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231.
Learning organisation literature has widely discussed the connections between “double-loop” learning and its significance to organisational performance, but paying little attention to tools and systems that can operationalise “double-loop” learning in organisations. This paper investigates the impact of applying a systems approach for service operations design, expressed as the Vanguard Method (Seddon, Freedom from command and control: a better way to make the work work, 2003), in order to activate “double-loop” learning in service organisations. Two case studies were conducted in the banking mortgage operations and adults’ social care services in the UK, using the dimensions of the learning organisation questionnaire (DLOQ), semi-structured interviews, observations, and documents. The findings of the cross-case analysis support the link of applying the Vanguard Method with operationalising “double-loop” learning through three main factors, namely systematic-operations improvement, organisational capacity development, and outside-in mode of work; that are all embedded into the seven dimensions of the DLOQ. The value of this paper is the introduction of a service operations design tool that can activate “double-loop” learning performance in the fast changing knowledge era. It also provides an impetus for service organisations to creatively influence employees’ competencies to effectively improve internal systems.  相似文献   
232.
美国东北部早熟和晚熟玉米杂交种年际间产量稳定性   总被引:2,自引:0,他引:2  
玉米是美国东北部奶牛业的主要能量来源,杂交种的选择是提高玉米产量、降低生产成本的关键和前提。连续5年在美国麻省大学农学实验站的典型砂壤土耕地上进行试验,结合当地气象部门提供的生育期间玉米的生长期生长度日数和降雨量,对3个早熟杂交种和3个晚熟杂交种的产量进行了年际间稳定性比较。结果表明:产量与年际间气候条件无关,无论是青贮饲料产量还是穗棒产量,晚熟品种的产量均高于早熟品种(2001年杂交种E409L)。5年平均晚熟品种的青贮饲料产量和穗棒产量分别比早熟品种高出10.9%和8.0%。相同年份品种间产量存在差异,同一品种年际间产量差异显著。低温年份,相对冷凉的生育前期和温热的生育后期不利于美国东北部玉米生产。生育期间较高的降雨量有利于青贮产量的形成。选择种植晚熟品种是该区农民提高玉米产量、降低生产成本的有效途径。只有热量多且雨量充沛的年份才有利于玉米产量潜力的挖掘。有关某种玉米基因型对当地气候适应性方面的知识,将有利于育种者选择有价值的种质资源。表6,参17。  相似文献   
233.
234.
An improved hybrid position/force controller design of a flexible robot manipulator is presented using a sliding observer. The friction between the end effector and the environment is considered and compensated. For systematic reasons the controller is designed taking into consideration the rigid link subsystems and the flexible joints. The proposed control system satisfies the stability of the two subsystems and copes with the uncertainty of robot dynamics. A sliding observer is designed to estimate the time derivative of the torque applied as input to the rigid part of the robot. For the stability of the observer, it is assumed that the uncertainty of the observed system is bounded. A MRAC algorithm is used for the estimation of the friction forces at the contact point between the end effector and the environment. Finally simulation and experimental results are given, to demonstrate the effectiveness of the proposed controller.  相似文献   
235.
Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.Received 30 November 2004; received after revision 24 January 2005; accepted 5 February 2005  相似文献   
236.
Hsp70 chaperones: Cellular functions and molecular mechanism   总被引:36,自引:0,他引:36  
Hsp70 proteins are central components of the cellular network of molecular chaperones and folding catalysts. They assist a large variety of protein folding processes in the cell by transient association of their substrate binding domain with short hydrophobic peptide segments within their substrate proteins. The substrate binding and release cycle is driven by the switching of Hsp70 between the low-affinity ATP bound state and the high-affinity ADP bound state. Thus, ATP binding and hydrolysis are essential in vitro and in vivo for the chaperone activity of Hsp70 proteins. This ATPase cycle is controlled by co-chaperones of the family of J-domain proteins, which target Hsp70s to their substrates, and by nucleotide exchange factors, which determine the lifetime of the Hsp70-substrate complex. Additional co-chaperones fine-tune this chaperone cycle. For specific tasks the Hsp70 cycle is coupled to the action of other chaperones, such as Hsp90 and Hsp100.Received 21 October 2004; received after revision 24 November 2004; accepted 6 December 2004  相似文献   
237.
Recent reports describe successful treatment using copper chelation therapy in neurodegenerative animal models. However, the success claimed for chelation therapy in neurodegenerative diseases is still rather controversial. To acquire new information on copper metabolism/homeostasis, we utilized cuprizone, a very sensitive and selective copper-chelating agent with well-known neurotoxic properties, as a relevant chemical model in mice. Upon cuprizone treatment, mice developed a pronounced astrocytosis, with brain oedema and spongiosis characterised by vacuolisations of the neuropil predominantly in the white matter. In addition, cuprizone treatment severely altered copper and zinc homeostasis in the central nervous system (CNS) as well as in all other tissues examined, with increasing metal ion concentrations particularly in the CNS. Concomitant with this increase in the Cu and Zn concentration in the brain, metallothionein-I and -II were also highly immunoreactive in astrocyte, consistent with the astrocytosis and demyelination observed in our and other laboratories.Received 23 February 2005; received after revision 3 May 2005; accepted 13 May 2005  相似文献   
238.
239.
Leptin receptor action and mechanisms of leptin resistance   总被引:13,自引:0,他引:13  
The adipose tissue-derived hormone leptin regulates energy balance and neuroendocrine function. Resistance to the appetite-suppressing effects of leptin is associated with common forms of obesity. Here, we review the mechanisms by which leptin activates intracellular signals and the roles that these signals play in leptin action in vivo. Furthermore, we discuss potential mechanisms of leptin resistance, specifically focusing on data regarding the neuroanatomical locus of leptin resistance and potential mechanisms by which expression of the suppressor of cytokine signaling-3 may impair leptin action.Received 30 September 2004; received after revision 12 November 2004; accepted 23 November 2004  相似文献   
240.
Epitopes presented by major histocompatibility complex (MHC) class I molecules are selected by a multi-step process. Here we present the first computational prediction of this process based on in vitro experiments characterizing proteasomal cleavage, transport by the transporter associated with antigen processing (TAP) and MHC class I binding. Our novel prediction method for proteasomal cleavages outperforms existing methods when tested on in vitro cleavage data. The analysis of our predictions for a new dataset consisting of 390 endogenously processed MHC class I ligands from cells with known proteasome composition shows that the immunological advantage of switching from constitutive to immunoproteasomes is mainly to suppress the creation of peptides in the cytosol that TAP cannot transport. Furthermore, we show that proteasomes are unlikely to generate MHC class I ligands with a C-terminal lysine residue, suggesting processing of these ligands by a different protease that may be tripeptidyl-peptidase II (TPPII).Received 26 November 2004; received after revision 4 February 2005; accepted 4 March 2005S. Tenzer and B. Peters contributed equally to this work.  相似文献   
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