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41.
The very low density lipoprotein receptor (VLDL-r) is a cell-surface molecule specialized for the internalization of multiple diverse ligands, including apolipoprotein E (apoE)-containing lipoprotein particles, via clathrin-coated pits. Its structure is similar to the low-density lipoprotein receptor (LDL-r), although the two have substantially different systemic distributions and regulatory pathways. The present work examines the distribution of VLDL-r in the central nervous system (CNS) and in relation to senile plaques in Alzheimer disease (AD). VLDL-r is present on resting and activated microglia, particularly those associated with senile plaques (SPs). VLDL-r immunoreactivity is also found in cortical neurons. Two exons of VLDL-r mRNA are differentially spliced in the mature receptor mRNA. One set of splice forms gives rise to receptors containing (or lacking) an extracellular O-linked glycosylation domain near the transmembrane portion of the molecule. The other set of splice forms appears to be brain-specific, and is responsible for the presence or absence of one of the cysteine-rich repeat regions in the binding region of the molecule. Ratios of the receptor variants generated from these splice forms do not differ substantially across different cortical areas or in AD. We hypothesize that VLDL-r might contribute to metabolism of apoE and apoE/A beta complexes in the brain. Further characterizations of apoE receptors in Alzheimer brain may help lay the groundwork for understanding the role of apoE in the CNS and in the pathophysiology of AD.  相似文献   
42.
The Landau-Lifshitz (LL)equation of micromagnetism governs rich variety of the evolution of magnetization patterns in ferromagnetic media. This is due to the complexity of physical quantities appearing in the LL equation. This complexity causes also an interesting mathematical properties of the LL equation: nonlocal character for some quantities,nonconvex side-constraints, strongly nonlinear terms. These effects influence also the numerical approximations. In this work, recent developments on the approximation of weak solutions, together with the overview of well-known methods for strong solutions,are addressed. Author is supported by the Fund for Scientific Research - Flanders FWO (Belgium).  相似文献   
43.
The purpose of this study was to analyse the validity and the economic efficiency of a portable monitor of respiratory parameters (PMRP), used in a home setting for the diagnosis of sleep apnoea/hypopnoea syndrome (SAHS). Eighty nine patients with suspected SAHS were studied in two settings: in the sleep laboratory using full-polysomnography (full-PSG); and at the patient's home using a PMRP. In the home setting, 50 patients were assisted by a technician and 39 set up the equipment themselves. SAHS (apnoea/hypopnoea index (AHI) >10 events x h(-1) by means of full-PSG) was diagnosed in 75 of the 89 patients. An acceptable agreement was obtained between the AHI measured by full-PSG and PMRP, according to the Bland and Altman method of concordance (mean bias 2.56; 95% confidence interval 3.25). Sensitivity and specificity of PMRP were adequate for diagnostic purposes; however, their values rely on the prior PMRP-AHI cut-off point selected with reference to full-PSG-AHI >10. The clinical therapeutic decision taken after PMRP agreed with that taken with full-PSG in 79 patients (89%). Although 10% of the studies with an individual set-up needed repetition, both of the domiciliary modalities (with and without a technician's intervention) were, economically, about three times more efficient than full-PSG. In conclusion, we believe that patients with a suspected sleep apnoea/hypopnoea syndrome should initially be studied in a home setting with a portable monitor of respiratory parameters, since it is a reliable method with an acceptable cost-effective profile.  相似文献   
44.
1. We used electrophysiological and binding techniques to determine the effects of oxygen free radicals (OFRs) generated by dihydroxyfumaric acid (DHF, 5 mM) on calcium current and dihydropyridine binding sites in guinea-pig isolated ventricular myocytes. 2. Binding of [3H]-PN200-110 to isolated ventricular myocytes revealed one population of binding sites with a KD of 0.11 +/- 0.01 nM and Bmax of 139.1 +/- 6.9 fmol mg-1 protein (n = 24). After 15 min of exposure to DHF, the density, but not the affinity of [3H]-PN200-110 binding sites was significantly (P < 0.01) reduced to 35% of the control value (Bmax = 49.4 +/- 3.7 fmol mg-1 protein, KD = 0.11 +/- 0.01 nM, n = 15). In the presence of superoxide dismutase (SOD) and catalase (CAT) the reduction in [3H]-PN200-110 binding sites was almost completely prevented (Bmax = 120.5 +/- 7.4 in control, n = 4 and 98.8 +/- 7.4 fmol mg-1 protein in DHF plus SOD and CAT, n = 4). KD values were not modified (0.08 +/- 0.01 in control and 0.09 +/- 0.01 nM in DHF plus SOD and CAT). 3. The time-course of the reduction of [3H]-PN200-110 binding sites by OFRs was paralleled by the decrease in L-type calcium current (Ica,L) measured in patch-clamped guinea-pig ventricular myocytes either in the absence or in the presence of EGTA in the patch pipette. In the former conditions OFRs induced the appearance of calcium-dependent alterations, i.e. the transient inward current, within 10 min. After 30 min of incubation with DHF, [3H]-PN200-110 binding sites were reduced to 25% of the control value. 4. In myocytes incubated with the antilipoperoxidant agent, butylated hydroxytoluene (BHT, 50 microM), the decrease in [3H]-PN200-110 binding sites caused by DHF was partially prevented (Bmax values after 30 min exposure to DHF were 55.5 +/- 1.9 and 23.7 +/- 5.9 fmol mg-1 protein in the presence and in the absence of BHT respectively, P < 0.05). BHT did not affect the decrease in [3H]-PN200-110 binding sites during the first 15 min of exposure to DHF, but was able to prevent completely the further decrease occurring during the following 15 min of incubation with OFRs. 5. Our results demonstrate that the OFR-induced decrease in calcium current is associated with a reduction in DHP binding sites. The decrease in calcium current and in calcium channels may be implicated in the mechanical dysfunction associated with oxidative stress.  相似文献   
45.
46.
Nutrient export from agricultural land to surface waters is a significant environmental concern within the Great Lakes Basin (GLB). A field-based watershed-scale study was completed to investigate spatial and temporal variations of phosphorus and nitrate to assess nutrient transport pathways and groundwater-surface water interactions in an agriculturally dominated clay plain system. This was conducted in the 127 km2 Upper Parkhill Watershed, near Lake Huron in southwestern Ontario, Canada. Data collection occurred from June 2018 to May 2019 via continuous sensor deployment and discrete sampling of stream water, groundwater, hyporheic zone, and tile drainage water. Samples were analyzed for various nutrient species (total, total dissolved, soluble reactive, and particulate phosphorus, and nitrate-N) to examine the hydrological dynamics of principal transport pathways of agriculturally-derived nutrients. Total phosphorus and nitrate concentrations in stream water ranged from 0.007 to 0.324 mg/L and 0.32 to 13.13 mg NO3?-N/L, respectively. Tile drainage water total phosphorous concentrations varied from 0.006 to 0.066 mg/L. Groundwater total dissolved phosphorus concentrations ranged from <0.003 to 0.085 mg/L. Transport of phosphorus through tile drainage was observed to be greater than through groundwater over the study period. No distinct relationship was observed between nutrient concentrations in the hyporheic zone and the vertical hydraulic gradient within this zone in the studied stream reach. Preliminary correlations were discerned between water quality observations and recognized land management practices. Given the elevated stream nutrient concentrations, these results are consequential for the continual improvement of strategies and programs devised to conserve water resources within the GLB.  相似文献   
47.
While face‐to‐face interaction is fundamental in agile software development, distributed environments must rely extensively on mediated interactions. Practicing agile principles in distributed environments therefore poses particular control challenges related to balancing fixed vs. evolving quality requirements and people vs. process‐based collaboration. To investigate these challenges, we conducted an in‐depth case study of a successful agile distributed software project with participants from a Russian firm and a Danish firm. Applying Kirsch's elements of control framework, we offer an analysis of how control was enacted through the project context and in the participants' mediated communication. The analysis reveals that formal measurement and evaluation control were persistently enacted through mediated communication. These formal control practices were, however, predominantly carried out in conjunction with informal roles and relationships such as clan‐like control inherent in agile development. Overall, the study demonstrates that, if appropriately applied, communication technologies can significantly support distributed, agile practices by allowing concurrent enactment of both formal and informal controls. The paper discusses these findings as they relate to previous research and concludes with their implications for future research.  相似文献   
48.
We introduce the concept of very true operator on an effect algebra. Although an effect algebra is only partial, we define it in the way which is in accordance with traditional definitions in residuated lattices or basic algebras. This is possible if we require monotonicity as an additional condition. We prove that very true operators on effect algebras can be characterized by means of certain subsets which are conditionally complete.  相似文献   
49.
Virtualized datacenters and clouds are being increasingly considered for traditional High-Performance Computing (HPC) workloads that have typically targeted Grids and conventional HPC platforms. However, maximizing energy efficiency and utilization of datacenter resources, and minimizing undesired thermal behavior while ensuring application performance and other Quality of Service (QoS) guarantees for HPC applications requires careful consideration of important and extremely challenging tradeoffs. Virtual Machine (VM) migration is one of the most common techniques used to alleviate thermal anomalies (i.e., hotspots) in cloud datacenter servers as it reduces load and, hence, the server utilization. In this article, the benefits of using other techniques such as voltage scaling and pinning (traditionally used for reducing energy consumption) for thermal management over VM migrations are studied in detail. As no single technique is the most efficient to meet temperature/performance optimization goals in all situations, an autonomic approach that performs energy-efficient thermal management while ensuring the QoS delivered to the users is proposed. To address the problem of VM allocation that arises during VM migrations, an innovative application-centric energy-aware strategy for Virtual Machine (VM) allocation is proposed. The proposed strategy ensures high resource utilization and energy efficiency through VM consolidation while satisfying application QoS by exploiting knowledge obtained through application profiling along multiple dimensions (CPU, memory, and network bandwidth utilization). To support our arguments, we present the results obtained from an experimental evaluation on real hardware using HPC workloads under different scenarios.  相似文献   
50.
This paper proposes a method for designing robust H?? static output feedback stabilization of Takagi-Sugeno (T-S) fuzzy systems under actuator saturation. In this paper, the input saturation is represented by a polytopic model and the modeling error is assumed a norm-bounded uncertainty. A set invariance condition for robust H?? static output feedback system under actuator saturation is first established. Then, the estimation of the largest domain of attraction for the system is formulated and solved as a Linear Matrix Inequality (LMI) optimization problem. Two examples are used to demonstrate the effectiveness of the proposed design method.  相似文献   
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