Activity-dependent CREB phosphorylation: Convergence of a fast, sensitive calmodulin kinase pathway and a slow, less sensitive mitogen-activated protein kinase pathway

The cAMP-responsive element binding protein (CREB), a key regulator of gene expression, is activated by phosphorylation on Ser-133. Several different protein kinases possess the capability of driving this phosphorylation, making it a point of potential convergence for multiple intracellular signaling cascades. Previous work in neurons has indicated that physiologic synaptic stimulation recruits a fast calmodulin kinase IV (CaMKIV)-dependent pathway that dominates early signaling to CREB. Here we show in hippocampal neurons that the fast, CaMK-dependent pathway can be followed by a slower pathway that depends on Ras/mitogen-activated protein kinase (MAPK), along with CaMK. This pathway was blocked by dominant-negative Ras and was specifically recruited by depolarizations that produced strong intracellular Ca2+ transients. When both pathways were recruited, phosphorylated CREB (pCREB) formation was overwhelmingly dominated by the CaMK pathway between 0 and 10 min, and by the MAPK pathway at 60 min, whereas the two pathways acted in concert at 30 min. The Ca2+ signals that produced only rapid CaMK signaling to pCREB or both rapid CaMK and slow MAPK signaling deviated significantly for only ≈1 min, yet their differential impact on pCREB extended over a much longer period, between 20 and 60 min and beyond, which is of likely significance for gene expression. The CaMK-dependent MAPK pathway may inform the nucleus about stimulus amplitude. In contrast, the CaMKIV pathway may be well suited to conveying information on the precise timing of localized synaptic stimuli, befitting its greater speed and sensitivity, whereas the previously described calcineurin pathway may carry information about stimulus duration.

Local convergence of quasi-Newton methods under metric regularity

We consider quasi-Newton methods for generalized equations in Banach spaces under metric regularity and give a sufficient condition for q-linear convergence. Then we show that the well-known Broyden update satisfies this sufficient condition in Hilbert spaces. We also establish various modes of q-superlinear convergence of the Broyden update under strong metric subregularity, metric regularity and strong metric regularity. In particular, we show that the Broyden update applied to a generalized equation in Hilbert spaces satisfies the Dennis–Moré condition for q-superlinear convergence. Simple numerical examples illustrate the results.

Numerical methods for strong solutions of stochastic differential equations: an overview

This paper gives a review of recent progress in the design of numerical methods for computing the trajectories (sample paths) of solutions to stochastic differential equations. We give a brief survey of the area focusing on a number of application areas where approximations to strong solutions are important, with a particular focus on computational biology applications, and give the necessary analytical tools for understanding some of the important concepts associated with stochastic processes. We present the stochastic Taylor series expansion as the fundamental mechanism for constructing effective numerical methods, give general results that relate local and global order of convergence and mention the Magnus expansion as a mechanism for designing methods that preserve the underlying structure of the problem. We also present various classes of explicit and implicit methods for strong solutions, based on the underlying structure of the problem. Finally, we discuss implementation issues relating to maintaining the Brownian path, efficient simulation of stochastic integrals and variable-step-size implementations based on various types of control.

Geometric versus Model Predictive Control based guidance algorithms for fixed-wing UAVs in the presence of very strong wind fields.

The recent years have witnessed increased development of small, autonomous fixed-wing Unmanned Aerial Vehicles (UAVs). In order to unlock widespread applicability of these platforms, they need to be capable of operating under a variety of environmental conditions. Due to their small size, low weight, and low speeds, they require the capability of coping with wind speeds that are approaching or even faster than the nominal airspeed. In this thesis, a nonlinear-geometric guidance strategy is presented, addressing this problem. More broadly, a methodology is proposed for the high-level control of non-holonomic unicycle-like vehicles in the presence of strong flowfields (e.g. winds, underwater currents) which may outreach the maximum vehicle speed. The proposed strategy guarantees convergence to a safe and stable vehicle configuration with respect to the flowfield, while preserving some tracking performance with respect to the target path. As an alternative approach, an algorithm based on Model Predictive Control (MPC) is developed, and a comparison between advantages and disadvantages of both approaches is drawn. Evaluations in simulations and a challenging real-world flight experiment in very windy conditions confirm the feasibility of the proposed guidance approach.

Existence and weak-strong uniqueness for the Navier-Stokes-Smoluchowski system over moving domains

This dissertation concerns the well-posedness of the Navier-Stokes-Smoluchowski system. The system models a mixture of fluid and particles in the so-called bubbling regime. The compressible Navier-Stokes equations governing the evolution of the fluid are coupled to the Smoluchowski equation for the particle density at a continuum level. First, working on fixed domains, the existence of weak solutions is established using a three-level approximation scheme and based largely on the Lions-Feireisl theory of compressible fluids. The system is then posed over a moving domain. By utilizing a Brinkman-type penalization as well as penalization of the viscosity, the existence of weak solutions of the Navier-Stokes-Smoluchowski system is proved over moving domains. As a corollary the convergence of the Brinkman penalization is proved. Finally, a suitable relative entropy is defined. This relative entropy is used to establish a weak-strong uniqueness result for the Navier-Stokes-Smoluchowski system over moving domains, ensuring that strong solutions are unique in the class of weak solutions.

Strong designated verifier signature in a multi-user setting

The security of strong designated verifier (SDV) signature schemes has thus far been analyzed only in a two-user setting. We observe that security in a two-user setting does not necessarily imply the same in a multi-user setting for SDV signatures. Moreover, we show that existing security notions do not adequately model the security of SDV signatures even in a two-user setting. We then propose revised notions of security in a multi-user setting and show that no existing scheme satisfies these notions. A new SDV signature scheme is then presented and proven secure under the revised notions in the standard model. For the purpose of constructing the SDV signature scheme, we propose a one-pass key establishment protocol in the standard model, which is of independent interest in itself.

Trust and strong ties in the selection and evaluation of business advisors by small firms

Principal Topic A small firm is unlikely to possess internally the full range of knowledge and skills that it requires or could benefit from for the development of its business. The ability to acquire suitable external expertise - defined as knowledge or competence that is rare in the firm and acquired from the outside - when needed thus becomes a competitive factor in itself. Access to external expertise enables the firm to focus on its core competencies and removes the necessity to internalize every skill and competence. However, research on how small firms access external expertise is still scarce. The present study contributes to this under-developed discussion by analysing the role of trust and strong ties in the small firm's selection and evaluation of sources of external expertise (henceforth referred to as the 'business advisor' or 'advisor'). Granovetter (1973, 1361) defines the strength of a network tie as 'a (probably linear) combination of the amount of time, the emotional intensity, the intimacy (mutual confiding) and the reciprocal services which characterize the tie'. Strong ties in the context of the present investigation refer to sources of external expertise who are well known to the owner-manager, and who may be either informal (e.g., family, friends) or professional advisors (e.g., consultants, enterprise support officers, accountants or solicitors). Previous research has suggested that strong and weak ties have different fortes and the choice of business advisors could thus be critical to business performance) While previous research results suggest that small businesses favour previously well known business advisors, prior studies have also pointed out that an excessive reliance on a network of well known actors might hamper business development, as the range of expertise available through strong ties is limited. But are owner-managers of small businesses aware of this limitation and does it matter to them? Or does working with a well-known advisor compensate for it? Hence, our research model first examines the impact of the strength of tie on the business advisor's perceived performance. Next, we ask what encourages a small business owner-manager to seek advice from a strong tie. A recent exploratory study by Welter and Kautonen (2005) drew attention to the central role of trust in this context. However, while their study found support for the general proposition that trust plays an important role in the choice of advisors, how trust and its different dimensions actually affect this choice remained ambiguous. The present paper develops this discussion by considering the impact of the different dimensions of perceived trustworthiness, defined as benevolence, integrity and ability, on the strength of tie. Further, we suggest that the dimensions of perceived trustworthiness relevant in the choice of a strong tie vary between professional and informal advisors. Methodology/Key Propositions Our propositions are examined empirically based on survey data comprising 153 Finnish small businesses. The data are analysed utilizing the partial least squares (PLS) approach to structural equation modelling with SmartPLS 2.0. Being non-parametric, the PLS algorithm is particularly well-suited to analysing small datasets with non-normally distributed variables. Results and Implications The path model shows that the stronger the tie, the more positively the advisor's performance is perceived. Hypothesis 1, that strong ties will be associated with higher perceptions of performance is clearly supported. Benevolence is clearly the most significant predictor of the choice of a strong tie for external expertise. While ability also reaches a moderate level of statistical significance, integrity does not have a statistically significant impact on the choice of a strong tie. Hence, we found support for two out of three independent variables included in Hypothesis 2. Path coefficients differed between the professional and informal advisor subsamples. The results of the exploratory group comparison show that Hypothesis 3a regarding ability being associated with strong ties more pronouncedly when choosing a professional advisor was not supported. Hypothesis 3b arguing that benevolence is more strongly associated with strong ties in the context of choosing an informal advisor received some support because the path coefficient in the informal advisor subsample was much larger than in the professional advisor subsample. Hypothesis 3c postulating that integrity would be more strongly associated with strong ties in the choice of a professional advisor was supported. Integrity is the most important dimension of trustworthiness in this context. However, integrity is of no concern, or even negative, when using strong ties to choose an informal advisor. The findings of this study have practical relevance to the enterprise support community. First of all, given that the strength of tie has a significant positive impact on the advisor's perceived performance, this implies that small business owners appreciate working with advisors in long-term relationships. Therefore, advisors are well advised to invest into relationship building and maintenance in their work with small firms. Secondly, the results show that, especially in the context of professional advisors, the advisor's perceived integrity and benevolence weigh more than ability. This again emphasizes the need to invest time and effort into building a personal relationship with the owner-manager, rather than merely maintaining a professional image and credentials. Finally, this study demonstrates that the dimensions of perceived trustworthiness are orthogonal with different effects on the strength of tie and ultimately perceived performance. This means that entrepreneurs and advisors should consider the specific dimensions of ability, benevolence and integrity, rather than rely on general perceptions of trustworthiness in their advice relationships.

Proton-transfer versus nontransfer in compounds of the diazo-dye precursor 4-(phenyldiazenyl) aniline (aniline yellow) with strong organic acids: the 5-sulfosalicylate and the dichroic benzenesulfonate salts, and the 1:2 adduct with 3,5-dinitrobenzoic

The structures of two 1:1 proton-transfer red-black dye compounds formed by reaction of aniline yellow [4-(phenyldiazenyl)aniline] with 5-sulfosalicylic acid and benzenesulfonic acid, and a 1:2 nontransfer adduct compound with 3,5-dinitrobenzoic acid have been determined at either 130 or 200 K. The compounds are 2-(4-aminophenyl)-1-phenylhydrazin-1-ium 3-carboxy-4-hydroxybenzenesulfonate methanol solvate, C12H12N3+.C7H5O6S-.CH3OH (I), 2-(4-aminophenyl)-1-hydrazin-1-ium 4-(phenydiazinyl)anilinium bis(benzenesulfonate), 2C12H12N3+.2C6H5O3S-, (II) and 4-(phenyldiazenyl)aniline-3,5-dinitrobenzoic acid (1/2) C12H11N3.2C~7~H~4~N~2~O~6~, (III). In compound (I) the diaxenyl rather than the aniline group of aniline yellow is protonated and this group subsequently akes part in a primary hydrogen-bonding interaction with a sulfonate O-atom acceptor, producing overall a three-dimensional framework structure. A feature of the hydrogen bonding in (I) is a peripheral edge-on cation-anion association involving aromatic C--H...O hydrogen bonds, giving a conjoint R1/2(6)R1/2(7)R2/1(4)motif. In the dichroic crystals of (II), one of the two aniline yellow species in the asymmetric unit is diazenyl-group protonated while in the other the aniline group is protonated. Both of these groups form hydrogen bonds with sulfonate O-atom acceptors and thee, together with other associations give a one-dimensional chain structure. In compound (III), rather than proton-transfer, there is a preferential formation of a classic R2/2(8) cyclic head-to-head hydrogen-bonded carboxylic acid homodimer between the two 3,5-dinitrobenzoic acid molecules, which in association with the aniline yellow molecule that is disordered across a crystallographic inversion centre, result in an overall two-dimensional ribbon structure. This work has shown the correlation between structure and observed colour in crystalline aniline yellow compounds, illustrated graphically in the dichroic benzenesulfonate compound.

Research Monograph: Managing ubiquitous eco cities: telecommunication infrastructure networks, technology convergence and intelligent urban management systems

Efficient and effective urban management systems for Ubiquitous Eco Cities require having intelligent and integrated management mechanisms. This integration includes bringing together economic, socio-cultural and urban development with a well orchestrated, transparent and open decision making mechanism and necessary infrastructure and technologies. In Ubiquitous Eco Cities telecommunication technologies play an important role in monitoring and managing activities over wired, wireless or fibre-optic networks. Particularly technology convergence creates new ways in which the information and telecommunication technologies are used and formed the back bone or urban management systems. The 21st Century is an era where information has converged, in which people are able to access a variety of services, including internet and location based services, through multi-functional devices such as mobile phones and provides opportunities in the management of Ubiquitous Eco Cities. This research paper discusses the recent developments in telecommunication networks and trends in convergence technologies and their implications on the management of Ubiquitous Eco Cities and how this technological shift is likely to be beneficial in improving the quality of life and place of residents, workers and visitors. The research paper reports and introduces recent approaches on urban management systems, such as intelligent urban management systems, that are suitable for Ubiquitous Eco Cities.

Managing ubiquitous eco cities : the role of urban telecommunication infrastructure networks and convergence technologies

A successful urban management system for a Ubiquitous Eco City requires an integrated approach. This integration includes bringing together economic, socio-cultural and urban development with a well orchestrated, transparent and open decision making mechanism and necessary infrastructure and technologies. Rapidly developing information and telecommunication technologies and their platforms in the late 20th Century improves urban management and enhances the quality of life and place. Telecommunication technologies provide an important base for monitoring and managing activities over wired, wireless or fibre-optic networks. Particularly technology convergence creates new ways in which the information and telecommunication technologies are used. The 21st Century is an era where information has converged, in which people are able to access a variety of services, including internet and location based services, through multi-functional devices such as mobile phones and provides opportunities in the management of Ubiquitous Eco Cities. This paper discusses the recent developments in telecommunication networks and trends in convergence technologies and their implications on the management of Ubiquitous Eco Cities and how this technological shift is likely to be beneficial in improving the quality of life and place. The paper also introduces recent approaches on urban management systems, such as intelligent urban management systems, that are suitable for Ubiquitous Eco Cities.