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The presence of amyloid plaques in the brain is a typical characteristic of Alzheimer's disease (AD). Amyloid plaques are formed from the deposits of aggregated amyloid β peptide (Aβ). The toxicity induced by Aβ aggregates is correlated with Aβ-membrane interactions. The mutual influences between aggregation and membranes are complicated and unclear. In recent years advanced experiments and findings are emerging to give us more detailed information on Aβ-membrane interactions. In this review, we mainly focus on the Aβ-membrane interactions and membrane-induced Aβ structures. The mechanism of Aβ-membrane interactions is also summarized, which provides insights into the prevention and treatment of AD.

Additional file 1: Table S1. Perinatal Outcomes of Women with GDM Who were not taken into subgroup analyses.

A novel auto design method of acoustic filter based on genetic programming (GP) is proposed in this paper. Unlike the model-based auto optimization method by genetic algorithms that optimize acoustic filters only in the parameter domain, the proposed method can optimizes the acoustic filter in both the structure region and the parameter region simultaneously thanks to its tree representation of individuals. In the proposed method, the widely used acoustic components have been equivalent to the basic elements in the topology. The acoustic filter individuals in GP are composed of these elements. Transfer matrix method is employed to calculate the transmission loss of the acoustic filter individuals. By a certain number of generations, the GP finds the individuals with good fitness value. The feasibility of the method is validated by two numerical experiments. The first case study is to validate the searching ability of the method. The result shows that the proposed method has excellent ability to search the optimal solution with transmission loss curve close to the objective transmission loss curve. The second experiment is based on a typical automobile muffler design strategies that requires a high noise reduction magnitude at two specified frequency band and a certain noise reduction magnitude at the whole frequency band, the evolution result meets the design requirements well. The results of these two numerical experiments demonstrate that the proposed method has excellent searching ability and is feasible in the auto design of acoustic filter.

Although metabolomics are desirable to understand the pathophysiology of gestational diabetes mellitus (GDM), comprehensive metabolomic studies of GDM are rare. We aimed to offer a holistic view of metabolites alteration in GDM patients and investigate the possible multimarker models for GDM diagnosis. Biochemical parameters and perinatal data of 131 GDM cases and 138 controls were collected. Fasting serum samples at 75 g oral glucose tolerance test were used for metabolites by ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry, ultra performance liquid chromatography-triple triple-quadrupole-mass spectrometry and gas chromatography- time-of- flight mass spectrometry platforms. Significant changes were observed in free fatty acids, bile acids, branched chain amino acids, organic acids, lipids and organooxygen compounds between two groups. In receiver operating characteristic (ROC) analysis, different combinations of candidate biomarkers and metabolites in multimarker models achieved satisfactory discriminative abilities for GDM, with the values of area under the curve (AUC) ranging from 0.721 to 0.751. Model consisting of body mass index (BMI), retinol binding protein 4 (RBP4), n-acetylaspartic acid and C16:1 (cis-7) manifested the best discrimination [AUC 0.751 (95% CI: 0.693-0.809), p < 0.001], followed by model consisting of BMI, Cystatin C, acetylaspartic acid and 6,7-diketoLCA [AUC 0.749 (95% CI: 0.691-0.808), p < 0.001]. Metabolites alteration reflected disorders of glucose metabolism, lipid metabolism, amino acid metabolism, bile acid metabolism as well as intestinal flora metabolism in GDM state. Multivariate models combining clinical markers and metabolites have the potential to differentiate GDM subjects from healthy controls.

The preproghrelin (GHRL) Leu72Met polymorphism (rs 696217) is associated with obesity, reduced glucose-induced insulin secretion in healthy or diabetic subjects, and reduced serum creatinine (Scr) levels in type 2 diabetes. We evaluated the association of the Leu72Met polymorphism with measures of insulin sensitivity in non-diabetic control individuals and type 2 diabetics, and whether this variation contributes to the development of diabetic nephropathy (DN) in type 2 diabetes. A case–control study was performed of 291 non-diabetic control subjects and 466 patients with type 2 diabetes, of whom 238 had DN with overt albuminuria (DN group; albuminuric excretion rate [AER] ≥ 300 mg/24 h) and 228 did not have DN, but had diabetes for more than 10 years (non-DN group). Genotyping was performed using a TaqMan PCR assay. The Leu/Leu, Leu/Met, and Met/Met genotype frequencies were significantly different between the non-DN and DN groups (p = 0.011). The frequency of the variant genotypes (Leu/Met, Met/Met) was significantly lower in the DN group than the non-DN group (23.5 vs. 36.0 %, p = 0.003). Met/Met non-diabetic control subjects had lower BMI and Scr levels and higher eGFR level than Leu/Leu or Leu/Met individuals (p < 0.05). Leu/Met and Met/Met type 2 diabetics had significantly lower AER and Scr levels and higher eGFR level than Leu/Leu type 2 diabetics (all p < 0.001). The GHRL Leu72Met polymorphism may help to maintain normal renal function and may protect against the development of DN by reducing albuminuria and improving renal function in Chinese patients with type 2 diabetes.

The aim of the current study is to assess whether total bile acid (TBA) level in first trimester pregnancy is associated with gestational diabetes mellitus (GDM). Biochemical parameters including serum TBA of 742 pregnant women were collected within 12 weeks of gestation and compared. At 24–28th weeks of gestation, 75 g oral glucose tolerance test (OGTT) was performed. The perinatal data of 330 women were collected. The results demonstrated women with GDM (n = 268) had higher first-trimester serum levels of TBA compared with healthy subjects (n = 474) (2.3 ± 1.4 μmol/L vs. 1.9 ± 1.0 μmol/L, P P P

The aim of this study was to explore the relationship between serum magnesium and peripheral nerve function in patients with type 2 diabetes (T2DM). A total of 978 T2DM patients were included in the study. Patients were divided into tertiles according to serum magnesium concentration (low tertile: ≤0.85 mmol/L; medium tertile: 0.85 to 0.92 mmol/L; and high tertile: >0.92 mmol/L). All participants underwent nerve conduction (NC) studies. Composite z scores of conduction velocity, latency, and amplitude were constructed, respectively. The serum magnesium levels were significantly lower in patients with abnormal NC than in those with normal NC (0.87 [0.82, 0.92] vs. 0.88 [0.83, 0.93] mmol/L, P = 0.048). The composite z score of amplitude significantly increased with increasing tertiles of magnesium (−0.60 ± 0.02 vs. −0.57 ± 0.02 vs. −0.48 ± 0.03, P for trend = 0.001). After adjusting for all potential confounders, lower serum magnesium levels were still associated with lower composite z score of amplitude (β = 0.095, P = 0.014). In patients with T2DM, lower serum magnesium levels were significantly associated with lower composite z score of amplitude, indicating magnesium might affect peripheral nerve function through axonal degeneration.

Whether the DD genotype of the angiotensin-I converting enzyme (ACE) I/D variation contributes to end-stage renal disease (ESRD) risk in type 2 diabetes mellitus (T2DM) remains controversial. Differences in study design, case and control definition, sample size and ethnicity may contribute to the discrepancies reported in association studies. We performed a case–control study to evaluate the association of the ACE I/D variation with ESRD risk in Chinese patients with T2DM receiving hemodialysis and analyzed the genotype–phenotype interaction. Unrelated Chinese patients (n = 432) were classified into the non-diabetic nephropathy (DN) control group (n = 222, duration of diabetes >10 years, no signs of renal involvement) and the DN-ESRD group (n = 210; ESRD due to T2DM, receiving hemodialysis). Polymerase chain reaction was used to genotype ACE I/D for all 432 subjects. The frequencies of the ID + DD genotypes were higher in the DN-ESRD group than non-DN control group (65.2 vs. 50.9 %; adjusted OR 1.98 (95 % CI, 1.31–3.00; P = 0.001). In the DN-ESRD group, the DD genotypic subgroup had significantly elevated HbA1c and diastolic blood pressure (DBP) compared to the II subgroup (both P

This paper studies the content-based music retrieval and the methods for main modules. It improves the defect of DTW algorithm, which needs longer running time for melody matching, and proposes a DTW melody matching algorithm based on numerical index. It first establishes numerical index according to pitch difference information in the melody feature library. Then it performs rough matching based on the index to find possibly similar fragments with the humming melody, to be matched with DTW algorithm in detail. The experiments verify that the improved algorithm not only reduces the running time of DTW algorithm but also improves the speed of melody matching.

Elongator is a multiprotein complex composed of two subcomplexes, Elp1-3 and Elp4-6. Elongator is highly conserved between yeast and humans and plays an important role in RNA polymerase II-mediated transcriptional elongation and many other processes, including cytoskeleton organization, exocytosis, and tRNA modification. Here, we determined the crystal structure of the Elp4-6 subcomplex of yeast. The overall structure of Elp4-6 revealed that Elp6 acts as a bridge to assemble Elp4 and Elp5. Detailed structural and sequence analyses revealed that each subunit in the Elp4-6 subcomplex forms a RecA-ATPase-like fold, although it lacks the key sequence signature of ATPases. Site-directed mutagenesis and biochemical analyses indicated that the Elp4-6 subcomplex can assemble into a hexameric ring-shaped structure in vitro and in vivo. Furthermore, GST pulldown assays showed that the ring-shaped assembly of the Elp4-6 subcomplex is important for its specific histone H3 binding. Our results may shed light on the substrate recognition and assembly of the holo-Elongator complex.

Due to the indistinct nature of symptoms for Cerebral Small Vessel Disease (CSVD), diagnosis is often missed. With significant deterioration of movement disorder, risk of falls increases dramatically. Comparison study was conducted to explore the association between balance function and gait instability, and the treatment effectiveness of visual feedback balance training on the gait disorder in CSVD patients. Fifty-six patients with CSVD were studied. They were randomly divided into observation and control groups, and were given conventional gait rehabilitation training, including single-leg weight, shift of the center of gravity, step and hip extension training, stepping up and down on stairs with the affected leg, standing up with hip extension and support of the leg, lateral walking, and in situ walking. Training was performed twice a day for 20 minutes each for 4 consecutive weeks. In addition, the observation group received balance training using Pro-Kin visual feedback balance training system. Both groups were evaluated prior and post-treatment using the Tinetti Scale and the Pro-Kin Visual Feedback Balance Training System. For the Tinetti Scale, lower score indicates more serious gait balance dysfunction. For the Pro-Kin, greater length means poorer balance function. Larger area means poorer balance function. Smaller value of the 2 parameters indicates better balance function. After training, the trajectory lengths and areas of orbital motions were significantly decreased (P

The establishment of epithelial cell polarity requires the assembly of multiprotein complexes and is crucial during epithelial morphogenesis. Three scaffolding proteins, Dlg1, MPP7, and Mals3, can be assembled to form a complex that functions in the establishment and maintenance of apicobasal polarity in epithelial tissues through their L27 domains. Here we report the crystal structure of a 4-L27-domain complex derived from the human tripartite complex Dlg1-MPP7-Mals3 in combination with paramagnetic relaxation enhancement measurements. The heterotrimer consists of 2 pairs of heterodimeric L27 domains. These 2 dimers are asymmetric due to the large difference between the N- and C-terminal tandem L27 domain of MPP7. Structural analysis combined with biochemical experiments further reveals that the loop αA-αB and helix αB of the C-terminal L27 domain of MPP7 play a critical role in assembling the entire tripartite complex, suggesting a synergistic tandem L27-mediated assembling event.—Yang, X., Xie, X., Che...

The aim of the present study was to evaluate the relationship of the manganese superoxide dismutase (MnSOD) Val16Ala (V16A) polymorphism with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) in Chinese patients, a case-control study was performed. This case-control study included 172 non-diabetic (non-DM) subjects and 257 T2DM patients with or without DN. Among T2DM patients, 154 had DN [albumin excretion rate (AER)or= 30 mg/24 h] and 103 did not (AER30 mg/24 h), but the latter with known diabetes durationor=10 years. The DN patients were further divided into groups with microalbuminuria (DN-1; n = 92; 300AERor= 30 mg/24 h) and overt albuminuria nephropathy (DN-2; n = 62; AERor= 300 mg/24 h). PCR-restriction fragment length polymorphism (RFLP) was used to detect genotypes of the V16A polymorphism for all subjects. The genotypic distributions of the V16A polymorphism in non-DM and T2DM subjects were in Hardy-Weinberg equilibrium and Ala allelic frequencies did not differ (11.9% vs. 9.1%; P0.05). The AA+VA genotypic frequencies of DN patients were significantly lower than those of non-DN patients (11.6% vs. 24.3%; P = 0.008). Multiple logistic regression analysis revealed that except for HbA1C, triglyceride, and BMI, which were high risk factors for the development of DN, the AA+VA genotype of the MnSOD-V16A polymorphism was an independent protective factor from the development of DN (odds ratio = 0.42; 95% CI = 0.18-0.95; P = 0.037) in T2DM patients. Our results suggested that the MnSOD-V16A polymorphism is associated with decreased risk of diabetic nephropathy in Chinese patients with type 2 diabetes.

The MAS solid-state NMR has been a powerful technique for studying membrane proteins within the native-like lipid bilayer environment. In general, RF irradiation in MAS NMR experiments can heat and potentially destroy expensive membrane protein samples. However, under practical MAS NMR experimental conditions, detailed characterization of RF heating effect of lipid bilayer samples is still lacking. Herein, using

Noise from cooling fans is main noise source of the electronic instrument. It consists of rotation noise superimposed by the discrete tones which is related to blade rotation. The aim of present research is to realize the feasibility of using a single loudspeaker to cancel rotation-locked tones with a duct. A photoelectric rotating speed sensor, a loudspeaker which would be located under the PVC pipe and a digital signal processor are employed. An adaptive feedforward system is implemented experimentally to drive the secondary source. The waveform synthesis method is used to adaptively abate noise with traditional least mean square (LMS) algorithm based on steepest descent principle. And simulations have been conducted to verify the convergence and stability of the novel system. Noise characteristics of the cooling fan with/without our active noise controller are compared experimentally. It was found in the experiments that reduction of sound power level is 20dB at the fan's blade passing frequency (BPF) .

The association between thyroid stimulating hormone (TSH) and type 2 diabetes mellitus (T2DM) is well known. However, whether TSH is related to diabetic peripheral neuropathy (DPN) has not been studied. The aim of this study was to explore the relationship between TSH and DPN in Chinese patients with T2DM.In this cross-sectional study, 605 patients with T2DM were enrolled. Subclinical hypothyroidism (SCH) was defined as an elevated TSH level (4.0mIU/L) and a normal free thyroxine level. DPN was evaluated by neurological symptoms, neurological signs, and electromyogram.Serum TSH levels were significantly higher in DPN and signs of DPN compared with non-DPN T2DM patients (both P0.01).The prevalence of DPN and signs of DPN in SCH subjects was higher than that in euthyroid subjects (both P0.01). Spearman's correlation analysis showed that the serum TSH level was positively associated with DPN (r=0.172, P0.01). A significant independent association between TSH and DPN was found by multiple logistic regression analysis after adjusting for potential confounding variables [odds ratio (OR)=1.365, P0.01]. The patients were sequentially assigned to quartiles according to TSH level. Compared with quartile 1, patients in quartile 2 (P0.01), quartile 3 (P=0.01), and quartile 4 (P0.01) had a higher risk of DPN. Receiver-operating characteristic curve analysis revealed that the optimal cutoff point of TSH to indicate DPN was 3.045mIU/L in men and 2.94mIU/L in women.TSH level is independently associated with DPN in Chinese population with T2DM. A high serum TSH level may be a potential risk factor for DPN.

Patients with white matter lesions (WMLs) often present with problems of balance. The aim of this study was to verify the effects of combined Pro-kin system and conventional balance training to improve balance ability in WMLs patients. This is a randomized controlled study, and 40 participants were divided into 2 groups: the intervention group (n=18) received Pro-kin system with additional conventional balance training for 20 minutes per session, 5 times a week, for 2 weeks. The control group (n = 19) received only conventional balance training. Outcome measures were examined before and after the 2 weeks intervention using the Berg Balance Scale (BBS), Timed Up and Go (TUG) test, and Pro-kin system. After completion of the 2 weeks intervention, BBS, TUG, and Pro-kin system results significantly improved in the intervention group (P

The exponential stability of a class of nonlinear systems by means of alternate control is studied. An exponential stability criterion is given in terms of a set of linear matrix inequalities. Numerical simulations are presented to verify the correction of the obtained results.

Background The clinical features of atherosclerotic lesions in ketosis-onset diabetes are largely absent. We aimed to compare the characteristics of lower limb atherosclerotic lesions among type 1, ketosis-onset and non-ketotic type 2 diabetes. Methods A cross-sectional study was performed in newly diagnosed Chinese patients with diabetes, including 53 type 1 diabetics with positive islet-associated autoantibodies, 208 ketosis-onset diabetics without islet-associated autoantibodies, and 215 non-ketotic type 2 diabetics. Sixty-two subjects without diabetes were used as control. Femoral intima-media thickness (FIMT), lower limb atherosclerotic plaque and stenosis were evaluated and compared among the four groups based on ultrasonography. The risk factors associated with lower limb atherosclerotic plaque were evaluated via binary logistic regression in patients with diabetes. Results After adjusting for age and sex, the prevalence of lower limb plaque in the patients with ketosis-onset diabetes (47.6%) was significantly higher than in the control subjects (25.8%, p = 0.013), and showed a higher trend compared with the patients with type 1 diabetes (39.6%, p = 0.072), but no difference was observed in comparison to the patients with non-ketotic type 2 diabetes (62.3%, p = 0.859). The mean FIMT in the ketosis-onset diabetics (0.73 ± 0.17 mm) was markedly greater than that in the control subjects (0.69 ± 0.13 mm, p = 0.045) after controlling for age and sex, but no significant differences were found between the ketosis-onset diabetics and the type 1 diabetics (0.71 ± 0.16 mm, p = 0.373), and the non-ketotic type 2 diabetics (0.80 ± 0.22 mm, p = 0.280), respectively. Age and FIMT were independent risk factors for the presence of lower limb plaque in both the ketosis-onset and non-ketotic type 2 diabetic patients, while sex and age in the type 1 diabetic patients. Conclusions The prevalence and risk of lower limb atherosclerotic plaque in the ketosis-onset diabetes were remarkably higher than in the control subjects without diabetes. The features and risk factors of lower limb atherosclerotic lesions in the ketosis-onset diabetes resembled those in the non-ketotic type 2 diabetes, but different from those in the type 1 diabetes. Our findings provide further evidences to support the classification of ketosis-onset diabetes as a subtype of type 2 diabetes rather than idiopathic type 1 diabetes.

The derivative-based trapezoid rule for the Riemann-Stieltjes integral is presented which uses 2 derivative values at the endpoints. This kind of quadrature rule obtains an increase of two orders of precision over the trapezoid rule for the Riemann-Stieltjes integral and the error term is investigated. At last, the rationality of the generalization of derivative-based trapezoid rule for Riemann-Stieltjes integral is demonstrated.

Manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPX1), and catalase (CAT) provide the primary antioxidant defense system. Impaired antioxidant defense increases oxidative stress and contributes to the development of type 2 diabetes and diabetic cardiovascular disease (CVD). We preformed a case–control study in Chinese type 2 diabetes patients, to determine if the MnSOD Val16Ala (T→C), GPX1 Pro198Leu (C→T), and CAT −262C/T (C→T) functional polymorphisms contribute to the development of type 2 diabetes or diabetic CVD. Patients with type 2 diabetes (n = 168) were divided into the non-CVD group (n = 83, >10 year since diagnosis) and CVD group (n = 85, history of ischemic CVD). Genotyping was performed using PCR–restriction fragment length polymorphism (PCR–RFLP) or PCR-based direct sequencing. The genotypic distribution in the non-CVD- and CVD-group and the clinical parameters in genotypic groups were not significantly different in the three polymorphic sites, respectively. Among eight genotypic combinations, the most common TT+CC+CC genotype (59.5%) was associated with higher triglyceride levels than the TT+CT+CC genotype, the second frequent one (14.9%; 1.77 ± 0.12 vs. 1.21 ± 0.11 mmol/l, P = 0.001), and all non-TT+CC+CC genotypes (40.5%; 1.77 ± 0.12 vs. 1.43 ± 0.12 mmol/l, P = 0.048). In the CVD group, significantly elevated triglyceride levels were also observed in patients with TT+CC+CC compared to patients with TT+CT+CC (2.00 ± 0.18 vs. 1.37 ± 0.16 mmol/l, P = 0.018) or non-TT+CC+CC genotypes (2.00 ± 0.18 vs. 1.65 ± 0.19 mmol/l, P = 0.070). The common MnSOD, GPX1, and CAT TT+CC+CC genotype may contribute to hypertriglyceridemia in Chinese patients with type 2 diabetes or diabetic CVD.

OBJECTIVE Oxidative stress is a major contributing factor in the development of diabetic nephropathy. Peroxisome proliferator–activated receptor γ heterozygous mice and Pro12Ala polymorphism in PPARG exhibited increased resistance to oxidative stress. Smoking increases the production of reactive oxygen species, which accelerates oxidative stress under hyperglycemia. To determine whether the Pro12Ala polymorphism, alone or in combination with smoking, contributes to the development of diabetic nephropathy, a case-control study was performed in 760 Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Among patients, 532 had diabetic nephropathy with microalbuminuria (n = 245) or overt albuminuria (n = 287), and 228 did not show either of these symptoms but had had diabetes for ≥10 years and were not undergoing antihypertension treatment. RESULTS After adjustment for confounders, the Pro/Pro genotype was significantly associated with diabetic nephropathy (odds ratio 2.30 [95% CI 1.18–4.45], P = 0.014); smoking was also an independent risk factor for diabetic nephropathy (1.99 [1.08–3.68], P = 0.029). In addition, we identified possible synergistic effects; i.e., the high-risk group (smokers with the Pro/Pro genotype) showed 4.52 times higher risk (1.78–11.48, P = 0.002) of diabetic nephropathy than the low-risk group (nonsmokers with the Pro/Ala genotype) in a multiple logistic regression analysis controlled for the confounders. CONCLUSIONS Our results indicated that the Pro/Pro genotype and smoking were significant independent risk factors for diabetic nephropathy. The possible synergistic effects of genotype and smoking may aggravate oxidative stress and contribute to the development of diabetic nephropathy.

With the base of proposing materialized view similarity function, the paper proposes clustering-based dynamic materialized view selection algorithm. It firstly clusters materialized views, and then dynamically adjusts materialized view set. So, it eliminates the "jitter", which dynamic materialized view selection algorithm generally has. The experimental results show that the algorithm not only improves the overall query response performance, but also reduces the computational cost which will bespent during updating materialized view.