86 resultados para Special Functions and Pathways


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Mitochondrial calcium regulation plays a number of important roles in neurons. Mitochondrial DNA (mtDNA) is highly polymorphic, and its interindividual variation is associated with various neuropsychiatric diseases and mental functions. An mtDNA polymorphism, 10398A>G, was reported to affect mitochondrial calcium regulation. Volume of hippocampus and amygdala is reportedly associated with various mental disorders and mental functions and is regarded as an endophenotype of mental disorders. The present study investigated the relationship between the mtDNA 10398A>G polymorphism and the volume of hippocampus and amygdala in 118 right-handed healthy subjects. The brain morphometry using magnetic resonance images employed both manual tracing volumetry in the native space and voxel-based morphometry (VBM) in the spatially normalized space. Amygdala volume was found to be significantly larger in healthy subjects with 10398A than in those with 10398G by manual tracing, which was confirmed by the VBM. Brain volumes in the other gray matter regions and all white matter regions showed no significant differences associated with the polymorphism. These provocative findings might provide a clue to the complex relationship between mtDNA, brain structure and mental disorders.

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Qualitative and quantitative methods were used in this research to distinguish the prevailing D/discourses (words, tools, beliefs, thinking styles) in police training and to analyse the ‘discourse-practice’ (Cherryholmes 1988, p.1) framework of policing in a training environment. The manifestations, functions and consequences of the D/discourses raise concerns about the efficacy of training (its doctrinal intent and value versus its educative intent and value) and its implications for individuals’ identity, subjectivity, agency, learning, and “membership” within the policing community. The literature revealed that police training acts as a formally sanctioned vehicle for police culture, subcultures, and D/discourses. This is complicated by (a) the predominance of pedagogical training practices that support a trainer-centred approach and standardised lecture format for training, (b) police training focusing predominantly on law enforcement at the cost of higher-order conceptual skills, and (c) Australian and international studies of police management education which reveal a subculture resistant to theoretical analysis and critical reflection, and a set of unconscious and unchallengeable assumptions regarding police work, conduct, and leadership. A backdrop to this research and findings is the agenda of Australian and New Zealand police services for police to become a profession.

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Qualitative and quantitative methods were used in this research to distinguish the prevailing D/discourses (words, tools, beliefs, thinking styles) in police training and to analyse the ‘discourse-practice’ (Cherryholmes 1988: 1) framework of policing in a training environment. The manifestations, functions and consequences of the D/discourses raise concerns about the efficacy of training (its doctrinal intent and value versus its educative intent and value) and its implications for individuals’ identity, subjectivity, agency, learning, and “membership” within the policing community. The literature revealed that police training acts as a formally sanctioned vehicle for police culture, subcultures, and D/discourses. This is complicated by (a) the predominance of pedagogical training practices that support a trainer-centred approach and standardised lecture format for training, (b) police training focusing predominantly on law enforcement at the cost of higher- rder conceptual skills, and (c) Australian and international studies of police management education which  reveal a subculture resistant to theoretical analysis and critical reflection, and a set of unconscious and unchallengeable assumptions regarding police work, conduct, and leadership. The agenda of Australian and New Zealand police services for police to become a profession provides a backdrop to this research and findings.

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Monotonicity with respect to all arguments is fundamental to the definition of aggregation functions. It is also a limiting property that results in many important nonmonotonic averaging functions being excluded from the theoretical framework. This work proposes a definition for weakly monotonic averaging functions, studies some properties of this class of functions, and proves that several families of important nonmonotonic means are actually weakly monotonic averaging functions. Specifically, we provide sufficient conditions for weak monotonicity of the Lehmer mean and generalized mixture operators. We establish weak monotonicity of several robust estimators of location and conditions for weak monotonicity of a large class of penalty-based aggregation functions. These results permit a proof of the weak monotonicity of the class of spatial-tonal filters that include important members such as the bilateral filter and anisotropic diffusion. Our concept of weak monotonicity provides a sound theoretical and practical basis by which (monotonic) aggregation functions and nonmonotonic averaging functions can be related within the same framework, allowing us to bridge the gap between these previously disparate areas of research.

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Lecturers using tablet PCs with specialised pens can utilise real-time changes in lecture delivery via digital inking. We investigated student perceptions and lecturer experiences of tablet PC lectures in large-enrolment biomedicine subjects. Lecturers used PowerPoint or Classroom Presenter software for lecture preparation and in-lecture pen-based inking. Using surveys and lecturer interviews, students and lecturers were asked to reflect on their tablet PC lectures in comparison to non-tablet lectures that used prepared images and a laser pointer. Quantitative survey responses suggested that students felt that the tablet lectures were more interesting, that they were more capable of keeping up with the lecturer, and they enhanced their understanding of the lecture content. Qualitative analysis of written comments indicated that students appreciated the real-time writing and drawings, particularly because these were visible on lecture recordings. When reflecting on their non-tablet lectures, most lecturers used the pen-based writing, drawing and highlighting tablet functions and reduced lecture pace and content for their tablet lectures. Long-term tablet use led to lecturers making more use of digital inking, with less use of prepared images. Our results support the idea that tablet PC-supported lectures are conducive to improved management of cognitive load via reduced lecture pace and content.

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Interleukins 2 and 15 (IL-2 and IL-15) are highly differentiated but related cytokines with overlapping, yet also distinct functions, and established benefits for medical drug use. The present study identified a gene for an ancient third IL-2/15 family member in reptiles and mammals, interleukin 15-like (IL-15L), which hitherto was only reported in fish. IL-15L genes with intact open reading frames (ORFs) and evidence of transcription, and a recent past of purifying selection, were found for cattle, horse, sheep, pig and rabbit. In human and mouse the IL-15L ORF is incapacitated. Although deduced IL-15L proteins share only ~21 % overall amino acid identity with IL-15, they share many of the IL-15 residues important for binding to receptor chain IL-15Rα, and recombinant bovine IL-15L was shown to interact with IL-15Rα indeed. Comparison of sequence motifs indicates that capacity for binding IL-15Rα is an ancestral characteristic of the IL-2/15/15L family, in accordance with a recent study which showed that in fish both IL-2 and IL-15 can bind IL-15Rα. Evidence reveals that the species lineage leading to mammals started out with three similar cytokines IL-2, IL-15 and IL-15L, and that later in evolution (1) IL-2 and IL-2Rα receptor chain acquired a new and specific binding mode and (2) IL-15L was lost in several but not all groups of mammals. The present study forms an important step forward in understanding this potent family of cytokines, and may help to improve future strategies for their application in veterinarian and human medicine.

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Skeletal muscle makes up approximately 40% of the total body mass, providing structural support and enabling the body to maintain posture, to control motor movements and to store energy. It therefore plays a vital role in whole body metabolism. Skeletal muscle displays remarkable plasticity and is able to alter its size, structure and function in response to various stimuli; an essential quality for healthy living across the lifespan. Exercise is an important stimulator of extracellular and intracellular stress signals that promote positive adaptations in skeletal muscle. These adaptations are controlled by changes in gene transcription and protein translation, with many of these molecules identified as potential therapeutic targets to pharmacologically improve muscle quality in patient groups too ill to exercise. MicroRNAs (miRNAs) are recently identified regulators of numerous gene networks and pathways and mainly exert their effect by binding to their target messenger RNAs (mRNAs), resulting in mRNA degradation or preventing protein translation. The role of exercise as a regulatory stimulus of skeletal muscle miRNAs is now starting to be investigated. This review highlights our current understanding of the regulation of skeletal muscle miRNAs with exercise and disease as well as how they may control skeletal muscle health.

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The composition of milk includes factors required to provide appropriate nutrition for the growth of the neonate. However, it is now clear that milk has many functions and comprises bioactive molecules that play a central role in regulating developmental processes in the young while providing a protective function for both the suckled young and the mammary gland during the lactation cycle. Identifying these bioactives and their physiological function in eutherians can be difficult and requires extensive screening of milk components that may function to improve well-being and options for prevention and treatment of disease. New animal models with unique reproductive strategies are now becoming increasingly relevant to search for these factors.

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Epithelial cell adhesion molecule (EpCAM), a cancer stem cell (CSC) marker is over expressed in epithelial cancers and in retinoblastoma (RB). We fabricated an EpCAM targeting aptamer-siRNA chimera and investigated its anti-tumor property and EpCAM intracellular domain (EpICD) mediated signaling in epithelial cancer. The anti-tumor efficacy of EpCAM aptamer-siEpCAM chimera (EpApt-siEp) was evaluated by qPCR, northern and Western blotting in WERI-Rb1- RB cell line, primary RB tumor cells and in MCF7- breast cancer cell line. Anti-tumor activity of EpApt-siEp was studied in vivo using epithelial cancer (MCF7) mice xenograft model. The mechanism and pathways involved in the anti-tumor activity was further studied using protein arrays and qPCR. EpApt-siEp chimera was processed in vitro by dicer enzyme. Treatment of the WERI-Rb1 and MCF7 cells with EpApt-siEp revealed statistically significant down regulation of EpCAM expression (P<0.005) and concomitant reduction in cellular proliferation. In primary RB cells cultured from RB tumors, EpApt-siEp silenced EpCAM, significantly inhibited (P<0.01) cell proliferation and induced cytotoxicity. Knockdown of EpICD expressed in RB primary tumors led to repression of pluripotency markers, SOX2, OCT4, NANOG, and CD133. In vivo studies showed complete tumor growth regression without any toxicity in animals (P<0.001) and tumor tissues showed significant downregulation (P<0.05) of EpCAM, MRP1, ABCG2, stathmin, survivin and upregulation of ATM (P<0.05) leading to apoptosis by intrinsic pathway with minor alteration in cytokines. Our results revealed that EpApt-siEp potentially eradicated EpCAM positive cancer cells through CSC marker suppression and apoptosis, while sparing normal EpCAM negative adjacent cells.

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 This research was focused upon members of the ADAMTS family of 'proteinases', proteins that have enzymatic activity. Their dysregulation can cause developmental defects and disease. This thesis describes the expression and regulation of ADAMTS15, as well as new developmental functions and inhibition of ADAMTS5 in arthritis.

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Electrical load forecasting plays a vital role in order to achieve the concept of next generation power system such as smart grid, efficient energy management and better power system planning. As a result, high forecast accuracy is required for multiple time horizons that are associated with regulation, dispatching, scheduling and unit commitment of power grid. Artificial Intelligence (AI) based techniques are being developed and deployed worldwide in on Varity of applications, because of its superior capability to handle the complex input and output relationship. This paper provides the comprehensive and systematic literature review of Artificial Intelligence based short term load forecasting techniques. The major objective of this study is to review, identify, evaluate and analyze the performance of Artificial Intelligence (AI) based load forecast models and research gaps. The accuracy of ANN based forecast model is found to be dependent on number of parameters such as forecast model architecture, input combination, activation functions and training algorithm of the network and other exogenous variables affecting on forecast model inputs. Published literature presented in this paper show the potential of AI techniques for effective load forecasting in order to achieve the concept of smart grid and buildings.