Multiple Pathways Analysis of Brain Functional Networks from EEG Signals: An Application to Real Data

In the present study, we propose a theoretical graph procedure to investigate multiple pathways in brain functional networks. By taking into account all the possible paths consisting of h links between the nodes pairs of the network, we measured the global network redundancy R (h) as the number of parallel paths and the global network permeability P (h) as the probability to get connected. We used this procedure to investigate the structural and dynamical changes in the cortical networks estimated from a dataset of high-resolution EEG signals in a group of spinal cord injured (SCI) patients during the attempt of foot movement. In the light of a statistical contrast with a healthy population, the permeability index P (h) of the SCI networks increased significantly (P < 0.01) in the Theta frequency band (3-6 Hz) for distances h ranging from 2 to 4. On the contrary, no significant differences were found between the two populations for the redundancy index R (h) . The most significant changes in the brain functional network of SCI patients occurred mainly in the lower spectral contents. These changes were related to an improved propagation of communication between the closest cortical areas rather than to a different level of redundancy. This evidence strengthens the hypothesis of the need for a higher functional interaction among the closest ROIs as a mechanism to compensate the lack of feedback from the peripheral nerves to the sensomotor areas.

Differential effects of TR ligands on hormone dissociation rates: Evidence for multiple ligand entry/exit pathways

Some nuclear receptor (NR) ligands promote dissociation of radiolabeled bound hormone from the buried ligand binding cavity (LBC) more rapidly than excess unlabeled hormone itself This result was interpreted to mean that challenger ligands bind allosteric sites on the LBD to induce hormone dissociation, and recent findings indicate that ligands bind weakly to multiple sites on the LBD surface. Here we show, that a large fraction of thyroid hormone receptor (TR) ligands promote rapid dissociation (T(1/2) < 2 h) of , radiolabeled T(3) vs. T(3) (T(1/2), approximate to 5-7 h). We cannot discern relationships between this effect and ligand size, activity or affinity for TR beta. One ligand, GC-24, binds the TR LBC and (weakly) to the TR beta-LBD surface that mediates dimer/heterodimer interaction, but we cannot link this interaction to rapid T(3) dissociation. Instead, several lines of evidence suggest that the challenger ligand must interact with the buried LBC to promote rapid T(3) release. Since previous molecular dynamics simulations suggest that TR ligands leave the LBC by several routes, we propose that a subset of challenger ligands binds and stabilizes a partially unfolded intermediate state of TR that arises during T(3) release and that this effect enhances hormone dissociation. (C) 2009 Elsevier Ltd. All rights reserved.

Mitochondrial ion transport pathways: Role in metabolic diseases

Mitochondria are the central coordinators of energy metabolism and alterations in their function and number have long been associated with metabolic disorders such as obesity, diabetes and hyperlipidemias. Since oxidative phosphorylation requires an electrochemical gradient across the inner mitochondrial membrane, ion channels in this membrane certainly must play an important role in the regulation of energy metabolism. However, in many experimental settings, the relationship between the activity of mitochondrial ion transport and metabolic disorders is still poorly understood. This review briefly summarizes some aspects of mitochondrial H(+) transport (promoted by uncoupling proteins, UCPs). Ca(2+) and K(+) uniporters which may be determinant in metabolic disorders. (C) 2009 Elsevier B.V. All rights reserved.

Formation and decomposition of N-alkyinaphthalimides: experimental evidences and ab initio description of the reaction pathways

The kinetics of hydrolysis of 1,8-N-butyl-naphthalimide (1,8-NBN) to 1,8-N-butyl-naphthalamide (1,8-NBAmide) and of 2,3-N-butyl-naphthalimide (2,3-NBN) to 2,3-N-butyl-naphthalamide (2,3-NBAmide), as well as the formation of the respective anhydrides from the amides were investigated in a wide acidity range. 1,8-NBN equilibrates with 1,8-NBAmide in mild alkali. Under the same conditions 2,3-NBN quantitatively yields 2,3-NBAmide. Over a wide range of acidities the reactions of the 1,8- and 2,3-N-butyl-naphthalamides (or imides) yield similar products but with widely different rates and at distinct pH`s. Anhydride formation in acid was demonstrated for 1,8-NBAmide. The reactions mechanisms were rationalized in the manifold pathways of ab initio calculations. The differences in rates and pH ranges in the reactions of the 1,8- and 2,3-N-butyl-naphthalamides were attributed to differences in the stability of the tetrahedral intermediates in alkali as well as the relative stabilities of the five and six-membered ring intermediates. The rate of carboxylic acid assisted 1,8-N-Butyl-naphthalamide hydrolysis is one of the largest described for amide hydrolysis models. Copyright (C) 2010 John Wiley & Sons, Ltd.

Simple Question, Complex Answer : Pathways Towards a 50% Decrease in Building Energy Use

Addressing building energy use is a pressing issue for building sector decision makers across Europe. In Sweden, some regions have adopted a target of reducing energy use in buildings by 50% until 2050. However, building codes currently do not support as ambitious objectives as these, and novel approaches to addressing energy use in buildings from a regional perspective are called for. The purpose of this licentiate thesis was to provide a deeper understanding of most relevant issues with regard to energy use in buildings from a broad perspective and to suggest pathways towards reaching the long-term savings objective. Current trends in building sector structure and energy use point to detached houses constructed before 1981 playing a key role in the energy transition, especially in the rural areas of Sweden. In the Swedish county of Dalarna, which was used as a study area in this thesis, these houses account for almost 70% of the residential heating demand. Building energy simulations of eight sample houses from county show that there is considerable techno-economic potential for energy savings in these houses, but not quite enough to reach the 50% savings objective. Two case studies from rural Sweden show that savings well beyond 50% are achievable, both when access to capital and use of high technology are granted and when they are not. However, on a broader scale both direct and indirect rebound effects will have to be expected, which calls for more refined approaches to energy savings. Furthermore, research has shown that the techno-economic potential is in fact never realised, not even in the most well-designed intervention programmes, due to the inherent complexity of human behaviour with respect to energy use. This is not taken account of in neither current nor previous Swedish energy use legislation. Therefore an approach that considers the technical prerequisites, economic aspects and the perspective of the many home owners, based on Community-Based Social Marketing methodology, is suggested as a way forward towards reaching the energy savings target.

Pathways in real-life learning

The pathway to expertise is a long journey, and few make it. Regardless of discipline, the journey is similar; what differentiates the journey is the
knowledge that underpins the profession. This research explores expert
teachers and the knowledge that underpins the teaching profession. Much research in teacher education has concentrated on individual elements of expert teaching. There has been less emphasis on understanding the complex real-life process of expert teaching in its entirety. The model presented here looks at an integrated approach to understanding the development of expert teachers through real-life learning experiences and related factors

Predatory pricing and the expectation of recoupment in Australia : Boral and the pathways forward

High Court decision, Boral v ACCC in which the Court overturned the decision of the Full Federal Court and held that Boral's strategy of below cost pricing did not contravene s 46 of the Trade Practices Act - suggestion that the test of recoupment be the central test with respect to predatory pricing cases.

Referral of the Halocypridina Thaumatocypris (Miocene, Australia) to the Cladocopina (Ostracoda, Halocyprida)

B. K. Nadeau in 1955 identified as Thaumatocypris ostracodes from the middle Miocene Glenample Clay of Victoria, southeastern Australia. Nadeau's collection of Ostracoda from the Glenample Clay was located in the collections of the Museum of Victoria, Melbourne. Examination of that material indicates that the Glenample Clay specimens attributed by Nadeau to Thaumatocypris belong to Polycope sanctacatherinae Whatley & Downing 1983. As a result, it is concluded that Thaumatocypris has not been collected in the Miocene of Australia. Furthermore, in a broader  biostratigraphic/palaeobiogeographic context, the result confirms that no member of the Suborder Halocypridina has been reported so far from the Tertiary Period.

How acceptable is a referral and telephone-based outcall programme for men diagnosed with cancer? A feasibility study

The objective of this study was to determine the feasibility and acceptability of a referral and outcall programme from a telephone-based information and support service, for men newly diagnosed with colorectal or prostate cancer. A block randomized controlled trial was performed involving 100 newly diagnosed colorectal and prostate cancer patients. Patients were referred to the Cancer Information Support Service (CISS) through clinicians at diagnosis. Clinicians were randomized into one of three conditions. Active referral 1: specialist referral with four CISS outcalls: (1) ≤1 week of diagnosis; (2) at 6 weeks; (3) 3 months; and (4) 6 months post diagnosis. Active referral 2: specialist referral with one CISS outcall ≤1 week of diagnosis. Passive referral: specialist recommended patient contacts CISS, but contact at the patient's initiative. Patients completed research questionnaires at study entry (before CISS contact), then 4 and 7 months post diagnosis. Overall, 96% of participants reported a positive experience with the referral process; 87% reported they were not concerned about receiving the calls; and 84% indicated the timing of the calls was helpful. In conclusion, the referral and outcall programme was achievable and acceptable for men newly diagnosed with colorectal or prostate cancer.

Pathways to health through Australian woodlands and forests: `Sign-posts` from recent research and practice

Health is inherently 'ecological' and the natural environment plays a crucial role in human health and well-being. Yet we do not necessarily design, manage or market such areas in ways that acknowledge this link. This paper draws on recent research by a Deakin University team exploring the links between use of and involvement in the maintenance of forests/woodlands, and health and well-being outcomes. Qualitative and quantitative methods have been used to collect data from forest/woodland users and tram volunteers contributing to management and maintenance of such areas, concerning their perceptions of the impacts of the experience
on their health and well-being. In two of the projects, samples of 'users' and 'volunteers' were compared with samples 'non-users' and 'non-volunteers'. Several of the studies included the use of scales of self-rated health, social cohesion, and frequency of use of medical services.The studies have identified a range of perceived physical, mental and social health benefits resulting from use of and/or engagement with forests/woodlands. Study findings have implications for design, management and marketing of such areas, since they identity factors influencing use of and engagement with such areas, and have the potential to promote more widespread recognition of the value of such areas and more commitment to them by individuals, communities and governments. The challenge for us is to build on this research base to more clearly Signpost the mutually beneficial links between forest and woodland ecosystems and human health and well-being, creating new and better pathways to a healthy future.

Multiple pathways contribute to the hyperproliferative responses from truncated granulocyte colony-stimulating factor receptors

Mutations in the granulocyte colony-stimulating factor receptor (G-CSF-R) gene leading to a truncated protein have been identified in a cohort of neutropenia patients highly predisposed to acute myeloid leukemia. Such mutations act in a dominant manner resulting in hyperproliferation but impaired differentiation in response to G-CSF. This is due, at least in part, to defective internalization and loss of binding sites for several negative regulators, leading to sustained receptor activation. However, those signaling pathways responsible for mediating the hyperproliferative function have remained unclear. In this study, analysis of an additional G-CSF-R mutant confirmed the importance of residues downstream of Box 2 as important contributors to the sustained proliferation. However, maximal proliferation correlated with the ability to robustly activate signal transducer and activator of transcription (STAT) 5 in a sustained manner, whereas co-expression of dominant-negative STAT5, but not dominant-negative STAT3, was able to inhibit G-CSF-stimulated proliferation from a truncated receptor. Furthermore, a Janus kinase (JAK) inhibitor also strongly reduced the proliferative response, whereas inhibitors of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) or phosphatidylinositol (PI) 3-kinase reduced proliferation to a lesser degree. These data suggest that sustained JAK2/STAT5 activation is a major contributor to the hyperproliferative function of truncated G-CSF receptors, with pathways involving MEK and PI 3-kinase playing a reduced role.

Effects of cannabinoid receptors on skeletal muscle oxidative pathways

The endocannabinoids, a recently discovered endogenous, lipid derived, signaling system regulating energy metabolism, have effects on central and peripheral energy metabolism predominantly via the cannabinoid receptor type 1 (CB1). CB1 is expressed centrally in the hypothalamus and nucleus accumbens and peripherally in adipocytes and skeletal muscle. This study determined the effect of endocannabinoids on the expression of genes regulating energy metabolism in human skeletal muscle. Primary cultures of myotubes (lean and obese; n = 3/group) were treated with the cannabinoid receptor agonist, anandamide (AEA) (0.2 and 5 μM) and the CB1 specific antagonist AM251 (0.2 and 5 μM) separately and in combination for 24 h. The expression of mRNA for AMP-activated protein kinase (AMPK) alpha 1 (α1) and alpha 2 (α2), pyruvate dehydrogenase kinase 4 (PDK4) and peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) were determined using ‘Real Time’ RT-PCR. AMPKα1 mRNA increased in lean and obese myotubes in response to AM251 (P < 0.05). AEA inhibited the effect of AM251 on AMPKα1 mRNA levels in myotubes from lean and obese subjects (P < 0.05); the dose–response curve was shifted to the left in the obese. In response to AM251, irrespective of the presence of AEA, PDK4 expression was decreased in lean and obese myotubes (P < 0.05). Taken together these data suggest that endocannabinoids regulate pathways affecting skeletal muscle oxidation, effects particularly evident in myotubes from obese individuals.

Mental health and wellbeing of Australian adolescents: pathways to vulnerability and resilience

The Australian Temperament Project (ATP) provides a unique lens through which to view he pathways to vulnerability and resilience that Australian children take from infancy to adolescence, and beyond. Commencing in 1983, the ATP is now completing its 24th year and 14th wave of data collection. The present paper provides an overview of the data on adolescent antisocial behaviour, substance use, internalising problems and aspects of positive development and wellbeing. Several pathways to vulnerability or resilience are described that vary in their age of onset. Constellations of common risk factors suggest that there may be overlapping priming factors for later mental health problems. A different mix of factors relates to pathways to wellbeing. This unique Australian study provides invaluable insights into stability and change in the pathways to mental health that children take across life.