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China Three Gorges Corporation (CTG) currently owns 57 large dams all over the world. These dams are operated by different entities independently. To better share information and to provide efficient technical support for these dams, it's necessary to establish a management information system for safety and flood control, as a standardized operation platform, to collect real-time data, and to provide auxiliary safety analysis as well as functions such as expert consulting and emergency response for their operators. This paper describes the positioning, modules, system integration as well as innovative features of the system.

We present an approach for approximately solving discrete-time stochastic optimal-control problems by combining direct trajectory optimization, deterministic sampling, and policy optimization. Our feedback motion-planning algorithm uses a quasi-Newton method to simultaneously optimize a reference trajectory, a set of deterministically chosen sample trajectories, and a parameterized policy. We demonstrate that this approach exactly recovers LQR policies in the case of linear dynamics, quadratic objective, and Gaussian disturbances. We also demonstrate the algorithm on several nonlinear, underactuated robotic systems to highlight its performance and ability to handle control limits, safely avoid obstacles, and generate robust plans in the presence of unmodeled dynamics., final revisions for RA-L

The endothelin receptor type B (ETBR) regulates water and electrolyte balance and blood pressure, in part, by inhibiting renal sodium transport. Our preliminary study found that the ETBR-mediated diuresis and natriuresis are impaired in hypertension with unknown mechanism. Persistently increased activity of G protein-coupled receptor kinase 4 (GRK4), caused by increased expression or genetic variants (eg, GRKγ142V), impairs the ability of the kidney to excrete a sodium load, in part, by impairing renal dopamine D(1) receptor function through persistent phosphorylation. Our present study found that although renal ETBR expression was not different between Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs), renal ETBR phosphorylation was higher in SHRs. The role of hyper-phosphorylation in impaired ETBR-function was supported by results in human (h) GRK4γ transgenic mice. Stimulation of ETBR by BQ3020-induced natriuresis in human (h) GRK4γ wild-type (WT) mice. However, in hGRK4γ 142V transgenic mice, the renal ETBR was hyperphosphorylated and ETBR-mediated natriuresis and diuresis were not evident. There were co-localization and co-immunoprecipitation of ETBR and GRK4 in renal proximal tubule (RPT) cells from both WKY and SHRs but was greater in the latter than the former group. SiRNA-mediated downregulation of GRK4 expression, recovered the impaired inhibitory effect of ETBR on Na(+)-K(+)-ATPase activity in RPT cells from SHR. In vivo downregulation of renal GRK4 expression, via ultrasound-targeted microbubble destruction, decreased ETBR phosphorylation and restored ETBR-mediated natriuresis and diuresis in SHRs. This study provides a mechanism by which GRK4, via regulation of renal ETBR function, participates in the pathogenesis of hypertension.

Variable stiffness actuators (VSAs) have demonstrated remarkable potential advantages in safety and efficiency. However, the performance of previous actuators is not sufficient for leg motion of bipedal robots, which needs high torque with fast adjustment and wide range of stiffness. In this study, we developed “lever and parallel mechanism” VSA (LaP-VSA),intending to achieve high-performance specifications. It features parallel mechanism and lever force transmission to achieve high performance. The experimental results demonstrate wide range of variable stiffness, large torque output, and fast stiffness adjustment.

Both renin–angiotensin systems and insulin participate in kidney-involved blood pressure regulation. Activation of angiotensin II type 2 receptor (AT 2 R) decreases sodium reabsorption in renal proximal tubule (RPT) cells, whereas insulin produces the opposite effect. We presume that AT 2 R has an inhibitory effect on insulin receptor expression in RPT cells, which may affect renal sodium transport and therefore be of physiological or pathological significance. Our present study found that activation of AT 2 R inhibited insulin receptor expression in a concentration and time-dependent manner in RPT cells from Wistar-Kyoto (WKY) rats. In the presence of a protein kinase C (PKC) inhibitor (PKC inhibitor peptide 19–31, 10 −6 mol/L) or a phosphatidylinositol 3 kinase inhibitor (wortmannin, 10 −6 mol/L), the inhibitory effect of AT 2 R on insulin receptor was blocked, indicating that both PKC and phosphatidylinositol 3 kinase were involved in the signaling pathway. There was a linkage between AT 2 R and insulin receptor which was determined by both laser confocal microscopy and coimmunoprecipitation. However, the effect of AT 2 R activation on insulin receptor expression was different in RPT cells from spontaneously hypertensive rats (SHRs). Being contrary to the effect in WKY RPT cells, AT 2 R stimulation increased insulin receptor in SHR RPT cells. Insulin (10 −7 mol/L, 15 minutes) enhanced Na + -K + -ATPase activity in both WKY and SHR RPT cells. Pretreatment with CGP42112 decreased the stimulatory effect of insulin on Na + -K + -ATPase activity in WKY RPT cells, whereas pretreatment with CGP42112 increased it in SHR RPT cells. It is suggested that activation of AT 2 R inhibits insulin receptor expression and function in RPT cells. The lost inhibitory effect of AT 2 R on insulin receptor expression may contribute to the pathophysiology of hypertension.

The characteristics of coronary stenosis vary among the different countries or areas. 11,267 patients who have undergone coronary angiography (CAG) from three Southwest China hospitals were investigated. Patient characteristics, coronary stenosis and stent-implant information were recorded and analyzed according to two criteria: "visible stenosis" and "≥ 50% stenosis". The patients who have undergone CAG increased year by year, with patients from 60 to 69 years-old taking the highest ratio (34.69%). Based on the "≥ 50% stenosis" criteria, the stenotic frequency was 40.54% for Southwest China patients getting CAG. Only 8.14% patients suffered ≥ 3 stenotic vessels, while 11.58 and 20.82% patients had 2 or 1 stenotic vessel, respectively. However, when using the "visible stenosis" criteria, the stenotic frequency increased to 64.68%. The prevalence of stenosis increased with age based on the "visible stenosis" criteria. There were more male patients with stenosis than female except patients over 80 years old. The stenosis affected almost all main coronary arteries and their branches, with the most affected artery being the left anterior descending artery. There were 3246 cases (28.8%) implanted with 5423 stents with a concurrent age-dependent increasing tendency for stent-implant frequency and average implanted stent number. The numbers of patients who have undergone CAG and suffered from CVD increased rapidly. In these patients, positive rate of CAG was 64.67%, which increased to 72.2% in patients over 60-years old. The incidence of ≥ 75% stenosis and multiple stenosis increased with age, however it should be noticed there were 18.93% for ≥ 75% stenosis and 19.52% for multiple stenosis in patients under 40 years old.

Background The aim of this study was to investigate the effect of long-term low salt diet on blood pressure and its underlying mechanisms. Methods Male Sprague-Dawley (SD) rats were divided into normal salt diet group (0.4%) and low salt diet group (0.04%). Blood pressure was measured with the non-invasive tail-cuff method. The contractile response of isolated mesenteric arteries was measured using a small vessel myograph. The effects on renal function of the intrarenal arterial infusion of candesartan (10 μg/kg/min), an angiotensin II receptor type 1 (AT1R) antagonist, were also measured. The expressions of renal AT1R and mesenteric arterial α1A, α1B, and α1D adrenergic receptors were quantified by immunoblotting. Plasma levels of angiotensin II were also measured. Results Systolic blood pressure was significantly increased after 8 weeks of low salt diet. There were no obvious differences in the renal structure between the low and normal salt diet groups. However, the plasma angiotensin II levels and renal AT1R expression were higher in low than normal salt diet group. The intrarenal arterial infusion of candesartan increased urine flow and sodium excretion to a greater extent in the low than normal salt diet group. The expressions of α1A and α1D, but not α1B, adrenergic receptors, and phenylephrine-induced contraction were increased in mesenteric arteries from the low salt, relative to the normal salt diet group. Conclusion Activation of the renin-angiotensin and sympathetic nervous systems may be involved in the pathogenesis of long-term low salt diet-induced hypertension.

The adverse environment in early life can modulate adult phenotype, including blood pressure. Our previous study shows, in a rat streptozotocin (STZ)-induced maternal diabetes model, fetal exposure to maternal diabetes is characterized by established hypertension in the offspring. However, the exact mechanisms are not known. Our present study found, as compared with male control mother offspring (CMO), male diabetic mother offspring (DMO) had higher blood pressure with arterial dysfunction, i.e., decreased acetylcholine (Ach)-induced vasodilation. But there is no difference in blood pressure between female CMO and DMO. The decreased Ach-induced vasodilation was related to decreased nitric oxide (NO) production in the endothelium, not NO sensitivity in vascular smooth muscle because sodium nitroprusside (SNP)-mediated vasodilation was preserved; there was decreased NO production and lower eNOS phosphorylation in male DMO. The reactive oxygen species (ROS) level was increased in male DMO than CMO; normalized ROS levels with tempol increased NO production, normalized Ach-mediated vasodilation, and lowered blood pressure in male DMO rats. It indicates that diabetic programming hypertension is related to arterial dysfunction; normalizing ROS might be a potential strategy for the prevention of hypertension in the offspring.

Objective:To perform a meta-analysis examining the effectiveness of platelet-rich plasma and platelet-rich fibrin matrix for improving healing of rotator cuff injuries.Data sources/design:A meta-analysis of eligible studies was performed after searching Medline, Cochrane, and EMBASE on 14 December 2015.Setting:University hospital.Participants:Patients with rotator cuff injuries.Review methods/intervention:Databases were searched using the keywords “PRP or platelet-rich plasma,” “PRFM or platelet-rich fibrin matrix,” “rotator cuff,” and “platelet-rich” for studies comparing outcomes of patients with rotator cuff injuries that did and did not receive a platelet-rich product.Main measures:The primary outcome was a functional score change from pre- to post-treatment (Scorepost–Scorepre). The secondary outcome was a visual analogue scale (VAS) pain score change from pre- to post-treatment (VASpost–VASpre).Results:A total of 11 studies were included in the meta-analysis. The total number of patients that received platelet-rich plasma or platelet-rich fibrin matrix was 320 and the number of control patients was 318. The standard difference in means of the functional scores was similar between patients administered platelet-rich plasma/fibrin matrix and patients in the control group (standard difference in means for functional scores = 0.029; 95% confidence interval (CI): –0.132 to 0.190; p = 0.725). The standard difference in means was similar between patients administered platelet-rich plasma and the controls (standard difference in means = 0.142; 95% CI: –0.080 to 0.364; p = 0.209).Conclusion:The results of this meta-analysis do not support the use of platelet-rich plasma/platelet-rich fibrin matrix in patients with rotator cuff injuries.

Long noncoding RNAs (lncRNAs), a new class of RNAs with no protein-coding potential, have been reported to have crucial roles in the regulation of a variety of tumors. However, the functions and molecular mechanisms of lncRNAs to osteosarcoma are still largely unknown. The purpose of this study is to examine the expression, functions and molecular mechanisms of a new lncRNA FGFR3 antisense transcript 1 (FGFR3-AS1) in osteosarcoma. The expression of FGFR3-AS1 was examined by real-time quantitative PCR. The regulation of FGFR3 by FGFR3-AS1 was examined by RNase protection assay, real-time quantitative PCR, western blotting, and luciferase reporter assay. The effects of FGFR3-AS1 on osteosarcoma cell proliferation and cell cycle were determined by Cell Counting Kit-8, Ethynyl deoxyuridine incorporation assay and flow cytometry. FGFR3-AS1 was upregulated in osteosarcoma. Increased FGFR3-AS1 expression correlates with large tumor size, advanced Enneking stage, metastasis and poor survival. Through antisense pairing with FGFR3 3'UTR, FGFR3-AS1 increases FGFR3 mRNA stability and upregulates FGFR3 expression. The expression of FGFR3-AS1 and FGFR3 is positively correlated in osteosarcoma tissues. Knockdown of FGFR3-AS1 inhibits the proliferation and cell cycle progression of osteosarcoma cells in vitro. Moreover, knockdown of FGFR3-AS1 inhibits xenograft tumor growth of osteosarcoma cells in vivo. These data demonstrate the mechanisms of how antisense noncoding RNA regulate the expression of sense genes, and show the pivotal functions of FGFR3-AS1 in osteosarcoma.

Epidemiological and experimental studies suggest that maternal diabetes mellitus programs hypertension that is associated with impaired sodium excretion in the adult offspring. However, the underlying mechanisms are not clear. Because dopamine receptor function is involved in the pathogenesis of hypertension, we hypothesized that impaired renal dopamine D 1 receptor function is also involved in the hypertension in offspring of maternal diabetes mellitus. Maternal diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (35 mg/kg) to pregnant Sprague-Dawley rats at day 0 of gestation. Compared with the offspring of mothers injected with citrate buffer (control mother offspring), the diabetic mother offspring (DMO) had increased systolic blood pressure and impaired D 1 receptor-mediated diuresis and natriuresis, accompanied by increased renal PKC (protein kinase C) expression and activity, GRK-2 (G protein–coupled receptor kinase-2) expression, D 1 receptor phosphorylation, D 1 receptor/Gαs uncoupling, and loss of D 1 receptor-mediated inhibition of Na + -K + -ATPase activity in renal proximal tubule cells from DMO. Inhibition of PKC reduced the increased GRK-2 expression and normalized D 1 receptor function in primary cultures of renal proximal tubule cells from DMO. In addition, DMO, relative to control mother offspring, in vivo, had increased oxidative stress, indicated by decreased renal glutathione and increased renal malondialdehyde and urine 8-isoprostane. Normalization of oxidative stress with tempol also normalized the renal D 1 receptor phosphorylation, D 1 receptor-mediated diuresis and natriuresis, and blood pressure in DMO. Our present study indicates that maternal diabetes mellitus–programed hypertension in the offspring is caused by impaired renal D 1 receptor function because of oxidative stress that is mediated by increased PKC-GRK-2 activity.

The aim of the present study was to screen the differentially expressed genes (DEGs) associated with familial combined hyperlipidemia (FCHL) and examine the changing patterns. The transcription profile of {"type":"entrez-geo","attrs":{"text":"GSE18965","term_id":"18965"}}GSE18965 was obtained from the NCBI Gene Expression Omnibus database, including 12 FCHL samples and 12 control specimens. The DEGs were identified using a linear models for microarray data package in the R programming language. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was also performed. Protein-protein interaction (PPI) networks of the DEGs were constructed using the EnrichNet online tool. In addition, cluster analysis of the genes in networks was performed using ClusterONE. A total of 879 DEGs were screened, including 394 upregulated and 485 downregulated genes. Enrichment analysis identified four important KEGG pathways associated with FCHL: One carbon pool by folate, α-linolenic acid metabolism, asthma and the glycosphingolipid biosynthesis-globo series. GO annotation identified 12 enriched biological processes, including one associated with hematopoiesis and four associated with bone cell differentiation. This identification was in accordance with clinical data and experiments into hyperlipidemia and bone lesions. Based on PPI networks, these DEGs had a close association with immune responses, hormone responses and cytokine-cytokine receptors. In conclusion, these DEGs may be used as specific therapeutic molecular targets in the treatment of FCHL. The present findings may provide the basis for understanding the pathogenesis of FCHL in future studies. However, further experiments are required to confirm these results.

Based on the idea that time-effect deformation can be regarded as a state vector indicating the characteristics of concrete dams, a hydrostatic seasonal state (HSS) model is proposed for improving the accuracy of the data analysis of concrete dams. According to the theory of non-stationary time series, the state equation of the HSS model is represented for objectively extracting the time-effect deformation from monitoring data of total deformation and to interpret its evolution accurately. In this study, the HSS model is applied to an arch dam case, and it is estimated by using the expectation-maximisation algorithm. The results illustrate that the HSS model can efficiently estimate the time-effect deformation from monitoring data of total deformation. Compared with the hydrostatic seasonal time model, the proposed HSS model shows an improvement in fitting precision and prediction ability.

Bone grafting is a very useful approach to reconstruction of skeletal defects. However, the clinical use of autografts, allografts, and synthetic products is associated with a number of problems. The use of bone xenotransplantation, on the other hand, is associated with strong immune response, and therefore clear understanding of the mechanisms of immune rejection is essential. In this study, we used rabbit-to-rat xenotransplantation model to investigate the role of IL-17, and the relationship between IL-17, IL-23 and RANKL in inflammatory response during the bone grafting. Rabbit hindlimb bone was transplanted to rats, and half of the xenograft recipient animals received injection of IL-17 neutralizing antibodies before xenotransplantation. Sham control rats did not receive bone transplants. In the xenotransplant group, significant mononuclear cell infiltration and erosion/resorption of graft bone were observed. Administration of IL-17 neutralizing antibodies decreased mononuclear cell infiltration and inhibited bone resorption. The levels of IL-17+, IL-23+, and RANKL+ cells were elevated in xenotransplanted group from compared to the sham control. IL-17+ and RANKL+ cells infiltration was decreased upon administration of IL-17 neutralizing antibodies. No significant difference in the level of IL-23 in xenotransplanted groups with and without IL-17 antibodies was observed. Our results indicate that RANKL, IL-17, and IL-23 participate in the immune rejection of bone xenotransplantion. The IL-17/RANKL pathway may play a very important role in the bone resorption during rejection of fresh bone xenotransplants.

The investigation of abnormal increases in uplift pressure can lead to the discovery of seepage paths that may cause damage to concrete arch dams. A new methodology has been developed in this study in order to analyze the causes of abnormally high uplift pressure increases and their influence on the structural safety assessments of dams. A series of borehole video tests were performed on an area of the Huaguangtan Dam and its foundations in order to investigate seepage phenomena under different working conditions. The reasons for the existence of the seepage paths causing abnormally high uplift pressures were identified by examining stresses on the dam, using a detailed three-dimensional numerical model. The results from the monitoring and on-site inspection showed that the high uplift pressure did not constitute a direct threat to the dam’s safety. However, grouting treatment of the existing cracks was recommended so as to prevent them from developing further within the dam’s foundations and to ensure the long-term stability of the foundation seepage. It was concluded that the methodology in this study could be used to solve practical engineering problems effectively as well as acting as a frame of reference for similar projects.

This study aimed to analyze the correlation between single nucleotide polymorphisms (SNPs) of the actin, aortic smooth muscle (ACTA2) gene and coronary artery stenosis in patients with type 2 diabetes mellitus (T2DM). Eight SNPs from the promoter region of the ACTA2 gene were screened. Patients with T2DM (n=251) were divided into two groups, those with severe coronary stenosis (SCS+ group; n=168) and those without severe coronary stenosis (SCS− group; n=83). Patients were also divided according to lesion branching into those whose lesions involved less than three branches (LCA− group) and those whose lesions involved at least three branches (LCA+ group). The clinical and laboratory data of the patients were collected, and the genotyping of eight SNPs was conducted followed by statistical analysis. Of the eight SNPs, only the rs1324551 SNP was identified to be significantly different between the SCS+ and SCS− groups (P

Our aim was to report a modified reverse sural adipofascial flap for treating posttraumatic distal tibial or calcaneal osteomyelitis. We retrospectively reviewed the records of 15 patients with posttraumatic distal tibial or calcaneal osteomyelitis treated with modified reverse sural adipofascial flaps between 2005 and 2010. The flap was raised through 2 short incisions in the posterior aspect of the lower leg. The raw surface of the flap was covered with a full-thickness skin graft. Donor sites were closed primarily. Lower Extremity Functional Scale (LEFS) scores and 2-point discrimination (TPD) were recorded preoperatively and postoperatively. There were 12 males and 3 females, with an average age of 39 years (range = 18-55 years). Twelve lesions were in the distal tibia and 3 in the calcaneus. The flap ranged in size from 11 × 5 cm to 16 × 7 cm. All flaps survived, and skin grafts healed without complications. Recipient sites had an anatomic contour, and all patients were able to ambulate without the assistance of special shoes or orthoses. No infections recurred, and no ulcers of the grafted skin occurred with the regular wearing of shoes. The follow-up duration was 18.7 ± 6.8 months (range = 12-36 months). The mean LEFS score increased from 22.4 ± 8.3 preoperatively to 53.0 ± 11.2 postoperatively ( P = .001). TPD markedly recovered at 24 months postoperatively. The modified reverse sural adipofascial flap provides good outcomes in treating distal tibial and calcaneal osteomyelitis with minimal donor site morbidity.

Background While free flaps can be used in many cases to cover soft tissue defects in the distal leg and ankle in a single stage, factors such as diabetes and advanced age can interfere with success of vascular anastomoses. Methods Twenty-five patients with deep tissue exposure of the distal leg and ankle underwent reconstruction with a modified reverse sural adipofascial flap. Seventeen cases were due to trauma (13 due to high velocity trauma). All 17 had anterior tibial soft tissue defects without significant rear calf soft tissue injury. Eight patients had iatrogenic soft tissue defects due to orthopaedic surgeries for fractures. The flap is raised through two small incisions (3–5 cm) in the posterior aspect of the leg and the subcutaneous fat is split such that some is preserved with the skin. Once the flap is in place, it is covered by a full-thickness skin graft and the donor site is closed primarily. Results Twenty-one flaps survived. Four had partial loss of the skin graft on the flap, which healed spontaneously without secondary resurfacing. Anatomic contour was obtained in the recipient sites of all 25 patients. All donor sites healed primarily with the preservation of protective sensation in the calf and acceptable aesthetic appearance. Numbness in the lateral dorsal foot improved gradually and only minor residual numbness was noted at 1 year postoperatively. Conclusions The modified reverse sural adipofascial flap preserved the sensation of the donor site and the anatomic contour of both recipient and donor sites.

Active learning is innately very suitable for addressing class imbalance problems, as the actively selected training set is significantly less unbalanced than the real distribution. An improved active learning algorithm named CMIES (correcting mistakes in early stages) was proposed. It is based on the belief that a learner can learn more from correcting a mistake than ascertaining something uncertain. In early stages of active learning, the confidence of the classifier is very low. Even instance with the highest probability to be positive according to the current classifier is quite likely to be actually negative, especially with unbalanced data distribution. Correcting such a mistake is much more beneficial than learning from the most uncertain instance, resulting in extreme shrinkage of the version space and thus great improvement of the classification performance.

In this article, we address issues about human motor control system that can achieve two apparently contrasting goals at the same time, namely, dynamic stability and flexibility of movement, in particular, during bipedal standing and walking. Arguments are made based on the steady states of the system for those motor behaviors, i.e., upright posture and periodic gait, for which stability and flexibility are quantitatively analyzed. We hypothesize that those steady states are nominal, meaning that the neural feedback controller does not necessarily force the state point to be close to those nominal steady states. If this is the case, conventional measures to assess stability of those nominal steady states could end up with inappropriate conclusions. To explore this idea, we describe models with intermittent feedback controllers, in which active control torques are alternately activated and inactivated in a state-dependent manner, by exploiting stable modes (stable manifolds of a saddle-type equilibrium point) embedded in the phase space of unstable body dynamics without active control. We then suggest such intermittent control is a promising strategy that might resolve the trade-off between stability and flexibility.

Other than average gait interval, stride-to-stride variability is believed to convey important information about neural control mechanism. Long-range correlation is found in stride interval variability and scaling index is used to describe the fractal-like behavior. However, the physiological origin and specific mechanism are still unknown. According to our simulation finding, it is found that phase resetting could produce long-range correlation time series data. Consider that phase resetting is also related to the supraspinal neural control system, this paper proposes that it may function as an original mechanism for the gait variability.

To investigate the stenotic coexistence among coronary, renal and extracranial arteries and check the predictive value of stenosis between these arteries in Chinese patients. The stenosis of three arteries was evaluated by angiography in 1,228 Chinese patients with clinically diagnosed coronary artery disease (CAD) or high CAD risk factors. Based on the criteria of stenotic diameter of ≥50 %, we found that the rate of stenosis for the coronary artery was highest (48.5 %), extracranial artery stenosis rate was intermediate at 20.2 % and the renal artery with the stenosis rate of 14.3 % was the lowest. The stenotic coexistence rates were 14.3 % between the coronary and extracranial arteries, 10.9 % between coronary and renal arteries, 10.1 % between the extracranial and renal arteries, and only 2.69 % among all three arteries. The stenosis predictive value of the coronary artery for extracranial or renal arteries was lower, but the non-stenosis predictive value was higher. The predictive value of extracranial or renal artery for coronary artery stenosis was higher, while the non-stenosis predictive value was lower. Both the stenosis and non-stenosis predictive values were higher between the extracranial and renal arteries. Cohen’s Kappa value was less than 0.40 between coronary and extracrainal or renal artery but more than 0.40 between extracranial and renal artery. The results were similar when the criteria of stenosis were judged as ≥75 or ≥25 % respectively. We also did analysis within the subgroups with hypertension, diabetes, stroke and transient ischemia attach, got similar results. For Chinese patients with clinically diagnosed CAD or with highly risk factors, non-stenosis of the coronary artery is indicative of reduced stenosis of the extracranial and renal arteries, while extracranial or renal arteries stenosis is indicative of increased coronary artery stenosis.

The expression of high mobility group protein A1 (HMGA1) protein has been closely related to various malignant and prognostic degrees of tumor. To investigate the influence of down-regulating HMGA1 on the tumor and the mechanism underlying antitumor of HMGA1, we transfected the HMGA1 shRNA vector into the osteogenic sarcoma MG-63 cell and observed the changes of cell proliferation, invasion abilities, and the tumor growth. HMGA1 gene expression could be efficiently inhibited, and cell proliferation, migration, invasion, and matrix metalloprotease level were also decreased. BALB/C nude mice injected with the MG-63 cells transfected HMGA1 shRNA showed the significant lower tumor weight, tumor volume, and longer tumor-forming time compared with the control group. Our results suggest that knockdown of HMGA1 could inhibit growth and metastasis potentials of MG-63 cells, which may be a therapeutic target protein for osteogenic sarcoma and may be of biological importance.

Background: Activation of renal D3 receptor induces natriuresis and diuresis in Wistar-Kyoto (WKY) rats; in the presence of ETB receptor antagonist, the natriuretic effect of D3 receptor in WKY rats is reduced. We hypothesize that ETB receptor activation may regulate D3 receptor expression in renal proximal tubule (RPT) cells from WKY rats, which is impaired in RPT cells from spontaneously hypertensive rats (SHRs). Methods: D3 receptor expression was determined by immunoblotting; the D3/ETB receptor linkage was checked by coimmunoprecipitation; Na+-K+-ATPase activity was determined as the rate of inorganic phosphate released in the presence or absence of ouabain. Results: In RPT cells from WKY rats, the ETB receptor agonist BQ3020 increased D3 receptor protein. In contrast, in RPT cells from SHRs, BQ3020 did not increase D3 receptor. There was coimmunoprecipitation between D3 and ETB receptors in RPT cells from WKY and SHRs. Activation of ETB receptor increased D3/ETB coimmunoprecipitation in RPT cells from WKY rats, but not from SHRs. The basal levels of D3/ETB receptor coimmunoprecipitation were greater in RPT cells from WKY rats than in those from SHRs. Stimulation of D3 receptor inhibited Na+-K+-ATPase activity, which was augmented by the pretreatment with the ETB receptor agonist BQ3020 in WKY RPT cells, but not in SHR RPT cells. Conclusion: ETB receptors regulate and physically interact with D3 receptors differently in WKY rats and SHRs. The impaired natriuretic effect in SHRs may be, in part, related to impaired ETB and D3 receptor interactions.

Essential hypertension is one of the most common risk factors in developed and developing countries, affecting ~25% of the middle-aged adult population. The long-term regulation of blood pressure rests on renal and nonrenal mechanisms.1 Ion transport in the renal proximal tubule (RPT) and thick ascending limb of Henle, which is increased in essential hypertension, is regulated by numerous hormones and humoral factors, including insulin and dopamine. Activation of dopamine receptor inhibits sodium reabsorption, whereas activation of insulin receptor increases sodium reabsorption in RPTs.2–5 Insulin is an important regulator of renal salt and water excretion, and hyperinsulinemia has been implicated to play a role in hypertension.3–5 Diabetes mellitus is associated with Na+ and water retention and extracellular fluid volume expansion.4 There is evidence that insulin directly stimulates fluid absorption in rabbit proximal convoluted tubules.5 This stimulatory effect on the proximal tubule is associated with increased Na+/H+ exchanger and Na+–K+ ATPase activities. Dopamine is an endogenous catecholamine that regulates/modulates many cellular activities, including blood pressure and transmembrane ion transport. Dopamine receptors are classified into the D1- and D2-like subtypes based on their structure and pharmacology. D1-like receptors, consisted of D1 and D5 receptors, stimulate adenylyl cyclase activity, whereas D2-like receptors, consisted of D2, D3, and D4 receptors, inhibit adenylyl cyclase activity and regulate/modulate the activity of several ion channels.2 Increasing pieces of evidence show an interaction between insulin and dopamine receptors.3,6,7 Hyperinsulinemic animals and patients with noninsulin-dependent diabetes have defective renal dopaminergic system.6 In obese Zucker rats, a model of type 2 diabetes, renal D1 receptor is downregulated and dopamine fails to produce both diuresis and natriuresis. Treatment with the insulin sensitizer rosiglitazone, a peroxisome proliferator–activated receptor-γ agonist, decreases plasma insulin levels and restores renal D1-receptor function. Chronic exposure of cells to insulin causes both a reduction in D1-receptor abundance, and uncoupling of D1 receptor from G protein/effector complex;3 there is also a diminution of the inhibitory effect of dopamine on Na+–K+ ATPase activity in hyperinsulinemic rats.7 As a major receptor subtype, the D5 receptor, like the Dl receptor, is expressed in RPTs.2,8 Disruption of the D5 receptor gene produces hypertension in mice, and a high salt diet increases their blood pressure further.9,10 Activation of the D5 receptor stimulates cyclic adenosine monophosphate (cAMP) production.9,11 Therefore, it is possible that the natriuretic effect of dopamine is partially mediated by the D5 receptor. Hence, we hypothesized that insulin may increase D5 receptor expression and function, which may be aberrant in hypertensive states. To test the hypothesis mentioned earlier, we evaluated insulin and D5 receptor interaction in immortalized RPT cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs), and the physiological significance of any interaction in D5 receptor cDNA-transfected HEK293 (HEK293-D5) cells. These RPT cells behave similarly to freshly obtained RPT cells, at least with regard to dopamine receptors and responses to G protein stimulation.12,13

Ubiquitin-dependent proteolysis is an important mechanism that suppresses the beta-catenin transcription factor in cells without Wnt stimulation. A critical step in this regulatory pathway is to create a SCF(beta-TrCP) E3 ubiquitin ligase binding site for beta-catenin. Here we show that the SCF(beta-TrCP) binding site created by phosphorylation of beta-catenin is highly vulnerable to protein phosphatase 2A (PP2A) and must be protected by the adenomatous polyposis coli (APC) tumor suppressor protein. Specifically, phosphorylated beta-catenin associated with the wild-type APC protein is recruited to the SCF(beta-TrCP) complex, ubiquitin conjugated, and degraded. A mutation in APC that deprives this protective function exposes the N-terminal phosphorylated serine/threonine residues of beta-catenin to PP2A. Dephosphorylation at these residues by PP2A eliminates the SCF(beta-TrCP) recognition site and blocks beta-catenin ubiquitin conjugation. Thus, by acting to protect the E3 ligase binding site, APC ensures the ubiquitin conjugation of phosphorylated beta-catenin.

Background The use of a free, vascularized fibular graft is an important technique for the reconstruction of large defects in long bones. The technique has many advantages in strong, tubular bones; a more reliable vascular anatomy with a large vascular diameter and long pedicle is used, minimizing donor-site morbidity. Due to limitations in both fibular anatomy and mechanics, they cannot effectively be used to treat large limb bone defects due to their volume and strength. Methods From 1990 to 2001, 16 clinical cases of large bone defects were treated using vascularized double-barrel fibular grafts. Patients were evaluated for an average of 10 months after surgery. Results All the patients achieved bony union; the average bone union took 10 months post surgery, and no stress fractures occurred. Compared with single fibular grafts, the vascularized double-barrel fibular grafts greatly facilitate bony union and are associated with fewer complications, suggesting that the vascularized double-barrel fibular graft is a valuable procedure for the correction of large bone defects in large, long bones in addition to enhancing bone intensity. Conclusions The vascularized double-barrel fibular graft is superior to the single fibular graft in stimulating osteogenous activity and biological mechanics for the correction of very large bone defects in large, long bones. Free vascularized folded double-barrel fibular grafts can not only fill up large bone defects, but also improve the intensity margin. Therefore, this study also widens its application and enlarges the treatment targets. However, in the case of bone deformability, special attention should be paid to bone fixation and protection of donor and recipient sites.

An active learning SVM technique taking advantage of the cluster assumption was proposed. In each active learning iteration, unlabeled instances in the SVM margin were first grouped into two clusters. Then from each cluster, points most similar to the other cluster were selected for labeling. Such points lying near the border between clusters were expected to become support vectors with higher probability. The clustering process was performed in the same kernel space as SVM. With semi-supervised K-medoids, labeled instances were also used to improve the clustering performance. Experiments showed that the proposed method was efficient and robust (to poor initial samples).

An improved active learning method taking advantage of feature selection technique is proposed. In early stages of active learning, the whole dataset is described using only the few key features, so that its overall distribution characteristic can be learned easily, reducing active learning's possibility of falling into bad local optimum. As active learning proceeds, more and more data get labeled. Only then are detailed features of the dataset gradually added to further enhance the model's classification performance. Experiments show that it is more efficient and more robust than traditional technique.

Chiral selective cation-exchange membrane (CSCM) and chiral selective anion-exchange membrane (CSAM) were prepared by blending poly(vinyl alcohol) (PVA) as basic material, β-cyclodextrin (β-CD) as chiral selector, and ion-exchange materials. Chiral selective capacities of these membranes were evaluated by electrodialysis resolution experiment. Electrodialysis separation of dl -4-hydroxyphenylglycine (HPG) racemic mixture showed that the chiral selective membranes had resolution effect. In acid medium, d -HPG + took the precedence over l -HPG + in passing through the CSCM and the selectivity α d / l of two kinds of CSCM were 1.21 and 1.34, respectively. In base medium, l -HPG − took the precedence over d -HPG − in passing through the CSAM and the selectivity α d / l was 0.84.

Stability of human gait is the ability to maintain upright posture during walking against external perturbations. It is a complex process determined by a number of cross-related factors, including gait trajectory, joint impedance and neural control strategies. Here, we consider a control strategy that can achieve stable steady-state periodic gait while maintaining joint flexibility with the lowest possible joint impedance. To this end, we carried out a simulation study of a heel-toe footed biped model with hip, knee and ankle joints and a heavy head-arms-trunk element, working in the sagittal plane. For simplicity, the model assumes a periodic desired joint angle trajectory and joint torques generated by a set of feed-forward and proportional-derivative feedback controllers, whereby the joint impedance is parametrized by the feedback gains. We could show that a desired steady-state gait accompanied by the desired joint angle trajectory can be established as a stable limit cycle (LC) for the feedback controller with an appropriate set of large feedback gains. Moreover, as the feedback gains are decreased for lowering the joint stiffness, stability of the LC is lost only in a few dimensions, while leaving the remaining large number of dimensions quite stable: this means that the LC becomes saddle-type, with a low-dimensional unstable manifold and a high-dimensional stable manifold. Remarkably, the unstable manifold remains of low dimensionality even when the feedback gains are decreased far below the instability point. We then developed an intermittent neural feedback controller that is activated only for short periods of time at an optimal phase of each gait stride. We characterized the robustness of this design by showing that it can better stabilize the unstable LC with small feedback gains, leading to a flexible gait, and in particular we demonstrated that such an intermittent controller performs better if it drives the state point to the stable manifold, rather than directly to the LC. The proposed intermittent control strategy might have a high affinity for the inverted pendulum analogy of biped gait, providing a dynamic view of how the step-to-step transition from one pendular stance to the next can be achieved stably in a robust manner by a well-timed neural intervention that exploits the stable modes embedded in the unstable dynamics.

An increasing number of microRNAs (miRNAs) have been identified as diagnostic and prognostic biomarkers, as well as additional therapeutic tools, in skeletal diseases. Recent studies have established the pathophysiological role of miR‑214, using human osteoporotic bone specimens. However, miR‑214 expression levels and the underlying regulatory mechanism in human osteosarcoma remain unclear. Quantitative polymerase chain reaction (qPCR) was used to examine the expression of miR‑214 in human osteosarcoma tissues and cells. Transfection of the cells with either a miR‑214 expressing‑plasmid, mimic or inhibitor was performed, in order to investigate the role of miR‑214 in osteosarcoma. In this study, miR‑214 was shown to be significantly increased in the majority of 15 examined osteosarcoma tissues and in the Saos‑2 human osteosarcoma cell line. Overexpression of miR‑214 in Saos‑2 cells induced cell proliferation, while inhibition of miR‑214 promoted Saos‑2 cell apoptosis in vitro. Furthermore, ectopic expression of miR‑214 markedly promoted osteosarcoma development in a subcutaneous xenotransplantation model in BALB/c athymic nude mice. The role of miR‑214 in osteocarcinogenesis was further investigated and phosphatase and tensin homolog (PTEN) was determined to be a direct target of miR‑214 in Saos‑2 cells. The proliferation‑promoting effect of PTEN knockdown was similar to that of miR‑214 overexpression. This study revealed that miR‑214 exerted a crucial role in promoting osteosarcoma progression and this suggests that modulation of miR‑214 levels may provide a novel therapeutic approach in cancer treatment.

G-protein–coupled receptor kinase 4 (GRK4) gene variants, via impairment of renal dopamine receptor and enhancement of renin–angiotensin system functions, cause sodium retention and increase blood pressure. Whether GRK4 and the angiotensin type 1 receptor (AT 1 R) interact in the aorta is not known. We report that GRK4 is expressed in vascular smooth muscle cells of the aorta. Heterologous expression of the GRK4γ variant 142V in A10 cells increased AT 1 R protein expression and AT 1 R-mediated increase in intracellular calcium concentration. The increase in AT 1 R expression was related to an increase in AT 1 R mRNA expression via the NF-κB pathway. As compared with control, cells expressing GRK4γ 142V had greater NF-κB activity with more NF-κB bound to the AT 1 R promoter. The increased AT 1 R expression in cells expressing GRK4γ 142V was also associated with decreased AT 1 R degradation, which may be ascribed to lower AT 1 R phosphorylation. There was a direct interaction between GRK4γ and AT 1 R that was decreased by GRK4γ 142V. The regulation of AT 1 R expression by GRK4γ 142V in A10 cells was confirmed in GRK4γ 142V transgenic mice; AT 1 R expression was higher in the aorta of GRK4γ 142V transgenic mice than control GRK4γ wild-type mice. Angiotensin II–mediated vasoconstriction of the aorta was also higher in GRK4γ 142V than in wild-type transgenic mice. This study provides a mechanism by which GRK4, via regulation of arterial AT 1 R expression and function, participates in the pathogenesis of conduit vessel abnormalities in hypertension.