•A method to generate default configurations for simulation tools was proposed.•The value is based on the existing building datasets accumulated by BIM.•The datasets reflect the optimization ...experiences gained during previous design projects.•This method facilitates performance evaluations using simulations during early design phases.•Use of the method helps prevent design backsliding in subsequent design phases.
The purpose of this study is to develop a new system that automatically generates default configurations for simulations during early phases of building design. The system is expected to facilitate front loading, which can contribute to making the building design process more efficient and consistent. The default configuration is generated based on an existing building database created by an architectural firm for each architectural program. The increase in the use of building information modeling (BIM) will allow for the compilation of a sufficient amount of data to utilize this system. The optimal default configuration changes its features automatically to match the objective functions employed by each architectural firm. Moreover, it can be used to create a generic building type, such as green buildings, based on a green building database. In this paper, a basic concept that can be used to produce a default configuration from existing building datasets was proposed. Using a case study, the similarity between the default configuration design and optimal design is illustrated. The study demonstrates the potential ability of this method to prevent designers from making careless mistakes with initial condition inputs and to eliminate the need to rework the simulation process, which facilitates front loading.
Obesity and type 2 diabetes are risk factors of Alzheimer's disease (AD). We reported that a high fat diet (HFD) promotes amyloid precursor protein (APP) cleavage by β-site APP cleaving enzyme 1 ...(BACE1) without increasing BACE1 levels in APP transgenic mice. However, the detailed mechanism had remained unclear. Here we demonstrate that HFD promotes BACE1/Adaptor protein-2 (AP-2)/clathrin complex formation by increasing AP-2 levels in APP transgenic mice. In Swedish APP overexpressing Chinese hamster ovary (CHO) cells as well as in SH-SY5Y cells, overexpression of AP-2 promoted the formation of BACE1/AP-2/clathrin complex, increasing the level of the soluble form of APP β (sAPPβ). On the other hand, mutant D495R BACE1, which inhibits formation of this trimeric complex, was shown to decrease the level of sAPPβ. Overexpression of AP-2 promoted the internalization of BACE1 from the cell surface, thus reducing the cell surface BACE1 level. As such, we concluded that HFD may induce the formation of the BACE1/AP-2/clathrin complex, which is followed by its transport of BACE1 from the cell surface to the intracellular compartments. These events might be associated with the enhancement of β-site cleavage of APP in APP transgenic mice. Here we present evidence that HFD, by regulation of subcellular trafficking of BACE1, promotes APP cleavage.
High fat diet (HFD) is prevalent in many modern societies and HFD-induced metabolic condition is a growing concern worldwide. It has been previously reported that HFD clearly worsens cognitive ...function in amyloid precursor protein (APP) transgenic mice. On the other hand, we have demonstrated that voluntary exercise in an enriched environment is an effective intervention to rescue HFD-induced β-amyloid (Aβ) deposition and memory deficit. However, it had been unclear whether consumption of HFD after exercising abolished the beneficial effect of exercise on the inhibition of Alzheimer's disease (AD) pathology. To examine this question, we exposed wild type (WT) and APP mice fed with HFD to exercise conditions at different time periods. In our previous experiment, we gave HFD to mice for 20 weeks and subjected them to exercise during weeks 10-20. In the present study, mice were subjected to exercise conditions during weeks 0-10 or weeks 5-15 while being on HFD. Interestingly, we found that the effect of exercise during weeks 0-10 or weeks 5-15 on memory function was not abolished in WT mice even if they kept having HFD after finishing exercise. However, in APP transgenic mice, HFD clearly disrupted the effect of exercise during weeks 0-10 or weeks 5-15 on memory function. Importantly, we observed that the level of Aβ oligomer was significantly elevated in the APP mice that exercised during weeks 0-10: this might have been caused by the up-regulation of Aβ production. These results provide solid evidence that continuation of exercise is necessary to rescue HFD-induced aggravation of cognitive decline in the pathological setting of AD.
Abstract Evidence-based medicine (EBM) has come to be regarded as essential in all fields of medical sciences and practical medicine. In the field of diabetes and exercise, among the epidemiological ...studies of physical exercise, recent mega-trials such as the Diabetes Prevention Program (DPP) in the U.S. have shown that lifestyle intervention programs involving diet and/or exercise reduce the progression of impaired glucose tolerance (IGT) to type 2 diabetes. In studies examining the endocrinological and metabolic effects of exercise, it has been demonstrated that physical exercise promotes the utilization of blood glucose and free fatty acids in muscles and lowers blood glucose levels in well-controlled diabetic patients. Long-term, mild, regular jogging increases the action of insulin in both carbohydrate and lipid metabolism without influencing body mass index or maximal oxygen uptake. A significant correlation has been observed between delta MCR (Δinsulin sensitivity) and the average number of steps performed in a day. Our recent data suggested that the improved effectiveness of insulin that occurs as a result of physical exercise is attributable, at least in part, to increases in GLUT4 protein, IRS1 and PI3-kinase protein in skeletal muscle. As a prescription for exercise, aerobic exercise of mild to moderate intensity, including walking and jogging, 10–30 min a day, 3–5 days a week, is recommended. Resistance training of mild intensity with the use of light dumbbells and stretch cords should be combined in elderly individuals who have decreased muscle strength. An active lifestyle is essential in the management of diabetes, which is one of typical lifestyle-related diseases.
J. Neurochem. (2012) 121, 964–973.
We have recently reported that Presenilin 1 (PS1), a causative gene of familial Alzheimer disease (AD), down‐regulates the expression level of insulin receptor (IR) ...as well as its signaling through a γ‐secretase‐independent pathway. PS1 is phosphorylated by glycogen synthase kinase 3 β at the serine 353 and 357 residues. The main purpose of the present study was to clarify the effect of PS1 phosphorylation on IR/insulin signaling. Here, we demonstrate that the pseudo‐phosphorylation mutant of PS1 inhibited IR transcription and reduced IR expression compared with wild‐type PS1. Importantly, there was a decrease in expression of IR in AD brains, and the phosphorylation ratio of PS1 was negatively correlated with IR level in human brain samples. In the data from mouse models of AD, IR reduction was not observed at the pre‐Aβ deposition stage but became apparent in that of post‐Aβ deposition. Together with our previous reports, these results suggest that phosphorylated PS1 can promote the down‐regulation of insulin signaling, which may be a positive feed‐forward mechanism inhibiting insulin signaling. As insulin resistance is reported to be a risk factor for sporadic AD, this PS1‐mediated regulatory mechanism of brain insulin signaling may be causally associated with AD pathology.
The function of phosphorylated Presenilin 1 has not been elucidated. We demonstrate that phosphorylated Presenilin 1 at the serine 353 and 357 residues down‐regulated the expression of insulin receptor compared with wild‐type Presenilin 1, thus suggesting that phosphorylated PS1 may play the crucial role in a positive feed‐forward cycle inhibiting insulin signaling. From our findings, insulin signaling dysfunction may be associated with the pathogenesis of Alzheimer disease.
The present study was undertaken to analyze the acute and chronic effects of exercise on insulin sensitivity in elder diabetic patients using a horseback riding therapeutic equipment (Joba
®). The ...acute effects of exercise were examined by means of a single session of Joba
® riding that lasted for 30
min. The average glucose infusion rates (GIR) before and during exercise were regarded as an index of the insulin action in peripheral tissues by the euglycemic clamp. The chronic effects of exercise were studied by training the elder diabetic patients for 12 weeks using the Joba
® apparatus. The insulin sensitivity was determined pre- and post-training by a 90
min euglycemic clamp. In the acute study, average GIR during exercise was significantly higher than pre-exercise (7.8
±
0.4 versus 5.2
±
0.3
mg
kg
−1
min
−1,
P
<
0.01) and average GIR during recovery decreased to almost the same levels of pre-exercise (5.0
±
0.4
mg
kg
−1
min
−1;
P
<
0.01). The 12-week training resulted in a significant increase in the steady-state GIR (from 5.2
±
0.3 to 7.4
±
0.8
mg
kg
−1
min
−1;
P
<
0.05). The steady-state GIR after 12 weeks of detraining returned to pre-training levels (5.3
±
0.5
mg
kg
−1
min
−1;
P
<
0.05). In elder diabetic patients, mechanical horseback riding enhances the insulin-induced glucose uptake.
Aims
We conducted an intervention study to clarify how effectively a telemedicine system using a multi-functional videophone could be used in lifestyle guidance, with special focus on diet for ...diabetic patients cared for at home.
Methods
Patients were assigned to a 3-month intervention group or to a usual care group. In the intervention group, patients and a medical professional communicated bi-directionally through a videophone-based communication system for 30 min, once a week. The participants were encouraged to send pictures of each meal online, through the videophone system, in real time.
Results
In intra-subjective comparison, the 3-month intervention program resulted in a significant decrease in body weight (BW) (
p
< 0.0005) and average HbA1C level (
p
< 0.005) compared with before the intervention program. Three months after the conclusion of the intervention program, average HbA1C levels returned to almost the same levels as before intervention (
p
< 0.05). In the usual care group, average HbA1C level did not change significantly for 6 months.
Conclusions
3-month intensive communication using the multimodal videophone system led to a significant decrease in BW and average HbA1C level. This novel bi-directional communication is useful for improving conditions such as diabetes, BW, and hyperglycemia for homecare diabetes patients, thus, reducing cardiovascular risk.
Accumulating evidence suggests that some dietary patterns, specifically high fat diet (HFD), increase the risk of developing sporadic Alzheimer disease (AD). Thus, interventions targeting HFD-induced ...metabolic dysfunctions may be effective in preventing the development of AD. We previously demonstrated that amyloid precursor protein (APP)-overexpressing transgenic mice fed HFD showed worsening of cognitive function when compared with control APP mice on normal diet. Moreover, we reported that voluntary exercise ameliorates HFD-induced memory impairment and β-amyloid (Aβ) deposition. In the present study, we conducted diet control to ameliorate the metabolic abnormality caused by HFD on APP transgenic mice and compared the effect of diet control on cognitive function with that of voluntary exercise as well as that of combined (diet control plus exercise) treatment. Surprisingly, we found that exercise was more effective than diet control, although both exercise and diet control ameliorated HFD-induced memory deficit and Aβ deposition. The production of Aβ was not different between the exercise- and the diet control-treated mice. On the other hand, exercise specifically strengthened the activity of neprilysin, the Aβ-degrading enzyme, the level of which was significantly correlated with that of deposited Aβ in our mice. Notably, the effect of the combination treatment (exercise and diet control) on memory and amyloid pathology was not significantly different from that of exercise alone. These studies provide solid evidence that exercise is a useful intervention to rescue HFD-induced aggravation of cognitive decline in transgenic model mice of AD.
Background: Exercise and diet control are fundamental approaches to metabolic conditions caused by high fat diet (HFD).
Results: HFD-induced memory deficit and Aβ deposition were more ameliorated in the exercise- than in the diet control-induced mice.
Conclusion: Exercise was more effective than diet control in preventing HFD-induced AD development.
Significance: Exercise has the highest priority in the prevention of AD.
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