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Modeling of fluid flow in porous media is a pillar in geoscience applications. Previous studies have revealed that heterogeneity and fracture distribution have considerable influence on fluid flow. In this work, a numerical investigation of two-phase flow in heterogeneous fractured reservoir is presented. First, the discrete fracture model is implemented based on a hybrid-dimensional modeling approach, and an equivalent continuum approach is integrated in the model to reduce computational cost. A multilevel adaptive strategy is devised to improve the numerical robustness and efficiency. It allows up to 4-levels adaption, where the adaptive factors can be modified flexibly. Then, numerical tests are conducted to verify the the proposed method and to evaluate its performance. Different adaptive strategies with 3-levels, 4-levels and fixed time schemes are analyzed to evaluate the computational cost and convergence history. These evaluations demonstrate the merits of this method compared to the classical method. Later, the heterogeneity in permeability field, as well as initial saturation, is modeled in a layer model, where the effect of layer angle and permeability on fluid flow is investigated. A porous medium containing multiple length fractures with different distributions is simulated. The fine-scale fractures are upscaled based on the equivalent approach, while the large-scale fractures are retained. The conductivity of the rock matrix is enhanced by the upscaled fine-scale fractures. The difference of hydraulic property between homogeneous and heterogeneous situations is analyzed. It reveals that the heterogeneity may influence fluid flow and production, while these impacts are also related to fracture distribution and permeability. Article highlights: A multilevel adaptive implicit scheme up to 4-levels adaption is presented for two-phase ow in heterogeneous fractured reservoir. Discrete fracture model is combined with an equivalent continuum approach to reduce the complexity of fracture networks. The effects of permeability, orientation, size and number of fractures on hydraulic properties are studied. A comparison study of fluid flow and numerical performance between homogeneous and heterogeneous media is conducted. [ABSTRACT FROM AUTHOR]

Jackfruit is one of the major tropical fruits, but information on the phytochemicals and biological benefits of its pulp is limited. In this study, the phytochemicals and biological activities including antioxidant, antitumor and anti-inflammatory activities of five jackfruit pulp cultivars (M1, M2, M3, M7 and T5) were comparatively investigated. A total of 11 compounds were identified in all cultivars of jackfruit pulp, among which 4-hydroxybenzoic acid, caffeic acid, ferulic acid and tryptophan N-glucoside were reported for the first time in jackfruit. T5 exhibited the highest total phenolic content (7.69 ± 0.73 mg GAE/g DW), antioxidant capacity (109.8, 96.7 and 207 mg VCE/g DW for DPPH, ABTS and FRAP, respectively), antitumor activity (80.31%) and anti-inflammatory activity (78.44%) among five cultivars. These results can provide a reference for growers to choose jackfruit cultivar and offer an insight into the industrial application of jackfruit pulp derived-products. [ABSTRACT FROM AUTHOR]

Subsurface stormflow is a dominant runoff mechanism in steep humid mountainous areas. An insite measurement of subsurface stormflow suggests that the bedrock surface plays an important role in the runoff generation and routing process, which was rarely adopted in hydrological modelling studies. To improve the runoff simulation performance, the bedrock surface topographic index is introduced, and a modified TOPMODEL based on the bedrock surface topographic index is developed to simulate the runoff. The modified TOPMODEL is applied to the Huangbengliu (HBL), a steep watershed in Gongga Mountain, and proved to be more appropriate for the HBL watershed, especially for peak simulation. The Nash-Sutcliffe model efficiency (NSE) is improved from 0.24 to 0.58 in the calibration period and from 0.40 to 0.62 in the verification period. The result of this study can advance the understanding of the mechanism of flash floods and contribute flood control and disaster prevention in the HBL watershed and similar areas. [ABSTRACT FROM AUTHOR]

Landslides, collapses and cracks are the main types of geological hazards, which threaten the safety of human life and property at all times. In emergency surveying and mapping, it is time-consuming and laborious to use the method of field artificial investigation and recognition and using satellite image to identify ground hazards, there are some problems, such as time lag, low resolution, and difficult to select the map on demand. In this paper, a 10 cm per pixel resolution photogrammetry of a geological hazard -prone area of Taohuagou, Shanxi Province, China is carried out by DJ 4 UAV. The digital orthophoto model (DOM), digital surface model (DSM) and three-dimensional point cloud model (3 DPCM) are generated in this region. The method of visual interpretation of cracks based on DOM (as main) -3DPCM (as auxiliary) and landslide and collapse based on 3DPCM (as main) — DOM and DSM (as auxiliary) are proposed. Based on the low altitude remote sensing image of UAV, the shape characteristics, geological characteristics and distribution of the identified hazards are analyzed. The results show that using UAV low altitude remote sensing image, the method of combination of main and auxiliary data can quickly and accurately identify landslide, collapse and crack, the accuracy of crack identification is 93%, and the accuracy of landslide and collapse identification is 100%. It mainly occurs in silty clay and mudstone geology and is greatly affected by slope foot excavation. This study can play a great role in the recognition of sudden hazards by low altitude remote sensing images of UAV. [ABSTRACT FROM AUTHOR]

Installation time of ground support in many caverns excavation is mainly based on analytical and empirical method, instead of the robust numerical simulations. A novel graph method is proposed to determine the installation time of the support upon finite difference method (FDM) simulation. A three dimensional numerical model for the diversion tunnel of Guandi hydropower station is developed. The curve d-r between the convergence d and the excavation unloading rate r is built up upon one-step excavation simulation. Meanwhile, the curve d-l between d and the distance from the tunnel face l, is established via the step-by-step simulation. Using the dimensionless convergence λ instead of d in both curve d-r and curve d-l, curve λ-r and curve λ-l can be yielded to achieve the composite graph r-λ-l. When r = r0, l can be chose as l0 along the identical λ in the comprehensive graph r-λ-l, where r is the excavation unloading rate at the critical plastic state and l0 is the distance from the tunnel face to the support installation location. The proposed graph method is demonstrated to meet well with common sense upon the diversion tunnel of Guandi hydropower station and can be conveniently realized in other engineering practice. [ABSTRACT FROM AUTHOR]

Topography is a crucial characteristic reflecting the stability status of a landslide dam. The methods for measuring landslide dam topography in a laboratory-scale test study are currently operator dependent, time-consuming, or only applicable to the measurement of the two-dimensional section. In this paper, a laboratory-scale photogrammetric method based on the structure from motion (SfM) technique was proposed to measure the three-dimensional (3D) topography of a landslide dam. The SfM technique, which is a revolutionary, low-cost, user-friendly computer vision technique, was employed for reconstructing a landslide dam 3D computer model. A scientific method to determine the topography parameters of a landslide dam was put forward. Meanwhile, two materials with different particle sizes were used to simulate the formation process of the landslide dam in the laboratory-scale. Then, the measurement results of the two materials were compared. Five parameters of a landslide dam topography with 100 parallel measurement results for each parameter were obtained. The results show that the SfM technique could build a high-quality 3D point cloud in a laboratory scale. The proposed method of determining the topography parameters of a landslide dam was useful and has low measurement uncertainty. The material type affected the sparse density of the point cloud and then affected the measurement uncertainty of landslide dam topography parameters. The measurement uncertainty of the gravel-type landslide dam was significantly higher than that of the sand-type landslide dam. This research contributes to promoting the application of a photogrammetric method based on the SfM technique in geotechnical engineering laboratory-scale tests. [ABSTRACT FROM AUTHOR]

Background: Despite the fact that thyroid surgery has evolved towards minimal incisions and endoscopic approaches, the role of total endoscopic thyroidectomy (TET) in thyroid cancer has been highly disputed. We performed a systematic review and meta-analyses of peer reviewed studies in order to evaluate the safety and effectiveness of TET compared with conventional open thyroidectomy (COT) in papillary thyroid cancer (PTC).Method: Medical literature databases such as PubMed, Embase, the Cochrane Library, and Web of science were systematically searched for articles that compared TET and COT in PTC treatment from database inception until March 2019. The quality of the studies included in the review was evaluated using the Downs and Black scale using Review Manager software Stata V.13.0 for the meta-analysis.Results: The systematic review and meta-analysis were based on 5664 cases selected from twenty publications. Criteria used to determine surgical completeness included postoperative thyroglobulin (TG) levels, recurrence of the tumor after long-term follow-up. Adverse event and complication rate scores included transient recurrent laryngeal nerve (RLN) palsy, permanent RLN palsy, transient hypocalcaemia, permanent hypocalcaemia, operative time, number of removed lymph nodes, length of hospital stay and patient cosmetic satisfaction. TET was found to be generally equivalent to COT in terms of surgical completeness and adverse event rate, although TET resulted in lower levels of transient hypocalcemia (OR 1.66; p < 0.05), a smaller number of the retrieved lymph nodes (WMD 0.46; p < 0.05), and better cosmetic satisfaction (WMD 1.73; p < 0.05). COT was associated with a shorter operation time (WMD - 50.28; p < 0.05) and lower rates of transient RLN palsy (OR 0.41; p < 0.05).Conclusions: The results show that in terms of safety and efficacy, TET was similar to COT for the treatment of thyroid cancer. Indeed, the tumor recurrence rates and the level of surgical completeness in TET are similar to those obtained for COT. TET was associated with significantly lower levels of transient hypocalcemia and better cosmetic satisfaction, and thus is the better option for patients with cosmetic concerns. Overall, randomized clinical trials and studies with larger patient cohorts and long-term follow-up data are required to further demonstrate the value of the TET. [ABSTRACT FROM AUTHOR]

In this work, the effect of mechanical damage on the thermal conductivity of granite was experimentally investigated. Granite samples were artificially damaged through cyclic loading and unloading tests, with the strain evolution and acoustic emission activity monitored simultaneously. P-Wave velocity of the damaged samples was tested to evaluate the damage effect. Thermal conductivity of the undamaged and damaged granite samples was tested using optical scanning method. The influence of mechanical damage on thermal conductivity was analyzed. Thermal conductivity difference in different testing directions was analyzed based on the experiment results in six scanning lines on the two surfaces of each disk sample. The results indicate that thermal conductivity of damaged samples reduced compared with that of the undamaged samples, while the thermal inhomogeneity factor increased. Thermal conductivity increased in water-saturated condition for both undamaged and damaged samples. The increased rate of damaged samples was bigger than that of the undamaged samples. The mechanical damage treatment caused the increase in the thermal conductivity difference in different testing directions. The difference decreased when samples were water saturated. Research results in this work can provide better knowledge to the evolution mechanism of thermal conductivity of engineering rock masses. [ABSTRACT FROM AUTHOR]

Enterovirus 71 (EV71) infection can cause hand–foot-and-mouth disease (HFMD). Inactivated EV71 vaccine was effective to prevent EV71 derived HFMD. A highly efficient and economical process for producing EV71 is needed. In our study, the epidemic strain of EV71 (EV71-2013ZJHFMD) was obtained and purified. The Vero cells were cultured for production of EV71. The mini-bioreactor vessel (Amprotein Inc., China) packed with a 0.6 g polymer fiber carrier was used to determine the best seeding cell density, multiplicity of infection (MOI) and temperature. Then the optimized procedure was further applied in a 10 L disposable perfusion bioreactor ACPB (AmProtein Current Perfusion Bioreactor). The Vero cell culture and viral titer were monitored. The seeding density of 1.5 × 107 cells per 0.6 g disk was considered to be the most appropriate for the culture. The best MOI was 0.1 and the temperature was 32 °C. The total cell number increased from 1.5 × 109 to 3.0 × 1010. The maximum viral titers reached 1.0 × 108/mL 3 days post-infection in our optimized special culture procedure (serum-free during the harvest period, supplemented with 0.25% Lactalbumin Hydrolysate). The total volume of the harvested supernatant was 25 L and the total virus yield was 1.93 × 1012. The procedure using Vero cells grown on polymer fiber paper carriers was effective for the large-scale production of EV71. [ABSTRACT FROM AUTHOR]

The ground support system has a significant impact on tunnel safety while the installation time of initial support is commonly designed by empirical method. The three dimensional numerical model, based on the engineering practice, is analyzed by FLAC3D. In this paper, an improved LDP (longitudinal displacement profile) equation is proposed, which is more accurate in describing the convergence of tunnel before excavation face reaching. Then, a methodology is presented to determine the installation location of initial support in a more efficient and effective way. By simulating the process of excavation load releasing, the appropriate time for installing initial support is when the evolution of surrounding rock displacement has a tendency to increase rapidly, namely that the stability of rock mass arrives at the critical state. The mathematical relationship between the convergence of tunnel and the relative location to tunnel face can be established by fitting monitoring data with the improved LDP equation. Substituting the critical tunnel convergence into the LDP relationship, the corresponding installation location of initial support will be calculated. Meanwhile, several schemes with diverse geological conditions are carried out to validate the improved LDP and the methodology. [ABSTRACT FROM AUTHOR]

The buckling failure of stratified rock slopes intersected by a set of steep discontinuities that are approximately parallel to the slope surface is frequently encountered while constructing railways and roadways in mountainous areas. In this study, an analytical approach based on the energy equilibrium principle is presented to solve the flexural buckling stability of stratified rock slopes within the framework of multilayer beam theory. The generalized Hoek-Brown failure criterion is introduced to reflect the influences of slope size (scale effects) on the buckling stability. Subsequently, numerical and physical modellings from previous literatures are employed to validate the proposed approach. Furthermore, a practical case of Bawang Mountain landslide is also used for the comparative analysis. The study shows that the present analytical approach is capable to provide a more reasonable assessment for the buckling failure of stratified rock slopes, compared with several existing analytical approaches. Finally, a detailed parametric study is implemented, and the results indicate that the effects of rock strength, rock deformation modulus, geological strength index, layer thickness and disturbance degree of rock mass on the buckling failure of stratified rock slopes are more significant than that of rock type and slope angle. [ABSTRACT FROM AUTHOR]

VP35 of Ebola viruses (EBOVs) is an attractive potential target because of its multifunction. All-atom molecular dynamics (MD) simulations and Molecular Mechanics Generalized Born surface area (MM/GBSA) energy calculations are performed to investigate the single-walled carbon nanotube (SWCNT) as an inhibitor in wild-type (WT) VP35 as well as in three primary mutants (K248A, I295A, and K248A/I295A) through docking the SWCNT in the first basic patch (FBP) of VP35. The SWCNTs of all the four systems effectively bind to the FBP. Interestingly, the sites and orientations of the SWCNT binding to the I295A mutant and K248A/I295A double mutants change significantly to accommodate the variation of the VP35 conformation. Moreover, the VDW can provide the major forces for affinity binding in all four systems. [ABSTRACT FROM AUTHOR]

A coupled volume-of-fluid and level set (CLSVOF) method is applied for the simulation of droplet impacting on a solid surface. This two-phase flow approach combines the advantages of VOF and level set (LS) methods. Three cases are listed and simulated by CLSVOF method, and the wettability is evaluated by tracking the three-phase contact line (TPCL). Results showed that the change of liquid spreading ratio with time has a good fit with the experimental results of the above three cases and high accuracy is achieved by CLSVOF method compared with VOF method, which indicated that this model is suitable for researching the wetting problem. The spreading speed on good wettability surfaces is faster than that of on poor wettability surfaces significantly, and the recoiling phenomenon appears after the droplet spreading to its maximum. [ABSTRACT FROM AUTHOR]

Lecanicillium lecanii has been developed as biopesticides and widely used in the biological control of several insects in agricultural practice. However, the poor efficacy has blocked its application. The genetic manipulation has been proved as a useful tool to improve the virulence of entomopathogenic fungus. In this study, a scorpion toxin gene ( BmKit) from Buthus martensi was cloned and transferred into L. lecanii and then its resulting activity against cotton aphids ( Aphis gossypii) was assessed. The results showed that the engineered strain BmKit-12 grew significantly quicker than WT in host insects. The median lethal concentration (LC) for BmKit-12 was 7.1-fold lower than that for WT, and the median survival time (LT) for BmKit-12 was reduced by 26.5 % compared with that for WT. Although the conidial yield was reduced by 31.4 % on insect cadavers, the mycelia growth, sporulation, and conidia germination of BmKit-12 on plates were not significantly different from WT. Considering the lower amount of mycelia for BmKit-12 in host insects in late growth stage (fungal sporulation stage), we think the expression of BmKit may not affect the capability of sporulation. In conclusion, the expression of BmKit gene can significantly enhance the pathogenicity of L. lecanii against cotton aphids in a relatively cost-effective way. [ABSTRACT FROM AUTHOR]

Pathogenesis-related (PR) proteins encoded by plant defense genes play key roles in plant disease-resistance responses, specialized in systemic-acquired resistance. However, their roles in the response of wheat to fungal infection are still not well known. Our earlier studies have reported that a full-length TcLr19PR1 gene (818 bp) was isolated from wheat infected by leaf rust ( Puccinia triticina). Here, we showed that TcLr19PR1 was induced earlier and its expression level was higher in the incompatible interaction between seedling stage of wheat and P. triticina than in compatible interactions. TcLr19PR1 was strongly induced after P. triticina inoculation and ABA and SA treatments, in which the expression level of TcLr19PR1 significantly increased and reached the maximum at 12 and 72 h, respectively. Furthermore, the transgenic T-stable TcLr19PR1 lines generated in the susceptible wheat cultivar Zhengzhou 5389 background exhibited certain extent disease resistance against P. triticina infection by preventing disease development. In addition, Western blotting was conducted to confirm that TcLr19PR1 protein was induced by P. triticina infection in positive transgenic plants at the protein expression level. These findings suggest that TcLr19PR1 gene plays an important role in wheat development and resistance to leaf rust pathogen attack. [ABSTRACT FROM AUTHOR]

Objective: This review aims to compare the clinical results of bone-patellar tendon-bone (BPTB) autograft and BPTB allograft in primary anterior cruciate ligament (ACL) reconstruction. Methods: PubMed Medline, EMBASE, and the Cochrane Library were systematically searched for prospective or retrospective cohort studies that compared BPTB autograft with BPTB allograft in ACL reconstruction. The results of the eligible studies were independently extracted and analyzed according to the following: one-leg test, range of motion (ROM), overall International Knee Documentation Committee (IKDC), Lachman test, pivot shift test, Lysholm scores, Tegner scores, KT-1000 test, anterior knee pain, crepitus, and clinical failure. Random-effect and fixed-effect models were adopted to calculate the weight mean difference and the odds ratio for continuous and dichotomous variables with 95 % confidence interval. Results: Thirteen studies met the inclusion criteria, resulting in 1,046 (484 autografts and 562 allografts) patients available for the present study. A meta-analysis showed no significant differences between the two treatment groups in terms of the following: one-leg test ( p = 0.21), ROM ( p = 0.41), overall IKDC ( p = 0.25), Lysholm scores ( p = 0.25), Tegner scores ( p = 0.09), KT-1000 ( p = 0.69), Lachman test ( p = 0.89), positive pivot shift test ( p = 0.18), anterior knee pain ( p = 0.93), and crepitus (p = 0.96). However, a significant difference in clinical failure ( p = 0.01) in favor of autograft was observed. In the fresh-frozen subgroup, no difference in the evaluations, except for Tegner scores, were found between autograft and allograft. Conclusions: Therefore, BPTB autograft shows potential as an optimal choice for ACL reconstruction on the basis of earlier functional recovery and fewer graft failure. [ABSTRACT FROM AUTHOR]

Switching expansion reduction (SER) uses a switch valve instead of the throttle valve to realize electronically controlled pressure reduction for high pressure pneumatics. A comprehensive and interactive pneumatic simulation model according to the experimental setup of SER has been built. The mathematical model considers heat exchanges, source air pressure and temperature, environmental temperatures and heat transfer coefficients variations. In addition, the compensation for real gas effect is used in the model building. The comparison between experiments and simulations of SER indicates that, to compensate the real gas effect in high pressure discharging process, the thermal capacity of air supply container in simulation should be less than the actual value. The higher the pressure range, the greater the deviation. Simulated and experimental results are highly consistent within pressure reduction ratios ranging from 1.4 to 20 and output air mass flow rates ranging from 3.5 to 132 g/s, which verifies the high adaptability of SER and the validity of the mathematic model and the compensation method. [ABSTRACT FROM AUTHOR]

The purposes of this study were to investigate the effects of B cell translocation gene 2 (BTG2) on the proliferation, apoptosis, and invasion of triple-negative breast cancer and to provide an experimental basis for the future treatment of human triple-negative breast cancer. A pcDNA3.1-BTG2 eukaryotic expression vector was constructed and transfected into the MDA-MB-231 human triple-negative breast cancer cell line using lipofection. Then, relevant changes in the biological characteristics of the BTG2-expressing cell line were analyzed using MTT (tetrazolium blue), flow cytometry, and Transwell invasion chamber assays. Additionally, the effects of BTG2 expression on cyclin D1, caspase 3, and matrix metalloproteinases 1/2 (MMP-1/-2) expression were analyzed. Cell proliferation was significantly lower in the pcDNA3.1-BTG2-transfected group compared to the empty vector and blank control groups ( p < 0.05). There was no significant difference between the empty vector and blank control groups. FCM results demonstrated that there were significantly more cells in the G1 phase of the cell cycle and fewer S phase cells in the pcDNA3.1-BTG2 group than in the empty vector and blank control groups ( p < 0.05). Additionally, the proportion of cells that migrated across the membrane was significantly lower in the pcDNA3.1-BTG2 group than in the empty vector and blank control groups ( p < 0.05). Cyclin D1 and MMP-1/-2 expression were significantly lower in MDA-MB-231 cells transfected with pcDNA3.1-BTG2 as compared to the empty vector and blank control groups ( p < 0.05). Caspase 3 expression was significantly higher in MDA-MB-231 cells from the pcDNA3.1-BTG2 group compared to the empty vector and blank control groups ( p < 0.05). In conclusion, BTG2 may inhibit MDA-MB-231 proliferation and promote apoptosis. Additionally, BTG2 may also inhibit the invasion of MDA-MB-231 human triple-negative breast cancer cells. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the expression of microRNA-182 (miR-182) in triple-negative breast cancer (TNBC) tissues and the TNBC cell line MDA-MB-231 and to investigate the effects of mirR-182 on the cellular behavior of MDA-MB-231 and the expression of the target gene profilin 1 (PFN1), thus providing new methods and new strategies for the treatment of TNBC. Quantitative real-time PCR (qRT-PCR) was utilized to evaluate the expression of miR-182 in TNBC tissues, relatively normal tissues adjacent to TNBC and the TNBC cell line MDA-MB-231. Forty-eight hours after the MDA-MB-231 cells were transfected with the miR-182 inhibitor, qRT-PCR was utilized to detect the changes in miR-182 expression levels, and an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was utilized to determine the effects of miR-182 on cell viability. Flow cytometry was adopted to determine whether miR-182 affects the proliferation rates and apoptosis levels of the MDA-MB-231 cells. The transwell migration assay method was used to investigate the effects of miR-182 on the migration of the MDA-MB-231 cells. A luciferase reporter gene system was applied to validate that PFN1 was the target gene of miR-182. Western blot was used to measure the effects of miR-182 on the PFN1 protein expression levels in the cells. qRT-PCR results showed that compared with the relatively normal tissues adjacent to TNBC, miR-182 expression was significantly increased in the TNBC tissues and the MDA-MB-231 cells ( p < 0.01). Compared with the control group, MDA-MB-231 cells transfected with the miR-182 inhibitor and incubated for 48 h showed significantly decreased miR-182 expression ( p < 0.01). The results of an MTT assay showed that inhibition of miR-182 in MDA-MB-231 cells led to significantly reduced cell viability ( p < 0.05). Flow cytometry analysis indicated that inhibition of miR-182 expression resulted in significantly decreased cell proliferation ( p < 0.05) and significantly increased levels of apoptosis ( p < 0.05). The results of a transwell migration assay showed that after inhibited of miR-182 expression, the number of cells passing through the transwell membranes was significantly decreased ( p < 0.05). The results from a luciferase reporter gene system showed that compared with the control group, the relative luciferase activity of the group transfected with the miR-182 inhibitor was significantly increased ( p < 0.05). Western blot analysis showed that compared with the control group, PFN1 protein expression levels were significantly increased in the MDA-MB-231 cells transfected with the miR-182 inhibitor and incubated for 48 h ( p < 0.05). In conclusion, miR-182 is upregulated in TNBC tissues and cells. It promotes the proliferation and invasion of MDA-MB-231 cells and could negatively regulate PFN1 protein expression. Treatment strategies utilizing inhibition of miR-182 expression or overexpression of the PFN1 gene might benefit patients with TNBC. [ABSTRACT FROM AUTHOR]

We describe the phylogenetic analysis and expression pattern of the Xenopus radial spoke protein 3 ( RSP3) gene during early development. The Xenopus RSP3 protein presents characteristic features of the RSP3 family. It contains a radial spoke domain, which is 75 and 72 % identical to the corresponding region of human and Chlamydomonas RSP3 proteins, respectively. Examination of the phylogenetic relationship between the Xenopus RSP3 protein and its known homologues from different deuterostomes indicates that the RSP3 proteins are highly conserved among deuterostomes. Whole-mount in situ hybridization analyses show that Xenopus RSP3 is a maternal mRNA enriched in the animal hemisphere during cleavage stages. The expression is detected in the dorsal region of the embryo during gastrulation, then in the presumptive neuroectoderm at the end of gastrulation. During neurulation and at the subsequent stages, the expression of RSP3 mRNA is detected in the entire multiciliated cells of epidermis. At tail-bud stages, it is progressively expressed in the otic vesicles and sequentially expressed in the nephrostomes. Expression could be also detected in the floor plate of the neural tube. This expression pattern persists until at least late tail-bud stages. [ABSTRACT FROM AUTHOR]

Heparan sulfate proteoglycans (HSPGs) are involved in the regulation of cell growth, apoptosis and lipid metabolism in vitro. Syndecans are the primary form of HSPGs. Syndecan-1 is involved in the processes of cell growth, differentiation, adhesion, wound healing and inflammation. Additionally, as a sinusoidal transmembrane HSPG facing the plasma compartment, syndecan-1 is a promising target to be involved in lipoprotein physiology. We aimed to examine the possible correlation of syndecan-1 and lipid profile in type 2 diabetes mellitus. In this study, serum syndecan-1 was detected by ELISA, and potential correlations between syndecan-1 and triglyceride, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, lipoprotein a, apolipoprotein (apo) B, apoA1 and apoB/apoA1 were analyzed. Forty-one patients with type 2 diabetes and 31 age-matched, non-diabetic healthy subjects (controls) were enrolled. Syndecan-1 in patients with diabetes (26.15 ± 2.42 ng/ml) was significantly higher than that of the controls (16.85 ± 1.98 ng/ml, t = −2.98, P = 0.005). Serum syndecan-1 level correlated negatively with apoA1 ( r = −0.46, P = 0.003). Multiple regression analysis showed that apoA1 ( b = −0.43, P = 0.003) was a predictor of serum syndecan-1 levels in subjects with type 2 diabetes. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the importance of diffusion-weighted magnetic resonance imaging (DW-MRI) apparent diffusion coefficient (ADC) values to predict treatment response to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (LABC). Thirty-two patients with LABC underwent 2-4 cylces of NCT (docetaxel and epirubicin). The DW-MRI scans were performed within one week prior to chemotherapy and after the first course of treatment, respectively. Accordingly, tumor volumes, changes in tumor ADC values, and their degree of correlation were analyzed. The overall response (OR) was observed in 62.5% (95% CI, 45.7-79.3%) of patients after 2 cycles of NCT. The clinical complete response (CR) rate and pathological CR (pCR) rate were 15.6 and 9.4%, respectively. The stable disease (SD) rate was 34.4% (11 patients), and progressive disease (PD) was observed in only one patient (3.1%). After the first cycle of NCT, the ADC values in the CR + PR group significantly increased ( P < 0.001). The initial ADC values before chemotherapy in the OR group were significantly lower than those in the SD + PD group ( P < 0.001). The initial ADC values and the changes in tumor volume after chemotherapy were negatively correlated ( r = −0.58, P = 0.02). The lower the initial tumor ADC value was the more obvious the decrease in tumor volume after chemotherapy. The changes in ADC values of tumors after chemotherapy and the changes in tumor volume were positively correlated ( r = 0.96, P < 0.001). After chemotherapy, the greater the change in ADC value, the more the tumor volume was reduced. Using the initial ADC values of breast cancer tumors and the early changes in ADC values after NCT, we may be able to predict tumor response to chemotherapy. Tumors with low initial ADC values may be sensitive to chemotherapy; tumors with significantly increasing ADC values early after chemotherapy may be sensitive to chemotherapy. [ABSTRACT FROM AUTHOR]

Aim:Histone H2AX is a novel tumor suppressor and its phosphorylation at the C terminus (Ser139 and Tyr142) is required for tumor cell apoptosis. The aim of the present study was to elucidate the mechanisms underlying imatinib-induced C-terminal phosphorylation of H2AX in chronic myelogenous leukemia cells in vitro.Methods:BCR-ABL-positive K562 cells were used. Microscopy, Western blotting and flow cytometry were used to study the signaling pathways that regulate imatinib-induced H2AX phosphorylation and the apoptotic mechanisms.Results:Treatment of K562 cells with imatinib (1-8 μmol/L) induced phosphorylation of H2AX at Ser139 and Tyr142 in time- and dose-dependent manners. In contrast, imatinib at the same concentrations did not affect H2AX acetylation at Lys 5, and the acetylated H2AX maintained a higher level in the cells. Meanwhile, imatinib (1-8 μmol/L) activated caspase-3 and its downstream mammalian STE20-like kinase 1 (Mst1), and induced apoptosis of K562 cells. The caspase-3 inhibitor Z-VAD (40 μmol/L) reduced imatinib-induced H2AX phosphorylation at Ser139 and Tyr142 and blocked imatinib-induced apoptosis of K562 cells. Imatinib (4 μmol/L) induced expression of Williams-Beuren syndrome transcription factor (WSTF), but not wild-type p53-induced phosphatase 1 (Wip1) in K562 cells.Conclusion:The caspase-3/Mst1 pathway is required for H2AX C-terminal phosphorylation at Ser139 and Tyr142 and subsequent apoptosis in Bcr-Abl-positive K562 cells induced by imatinib. [ABSTRACT FROM AUTHOR]

The peripheral neutrophils are one of the main inflammatory cells and significantly influence the damage of endothelium. Type 2 diabetes is a manifestation of an ongoing low-grade inflammation. In diabetes, impairment of neutrophil adhesion to the endothelium and migration to the site of inflammation were detected, which associated closely with adhesion molecules expressed on neutrophils and endothelial cells. To detect the expression of syndecan-1 on neutrophils in patients with type 2 diabetes mellitus, we recruited 29 patients with type 2 diabetes mellitus without any diabetic complication and 24 healthy subjects (controls). Expression of syndecan-1 was determined by flow cytometry, and potential correlations between syndecan-1 and clinical characteristics were analyzed. On neutrophils, percentage of positive syndecan-1 cells was significantly higher in subjects with diabetes (10.363 ± 1.689%) than that of the controls (3.775 ± 0.634%, P = 0.001). An association between body mass index (BMI) and percentage of positive syndecan-1 neutrophils was detected ( r = 0.415, P = 0.025). When BMI was categorized into subgroups of ≤25 kg/m ( n = 10) and >25 kg/m ( n = 19), the average percentages of positive syndecan-1 neutrophils in patients with diabetes were 5.733 ± 1.842% and 12.642 ± 2.251%, respectively ( t = −2.137, P = 0.042). A multiple regression analysis showed that BMI (β = 0.783, P < 0.000) was a significant predictor of positive syndecan-1 neutrophils in subjects with type 2 diabetes. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (LABC) One hundred and twelve consecutive patients with clinical stage III LABC who had received NCT with docetaxel and epirubicin from March 2006 to March 2009 were included in this retrospective study. The pre-NCT treatment expression levels of Ki-67 proliferation index, estrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor 2 (HER-2), Topoisomerase II alpha (Topo-II), and nm23-H1 were detected by immunohistochemistry (IHC). A total of 361 cycles were administered with the median number of three cycles per patient (range, 2-6). The pCR rate was 9.8% (95% CI, 4.3-15.3%). In univariate analysis, poor tumor differentiation, both negative of ER/PgR, negative Topo-II, and positive nm23-H1 were found to be significantly predictive of a pCR. ER/PgR status and nm23-H1 were significant for pCR on multivariate analysis (P = 0.006 and 0.025, respectively). ER/PgR status and nm23-H1 are independent predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination chemotherapy in patients with LABC. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) in patients with locally advanced triple-negative breast cancers (TNBCs). Forty-one patients (18.6%) among 220 breast cancer patients were identified as TNBCs from March 2006 to 2009 were included in this prospective study. The pre-NCT treatment expression levels of Ki-67 proliferation index, estrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor 2 (HER-2), CK5/6, epidermal growth factor receptor (EGFR), cyclin D1, and nm23-H1 were detected by immunohistochemistry (IHC). A total of 180 cycles were administered with the median number of four cycles per patient (range, 4-6). The pCR rate was 34.1% (95% CI, 19.6-48.6%). In univariate analysis, early T stage, clinical response after 2 cycles, negative basal-like, negative EGFR, high Ki-67 proliferation index, and positive nm23-H1 were found to be significantly predictive of a pCR ( P = 0.010, 0.040, 0.007, 0.001, 0.019, and 0.010, respectively). Basal-like status and nm23-H1 status were significant for pCR on multivariate analysis ( P = 0.004 and 0.031, respectively). Basal-like status and nm23-H1 are independent predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination chemotherapy in patients with TNBCs. [ABSTRACT FROM AUTHOR]

Objectives: The aims of this study were to examine the effects of genetic and clinical factors on the maintenance dose of tacrolimus in patients following renal transplantation and to develop a tacrolimus-dosing model that could be combined with associated factors. Patients and methods: This study included 142 renal transplant recipients who received tacrolimus as immunosuppressive agent. CYP3A5, MDR1 and NR1I2 gene polymorphisms were identified based on the SNaPshot assay. The relationship between the genetic and clinical factors and tacrolimus maintenance dose as well as between dose-corrected tacrolimus concentration was examined. Results: CYP3A5 genotype, body weight, haematocrit, haemoglobin and total bilirubin significantly influenced the maintenance tacrolimus dose. The tacrolimus-dosing model derived from linear regression model accounted for 40.5% of total variations in the tacrolimus maintenance dose. Conclusions: A pharmacogenetics-based dosing model has been developed for the prediction of the tacrolimus maintenance dose in renal transplant recipients. This model may be useful in helping clinicians prescribe the initial tacrolimus dose with greater safety and effectiveness. [ABSTRACT FROM AUTHOR]

Cucumber downy mildew caused by Pseudoperonospora cubensis (Berk. and Curt.) Rostov. limits crop production in Shandong Province of China. Since management of downy mildew is strongly dependent on fungicides, a rational design of control programs requires a good understanding of the fungicide resistance phenomenon in field populations of the pathogen. A total of 106 and 97 isolates of P. cubensis were obtained in 2006 and 2007, respectively. The EC50 values for the growth of all the 106 isolates collected in 2006 were 0.0063–0.0688 µg ml−1 (average: 0.0196±0.0048 µg ml−1) azoxystrobin and these were therefore considered sensitive isolates. However, 57 field isolates of P. cubensis of the 97 collected in 2007 with EC50 values that ranged from 0.609 to >51.2 µg ml−1 were considered resistant to azoxystrobin. Fragments of the fungicide-targeted mitochondrial cytochrome b gene from total pathogen DNA were amplified using polymerase chain reaction and their sequences analyzed to elucidate the molecular mechanism of resistance. A single point mutation (GGT to GCT) in the cytochrome b gene, resulting in substitution of glycine by alanine at position 143, was found in the three selected azoxystrobin-resistant isolates of downy mildew. This substitution in cytochrome b exhibited different resistance levels, with the resistance factor from 21.15 to greater than 2618.9. In addition, the different resistance levels seemed to appear within 1 year (between 2006 and 2007). Therefore, growers of Shandong Province in China now are faced with a challenge in managing the azoxystrobin resistance in cucumber downy mildew. [ABSTRACT FROM AUTHOR]

Objective: To clarify whether the acupoints of Zusanli (ST36) and Sanyinjiao (SP6) have specific actions other than non-acupoints to bone. Methods: Forty Sprague-Dawley female rats were divided into five groups: Sham operated (sham) group; Ovariectomized (OVX, model) group; non-acupuncture group; OVX, needling on Zusanli and Sanyinjiao (Acp-A) group; OVX, needling on the reverse sides of Zusanli and Sanyinjiao (Acp-B) group; OVX, periostineal stimulation on the same height as points of Zusanli and Sanyinjiao (Acp-C) group. The experiment was continued for 23 weeks and then all animals were sacrificied. Results: OVX had a significantly higher body weight and lower bone mineral density (BMD) on the lumbar vertebrae, total femora and tibiae than sham rats, however, Acp-A showed a higher BMD compared with the other OVX groups. On the other hand, bone weights, bone strength and bone morphometry such as trabecular volume, trabecular separation, labeled width and bone formation rate also showed the same improvements in Acp-A as compared to the other OVX rats. Conclusion: The stimulation on Zusanli and Sanyinjiao specifically prevented the development of osteopenic rats compared with non-acupoints. [ABSTRACT FROM AUTHOR]

In this work, the effect of hydrological spatial variability on the heat production performance of a naturally fractured geothermal reservoir was investigated. Using the geological information of an abandoned natural gas exploration well in northern Songliao Basin, northeast China, the hydraulic properties of the fractured reservoir were studied based on DFN models. The heterogeneous distribution of reservoir hydrological properties was simulated using random field method. Evolution characteristics of production temperature, heat extraction rate, injection pressure, reservoir flow impedance, and the spatio-temporal distribution of temperature and pressure were studied. A sensitivity analysis was performed on correlation distance and coefficient of variation for the random field model. The results indicate that spatial variability of the hydrological parameters has significant influence on the heat production performance. Besides, correlation distance and coefficient of variation are two key parameters that influence the distributions of reservoir parameters and cause the variation of heat production performance in random field models. [ABSTRACT FROM AUTHOR]