuritogenesis and metal homeostasis. Particularly, we were interested in its neurotrophic function and molecular mechanism involved the prion protein (PrP) with the process. By combining genomic approaches, cellular assays and focal stimulation technique, we explored PrP could act as a guidance cue, attracting the growth cone (GC) protrusion forward and eventually neurite outgrowth. In the study, we made different forms of the recombinant prion proteins (recPrP) from mouse without GPI anchoring residues mimicking secreted forms of PrPC. Our data suggest that full-length and wild-type recPrP(23-231) protein, not its truncated forms at N or C-terminal (23-90, 23-120, 89-231), could attract GC turning toward the protein source and enhance neurite growth in a dosedependent manner. recPrP may act through homophilic interaction with the GPI-anchor PrPC and form trans-signaling complex with neural cell adhesion molecule (NCAM) on the target cells to induce multiple intracellular signaling cascades known for cell growth including the Src-family kinase Fyn, extracellular regulated kinases MEK-ERK and phosphatidylinositol 3-kinase (PI3K). In addition, we discovered the functional sites for PrP function as a signaling molecule in neuritogenesis lying directly on N-terminal copper binding sites by mutating these residues to partially or completely prevent copper binding. In detail, minimal change in the copper binding site could lead to changes in the protein structure preventing PrP from functioning correctly and disrupting all the copper-binding sites at the N-terminus could turn the protein to be toxic to neurons. Especially, copper coordination at non-octarepeat (non-OR) region was shown to be essential for PrP to activate the proper growth signaling. GSS-linked mutation P102L (P101L in mouse numbering) that impacts indirectly to non-OR copper coordination could also abolish the function of PrP on neuritogenesis. Altogether, our findings indicate the crucial role of copper binding sites in maintaining functional structure for PrP interaction in neuritogenesis and suggest a potential link between loss-of-function of the protein and prion disease initiation

INVESTIGATION OF INFLUENCES OF FABRICATION TOLERANCES ON OPERATIONAL CHARACTERISTICS OF PIEZO-ACTUATED STICK-SLIP MICRO-DRIVES

Piezo-actuated stick-slip micro-drives (PASSMDs) are often used in microrobotic applications due to their advantages of a straightforward design and good operational characteristics. In this work, influences of fabrication tolerances on operational characteristics of PASSMDs are theoretically investigated. A dynamic model describing the whole macroscopic movement of the driver’s runner and the actuators, and the microscopic behavior of the frictional contacts using the method of dimensionality reduction, was used. Three essential parameters of the drives including the angle between working surfaces of the runner, the alignment angle between two actuator blocks on each side of the runner, and the stiffness of an individual actuator, whose values are impacted by the tolerance of the fabrication and assembly process, were considered as the input of the investigation. By performing hybrid-dynamic simulations, influences of these parameters on the drives' operational characteristics, including the repeatability of the step length, the critical amplitude phenomenon, and the maximal-achievable driving frequency/velocity, were evaluated. Simulation results show that these parameters significantly influence on the characteristics of the drives. The contribution of this work is so important that several important phenomena of PASSMDs, which are experimentally detected, are physically explained for the first time. The results of this work could help designers to optimize for better generations of PASSMDs

Factors Influencing the Auditor Independence and Affects to Audit Quality of Supreme Audit Institution of Vietnam

Purpose: The aim of this study is to explore the factors affect to auditor independence, and impacts auditor independence to audit quality of Supreme Audit Institution (SAI).   Theoretical framework: This study explores factors affecting the auditor independence in public sector based on articles pertaining to public sector audits that were published in major publications in the 20th century. The theories were applied in order to build up research model about factors influencing the auditor independence and affects to SAI’s audit quality.   Design/methodology/approach: Research using complex techniques to analyze complex relationships in the SEM model. This result tests research model in Vietnam from the perspective of the state auditors’ perception with 225 valid responses.   Findings: The result found out three primary factors that affect the independence of public-sector auditors: political hegemony, auditor tenure and relationships with auditees. These factors have negative impact on state auditor’s independence, meanwhile auditor independence has a positive impact on SAI’s audit quality.   Research, Practical & Social implications: The study contributes to existing literature by providing empirical evidence for there is no suitable audit quality measurement framework for SAIs.   Originality/value: The results highlight strong importance of the auditor independence so that SAI Vietnam can have effective solutions to protect independence of state auditor from threats and improve the audit quality of SAI

Computing Crisp Bisimulations for Fuzzy Structures

Fuzzy structures such as fuzzy automata, fuzzy transition systems, weighted social networks and fuzzy interpretations in fuzzy description logics have been widely studied. For such structures, bisimulation is a natural notion for characterizing indiscernibility between states or individuals. There are two kinds of bisimulations for fuzzy structures: crisp bisimulations and fuzzy bisimulations. While the latter fits to the fuzzy paradigm, the former has also attracted attention due to the application of crisp equivalence relations, for example, in minimizing structures. Bisimulations can be formulated for fuzzy labeled graphs and then adapted to other fuzzy structures. In this article, we present an efficient algorithm for computing the partition corresponding to the largest crisp bisimulation of a given finite fuzzy labeled graph. Its complexity is of order $O((m\log{l} + n)\log{n})$, where $n$, $m$ and $l$ are the number of vertices, the number of nonzero edges and the number of different fuzzy degrees of edges of the input graph, respectively. We also study a similar problem for the setting with counting successors, which corresponds to the case with qualified number restrictions in description logics and graded modalities in modal logics. In particular, we provide an efficient algorithm with the complexity $O((m\log{m} + n)\log{n})$ for the considered problem in that setting

A new approach to weighted Hardy-Rellich inequalities: improvements, symmetrization principle and symmetry breaking

We investigate necessary and sufficient conditions on the weights for the Hardy-Rellich inequalities to hold, and propose a new way to use the notion of Bessel pair to establish the optimal Hardy-Rellich type inequalities. Our results sharpened earlier Hardy-Rellich and Rellich type inequalities in the literature. We also study several results about the symmetry and symmetry breaking properties of the Rellich type and Hardy-Rellich type inequalities, and then partially answered an open question raised by Ghoussoub and Moradifam. Namely, we will present conditions on the weights such that the Rellich type and Hardy-Rellich type inequalities hold for all functions if and only if the same inequalities hold for all radial functions.Comment: 22 page

On attractor's dimensions of the modified Leray-alpha equation

The primary objective of this paper is to investigate the modified Leray-alpha equation on the two-dimensional sphere $\mathbb{S}^2$, the square torus $\mathbb{T}^2$ and the three-torus $\mathbb{T}^3$. In the strategy, we prove the existence and the uniqueness of the weak solutions and also the existence of the global attractor for the equation. Then we establish the upper and lower bounds of the Hausdorff and fractal dimensions of the global attractor on both $\mathbb{S}^2$ and $\mathbb{T}^2$. Our method is based on the estimates for the vorticity scalar equations and the stationary solutions around the invariant manifold that are constructed by using the Kolmogorov flows. Finally, we will use the results on $\mathbb{T}^2$ to study the lower bound for attractor's dimensions on the case of $\mathbb{T}^3$.Comment: 24 page

India-China strategic competition in the Indian Ocean

The XXI is considered by major countries in the Asia-Pacific region as ‘the century of sea and ocean' and is accompanied by fierce competition among the nations to gain interest in the sea regions. On the basis that previously only considered the competition for military objectives, geostrategic bases and traffic channels through the straits, nowadays, countries worldwide have stepped up the competition for economic interests and marine resources. The development of military power and the competitive activities for resources at sea show clear the tendency to use the sea to contain the continent. In that context, the Indian Ocean, as the world's third largest ocean, has an important geographic location and rich and diverse natural resources; the arterial sea route is gradually becoming the center of new world geopolitics and an important area in the strategic competition between two 'Asian giants' - India and China. The competition between these countries in the Indian Ocean is growing and profoundly impacts the region's stability and security. This article focuses on the position and important role of the Indian Ocean in the policies of India and China, the fierce competition between the two countries in nearly two decades of the XXI century