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Investigating the dynamics and distribution of soil phosphorus (P) fractions can provide a basis for enhancing P utilization by crops. Four treatments from a 29-year long-term experiment in black soil with maize cropping were involved in this study: no fertilizer (CK), inorganic nitrogen and potassium (NK), inorganic nitrogen, phosphorus, and potassium (NPK), and NPK plus manure (NPKM). We analyzed soil P fractions in different soil layers using a modified Hedley sequential method. The long-term NPKM treatment significantly increased total P by 0.6–1.6 times in the different soil layers. The Olsen-P concentration far exceeded the environmental threshold for soil Olsen-P (50.6 mg kg−1) in the NPKM treatment in the 0–60 cm soil profile. Moreover, the concentrations and proportion of labile and partially labile inorganic P (Pi) fractions (i.e., NaHCO3-extracted Pi, NaOH-extracted Pi, and dilute HCl-extracted Pi) to the sum of all P fractions (Pt) in the 0–60 cm soil profile were higher in the NPKM treatment than in the NPK treatment, indicating that manure could promote the transformation of non-labile into more labile forms of P in soil, possibly by manure reducing P fixation by soil particles. Soil organic matter, Mehlich-3 extractable iron (Fe), and organic-bound aluminum were increased by fertilization, and were the main factors influencing the differences in the P fractions in the 0–20 cm soil layer. Soil mineral components, i.e., free Fe oxide and CaCO3, were the main factors influencing the P fractions in the subsoil. The soil P transformation process varied with soil layer and fertilization. Application of manure fertilizer can increase the labile (Olsen) P concentrations of the various soil layers, and thus should reduce the mineral P fertilizer requirement for crop growth and reduce potential environmental damage.

Only a small number of genes are bona fideoncogenes and tumor suppressors such as Ras, Myc, β-catenin, p53, and APC. However, targeting these cancer drivers frequently fail to demonstrate sustained cancer remission. Tumor heterogeneity and evolution contribute to cancer resistance and pose challenges for cancer therapy due to differential genomic rearrangement and expression driving distinct tumor responses to treatments. Here we report that intratumor heterogeneity of Wnt/β-catenin modulator δ-catenin controls individual cell behavior to promote cancer. The differential intratumor subcellular localization of δ-catenin mirrors its compartmentalization in prostate cancer xenograft cultures as result of mutation-rendered δ-catenin truncations. Wild-type and δ-catenin mutants displayed distinct protein interactomes that highlight rewiring of signal networks. Localization specific δ-catenin mutants influenced p120ctn-dependent Rho GTPase phosphorylation and shifted cells towards differential bFGF-responsive growth and motility, a known signal to bypass androgen receptor dependence. Mutant δ-catenin promoted Myc-induced prostate tumorigenesis while increasing bFGF-p38 MAP kinase signaling, β-catenin-HIF-1α expression, and the nuclear size. Therefore, intratumor δ-catenin heterogeneity originated from genetic remodeling promotes prostate cancer expansion towards androgen independent signaling, supporting a neomorphism model paradigm for targeting tumor progression.

ABSTRACTTight junctions (TJs) are the most apical components of junctional complexes in epithelial and endothelial cells. Barrier function is one of the major functions of TJ, which restricts the ions and small water-soluble molecules from passing through the paracellular pathway. Adherens junctions (AJs) play an important role in cell–cell adhesion and cell signaling. Gap junctions (GJs) are intercellular channels regulating electrical and metabolic signals between cells. It is well known that TJ integral membrane proteins, such as claudins and occludins, are the molecular building blocks responsible for TJ barrier function. However, recent studies demonstrate that proteins of other junctional complexes can influence and regulate TJ barrier function. Therefore, the crosstalk between different cell junctions represents a common means to modulate cellular activities. In this review, we will discuss the interactions among TJ, AJ, and GJ by focusing on how AJ and GJ proteins regulate TJ barrier function in different biological systems.

ABSTRACTCdc42 is a member of the Rho family of small GTPases that are at the crossroads of major oncogenic signaling pathways involved in both lung and prostate cancers. However, the therapeutic potential of Cdc42 regulation is still unclear due to the lack of pharmacological tools. Herein, we report that ZCL367 is a bona fideCdc42 inhibitor that suppressed cancer development and ZCL278 can act as a partial Cdc42 agonist. In lung cancer cell lines with varying EGFR and Ras mutations as well as both androgen-independent and androgen-dependent prostate cancer cell lines, ZCL367 impeded cell cycle progression, reduced proliferation, and suppressed migration. ZCL367 decreased Cdc42–intersectin interactions and reduced Cdc42-mediated filopodia formation. ZCL367 showed increased potency and selectivity for Cdc42 when compared to Rac1 and RhoA. ZCL367 reduced A549 tumorigenesis in a xenograft mouse model. Altogether, ZCL367 is a selective Cdc42 inhibitor and an excellent candidate for lead compound optimization for further anticancer studies.

Reverse hybrid therapy, modified from the hybrid regimen by changing the sequence of drug administration, achieves a high eradication rate for Helicobacter pyloriand is superior to standard triple therapy. Currently, the impacts of different proton pump inhibitors on the efficacy of this novel therapy remain unanswered. This study was conducted to compare the efficacies of esomeprazole- and pantoprazole-based reverse hybrid therapies for H. pylorieradication. From August 2015 to May 2016, H. pylori-infected patients receiving either a 14-day esomeprazole- or a pantoprazole-based reverse hybrid therapy (esomeprazole or pantoprazole 40?mg and amoxicillin 1?g twice-daily for 14 days, plus clarithromycin 500?mg and metronidazole 500?mg twice-daily for the initial seven days) for H. pylorieradication were included in the retrospective study. All the patients underwent a follow-up endoscopy with a rapid urease test and histological examination or a urea breath test at eight weeks after the end of anti-H. pyloritherapy to assess H. pyloristatus. To determine the independent factors affecting the treatment response, 12 clinical and endoscopic parameters were analyzed by multivariate analysis. In all, 123 H. pylori-infected outpatients were included for this study. Among them, 62 received the esomeprazole-based regimen and 61 received the pantoprazole-based regimen. Intention-to-treat (ITT) analysis demonstrated no differences in eradication rate between esomeprazole- and pantoprazole-based groups (90% vs 97%; P?=?0.273). Modified ITT (90% vs 98%) and per-protocol analysis (92% vs 98%) yielded similar results (P?=?0.115 and 0.116, respectively). Both groups had comparable frequencies of adverse events (16% vs 21%; P?=?0.779) and drug compliance (98% and 93%; P?=?0.207). The eradication rates were significantly related to increased body fat percentage (P?=?0.002) and the presence of diabetes (P?=?0.033). Multivariate analysis disclosed an increased body fat percentage (odds ratio: 0.072, 95% confidence interval: 0.008-0.623), which was the only independent predictor of treatment failure. Esomeprazole- and pantoprazole-based reverse hybrid regimens have comparable anti-H. pyloriefficacy and both achieve an eradication rate more than 90%. Increased body fat percentage is a clinical factor predicting eradication failure of reverse hybrid therapy.

Background:Necrotizing enterocolitis (NEC) is a devastating condition affecting premature infants and leads to high mortality and chronic morbidity. Severe form of NEC is associated with acute renal failure, fluid imbalance, hyponatremia, and acidosis. We investigated the effect of NEC on tight junction (TJ) proteins in kidneys using a NEC mouse model to investigate the basis for the observed renal dysfunction.Methods:NEC was induced in C57BL/6 mice by formula feeding and subjecting them to periods of hypoxia and cold stress. NEC was confirmed by gross and histological examination. We studied various markers of inflammation in kidneys and investigated changes in expression of several TJ proteins and AQP2 using immunofluorecent staining and western blotting.Results:We found markedly increased expression of NF?B, TGFß, and ERK1/2 along with claudin-1, -2, -3, -4, -8, and AQP-2 in NEC kidneys. The membrane localization of claudin-2 was altered in the NEC kidneys and its immunostaining signal at TJ was disrupted.Conclusion:NEC led to a severe inflammatory response not only in the gut but also in the kidneys. NEC increased expression of several TJ proteins and caused disruption of claudin-2 in renal tubules. These observed changes can help explain some of the clinical findings observed in NEC.

Intravascular optical coherence tomography (IV-OCT) is a new intervention imaging technology for the diagnosis of coronary heart disease. Because of its high-resolution and non-invasive characteristics, it is widely used in clinical medicine. It has a revolutionary impact on coronary artery disease diagnosis, prognosis and treatment decisions. This paper studied this hot topic, gave the basic concepts of intravascular OCT image sequences. In accordance with current development studies, the key technology for three-dimensional reconstruction of the coronary vascular system is proposed and analyzed. On this basis, we proposed future research directions on IV-OCT vascular three-dimensional reconstruction, including clinical trial frequency domain OCT (OFDI), the combination of IV-OCT and intravascular ultrasound (IVUS) and a preliminary study of intravascular photoacoustic (IVPA) imaging.

Nance-Horan syndrome (NHS) is a rare X-linked disorder characterized by congenital nuclear cataracts, dental anomalies, and craniofacial dysmorphisms. Mental retardation was present in about 30% of the reported cases. The purpose of this study was to investigate the genetic and clinical features of NHS in a Chinese family. Whole exome sequencing analysis was performed on DNA from an affected male to scan for candidate mutations on the X-chromosome. Sanger sequencing was used to verify these candidate mutations in the whole family. Clinical and ophthalmological examinations were performed on all members of the family. A combination of exome sequencing and Sanger sequencing revealed a nonsense mutation c.322G〉T (E108X) in exon 1 of NHSgene, co-segregating with the disease in the family. The nonsense mutation led to the conversion of glutamic acid to a stop codon (E108X), resulting in truncation of the NHS protein. Multiple sequence alignments showed that codon 108, where the mutation (c.322G〉T) occurred, was located within a phylogenetically conserved region. The clinical features in all affected males and female carriers are described in detail. We report a nonsense mutation c.322G〉T (E108X) in a Chinese family with NHS. Our findings broaden the spectrum of NHSmutations and provide molecular insight into future NHS clinical genetic diagnosis. 通过对一个中国Nance-Horan 综合征家系的临床表型及基因突变分析, 揭示本家系的致病遗传机制。 对该Nance-Horan 综合征家系的一个男性患者进行全外显子组测序, 结合此家系临床表型及遗传方式分析, 选定X 染色体上NHS基因上的一个无义突变 c.322G〉T (E108X) 为可疑致病突变。 通过聚合酶链式反应 (PCR) 和Sanger 测序, 对该家系内其他成员进行NHS基因突变分析, 同时对50 名健康对照者的NHS基因的突变检测结果进行对比。 另外, 将该突变的位点第108 位氨基酸残基进行多物种NHS 蛋白内序列比对。 最后, 对该家系成员眼部及全身的临床特点进行全面检查和分析。 全外显子组测序结合Sanger 测序发现 NHS基因第一个外显子上的 c.322G〉T (E108X) 突变为引起该家系临床病变的突变位点; 多物种 NHS 蛋白内序列比对发现该突变位点第108 位氨基酸残基位于高度保守区; 临床表型分析发现该家系内存在表型异质性。 此家系为国内首次报道的无义突变引起的Nance-Horan 综合征家系。

Through the three-dimensional heat transfer simulation of different periodic running of 3×3 tube group during one running period, the article draw the influence of vertical buried tube heat exchanger heat transfer performance under the different start-stop times, when total time is certain, shortening the continuous time of intermittent operation (increasing the start and stop times) helps promote the unit energy efficiency as the outlet water temperature change of the heat exchanger is toward to the favorable direction, and the trend of the change showed first increased and then decreased with the increase of start-stop times. Increasing the number of start and stop times do more contribution to promote the energy efficiency of the heat pump unit under the Working condition of refrigeration.

Environmental awareness is currently significant caring in all industrial sectors, particularly in the animal industries. Animals are directly affected by environmental conditions and climate changes. Working dog is costly production in time and money to be successful. Health and temperament are key factors to be successful in training dog program. Working training dog school, NPUST is located in mountainous areas. The weather has frequently extreme change in temperature and humidity. The changes cause the heat in in-house and humidity in the air that may cause the dog illness. Therefore, working training dog school has to provide an appropriate kennel environment for all dogs throughout the training program. In order to secure the dogs, the automatic environmental sensing should be deployed. Web sensors and radio frequency identification (RFID) technologies were integrated, and have been implemented that are the weather sensing system and in-out control system, combining with health care management. Web based monitoring systems have provided based on user-friendly interface along with real-time information. In addition, it is very attractive use when the system operating via more convenient for computer and mobile communication devices.

This paper proposes a monitoring system for factory aquaculture, which collects data and sends them via wireless sensor network (WSN). This monitoring system consists of front-end equipment and upper computer. The front-end equipment is a wireless sensor network consisting of several sensor nodes with different functions and one coordinator node. The upper computer includes monitoring software to monitor the water quality parameters. We mainly focus on designing the solution of monitoring system, the connection circuit between RS232 and SP3232E, as well as the flow of sampling application. Experimental results show that our monitoring system can meet the basic requirements for monitoring the water quality parameters.

n order to improve the safety of coal mine production and ensure the safe working of production facilities, we propose a wireless monitoring system for coal mine safety called WMS. WMS adopts Bluetooth technology as its transmission protocol according to the coal mine environment. It is designed for collecting environmental parameters of coal mine and running status parameters of important production facilities. It transmits the collected data to the upper computer via wireless network based on Bluetooth. The upper computer receives the collected data and saves them for processing and displaying. Our research shows a new way for monitoring coal mine production and it is really efficient.

Buried pipe crossing faults is an important part of underground city lifeline, which is influenced by many factors. It is necessary to calculate Soil-Pipe-Fluid interaction that includes fluid-structure interaction (FSI) and pipe-soil interaction. Under multi-action of site, fault movement, and earthquake, finite element model of buried liquid-conveying pipe is established by ADINA. Two-way fluid-structure coupling methods for fluid-structure interaction and definition of contact for pipe-soil interaction are introduced. Pipe-soil friction is defined in solid model; especially, flow assumption and fluid structure interface condition are defined in fluid model. Damage of buried liquid-conveying pipe under soil-pipe-fluid action is calculated under fluid-structure coupling with pipe-soil interaction. Influences of site soil and liquid velocity on effective stress and circumferential strain of buried liquid-conveying pipe are analyzed, and some advice is proposed for pipe protection.

The article developed a five-lump kinetic model for delayed coking through needle coke. The kinetic parameters were determined using the experimental results of the genetic algorithm method. The results showed the calculated concentration distribution agreed well with the experimental results. The results of five-lump kinetic model that composed of parallel and serial reactions and their activation energy also showed that the thermal sensitivity of coal tar pitch declined and that the orderly orientation strengthened under external magnetic field. This facilitates the formation of wide mesophase pitch structures in thermal conversion.

High temperature medium in the thermal pipeline will affect distortion and stress distribution of the pipe wall, so its very important to analyze the thermal mechanical coupling in thermal pipeline. Numerical simulation of buried thermal pipeline damage under the earthquake action is carried by finite element method-ADINA. Three-dimensional finite element modeling considered site condition is investigated; geometry model is constructed with native and parasolid method in ADINA. Gravity and earthquake force are defined in structure model, and temperature load in thermal model. According to the results of thermal mechanical coupling, the damage of buried thermal pipeline is analyzed. Influence of single temperature load on the stress and strain of buried thermal pipeline is very small, but the stress and circumferential strain increase rapidly under earthquake action. Also, the axial strain is very complex. The temperature load mainly affects axial strain under gravity and earthquake load; the increasing temperature enables to reduce axial strain, which makes axial destruction reduced. Finally, some advice is proposed.

This paper progresses to dynamically simulate and study the heat transfer process of horizontal ground heat exchangers in the multi-grooves by the use of numerical simulation based on the layout and heat extraction or rejection conditions of horizontal ground heat exchangers under the artificial lake. Effect of buried pipe type and groove spacing on the heat exchanger process is analyzed in detail. The influence of annual average water temperature change on the surrounding environment is evaluated with the introduction of parameters including summer weekly average maximum temperature rise and winter weekly average maximum temperature drop, in which can take the technical supports for the design of horizontal ground source heat pump system.

According to the application conditions of horizontal ground heat exchanger(HGHE) under artificial lake, this paper uses numerical simulation method to do dynamic simulation research of the heat transfer performance of HGHE, analyzes the effect of connection mode and pipe flow velocity on heat transfer performance of HGHE in detail，puts forward efficient HGHE loop formation mode，and will provide effective technical support for ground-source heat pump system design with HGHE.

Chemical forms of phosphorus in source and treated drinking water were studied in this paper. Removal of total phosphorus (TP) and microbially available phosphorus (MAP) by conventional treatment process of drinking water was examined. The results showed that particulate phosphorus constituted of most TP in source water. Content of total soluble phosphate (TSP) was about 30% of TP. Soluble reactive phosphate (SRP) can be measured in a few months during a year and its content was very low. Content of MAP was higher than content of TSP in source water, which showed that microbe can also use particle phosphorus. Ratio of TSP to TP increased evidently in treated water. This demonstrated that removal of TSP was more difficult than particulate phosphorus in conventional treatment process for drinking water. Removal of TP and MAP in conventional treatment process of drinking water was effective, with averaged removal efficiency of 66% and 69%, respectively. Coagulation-sedimentation and filtration removed TP efficiently. Enhanced coagulation may increases removal efficiency of MAP. Lower content of MAP can control biostability of drinking water.

The content of assimilable organic carbon (AOC) has been proposed to control the growth of heterotrophic microbe in drinking water distribution systme. However, recent results have shown that there are regions where it is predominantly phosphorus which determines the extent of microbial growth in drinking water. The growth of bacteria was studied in a drinking water distribution system where the content of AOC was high (40.84- 551.35 μg acetate-C/L) and the content of Microbially Available Phosphorus (MAP) was also high (0.69-8.01 μg PO43--P/L). It was AOC other than phosphorus that controlled the growth of bacteria in the drinking water distribution system. Comparably obvious linear relationship was found between the maximum HPC and the maximum content of AOC of the distribution system. Removal of organic matters is ideal approach to control water quality of the drinking water distribution system.

Poly(lactic acid) (PLA)/graphene nanocomposites were prepared by solution blending using chloroform as a mutual solvent. Transmission electron microscopy (TEM) was used to examine the quality of the dispersion of graphene in the PLA matrix. The isothermal crystallization behaviors of PLA and PLA/graphene nanocomposites were investigated by differential scanning calorimetry (DSC). The isothermal crystallization kinetics were analyzed by Avrami model based on the DSC data. The results showed that the well dispersed graphene nanosheets could act as a heterogeneous nucleating agent and lead to an acceleration of crystallization during the PLA isothermal crystallization process. According to the Arrhenius equation, the activation energies were found to be -106.9 and -46.6 kJ/mol for pure PLA and PLA/0.1 wt % graphene nanocomposite, respectively. The crystal morphology were characterized with polarizing optical microscope (POM).

Taking the advantages of FPGA's low cost and compact structure, an FPGA-based heterogeneous image fusion platform is established in this study. Altera's Cyclone IV series FPGA is adopted as the core processor of the platform, and the visible light CCD camera and infrared thermal imager are used as the image-capturing device in order to obtain dualchannel heterogeneous video images. Tailor-made image fusion algorithms such as gray-scale weighted averaging, maximum selection and minimum selection methods are analyzed and compared. VHDL language and the synchronous design method are utilized to perform a reliable RTL-level description. Altera's Quartus II 9.0 software is applied to simulate and implement the algorithm modules. The contrast experiments of various fusion algorithms show that, preferably image quality of the heterogeneous image fusion can be obtained on top of the proposed system. The applied range of the different fusion algorithms is also discussed.

Because the temperature of heat medium in thermal recovery wells is very high, and casing is heated during steam injection process, which has become the main reason of casing failure. Therefore, it is very important to analyze crack propagation and casing failure under thermal mechanical coupling. Three-dimensional finite element model is investigated; geometry model is constructed with native and parasolid method in ADINA. The casing is modeled by native method and strata are modeled by parasolid method, casing are subtracted and merged with strata by Boolean Operation. Gravity and displacement loads are defined in structure model, and temperature load in thermal model. In structural model, casing is treated as thermoplastic material, and strata are treated as hot isotropic material. In thermal model, all materials are treated as heat conduction material. Thermal-mechanical coupling is calculated with the thermo-mechanical coupled analysis solver in ADINA, and casing damage process is calculated. According to the calculating results, the mechanism of casing damage is analyzed.

Coating is one of important parts in fiber-reinforced composite. Under cyclic loading, the effect of coating on interfacial fatigue is investigated based on double shear-lag model. Stresses of components are obtained. Relationship for analyzing interfacial debonding is established by the Paris Formula. Interfacial fatigue on fiber/coating and coating/matrix is simulated. It can be seen that interfacial debonding on different interfaces meet energy conservation law in general.

Claudin-7, a member of the claudin family, is highly expressed in distal nephrons of kidneys and has been reported to be involved in the regulation of paracellular Cl−permeability in cell cultures. To investigate the role of claudin-7 in vivo, we generated claudin-7 knockout mice (Cln7−/−) by the gene-targeting deletion method. Here we report that Cln7−/−mice were born viable, but died within 12 days after birth. Cln7−/−mice showed severe salt wasting, chronic dehydration, and growth retardation. We found that urine Na+, Cl−, and K+were significantly increased in Cln7−/−mice compared with that of Cln7+/+mice. Blood urea nitrogen and hematocrit were also significantly higher in Cln7−/−mice. The wrinkled skin was evident when Cln7−/−mice were ∼1 wk old, indicating that they suffered from chronic fluid loss. Transepidermal water loss measurements showed no difference between Cln7+/+and Cln7−/−skin, suggesting that there was no transepidermal water barrier defect in Cln7−/−mice. Claudin-7 deletion resulted in the dramatic increase of aldosterone synthase mRNA level as early as 2 days after birth. The significant increases of epithelial Na+channel α, Na+-Cl−cotransporter, and aquaporin 2 mRNA levels revealed a compensatory response to the loss of electrolytes and fluid in Cln7−/−mice. Na+-K+-ATPase α1expression level was also greatly increased in distal convoluted tubules and collecting ducts where claudin-7 is normally expressed. Our study demonstrates that claudin-7 is essential for NaCl homeostasis in distal nephrons, and the paracellular ion transport pathway plays indispensable roles in keeping ionic balance in kidneys.

Signaling through the Rho family of small GTPases has been increasingly investigated for their involvement in a wide variety of diseases such as cardiovascular, pulmonary, and neurological disorders as well as cancer. Rho GTPases are a subfamily of the Ras superfamily proteins which play essential roles in a number of biological processes, especially in the regulation of cell shape change, cytokinesis, cell adhesion, and cell migration. Many of these processes demonstrate a common theme: the rapid and dynamic reorganization of actin cytoskeleton of which Rho signaling has now emerged as a major switch control. The involvement of dynamic changes of Rho GTPases in disease states underscores the need to produce effective inhibitors for their therapeutic applications. Fasudil and Y-27632, with many newer additions, are two classes of widely used chemical compounds that inhibit Rho kinase (ROCK), an important downstream effector of RhoA subfamily GTPases. These inhibitors have been successful in many preclinical studies, indicating the potential benefit of clinical Rho pathway inhibition. On the other hand, except for Rac1 inhibitor NSC23766, there are few effective inhibitors directly targeting Rho GTPases, likely due to the lack of optimal structural information on individual Rho-RhoGEF, Rho- RhoGAP, or Rho-RhoGDI interaction to achieve specificity. Recently, LM11A-31 and other derivatives of peptide mimetic ligands for p75 neurotrophin receptor (p75NTR) show promising effects upstream of Rho GTPase signaling in neuronal regeneration. CCG-1423, a chemical compound showing profiles of inhibiting downstream of RhoA, is a further attempt for the development of novel pharmacological tools to disrupt Rho signaling pathway in cancer. Because of a rapidly growing number of studies deciphering the role of the Rho proteins in many diseases, specific and potent pharmaceutical modulators of various steps of Rho GTPase signaling pathway are critically needed to target for therapeutic intervention in cardiovascular disease, neurological disorders, and cancer progression.

Bonding degradation at interface is one of main damage forms of composites, especially under fatigue loading. Interfacial bonding degradation of FRC under two-stage tension loading is studied, which is base for variable-amplitude cyclic loading existing widely in actual engineering. Based on the shear-lag model and considered the asymmetry of interfacial damage, the mechanical governing equations of fiber and matrix are established and related solutions are obtained firstly. Two kinds of loading models are chosen, one is low-high alternate loading, and the other is low early and high late loading. By the aid of the Paris law and the energy release theory, a relationship between debond rate and cycle number is established. Then the interfacial debonding is simulated under the two-stage tension loading. The rules of the crack growth are analyzed for low-high two-stage loadings. It is found that stress amplitude has great influence on interfacial debonding under two-stage loading. Low stress amplitude in a certain range can postpone interfacial bonding degradation. And interfacial damage extent is greater than that under constant-amplitude fatigue loading. Present study is helpful for analyzing the fatigue damage of engineering materials and structures.

It was shown that active queue management schemes implemented in the routers of communication networks supporting transmission control protocol (TCP) flows can be modelled as a feedback control system. In this paper based on Lyapunov function we developed an optimal controller to improve active queue management (AQM) router’s stability and response time, which are often in conflict with each other in system performance. Ns-2 simulations showed that optimal controller outperforms PI controller significantly.

We prospectively evaluated whether combined antenatal corticosteroid and vitamin K administration have any benefit, over and above that of corticosteroid or vitamin K used alone, in reducing the frequency and the degree of PIVH in premature newborns less than 35 weeks’ gestation. All of these 280 pregnant women were randomly allocated into five groups according to the in-patient sequence. Group A (vitamin K1 group) including 38 pregnant women (40 newborns) received antenatal intramuscular or intravenously injection of vitamin K1 10 mg per day for 2–7 days. Group B (single dose corticosteroid group) including 57 pregnant women (63 newborns) received antenatal intramuscular or intravenously injection of dexamethasone 10 mg per day for 1 day. Group C (two dose corticosteroid group) including 62 pregnant women (70 newborns) received antenatal intramuscular or intravenously injection of dexamethasone 10 mg per day for 2 days. Group D (combined using dexamethasone and vitamin K1) including 41 pregnant women (44 newborns) received dexamethasone 10 mg per day for 1 day and vitamin K110 mg per day for 2–7 days. Control group, including 82 pregnant women (87 newborns) were received neither dexamethasone nor vitamin K1 injection. The results showed PIVH was diagnosed in 17 of 40 (42.5%) in Group A, 34 of 63 (54.0%) in Group B, 36 of 70 (51.4%) in Group C, 14 of 44 (31.8%) in Group D, and 57 of 87 (65.2%) in control infants (p = 0.004). More infants in the control group had grade III or IV intracranial hemorrhage after birth (p = 0.049). After antenatal supplement of dexamethasone and vitamin K1, both the total incidence of PIVH and the frequency of severe PIVH decreased significantly. The total and severe incidence of PIVH in Group B (single doses dexamethasone) and Group C (two courses dexamethasone) there were no significant difference. It showed that after antenatal supplement of dexamethasone and vitamin K1, both the total incidence of PIVH and the frequency of severe PIVH decreased significantly, and combined antenatal corticosteroid and vitamin K administration have much benefit, over and above that of corticosteroid or vitamin K used alone.

Occludin is an integral membrane protein that is tyrosine phosphorylated when localized at tight junctions. When Ca2+was depleted from the culture medium, occludin tyrosine phosphorylation was diminished from Madin-Darby canine kidney epithelial cells in 2 min. This dephosphorylation was correlated with a significant reduction in transepithelial electrical resistance (TER), indicating a global loss of the tight junction barrier function. Reconstitution of Ca2+resulted in a robust tyrosine rephosphorylation of occludin that was temporally associated with an increase in TER. Moreover, we demonstrate in this study that occludin was colocalized with the nonreceptor tyrosine kinase c-Yes at cell junction areas and formed an immunoprecipitable complex with c-Yes in vivo. This complex dissociated when the cells were incubated in medium without Ca2+or treated with a c-Yes inhibitor, CGP77675. In the presence of CGP77675 after Ca2+repletion, occludin tyrosine phosphorylation was completely abolished and both tight junction formation and the increase of the TER were inhibited. Our study thus provides strong evidence that occludin tyrosine phosphorylation is tightly linked to tight junction formation in epithelial cells, and that the nonreceptor tyrosine kinase c-Yes is involved in the regulation of this process.

In the Madin-Darby canine kidney epithelial cell line, the proteins occludin and ZO-1 are structural components of the tight junctions that seal the paracellular spaces between the cells and contribute to the epithelial barrier function. In Ras-transformed Madin-Darby canine kidney cells, occludin, claudin-1, and ZO-1 were absent from cell–cell contacts but were present in the cytoplasm, and the adherens junction protein E-cadherin was weakly expressed. After treatment of the Ras-transformed cells with the mitogen-activated protein kinase kinase (MEK1) inhibitor PD98059, which blocks the activation of mitogen-activated protein kinase (MAPK), occludin, claudin-1, and ZO-1 were recruited to the cell membrane, tight junctions were assembled, and E-cadherin protein expression was induced. Although it is generally believed that E-cadherin–mediated cell–cell adhesion is required for tight junction assembly, the recruitment of occludin to the cell–cell contact area and the restoration of epithelial cell morphology preceded the appearance of E-cadherin at cell–cell contacts. Both electron microscopy and a fourfold increase in the transepithelial electrical resistance indicated the formation of functional tight junctions after MEK1 inhibition. Moreover, inhibition of MAPK activity stabilized occludin and ZO-1 by differentially increasing their half-lives. We also found that during the process of tight junction assembly after MEK1 inhibition, tyrosine phosphorylation of occludin and ZO-1, but not claudin-1, increased significantly. Our study demonstrates that down-regulation of the MAPK signaling pathway causes the restoration of epithelial cell morphology and the assembly of tight junctions in Ras-transformed epithelial cells and that tyrosine phosphorylation of occludin and ZO-1 may play a role in some aspects of tight junction formation.

We have investigated the effects of temperature on the conductance and voltage-dependent kinetics of cardiac gap junction channels between pairs of seven-day embryonic chick ventricle myocytes over the range of 14–26°C. Records of junctional conductance (Gj) and steady-state unit junctional channel activity were made using the whole-cell double patch-clamp technique while the bath temperature was steadily changed at a rate of about 4°C/min. The decrease inGjupon cooling was biphasic with a distinct break at 21°C. In 12 cell pairs,Q10was 2.2 from 26 to 21°C, while between 21 and 14°C it was 6.5. The meanGjat 22°C (Gj22) was 3.0±2.1 nS, ranging in different preparations from 0.24 to 6.4 nS. At room temperature, embryonic cardiac gap junctions contain channels with conductance states near 240, 200, 160, 120, 80 and 40 pS. In the present study, we demonstrate that cooling decreases the frequency of channel openings at all conductance levels, and at temperatures below 20°C shifts the prevalence of openings from higher to lower conductance states: all 240 pS openings disappear below 20°C; 200 pS openings are suppressed at 17°C; below 16°C 160 and 120 pS events disappear and only 80 and 40 pS states are seen. Temperature also affected the voltage-dependent kinetics of the channels. Application of a 6 sec, 80 mV voltage step across the junction (Vj80) caused a biexponential decay in junctional conductance. Decay was faster at lower temperatures, whereas the rate of recovery ofGjafter returning toVj0was slowed. Cooling reduced the fast decay time constant, increased both recovery time constants, and decreased the magnitude of GitGjdecay, thus leaving a 10–16% larger residual conductance (Gss/Ginit,±80 mVVj) at 18 than at 22°C. From these results we propose that embryonic chick cardiac gap junctions contain at least two classes of channels with different conductances and temperature sensitivities.

Formation of the blastocoel in earlyXenopusembryos was studied with a novel biotin-permeability assay and newly generated tight junction markers. The blastocoel forms at the first cleavage division since functional tight junctions which excluded biotin and established a segregated intraembryonic compartment were found at the 2-cell and all subsequent developmental stages. Unexpectedly, tight junctions before the 64-cell stage were not at their normal apical positions, but were found deep in the embryos, up to 200 μm from the apical surface. In these positions, the tight junctions left large areas of ion permeable lateral membranes exposed to the extraembryonic environment, explaining why electrophysiological experiments record a decrease in embryonic input resistances concomitant with early cleavage stages. Immunohistochemistry revealed that the recessed tight junctions did not influence the distribution of C-cadherin and Na+,K+ATPase. Both markers were present apical to recessed tight junctions, indicating that the maintenance of polarization of these basolateral markers does not require tight junctions. With further development, tight junctions assumed an increasingly apical location until, by the 2000-cell stage, they occupied their conventional positions between the blastomeres at the apical/lateral membrane boundaries.

We used the double whole-cell voltage-clamp technique on ventricle cell pairs isolated from 7-day chick heart to measure the conductance of their gap junctions (Gj) and junctional channels (?j) with a steady-state voltage difference (Vj) applied across the junction. Currents were recorded from single gap junction channels (ij) as symmetrical rectangular signals of equal size and opposite sign in the two cells, and ?j was measured from ij/Vj. We observed channel openings at six reproducible conductance levels with means of 42.6, 80.7, 119.6, 157.7, 200.4 and 240.3 pS. More than half of all openings were to the 80-and 160-pS conductance levels. The probability that a high conductance event (e.g., 160 or 240 pS) results from the random simultaneous opening of several 40-pS channels is small, based on their frequency of occurrence and on the prevalence of shifts between small and large conductance states with no intervening 40-pS steps. Our results are consistent with three models of embryonic cardiac gap junction channel configuration: a homogeneous population of 40-pS channels that can open cooperatively in groups of up to six; a single population of large channels with a maximal conductance near 240 pS and five smaller substates; or several different channel types, each with its own conductance.

ABSTRACTThe intestinal epithelial cells line the luminal surface of the entire gastrointestinal tract which is crucial for the absorption of nutrients and prevention of pathogens entering from the external environment. The epithelial barrier plays an important role in organ development, disease pathogenesis, and aging. The major component of an epithelial barrier is the single columnar epithelium and tight junctions. Tight junctions are located at the most apical region of the junctional complex and contain many integral membrane proteins, such as occludin, the claudin family, and junctional adhesion molecules (JAMs). The disruption of intestinal epithelial barriers may lead to several pathophysiological conditions causing malabsorption of nutrition and chronic inflammation. In this review, we provide an update on the alterations of epithelial barriers associated with gut diseases using experimental animal models; we appraise the role of tight junctions in neonatal necrotizing enterocolitis (NEC), inflammatory bowel disease (IBD), and colorectal cancer; we also compare some common features as well as differences and similarities in the pathophysiology of intestinal inflammation in neonatal (NEC) and adult (IBD) gut.

Members of the claudin family of tight junction proteins are critical for establishing epithelial barriers and for the regulation of paracellular transport. To understand their roles during kidney development, we first performed RT-PCR analyses and determined that 23 claudin family members were expressed in embryonic day (E) 13.5 mouse kidneys. Based on their developmental expression and phenotypes in mouse models, we hypothesized that 3 claudin members could affect nephron formation during kidney development. Using whole mount in situhybridization and immunohistochemistry, we demonstrated that Claudin-7(Cldn7) was expressed in the nephric duct, the emerging ureteric bud, and in tubules derived from ureteric bud branching morphogenesis. In contrast, Claudin-16(Cldn16) and Claudin-19(Cldn19) were expressed at later stages of kidney development in immature renal tubules that become the Loop of Henle. To determine if a loss of these claudins would perturb kidney development, we examined newborn kidneys from mutant mouse models lacking Cldn7or Cldn16. In both models, we noted no evidence for any congenital renal malformation and quantification of nephron number did not reveal a decrease in nephron number when compared to wildtype littermates. In summary, Cldn7, Cldn16,and Cldn19are expressed in different epithelial lineages during kidney development. Mice lacking Cldn7or Cldn16do not have defects in de novonephron formation, and this suggests that these claudins primarily function to regulate paracellular transport in the mature nephron.