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The power battery is a key component of the electric vehicle, and its State of health (SOH) parameters directly affect the safety and reliability of the electric vehicle. Considering the problem of the reduced SOH estimation accuracy of Li-ion battery, this paper proposes a joint algorithm of the firefly algorithm-back propagation neural network K-means (FA-BPNN-K-means) for SOH estimation to alleviate the wide voltage platform and severe polarization. In particular, the BPNN model of the battery is first established. The ohmic resistance, polarization resistance, and polarization capacitance of the battery are used as the input parameters of the model, and SOH was used as the output parameters. Secondly, the firefly algorithm (FA) is used to optimize BPNN for SOH estimation of Li-ion battery, solving the problem that BPNN is easy to fall into the local minimum and the convergence rate is slow. Finally, the predicted output of the FA-BPNN model is substituted into the K-means algorithm for clustering, and the data points for evaluation are obtained to reduce the cumulative error caused by the battery model. Compared with the BPNN algorithm, FA-BPNN-K-means joint optimization algorithm, obtaining lower error in SOH estimation, and it has good convergence. Besides, it is accompanied by higher prediction accuracy, which can guarantee the stable operation of the battery management system.

Accuracy of battery charge status (SOC) estimation plays a significant role in the management of electric vehicle power batteries. However, recently, abrupt changes from SOC data often occurs in the actual operation of electric vehicles and some errors appear in the establishment of battery models and noise models, which give rise to the poorly adaptive and robust performance of traditional algorithms in the process of SOC estimation. The fusion algorithm proposed in this paper can effectively improve the accuracy of models and SOC estimation of lithium-ion batteries. Based on the second-order R-C network model, this method optimizes the accuracy of parameter identification by adopting the adaptive recursive weighted least square algorithm (ARWLS). In addition, the adaptive fading extended Kalman filter algorithm (AFEKF) is applied to estimate the SOC of lithium-ion batteries. Additionally, via introducing a fading factor, the optimal Kalman gain is updated in real-time, which can reduce the impact of data mutation on battery modeling. Compared with the offline AEKF algorithm and the EKF algorithm, the adaptive recursive weighted least square-adaptive fading extended Kalman filter (ARWLS-AFEKF) fusion algorithm had higher accuracy and adaptability, which can be adapted to the variable noise environment.

Background Studies have linked mutations in genes encoding the eight-protein exocyst protein complex to kidney disease, but the underlying mechanism is unclear. Because Drosophila nephrocytes share molecular and structural features with mammalian podocytes, they provide an efficient model for studying this issue. Methods We silenced genes encoding exocyst complex proteins specifically in Drosophila nephrocytes and studied the effects on protein reabsorption by lacuna channels and filtration by the slit diaphragm. We performed nephrocyte functional assays, carried out super-resolution confocal microscopy of slit diaphragm proteins, and used transmission electron microscopy to analyze ultrastructural changes. We also examined the colocalization of slit diaphragm proteins with exocyst protein Sec15 and with endocytosis and recycling regulators Rab5, Rab7, and Rab11. Results Silencing exocyst genes in nephrocytes led to profound changes in structure and function. Abolition of cellular accumulation of hemolymph proteins with dramatically reduced lacuna channel membrane invaginations offered a strong indication of reabsorption defects. Moreover, the slit diaphragm's highly organized surface structure-essential for filtration-was disrupted, and key proteins were mislocalized. Ultrastructural analysis revealed that exocyst gene silencing led to the striking appearance of novel electron-dense structures that we named "exocyst rods," which likely represent accumulated membrane proteins following defective exocytosis or recycling. The slit diaphragm proteins partially colocalized with Sec15, Rab5, and Rab11. Conclusions Our findings suggest that the slit diaphragm of Drosophila nephrocytes requires balanced endocytosis and recycling to maintain its structural integrity and that impairment of the exocyst complex leads to disruption of the slit diaphragm and nephrocyte malfunction. This model may help identify therapeutic targets for treating kidney diseases featuring molecular defects in vesicle endocytosis, exocytosis, and recycling.

Based on the field monitoring data from the structural health monitoring system of Xihoumen Bridge, the full-scale wind field characteristics (10-min mean wind speed and direction, turbulence intensity, gust factor, wind spectrum power density, and integral length) were calculated. Moreover, the relationship between turbulence intensity and mean wind characteristics (10-min mean wind speed and mean wind direction), the relationship between gust factor and mean wind characteristics, and the relationship between gust factor and turbulence intensity were analyzed. Additionally, wind-induced responses during Typhoons Meifa, HaiKui, and Chan-hom were analyzed and compared with designed values. The analysis results can provide a basis for the formulation of emergency plans and management measures when the bridge is hit by typhoons.

As a two-phase hybrid material, liquid-filled carbon nanotubes (CNTs) provide a great opportunity to design dexterous flexible nano-manipulator actuated by electric field. Here, we report a group of saline solution-filled CNTs with the end constraint can realize 360° all-round bending in a suitable electric field. The molecular dynamics (MD) simulation results show that saline solution-filled CNTs can be bent under the axial-lateral compound electric field, whereas the bending deflection increases with the increase of salinity, CNTs length and electric intensity. The deformation mechanism of saline solution-filled CNTs under the electric field is clarified by exploring the movement and distribution of salt ions in CNTs under the axial electric field. Moreover, based on the bending deformation characteristics of saline solution-filled CNTs, the MD simulations for the two-finger and four-finger nano grippers grasping diamond balls are carried out to demonstrate the micromanipulation functions of saline solution-filled CNTs. The findings will provide an important theoretical basis for the design and application of micromanipulation devices based on low dimensional carbon materials.

Reverse osmosis (RO) technology is currently the most progressive, energy-saving and efficient membrane separation technology . Meanwhile, graphene becomes a promising candidate for fabricating the RO membranes in water desalination due to its high salt rejection and water flux. The concept of “temporal selectivity” is first proposed in our previous work in terms of the time difference between the penetration time of an ion passing through the pore and the tangential slipping time for the ion sliding across the pore. Nevertheless, the temporal selectivity mechanism of multilayered graphene membrane remains ambiguous. In this paper, the RO process of saltwater through porous graphene column RO membrane is studied by using molecular dynamics (MD) simulations method, and the effects of rotating angular velocity and the thickness of RO membrane on desalination performance of seawater are considered first. The MD results show that the salt rejection increases with the rotation speed of porous membrane increasing while the water flux initially increases and then decreases . Meanwhile, the interfacial slip velocity increases linearly with angular velocity increasing. On the other hand, the increasing thickness of porous graphene membrane can enhance the selectivity and reduce the permeability of water molecules. As expected, the tri-layered porous graphene RO membrane can achieve high salt rejection at low interfacial slip velocity. In order to ensure high selectivity and energy conservation and efficient, the pore structure of the porous graphene RO membrane is optimized. The results show that the optimized nanopores can increase the water flux significantly, whereas the salt rejection is not changed appreciably. It is found that the pore size of the innermost layer membrane near the feed region has the most significant effect on the water flux. The water flux increases sharply with the increase of pore diameter and the salt rejection remains totally higher than 80%. Moreover, the RO membrane with a special Type 3 structure exhibits excellent performance in seawater desalination, specifically, the ultrahigh water flux reaches 20029 L·cm–2·d–1 and the super salt rejection arrives at 94%. The research results further clarify and verify the mechanism of the temporal selectivity in RO process, and improve the water flux under the condition of the same membrane thickness by designing gradient hole. The findings can conduce to the in-depth theoretical understanding of porous graphene-based membranes and designing and developing the large-scale seawater desalination devices and water filtration equipment.

BACKGROUND: Studies have linked mutations in genes encoding the eight-protein exocyst protein complex to kidney disease, but the underlying mechanism is unclear. Because Drosophila nephrocytes share molecular and structural features with mammalian podocytes, they provide an efficient model for studying this issue. METHODS: We silenced genes encoding exocyst complex proteins specifically in Drosophila nephrocytes and studied the effects on protein reabsorption by lacuna channels and filtration by the slit diaphragm. We performed nephrocyte functional assays, carried out super-resolution confocal microscopy of slit diaphragm proteins, and used transmission electron microscopy to analyze ultrastructural changes. We also examined the colocalization of slit diaphragm proteins with exocyst protein Sec15 and with endocytosis and recycling regulators Rab5, Rab7, and Rab11. RESULTS: Silencing exocyst genes in nephrocytes led to profound changes in structure and function. Abolition of cellular accumulation of hemolymph proteins with dramatically reduced lacuna channel membrane invaginations offered a strong indication of reabsorption defects. Moreover, the slit diaphragm’s highly organized surface structure—essential for filtration—was disrupted, and key proteins were mislocalized. Ultrastructural analysis revealed that exocyst gene silencing led to the striking appearance of novel electron-dense structures that we named “exocyst rods,” which likely represent accumulated membrane proteins following defective exocytosis or recycling. The slit diaphragm proteins partially colocalized with Sec15, Rab5, and Rab11. CONCLUSIONS: Our findings suggest that the slit diaphragm of Drosophila nephrocytes requires balanced endocytosis and recycling to maintain its structural integrity and that impairment of the exocyst complex leads to disruption of the slit diaphragm and nephrocyte malfunction. This model may help identify therapeutic targets for treating kidney diseases featuring molecular defects in vesicle endocytosis, exocytosis, and recycling.

BackgroundKidney stone formers with family history have a high rate of stone recurrence after kidney stone removal surgery and there is no effective medication available for treatment. It has been shown that hydroxycitric acid (HCA)-the major component of Garcinia cambogia extract, induces dissolution of the calcium oxalate crystal in vitro, suggesting that clinical-grade Garcinia cambogia has the potential to treat calcium oxalate kidney stone. In this study, we used the Drosophila genetic and non-genetic nephrolithiasis model to evaluate the effect of Garcinia cambogia and HCA on the prevention and removal of calcium oxalate stones in vivo. Methods: WT flies were reared in fly food with different concentrations of GCE for one week．The effect of GCE on preventing the formation of calcium oxalate stone was examined. WT and v-ATPase gene knockdown flies were reared in fly food containing 0.3% NaOx for one week, then fed different concentrations of GCE for one week．The effect of GCE on the removal of calcium oxalate stone was examined. Findings: Garcinia cambogia extract efficiently removes calcium oxalate kidney stones from Malpighian tubules in both genetic and non-genetic Drosophila models of nephrolithiasis in vivo. HCA directly dissolves calcium oxalate stones in Drosophila Malpighian tubules ex vivo. Interpretation: Clinical-grade Garcinia cambogia extract removes calcium oxalate kidney stones from Drosophila Malpighian tubules via directly dissolving calcium oxalate stones by HCA. Our study strongly suggests that clinical-grade Garcinia cambogia extract could be used to treat patients with nephrolithiasis in the future. Funding Statement: F.J.Z. was supported by grants from National Key Research Plan (2017YFA0104602) and F.F.H was supported by the National Key Technology Support Program of China (2013BAI09B06 and 2015BAI2B07), the State Key Program of National Natural Science Foundation of China (81430016), the Major International (Regional) Joint Research Project of National Natural Science Foundation of China (81620108003), the Major Scientific and Technological Planning Project of Guangzhou (15020010), and the Guangzhou Clinical Research Center for Chronic Kidney Disease Program (7415695988305). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The authors state: "Not applicable"

Kidney stone formers with family history have a high rate of stone recurrence after kidney stone removal surgery and there is no effective medication available for treatment. Here, we show that Garcinia cambogia extract (GCE) efficiently removes calcium oxalate kidney stones from Malpighian tubules in both genetic and non-genetic Drosophila models of nephrolithiasis, and hydroxycitrate -a major component of GCE, directly dissolves calcium oxalate stones in Drosophila Malpighian tubules ex vivo. Our study discovers a potential novel therapeutic strategy for the clinical treatment of nephrolithiasis and suggests that clinical-grade Garcinia cambogia extract could be used to treat patients with nephrolithiasis in the future.

In order to solve the problem that The estimation error of the standard nonlinear Kalman algorithm is caused by the inaccuracy of the system filter initial value and the unknown noise statistic characteristic in target tracking, a nonlinear target tracking algorithm based on residual Takagi-Sugeno fuzzy adaptive is proposed. Under the framework of determining sampled filtering, the general form of approximate Gaussian weighted integral under the condition of linearization error constraint is given. The sufficient condition for the bounded convergence of the proposed algorithm is proved by the Lyapunov second method and the Takagi-Sugeno model is introduced to constructs the noise estimator combined with the method of residual matching fuzzy criterion. It is verified that the algorithm has better tracking accuracy and robustness through unknown initial value information and target tracking model of time-varying noise measurement.

At present, Kalman filter is the most commonly used algorithm in the MIMU/GPS integrated navigation system. However, when the satellite signal is missing, inertial navigation system works independently instead of integrated navigation system, but with a serious problem of poor navigation accuracy due to the large drift error of micro inertial measurement unit. This paper puts forward a solution to this problem, which makes direct prediction of observation sequence in the absence of satellite signals. This method establishes the ARMA model of measurement values under the condition of historical observation, solves the parameters of the corresponding model, and obtains the predicted measurement values. The simulation experiments show that this measurement values obtained by the method can effectively modify the state error and further improve the precision of integrated navigation system.

Kalman filter algorithm is basically applied to the MIMU/GPS integrated navigation, but there are always accidents such as abnormal observation noise or noise mutation in reality, where may make the state covariance matrix lose symmetric even the emergence of the divergence of the filter with the consequences of leading to lower the accuracy of integrated navigation system. This paper aims to solve this problem using the principle of singular value decomposition. The main concept behind the algorithm is to achieve updating process via singular value decomposition factors of all the matrices consisting of error covariance, process noise covariance and measurement covariance, instead of Cholesky decomposition on the basis of the conventional Kalman filtering algorithm. The simulation experiments show that the robustness of the proposed algorithm based on singular value decomposition is superior to the Kalman filtering and the square-root filtering algorithm, and improves the navigation accuracy effectively.

Summary A method for identifying the distribution of moving heavy vehicle loads is proposed for cable-stayed bridges based on a sparse l1 optimization technique. This method is inspired by the recently developed compressive sensing (CS) theory, which is a technique for obtaining sparse signal representations for underdetermined linear measurement equations. In this study, sparse l1 optimization is employed to localize the moving heavy vehicle loads of cable-stayed bridges through cable force measurements. First, a simplified equivalent load of vehicles on cable-stayed bridges is presented. Then, the relationship between the cable forces and the moving heavy vehicle loads is established based on the influence lines. With the hypothesis of a sparse distribution of vehicle loads on the bridge deck (which is practical for long-span bridges), moving heavy vehicle loads are identified by minimizing the ‘l2-norm'of the difference between the observed and simulated cable forces caused by the moving vehicles penalized by the ‘l1-norm’ of the moving heavy vehicle load vector. A numerical example of an actual cable-stayed bridge is employed to verify the proposed method. The robustness and accuracy of this identification approach (with measurement noise for multi-vehicle spatial localization) are validated. Copyright © 2015 John Wiley & Sons, Ltd.

Summary Two studies have concluded that lithium exposure extends the lifespan of Caenorhabditis elegans. However, the effect of lithium on another widely used model organism, Drosophila melanogaster, remains unclear. Here, we demonstrate that chronic treatment with a low to moderate dose of lithium chloride does not extend lifespan in D. melanogaster and that the drug abolishes the female lifespan advantage in flies.

The Drosophila nephrocyte is a critical component of the fly renal system, and bears structural and functional homology to podocytes and proximal tubule cells of the mammalian kidney. Investigations of nephrocyte cell biological processes are fundamental to understanding the insect renal system. Nephrocytes are highly active in endocytosis and vesicle trafficking. Rab GTPases regulate endocytosis and trafficking, but specific functions of nephrocyte Rabs remain undefined. We analyzed Rab GTPase expression and function in Drosophila nephrocytes and found that 11 out of 27 Drosophila Rabs were required for normal activity. Rabs 1, 5, 7, 11, and 35 were most important. Nephrocyte specific Rab5 gene silencing eliminated all intracellular vesicles and the specialized plasma membrane structures essential for nephrocyte function; Rab7 silencing dramatically increased clear vacuoles and reduced lysosomes; Rab11 silencing increased lysosomes and reduced clear vacuoles. Our results suggest that Rab5 mediates endocytosis that is essential for maintenance of functionally critical nephrocyte plasma membrane structures, and that Rabs 7 and 11 mediate alternative downstream vesicle trafficking pathways leading to protein degradation and membrane recycling, respectively. Elucidating molecular pathways underlying nephrocyte function has the potential to yield important insights into human kidney cell physiology and mechanisms of cell injury that lead to disease. Limited treatment options and high incidence mean that discovering promising therapeutic targets in abnormal podocytes and proximal tubule cells is a priority. The Drosophila nephrocyte is emerging as a useful in vivo model system for molecular target identification and initial testing of therapeutic approaches.

The apoptosis of mesangial cells (MCs) plays a critical role in the pathological progress of MesPGN. Septin2, a filamentous GTPase, is implicated in the apoptotic progress of MCs in the rat MesPGN model. However, the molecular mechanism of SEPT2 in MCs apoptosis is not clear. Here, we present the FHL2-driven molecular network as the main mechanism of SEPT2-mediated rat primary MCs apoptosis. First, we proved that the expression of FHL2 and Septin2 were closely related with MCs apoptosis in anti-Thy1 nephritis model. Then, it was found that FHL2 was a new interaction protein of Septin2 and Septin2 knockdown could induce MC apoptosis by FHL2-mediatied signal pathways including p-ERK1 and p-AKT. We applied label-Free quantitative proteomics to identify the mechanism of Septin2/FHL2-regulated apoptosis. Bioinformatics analysis revealed that FHL2-driven molecular network composed of biological functions including glycolysis, oxidative stress, ribonucleotide metabolism, actin cytoskeleton regulation, and signaling pathway, was the main mechanism of SETP2-mediated apoptosis. Furthermore, we showed that the effect of Septin2 knockdown on MC apoptosis could be alleviated by the overexpression of FHL2. Overall, this study illustrated the FHL2-driven molecular network controlling SEPT2-mediated apoptosis in MCs and their potential roles in mesangial proliferative nephritis.

SUMMARY Stay cables are critical components in bridges. However, stay cables suffer from severe fatigue damage. Therefore, a monitoring technique to obtain the time history of the tension in stay cables is important. Because the acceleration of stay cables is readily measurable, approaches to identify cable tension based on frequency analysis and monitored cable acceleration have been widely investigated and used in practice. However, this type of approach can only identify a time-invariant tension of a stay cable over a specified duration, not the time-varying tension. This paper proposes an approach to identify the time-varying tension of stay cables by monitoring cable accelerations. The tension variation in stay cables is caused by vehicles passing over the bridge. The real-time identification algorithm that determines the time-varying tension of stay cables is proposed using an extended Kalman filter based on both the transversal monitored acceleration at a single location on the cable and the monitored wind speed on the bridge, where the time-varying tension is a state variable that is identified. A stay cable from the Nanjing Yangtze River No. 3 Bridge was used for the numerical study. The time-varying tension of the stay cable can be identified when either a single vehicle or multiple vehicles pass over the bridge. The robustness of the proposed approach is also investigated through deviations in the initial tension, initial displacement, and velocity of the stay cable. An experiment was conducted on a scaled stay cable with time-varying tension excited by wind. The time-varying cable tension of the cable was identified by the proposed approach and compared with the real time-varying cable tension. The identification accuracy and robustness of the proposed approach is verified through the experiment and numerical study. Copyright © 2013 John Wiley & Sons, Ltd.

The difficulty in accessing mammalian nephrons in vivo hinders the study of podocyte biology. The Drosophila nephrocyte shares remarkable similarities to the glomerular podocyte, but the lack of a functional readout for nephrocytes makes it challenging to study this model of the podocyte, which could potentially harness the power of Drosophila genetics. Here, we present a functional analysis of nephrocytes and establish an in vivo system to screen for renal genes. We found that nephrocytes efficiently take up secreted fluorescent protein, and therefore, we generated a transgenic line carrying secreted fluorescent protein and combined it with a nephrocyte-specific driver for targeted gene knockdown, allowing the identification of genes required for nephrocyte function. To validate this system, we examined the effects of knocking down sns and duf , the Drosophila homologs of nephrin and Neph1 , respectively, in pericardial nephrocytes. Knockdown of sns or duf completely abolished the accumulation of the fluorescent protein in pericardial nephrocytes. Examining the ultrastructure revealed that the formation of the nephrocyte diaphragm and lacunar structure, which is essential for protein uptake, requires sns . Our preliminary genetic screen also identified Mec2 , which encodes the homolog of mammalian Podocin. Taken together, these data suggest that the Drosophila pericardial nephrocyte is a useful in vivo model to help identify genes involved in podocyte biology and facilitate the discovery of renal disease genes.

Many genetic mutations have been identified as monogenic causes of nephrotic syndrome (NS), but important knowledge gaps exist in the roles of these genes in kidney cell biology and renal diseases. More animal models are needed to assess the functions of these genes in vivo, and to determine how they cause NS in a timely manner. Drosophila nephrocytes and human podocytes share striking similarities, but to what degree these known NS genes play conserved roles in nephrocytes remains unknown. Here we systematically studied 40 genes associated with NS, including 7 that have not previously been analysed for renal function in an animal model. We found that 85% of these genes are required for nephrocyte functions, suggesting that a majority of human genes known to be associated with NS play conserved roles in renal function from flies to humans. To investigate functional conservation in more detail, we focused on Cindr, the fly homolog of the human NS gene CD2AP. Silencing Cindr in nephrocytes led to dramatic nephrocyte functional impairment and shortened life span, as well as collapse of nephrocyte lacunar channels and effacement of nephrocyte slit diaphragms. These phenotypes could be rescued by expression of a wild-type human CD2AP gene, but not a mutant allele derived from a patient with CD2AP-associated NS. We conclude that the Drosophila nephrocyte can be used to elucidate clinically relevant molecular mechanisms underlying the pathogenesis of most monogenic forms of NS, and to efficiently generate personalized in vivo models of genetic renal diseases bearing patient-specific mutations.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive motor neuron death. More than 90 mutations in the copper-zinc superoxide dismutase (SOD1) gene cause a subset of familial ALS. Toxic properties have been proposed for the ALS-linked SOD1 mutants, but the nature of the toxicity has not been clearly specified. Cytoplasmic inclusion bodies containing mutant SOD1 and a number of other proteins are a pathological hallmark of mutant SOD1-mediated familial ALS, but whether such aggregates are toxic to motor neurons remains unclear. In this study, we identified a dynein subunit as a component of the mutant SOD1-containing high molecular weight complexes using proteomic techniques. We further demonstrated interaction and colocalization between dynein and mutant SOD1, but not normal SOD1, in cultured cells and also in G93A and G85R transgenic rodent tissues. Moreover, the interaction occurred early, prior to the onset of symptoms in the ALS animal models and increased over the disease progression. Motor neurons with long axons are particularly susceptible to defects in axonal transport. Our results demonstrate a direct "gain-of-interaction" between mutant SOD1 and dynein, which may provide insights into the mechanism by which mutant SOD1 could contribute to a defect in retrograde axonal transport or other dynein functions. The aberrant interaction is potentially critical to the formation of mutant SOD1 aggregates as well as the toxic cascades leading to motor neuron degeneration in ALS.

The purpose of this research is to develop nanoparticles (NPs) of star-shaped copolymer mannitol-functionalized PLGA-TPGS for Genistein delivery for liver cancer treatment, and evaluate their therapeutic effects in liver cancer cell line and hepatoma-tumor-bearing nude mice in comparison with the linear PLGA nanoparticles and PLGA-TPGS nanoparticles. The Genistein-loaded M-PLGA-TPGS nanoparticles (MPTN), prepared by a modified nanoprecipitation method, were observed by FESEM and TEM to be near-spherical shape with narrow size distribution. The nanoparticles were further characterized in terms of their size, size distribution, surface charge, drug-loading content, encapsulation efficiency and in vitro drug release profiles. The data showed that the M-PLGA-TPGS nanoparticles were found to be stable, showing almost no change in particle size and surface charge during 3-month storage of their aqueous solution. In vitro Genistein release from the nanoparticles exhibited biphasic pattern with burst release at the initial 4days and sustained release afterwards. The cellular uptake efficiency of fluorescent M-PLGA-TPGS nanoparticles was 1.25-, 1.22-, and 1.29-fold higher than that of the PLGA-TPGS nanoparticles at the nanoparticle concentrations of 100, 250, and 500μg/mL, respectively. In the MPTN group, the ratio of apoptotic cells increased with the drug dose increased, which exhibited dose-dependent effect and a significant difference compared with Genistein solution group (p

Mutations in copper-zinc superoxide dismutase (SOD1) have been linked to a subset of familial amytrophic lateral sclerosis (fALS), a fatal neurodegenerative disease characterized by progressive motor neuron death. An increasing amount of evidence supports that mitochondrial dysfunction and apoptosis activation play a critical role in the fALS etiology, but little is known about the mechanisms by which SOD1 mutants cause the mitochondrial dysfunction and apoptosis. In this study, we use proteomic approaches to identify the mitochondrial proteins that are altered in the presence of a fALS-causing mutant G93A-SOD1. A comprehensive characterization of mitochondrial proteins from NSC34 cells, a motor neuron-like cell line, was achieved by two independent proteomic approaches. Four hundred seventy unique proteins were identified in the mitochondrial fraction collectively, 75 of which are newly discovered proteins that previously had only been reported at the cDNA level. Two-dimensional gel electrophoresis was subsequently used to analyze the differences between the mitochondrial proteomes of NSC34 cells expressing wild-type and G93A-SOD1. Nine and 36 protein spots displayed elevated and suppressed abundance respectively in G93A-SOD1-expressing cells. The 45 spots were identified by MS, and they include proteins involved in mitochondrial membrane transport, apoptosis, the respiratory chain, and molecular chaperones. In particular, alterations in the post-translational modifications of voltage-dependent anion channel 2 (VDAC2) were found, and its relevance to regulating mitochondrial membrane permeability and activation of apoptotic pathways is discussed. The potential role of other proteins in the mutant SOD1-mediated fALS is also discussed. This study has produced a short list of mitochondrial proteins that may hold the key to the mechanisms by which SOD1 mutants cause mitochondrial dysfunction and neuronal death. It has laid the foundation for further detailed functional studies to elucidate the role of particular mitochondrial proteins, such as VDAC2, in the pathogenesis of familial ALS.

Mechanisms of angiotensin II and cAMP regulating the expression of angiotensin II type 1 (AT(1)) receptor mRNA were studied in neonatal rat cardiomyocytes. Angiotensin II induced a transient decrease of AT(1)-mRNA expression in time- and dose-dependent manner. Maximal decrease (49.2 +/- 9.5% of control) occurred at 6 h of angiotensin II (10 nmol/l) treatment. AT(1) receptor antagonists 4-ethyl-2-n-propyl-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxylic acid (DMP811) and losartan as well as 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) reversed the down-regulation of AT(1)-mRNA expression. 6 h of phorbol 12-myristate 13-acetate (PMA) stimulation caused a decrease of AT(1)-mRNA level. Treatment by angiotensin II plus actinomycin D for 6 h produced the same effect as actinomycin D alone. These results suggest that angiotensin II down-regulates AT(1)-mRNA level of rat cardiomyocytes by inhibiting the transcription of AT(1) gene, which is mediated by AT(1) receptor and related to the activation of protein kinase C. Stimulation by forskolin plus 3-isobutyl-1-methyl-xanthine (IBMX) decreased the expression of AT(1)-mRNA to 68.1 +/- 21.5% of control at 6 h treatment; while increased to 207.9 +/- 27.1% of control at 48 h treatment. A series of 5'-upstream deletion mutants of AT(1A) promoter were produced and then were recombined with pGL(3) basic vector utilizing luciferase as reporter gene. Among all the constructors, p(-201/+ 74)Luc was of the highest luciferase activity (5.9 times higher than control) after stimulation by forskolin for 48 h. Further deletion from -201 to -61 resulted in a large decrease of activity. These results indicate that cAMP induces a time-dependent bi-directional regulation of AT(1)-mRNA expression. The cAMP responsible element (CRE) cis-element located in the region -201/-61 of rat AT(1A) promoter is forskolin inducible, which may mediate the up-regulation of AT(1)-mRNA expression induced by cAMP long-lasting stimulation.

Summary This paper proposes an identification framework based on a restricted Boltzmann machine (RBM) for crack identification and extraction from images containing cracks and complicated background inside steel box girders of bridges. The original images that include fatigue crack and other background information are obtained by a consumer-grade camera inside the steel box girder. The original images are cut into a number of elements with small size as the input dataset, and a state representation vector is artificially labeled to every image element used for the crack identification. A deep learning model or network consisting of multiple processing RBM layers to learn the abstract features is constructed to match the input image elements with corresponding state representation vectors. Next, a three-layer RBM with 500; 500; and 2,000 hidden units is trained as the hidden layers in the deep learning network. A contrastive divergence learning algorithm is employed for training the deep network to update and obtain the optimal parameters (i.e., the biases and weights). The new input image elements labeled as crack are sorted out and assembled to form an output image. A deep network is modeled through the consumer-grade camera images containing cracks and complicated background information using the proposed approach. The accuracy and ability to identify cracks from new images with different resolutions using the trained deep network are validated. Furthermore, effects of element size on reconstruction error and identification accuracy are investigated. The results show that there exists optimal element size; that is, too small and too large element sizes both increase the reconstruction error and decrease the identification accuracy.

Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of progressive renal function decline and affects millions of people. In a recent study, 30% of SRNS cases evaluated were the result of monogenic mutations in 1 of 27 different genes. Here, using homozygosity mapping and whole-exome sequencing, we identified recessive mutations in kidney ankyrin repeat-containing protein 1 (KANK1), KANK2, and KANK4 in individuals with nephrotic syndrome. In an independent functional genetic screen of Drosophila cardiac nephrocytes, which are equivalents of mammalian podocytes, we determined that the Drosophila KANK homolog (dKank) is essential for nephrocyte function. RNAi-mediated knockdown of dKank in nephrocytes disrupted slit diaphragm filtration structures and lacuna channel structures. In rats, KANK1, KANK2, and KANK4 all localized to podocytes in glomeruli, and KANK1 partially colocalized with synaptopodin. Knockdown of kank2 in zebrafish recapitulated a nephrotic syndrome phenotype, resulting in proteinuria and podocyte foot process effacement. In rat glomeruli and cultured human podocytes, KANK2 interacted with ARHGDIA, a known regulator of RHO GTPases in podocytes that is dysfunctional in some types of nephrotic syndrome. Knockdown of KANK2 in cultured podocytes increased active GTP-bound RHOA and decreased migration. Together, these data suggest that KANK family genes play evolutionarily conserved roles in podocyte function, likely through regulating RHO GTPase signaling.

Significant progress has been made in critical care medicine during the past several decades. However, the mortality rate is still high in patients with sepsis, especially with acute kidney injury (AKI). Mesenchymal stem cells (MSCs) possess an ability to ameliorate renal injury from ischemia-reperfusion, but it is still unknown whether they have the ability to reduce sepsis-associated AKI.Male C57BL/6 mice underwent cecal ligation and puncture operation to induce sepsis and then received either normal saline or MSCs (1 × 10 cells intravenously) 3 h after surgery.Within 24 h after cecal ligation and puncture operation, the septic mice developed kidney injury and exhibited a higher mortality. Treatment with MSCs decreased serum creatinine and blood urea nitrogen levels and improved recovery of tubular function. mRNA levels of interleukin 6 (IL-6), IL-17, tumor necrosis factor α, interferon γ, CXCL1, CXCL2, CXCL5, CCL2, and CCL3 in kidney tissue were dramatically decreased after MSC treatment. Neutrophil infiltration in kidney and blood bacterial loads were attenuated after MSC injection. Moreover, mice treated with MSCs had a higher survival rate than the saline treatment group. Injected MSCs were mainly localized in the lungs, spleen, and abdominal cavity lymph node, but not in the kidneys.Treatment with MSCs can alleviate sepsis-associated AKI and improve survival in mice with polymicrobial sepsis. These effects may be mediated by the inhibition of IL-17 secretion and balance of the proinflammatory and anti-inflammatory states. Mesenchymal stem cells may be a potential new therapeutic agent for the prevention or reduction of sepsis-associated AKI.

A moving loads distribution identification method for cable-stayed bridges based on compressive sampling (CS) technique is proposed. CS is a technique for obtaining sparse signal representations to underdetermined linear measurement equations. In this paper, CS is employed to localize moving loads of cable-stayed bridges by limit cable force measurements. First, a vehicle-bridge model for cable-stayed bridges is presented. Then the relationship between the cable force and moving loads is constructed based on the influence lines. With the hypothesis of sparsity distribution of vehicles on bridge deck (which is practical for long-span bridges), the moving loads are identified by minimizing the ‘l2-norm of the difference between the observed and simulated cable forces caused by moving vehicles penalized by the ‘l1-norm’ of the moving load vector. The resultant minimization problem is convex and can be solved efficiently. A numerical example of a real cable-stayed bridge is carried out to verify the proposed method. The robustness and accuracy of the identification approach with limit cable force measurement for multi-vehicle spatial localization are validated.

The insect nephrocyte and the mammalian glomerular podocyte are similar with regard to filtration, but it remains unclear whether there is an organ or cell type in flies that reabsorbs proteins. Here, we show that the Drosophila nephrocyte has molecular, structural, and functional similarities to the renal proximal tubule cell. We screened for genes required for nephrocyte function and identified two Drosophila genes encoding orthologs of mammalian cubilin and amnionless (AMN), two major receptors for protein reabsorption in the proximal tubule. In Drosophila, expression of dCubilin and dAMN is specific to nephrocytes, where they function as co-receptors for protein uptake. Targeted expression of human AMN in Drosophila nephrocytes was sufficient to rescue defective protein uptake induced by dAMN knockdown, suggesting evolutionary conservation of Cubilin/AMN co-receptors function from flies to humans. Furthermore, we found that Cubilin/AMN-mediated protein reabsorption is required for the maintenance of nephrocyte ultrastructure and fly survival under conditions of toxic stress. In conclusion, the insect nephrocyte combines filtration with protein reabsorption, using evolutionarily conserved genes and subcellular structures, suggesting that it can serve as a simplified model for both podocytes and the renal proximal tubule.

An identification method based on interval analysis for moving forces on cable-stayed bridge with uncertain parameters and noisy measurements is presented. Although there have been many reports on moving force identification methods on bridges, they did not pay much attention to the problem of identifying loads on cable-stayed bridge. And the uncertainties of measurements and bridge parameters were ignored in previous studies. The influence matrix model of cable-stayed bridge was established from the finite element model or in-field test in this study - if using in-field test only, the proposed method will be a model-free method. The upper and lower bound of the identified loads is analyzed based on the interval theory, which is caused by the uncertainties of two kinds: 1) noisy cable tension force measurements; 2) uncertain bridge parameters or influence line test noise. The numerical demonstration and validation are carried out based on Nanjing No.3 Yangtze River Bridge. The main contributions of this paper are: a. to propose an identification method for cable-stayed bridge with uncertain parameters and noisy measurements; b. the location, speed and magnitude of vehicle loads can be estimated simultaneously with the upper and lower bounds.