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81.
82.
Regulatory changes occurring early in colorectal cancer development remain poorly investigated. Since the majority of cases develop from polyps in the adenoma-carcinoma transition, a search of early molecular features, such as aberrations in miRNA expression occurring prior to cancer development, would enable identification of potentially causal, rather than consequential, candidates in the progression of polyp to cancer. In the current study, by employing small RNA-seq profiling of colon biopsy samples, we described differentially expressed miRNAs and their isoforms in the adenoma-carcinoma transition. Analysis of healthy-adenoma-carcinoma sequence in an independent validation group enabled us to identify early deregulated miRNAs including hsa-miR-1246 and hsa-miR-215-5p, the expressions of which are, respectively, gradually increasing and decreasing. Loss-of-function experiments revealed that inhibition of hsa-miR-1246 lead to reduced cell viability, colony formation, and migration rate, thereby indicating an oncogenic effect of this miRNA in vitro. Subsequent western blot and luciferase reporter assay provided evidence of hsa-miR-1246 being involved in the regulation of target AXIN2 and CFTR genes’ expression. To conclude, the present study revealed possible involvement of hsa-miR-1246 in early colorectal cancer development and regulation of tumor suppressors AXIN2 and CFTR.  相似文献   
83.
Fine temperature control is essential in homeothermic animals. Both hyper- and hypothermia can have deleterious effects. Multiple, efficient and partly redundant mechanisms of adjusting the body temperature to the value set by the internal thermostat exist. The neural circuitry of temperature control and the neurotransmitters involved are reviewed. The GABAergic inhibitory output from the brain thermostat in the preoptic area POA to subaltern neural circuitry of temperature control (Nucleus Raphe Dorsalis and Nucleus Raphe Pallidus) is a function of the balance between the (opposite) effects mediated by the transient receptor potential receptor TRPM2 and EP3 prostaglandin receptors. Activation of TRPM2-expressing neurons in POA favors hypothermia, while inhibition has the opposite effect. Conversely, EP3 receptors induce elevation in body temperature. Activation of EP3-expressing neurons in POA results in hyperthermia, while inhibition has the opposite effect. Agonists at TRPM2 and/or antagonists at EP3 could be beneficial in hyperthermia control. Activity of the neural circuitry of temperature control is modulated by a variety of 5-HT receptors. Based on the theoretical model presented the “ideal” antidote against serotonin syndrome hyperthermia appears to be an antagonist at the 5-HT receptor subtypes 2, 4 and 6 and an agonist at the receptor subtypes 1, 3 and 7. Very broadly speaking, such a profile translates in a sympatholytic effect. While a compound with such an ideal profile is presently not available, better matches than the conventional antidote cyproheptadine (used off-label in severe serotonin syndrome cases) appear to be possible and need to be identified.  相似文献   
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Medium Access Control (MAC) protocols for Wireless Sensor Networks (WSN) are usually designed as random access protocols that apply different kinds of backoff strategies since Time Division Multiple Access (TDMA) based protocols with admission control are very complex and require additional mechanisms for synchronization. Without such mechanisms, fair or priority based medium access with Quality of Service (QoS) guarantees can hardly be achieved by existing protocols. Therefore, we developed a random access protocol which uses a new preamble-based medium access strategy that enables collision-free priority based access without the need of synchronization. In this paper we introduce different QoS strategies and their use cases. All strategies can be easily integrated in our protocol to meet the requirements of different target applications. Furthermore, we compare the performance of the strategies with a typical carrier-sense based protocol.  相似文献   
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A collection of new reversible glycosidase inhibitors of the iminoalditol type featuring N‐substituents containing perfluorinated regions has been prepared for evaluation of physicochemical, biochemical and diagnostic properties. The vast variety of feasible oligofluoro moieties allows for modular approaches to customised structures according to the intended applications, which are influenced by the fluorine content as well as the distance of the fluorous moiety from the ring nitrogen. The first examples, in particular in the D ‐galacto series, exhibited excellent inhibitory activities. A preliminary screen with two human cell lines showed that, at subinhibitory concentrations, they are powerful pharmacological chaperones enhancing the activities of the catalytically handicapped lysosomal D ‐galactosidase mutants associated with GM1 gangliosidosis and Morquio B disease.  相似文献   
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Various chemical products are synthesized in processes using gas/liquid reactors with bubbly flows. Hence, there is a significant interest in a more efficient process design as well as in process intensification with a strong focus on this reactor class. However, the design of industrial gas/liquid reactors requires more detailed information about the flow structures and characteristics of two‐ or multiphase systems. The basic models for two‐fluid model simulations of dispersed gas/liquid flows in bubble columns at high gas fractions are presented.  相似文献   
90.
Professional geropsychology is a growing area of practice and training. To meet the mental health needs of an aging population, increasing numbers of psychologists need to develop competence to work with older adults, their families, and related care systems. The Pikes Peak model for geropsychology training (Knight, Karel, Hinrichsen, Qualls, & Duffy, 2009) delineates attitude, knowledge, and skill competencies for professional geropsychology practice and makes recommendations for training. In this paper, we define and illustrate the Pikes Peak geropsychology practice competencies through a case example. In the case, an older man with complex needs seeks care through a generalist psychologist in an outpatient setting. The attitudes, knowledge, and skills that the psychologist needs to consider, and implications for training, are reviewed. Training recommendations and resources are provided, with a focus on the training needs of psychologists who wish to expand their practices to include older adults. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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