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OBJECTIVE To investigate the potential mechanism of the effect of metabolic syndrome (MetS) on prostate volume (PV) and the risk of benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and the relationships of MetS and the major pathogenic factors of MetS with the clinical progression of BPH/LUTS in older Chinese men. SUBJECTS AND METHODS We analyzed clinical data obtained from 506 ostensibly healthy men who underwent routine health check-ups and recruited 415 subjects from a group of previously studied men after 4 years. We evaluated the associations of major pathological factors of MetS, including insulin resistance, subclinical inflammatory state, and sex hormone changes, with PV, the risk of BPH and the clinical progression of BPH/LUTS by using multiple linear regression and logistic regression. RESULTS After adjustment for age, insulin, HOMA (homeostatic model assessment) index, leptin, resistin, adiponectin, C-reactive protein, tumor necrosis factor-α (TNF-α), sex hormone-binding globulin, and testosterone levels were significantly associated with PV (all P

Background Metabolic syndrome (MetS) and serum prostate-specific antigen (PSA) levels are correlated. To investigate the underlying effect of MetS on PSA levels, the relationship between the major pathogenic factors of MetS and serum PSA levels was studied. Methods A total of 506 ostensibly healthy men who underwent routine health check-ups were recruited to this study. We evaluated the effect of the major pathogenic factors of MetS, which included insulin resistance, a subclinical inflammatory state and sexual hormone changes, on serum PSA levels by using linear regression analysis and multivariate analysis after adjusting for age, BMI and prostate volume. Results When simultaneously adjusting for age, BMI, prostate volume and high-density lipoprotein cholesterol, serum insulin levels and SHBG levels were inversely correlated with serum PSA levels (P = 0.049 and P = 0.004, respectively), and testosterone levels were positively correlated with serum PSA levels (P = 0.039). In multivariate regression models, serum insulin levels and serum SHBG levels were significantly associated with serum PSA levels (both P Conclusions Among the major pathogenic factors of metabolic syndrome, insulin resistance and sexual hormone changes may be the most significant contributors to the decline in serum PSA levels.

A cost-effective design of concrete elements in compliance with sustainability principles requires to accurately predict the behavior of concrete under various loading conditions. Yet to date available approaches for the prediction and evaluation of recycled aggregate concretes (RAC) under triaxial load are very scarce, which may hinder the transition of such an eco-friendly concrete from lab-based technique to widespread applications. As a first attempt to iron out this issue, this study develops some reliable and accurate analytical tools on the basis of an experimental database containing the results of 193 cylindrical peak stress under axisymmetric triaxial load, 55 cubic peak stress under true triaxial load, 76 peak strains and 61 elastic moduli of RAC retrieved from an extensive review of the literature. First, a new empirical design-oriented model is presented refining the generic form of conventional confinement models for natural aggregate concrete while considering the impacts of RCAs. Then Grey Correlation Analysis (GCA) is conducted to look into the sensitivity of the key parameters that affect the triaxial behavior of RAC. The results of the GCA indicate that the triaxial behavior of RAC mainly depends on the effective water-to-cement binder ratio, aggregate-to-cement ratio, lateral stress conditions, exposure temperature, as well as the RCA replacement ratio. Having the input parameters identified by the GCA, three robust data-mining mathematic tools, namely Multiple Nonlinear Regression (MNR), Artificial Neural Network (ANN), and hybrid Genetic Algorithm Artificial Neural Network (GA-ANN) are employed to simulate the mechanical performances of RAC under triaxial load. The results demonstrate that the developed MNR equations and the neural network models satisfactorily predict the behavior of RAC under triaxial load; among those models (including the developed design-oriented one), the ANN optimized with GA performs the best. These arguably point to the possibility of the application of those models in the design and evaluation of structural members manufactured using RAC, especially for them under complex loading scenarios.

Total testosterone levels decline with age, while prostate volume and the prevalence of benign prostatic hyperplasia increase with age. We sought to investigate the correlation of serum testosterone levels with prostate volume in aging men. We analyzed clinical data obtained from 416 ostensibly healthy men who underwent routine health check-ups and recruited and collected data from these subjects 4 years later. We analyzed the correlation between prostate volume and relevant factors, as well as the correlation between changes in prostate volume and low testosterone over a 4-year period. Men with low testosterone had significantly larger prostate volume than those in the normal testosterone group (26.86 ± 8.75 vs. 24.06 ± 6.77 P = 0.02), and subjects with low testosterone had significantly higher levels of obesity-related factors, including waist circumference, body mass index, and insulin (all P P = 0.004), and prostate volume and 4-year changes in prostate volume were associated with low testosterone. With increased testosterone level, prostate volume showed a significant linear decreasing trend. These findings provide evidence of the relationship between testosterone and prostate volume. Additional large studies are needed to confirm these preliminary results.

In clinical practice, few prostate cancer (PCa) patients are associated with metabolic syndrome (MetS), while few others acquire MetS during treatment. Whether the treatment of PCa increases the occurrence of MetS remains to be confirmed. This study reviewed the changes in MetS patients before and after PCa treatment to evaluate the effects of various treatment methods on MetS. We analyzed data of 1162 PCa patients, whether or not diagnosed with MetS, and changes in MetS patients after PCa treatment. Data of lower urinary tract symptoms, C-reactive protein (CRP), platelet distribution width (PDW), prostate-specific antigen (PSA), Gleason score, clinical stage, treatment methods, and progressive incidents were evaluated using logistic regression according to MetS diagnosis. The results showed significant differences in the prevalence of MetS before (17.38%) and after (23.67%) PCa treatment (P

Concrete-filled steel tubular structural members can be recognized as an effective mean to improve the mechanical behavior in terms of strength, stiffness, ductility, and energy dissipation for the initial recycle aggregate concrete deficiencies compared with natural aggregate concrete. A small-scale model of square concrete-filled steel tubular column–reinforced concrete beam frame realized employing 100% recycled coarse aggregates was tested under combined axial loads and cyclic reversed lateral flexure. The failure modes, plastic hinges sequence, hysteresis loop, skeleton curve, stiffness degeneration, energy dissipation capacity, and ductility of the frame were presented and analyzed in detail. The structural behavior of square concrete-filled steel tubular column–reinforced concrete beam frame with 100% recycled coarse aggregates was compared with circular concrete-filled steel tubular column–reinforced concrete beam frame made with 100% recycled coarse aggregates. A fiber-based program model for the nonlinear analysis of concrete-filled steel tubular column–reinforced concrete beam frames incorporating recycled coarse aggregates was developed using SeismoStruct, to highlight the effect of recycled coarse aggregate content on mechanical behavior of recycled aggregate concrete and the confinement effect provided by outer tubes on core concrete. The analysis results show that the numerical model can well simulate and predict the seismic behavior of concrete-filled steel tubular column–reinforced concrete beam frames with 100% recycled coarse aggregate content. Both experimental and numerical results demonstrate that concrete-filled steel tubular column–reinforced concrete beam frames with large content of recycled coarse aggregates have a receivable seismic performance, and it is feasible to apply and popularize recycled aggregate concrete into concrete-filled steel tubular structures in seismic regions.

In this paper, the seismic behavior of L-shaped double-skin composite wall (DSCW) with concrete-filled steel tubes were investigated. The influence of different parameters, i.e., axial compression ratio, shear span-to-depth ratio, corrugation size, corrugated arrangement, flange size and CFST side column were discussed based on cyclic tests. The hysteresis behavior of DSCW specimens in terms of hysteresis curves, skeleton curves and rigidity deterioration were analyzed. The failure mechanism, as well as the composite effect between each component was also compared based on the strain analysis. It was concluded that the L-shaped DSCW has favorable seismic ductility and toughness with the maximum lateral drift angle of 3%. With the increase of axial compression ratio, the peak load of DSCW specimens increased while the post-peak ductility decreased. By contrast, the peak load of DSCW specimens decreased with the increase of shear span-to-depth ratio. More corrugations are effective to increase the seismic behavior of L-shaped DSCW and it was recommended that the corrugations should be arranged vertically. The flange size has limited influence on the failure processes and carrying capacity of DSCW specimens, while the stress distribution was highly dependent on the flange design of DSCW. The application of concrete-filled steel tubes (CFST) side column is effective to increase the seismic behavior of DSCW and also has significant influence on the composite effect between each component.

One of the most important issues that determine many properties are the types of coarse aggregate in recycled concrete. This paper is arming to experimental study the influence of two different types of coarse aggregate (recycled crushed rock aggregate and recycled pebbles aggregate) on the mechanical properties of recycled concrete. The properties of these two types of recycled coarse aggregate (RCA) derived from waste concrete were investigated. Using these RCA and corresponding types of natural coarse aggregates, recycled concrete specimens according to different replacement percentage were produced and tested. Finally, Analysis and comparisons of the mechanical properties of RAC, including compressive strength, flexural strength, elastic modulus and Poisson’s ratios etc., were made between these recycled concretes. The results show that different types of RCA have significant variance in mechanical properties. The recycled concrete containing crushed rock aggregate presents a lower relative strength and elastic modulus than that containing pebble aggregate while the toughness of them is contrary. The theoretical expression for stress-strain relationship and equations for the relationships between various strength of recycled concrete with each type of coarse aggregate are also presented.

Efficient apoptosis requires Bcl-2 family-mediated mitochondrial outer membrane permeabilization (MOMP), which releases pro-apoptotic proteins to the cytosol, activating apoptosis and inhibiting X-linked inhibitor of apoptosis protein (XIAP). XIAP is a member of the inhibitors of apoptosis protein family whose expression is elevated in many cancer types and participates in the release of pro-apoptotic proteins. To explore the association between XIAP and the Bcl-2 family, and the influence of XIAP on mitochondria, RNA interference of XIAP was performed in Caki-1 cells and the dynamic change in the levels of related proteins was compared with the original Caki-1 cells upon induction of apoptosis. Upon knockdown of XIAP, the release of cytochrome c (Cyt-c), second mitochondria-derived activator of caspase (Smac) and apoptotic protease activating factor 1 (Apaf-1) from mitochondria proceeded normally, whereas in Caki-1 cells, the release of these pro-apoptotic proteins was significantly prolonged, and incomplete. Downregulation of XIAP through small interfering RNA resulted in an increase of apoptosis and a marked decrease in Bcl-2 and Bcl-xl levels at 3 h. Additionally, the regulation of the level of XIAP protein affected the specific ratios of Bcl-2/Bax and Bcl-xl/Bax, which play decisive roles in cell death. In the present study, it was revealed that XIAP can feed back to mitochondria, delaying Cyt-c and Apaf-1 release. Furthermore, XIAP can limit the release of its inhibitor Smac with the involvement of Bcl-2 family proteins.

This paper focuses on the study of seismic-induced damage assessment of three-dimensional (3D) joints connected with T-shaped steel reinforced concrete (SRC) column-steel beams. Low cyclic reversed loading tests on one planar joint and nine 3D joints were firstly conducted to intensively investigate the seismic behavior of the hybrid joint. The damage index calculation models such as the displacement-based type, energy-based type and displacement & energy-based type were discussed and applied for all the specimens according to the experimental results. In addition, the effects of shape steel configuration type, loading angle and axial compression ratio on the damage development and accumulation for test specimens were analyzed through Park-Ang model. The analysis results show that the selected parameters of damage-index calculation models have great effect on the developing trends of damage curves. Under the same ability of relative deformation, the accumulated damage of the specimens configured with T-shaped steel are much larger than that of the specimens configured with channel-shaped and solid-web steels; moreover, the degree of damage accumulation for the specimens under 30° and 60° loading angles is slightly larger than that of the specimens under 45° loading angle. The specimens subjected to a lower axial force level have a faster damage development, but the damage accumulation is smaller than that of the specimens under a higher axial compression ratio.

This paper presents a critical assessment of the compressive behavior of reinforced recycled aggregate concrete (RRAC) columns. Previous research has demonstrated that recycled aggregate concrete (RAC), manufactured using crushed concrete aggregates obtained from construction and demolition waste, can be a feasible and environmentally friendly alternative to conventional concrete for the use in structural applications. Currently, very limited information is available in the literature about the methods to be used for designing RC elements manufactured with recycled concrete aggregates. With the aim of extending the available experimental data, a fiber section based nonlinear finite element (FE) model was developed so as to provide in-depth insights into the compressive behavior of RRAC columns. First, a comparison between simulation results of the compressive behavior of RRAC columns and available experimental results were made to validate the FE model. Then, using the validated FE model, a parametric study was performed to investigate the effects of different recycled concrete aggregate (RCA) contents, volumetric ratio and yield strength of longitudinal steel reinforcement, and spacing and yield strength of transverse steel reinforcement on the compressive behavior and load capacity of RRAC columns. Finally, based on the limited available experimental database, a grey correlation analysis was used to evaluate the parametric sensitivity of the compressive behavior of RRAC columns. The experimental and numerical investigations demonstrate that the method used for considering the additional water absorption of RCAs in manufacturing RAC has a significant influence on the compressive load capacity of RRAC columns and that the influence of the RCA content on the compressive load capacity of RRAC columns is lower when compared with other important parameters but this effect should not be ignored in modeling the behavior of RRAC columns.

Replacement rate is an important factor that affects the mechanical properties of recycled concrete. In order to study the influence of replacement rate on triaxial mechanical performance of recycled concrete, 20 recycled concrete cylinder specimens for conventional triaxial loading test with recycled aggregate replacement rate as changing parameters were designed. The results show that replacement rate has a great influence on peak stress of recycled concrete specimens under uniaxial stress, but the effects of replacement rate gradually decreased with the increase of lateral confining pressure. The influence of replacement rate on peak strain is larger than peak stress, the impact of replacement rate on peak strain gradually decreased with the increase of lateral confining pressure. The elastic modulus of recycled concrete specimens changes with different replacement rate, and the fluctuations is in the range of 20%. The results will provide reference for further theoretical study of recycled concrete.

For the purpose of researching the natural bonding behavior of different interfaces between steel and concrete in SRC structures, four specimens are designed to launch the monotonic push-out loading test. Each specimen is used to consider one case, including the bonding of the external flange, internal flange, web and whole cross-sections with the concrete. Failure process and modes of these specimens were observed during the test. Load-slip curves and ultimate bond strength are obtained and the bonding strength between different interfaces of steel and concrete was analyzed. The results show that the bonding strengths of different interfaces in SRC members are not equal. The minimum bonding strength occurs in web, the bonding strength of external flange is higher, and the maximum bonding strength occurs in internal flange, the ratio of the strength is 1:1.39:1.59.

Primary concrete of pebble coarse aggregate were used as the source of recycled aggregate concrete for pebble recycled coarse aggregate. Replacement rate of recycled aggregate for change parameter, 99 specimens were designed. The prism compressive strength, cube compressive strength and flexural strength were tested and achieved. The test results show that damage process and form of pebble coarse aggregate concrete are similar to those of normal concrete. It is gel adhesive failure between coarse aggregate and cement. Comparing with natural aggregate concrete, the strength indexes of recycled aggregate concrete of pebble coarse Aggregate slightly increase.

This paper presents a review of experimental tests performed for the characterization of the mechanical behavior of FRP-concrete members realized employing Recycled Aggregate Concrete (RAC). First, with the aim to define confinement effects on RAC, the mechanical behaviors of RAC under triaxial compression is discussed, highlighting the governing variables and their influence on the mechanical response. Different variables such as Recycled Concrete Aggregate (RCA) content, pre-wetting, confinement level, concrete age and RCA source are analyzed and their implication on the main mechanical properties is discussed. Then, the static and cyclic behavior of FRP-confined RAC members is reviewed. Considering the static behavior, columns under concentric compression and eccentric compression are analyzed. Finally, the limited number of results available from the literature are employed to derive a prediction model for the strength of multi-axial stressed and confined RAC by considering the RCA content as the main governing variable. The need for further research is pointed out at the end of the paper.

In order to evaluate whether concrete with recycled coarse aggregate can be applied for steel reinforced concrete (SRC) under the earthquake, low cyclic loading tests of SRC with different recycled coarse aggregate (RCA) replacement percentage were carried out in this paper. Based on the tests of three SRRC column specimens, the failure modes, the hysteresis curves, the skeleton curves, the ductility, and the stiffness degradation of SRRC columns are investigated. The influence of variation in the RCA replacement percentage on the SRRC column is analyzed in detail. Test results show that the seismic performance of SRRC column is reduced to an allowable extent with the increasing magnitude of the RCA replacement percentage. The SRRC column still has a good seismic performance and the recycled coarse aggregate can be applied for steel reinforced concrete through the proper design.

In order to reveal the constitutive behavior of recycled aggregate concrete (RAC) which is related to time effect, 33 prismatic specimens were designed to have uniaxial compression tests. The changing variation of elastic modulus and Poisson’s ratios of RAC specimens which were placed two years in the lab were inspected, and a related correction formula was put forward to describe the elastic modulus. The results show that with the aggregate replacement rate growing, the RAC brittleness was relatively obvious. Since time effect played a great role, the axial compressive strength and elastic modulus were larger than those of normal concrete and the standard age concrete which is calculated. Poisson's ratio did not change significantly and the values were relatively stable, while the higher replacement rate is, the lower values are.

In order to reveal the flexural behavior of normal section of steel reinforced recycled coarse aggregate concrete beams，6 steel reinforced recycled concrete beams were designed for flexural test，the study mainly considered the impact of coarse aggregate replacement rates and concrete strength grade two changing parameters on the flexural behavior of steel reinforced recycled coarse aggregate concrete beams. Through this test, the whole mechanical process、crack distribution and failure behavior of this kind of specimens were observed, and obtained the stress-strain distribution curves、the ultimate bearing capacity and load-displacement curves parameters. Based on the study measurement data, deeply analyzed the impact of coarse aggregate replacement rates and concrete strength grade on the flexural behavior of steel reinforced recycled coarse aggregate concrete beams. The result shows that: steel reinforced recycled coarse aggregate concrete beams’ failure pattern was similar to normal SRC beams, during loading process the section strain agreed with the plane-section assumption, and the beams have good bearing capacity and deformation performance.

In order to research the interface bond-slip behaviors of recycled aggregate concrete-filled square steel tube (RACFSST), ten specimens using waste concrete were designed for launch test. The three changing parameters were concrete strength grade, embedded length and recycled coarse aggregate replacement rate. The load–slip curves of square steel tubes and recycled aggregate concrete were obtained, and starting bond strength and ultimate bond strength influenced by each changing parameter were analyzed. The results show that the replacement rate had a slight influence on the starting bond strength and ultimate bond strength, while the embedded length had the opposite effect. The shorter embedded length specimens had larger bond strength. The concrete strength had a relatively large influence on them.

In order to evaluate safety performance of reinforced concrete poles accurately, 6 reinforced concrete pole specimens were selected randomly for the bending test. The mechanical behavior and failure mechanism of all specimens were studied, failure modes were revealed, and important experiment data were also obtained, such as cracking loading, ultimate loading, crack development shape, crack width and so on. Based on the experiment data, moment-crack width relationship curve and moment-deflection relationship curve were obtained. Research results showed that failure modes of specimens were similar to “less-reinforced beams”, based on limit state design method in normal use, security surplus factor is 1.27 before collapse damage.

8 channel steel reinforced concrete beams and 1 reinforced concrete beam are tested to study the capacity of channel steel reinforced concrete beam(CSRCB)under pure torque. The failure mode and process of the specimens are observed, And the working mechanism of channel steel skeleton and the concrete are analyzed. It is shown that the concrete strength, stirrup disposition and channel steel have significant effects on the torsional capacity of the beam. The calculation formula for torsional craze torque and ultimate torsional capacity of the CSRCB member are also proposed .

In order to research the mechanical property of angle steel reinforced concrete beams, 7 specimens were designed for pure torsion experiment. And three running parameters which are sectional steel disposition, thickness of concrete cover and concrete strength are taken into consideration. Base on the test, the torque-torsion angle curve, torque-strain curve, cracking torque, ultimate torque and other important data are obtain. The influences of those parameters are analyzed.

In order to reveal the performance of steel recycled concrete composite columns, 6 specimens were designed for axial compression loading experiment. And two factors which are recycled coarse aggregate replacement percentage and slenderness ratio of column are taken into consideration. The bearing capacity and load-displacement curves of composite columns are obtained. Based on the test, the failure patterns and the influence of recycled coarse aggregate replacement percentage and slenderness ratio to axial compression load-bearing capacity are analyzed. In the end, the calculation formula for axial compression load of steel recycled concrete composite columns is presented.

In order to study the mechanical behavior of recycled fine aggregate mortar, 11 kinds of different recycled fine aggregate replacement rate (ranged from 0% to 100%, level differential 10%) of cement mortar test specimens are designed. The failure pattern and the mechanical performance indexes of the cement mortar under different recycled fine aggregate replacement rate are gained by test. And the different physical indexes of natural fine aggregate and recycled fine aggregate are measured in detail. The experiment findings indicate that because the water absorption rate of the mortar with high porosity is higher, and there are mass microcracks in recycled fine aggregate interior due to damage accumulation, the lower apparent density, the higher water absorption rate and the quicker water absorption speed of recycled fine aggregate are caused. So the fluidity of recycled fine aggregate mortar is fine, but the water retention is bad, the compressive strength is lower than the natural fine aggregate mortar about 50%. But the replacement rate has little effect on the mortar strength.

Chronic allograft nephropathy (CAN) is a major cause of graft loss following kidney transplantation and may result from the interactions of various immune and non-immune factors. The aim of the present study was to establish an in vitro model of glomerular mesangial cell injury in order to examine the gene expression levels of indoleamine 2,3-dioxygenase (IDO), heme oxygenase-1 (HO-1) and interleukin-7 (IL-7) in mesangial cells during the healing process as well as to investigate the effects of various immunosuppressants on the expression of these genes. The HBZY-1 glomerular mesangial cell line was pre-treated in vitro with cytochalasin B for 2 h to induce reversible damage. Following the pre-treatment, the HBZY-1 cells were divided into five groups: Blank control group, cyclosporine A (CsA) group, tacrolimus (Tac) group, mycophenolate mofetil (MMF) group and rapamycin (RAPA) group. After treating the mesangial cells with each immunosuppressive drug for 6, 12 or 24 h, the mRNA and protein expression levels of IDO, HO-1 and IL-7 were examined using reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blot and immunohistochemical analyses. The results showed that expression levels of HO-1 were significantly upregulated in response to treatment with CsA, FK506, RAPA and MMF, whereas the expression levels of IL-7 were markedly downregulated by treatment with the above immunosuppressants. CsA, FK506 and MMF significantly enhanced the expression levels of IDO, whereas RAPA exhibited no apparent effect on IDO. The present study may contribute to the understanding of the pathogenesis of CAN and provide novel strategies for the prevention and treatment of CAN.

Deoxyhypusine synthase catalyzes the conversion of lysine to deoxyhypusine residue on the eukaryotic initiation factor 5A (elF-5A) precursor using spermidine as the substrate. Subsequent hydroxylation of the deoxyhypusine residue completes hypusine formation on elF-5A. Hypusine formation is one of the most specific polyamine-dependent biochemical events in eukaryotic cells. Although changes in polyamine metabolism have been demonstrated in human diploid fibroblasts during senescence (Chen and Chang, 1986, J. Cell. Physiol., 128:27-32.), it is unclear whether or not polyamine-dependent hypusine formation itself is an age-dependent biochemical event. In the present study, hypusine-forming activity was measured by a radiolabeling assay in cells whose polyamines have been depleted by prior treatment of alpha-difluoromethyl ornithine (DFMO). In addition, an in vitro cross-labeling assay was developed for simultaneous measurement of the deoxyhypusine synthase activity and protein substrate (elF-5A precursor) amount. We showed that the hypusine-forming activity in low-passage presenescent IMR-90 cells [population doubling level (PDL) = 15-23, termed young cells] was prominently induced by serum whereas little or no hypusine-forming activity could be detected in late-passage senescent cells (PDL = 46-54, termed old cells). The striking difference in hypusine-forming activity between young and old cells was due to changes in both deoxyhypusine synthase activity and elF-5A precursor amount in IMR-90 cells during senescence. However, Northern blot analysis showed no significant difference in the elF-5A messenger RNA (mRNA) between young and old cells, suggesting that the age-dependent attenuation of elF-5A precursor protein may be regulated at either translational or post-translational level.

The dosimetric characteristics of a multileaf collimator (MLC) retrofitted to a SL25 linear accelerator have been investigated. Central-axis depth dose, surface dose, penumbra, beam flatness and symmetry, field size factors, beam transmission through leaves and/or diaphragms, and leakage between the leaves were measured. Quantitative measurements of all beam parameters show good agreement with the design specifications of the manufacturer. No changes were observed in flatness, symmetry, penumbra, and penetration for both 6- and 25-MV photon beams when compared to the values for the standard collimator. No significant differences were observed in the penumbra as a function of leaf position. Transmission measurements in areas shielded by either X diaphragms or leaves plus diaphragms are less than 1% of dose within open field. The average leakage between leaves is about 2.5% for 6-MV and 3.5% for 25-MV photon beams. The peak value of the leakage at any point between leaves is less than 5%. The dosimetric features of shaped fields using the MLC are comparable to those of alloy shaped fields with the standard SL25 collimator.

We have previously shown that asparagine alone induces a 10–15-fold increase in ornithine decarboxylase (ODC) mRNA level in DF-40 mouse neuroblastoma cells. The induction is due to an accumulation of ODC mRNA through a post-transcriptional stabilization mechanism (Chen, Z.P. and Chen, K.Y. (1992) J. Biol. Chem., 267, 6946–6951). In the present study we showed that asparagine induced ODC gene expression in v-Ha- ras -transformed 3T3 ( ras -3T3) cells but not in 3T3 cells. Other growth related genes including c- src , c- ras , and c- fos were not affected by asparagine in ras -3T3 cells. Southern blot analysis indicated that the pronounced asparagine effect was not due to ODC gene amplification in ras -3T3 cells. The effect of asparagine on the induction of ODC mRNA could account for the significant increases in the ODC activity in ras -3T3 cells. We also examined the effect of asparagine on ODC gene expression in human KD cells and their transformed counterparts. Our findings strongly suggest that the induction of ODC mRNA by asparagine may represent a component of an altered growth regulatory program associated most prominently with cell transformation.

Plastins are a family of actin-binding proteins that are conserved throughout eukaryote evolution and expressed in most tissues of higher eukaryotes. In humans, two ubiquitous plastin isoforms (L and T) have been identified. The L isoform is expressed only in hemopoietic cell lineages, while the T isoform has been found in all other normal cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). However, L-plastin has been found in many types of malignant human cells of non-hemopoietic origin suggesting that its expression is induced accompanying tumorigenesis in solid tissues. To learn more about the nature of plastin genes and their potential role in malignancy, the L- and T- plastin genes were cloned and sequenced to characterize their structure and mechanisms of regulation of expression. Each gene was found to be approximately 90 kilobases in size and was composed of 16 exons. All exon-intron junction sequences were identified and shown to conform to the canonical junction sequences. It was evident from their similar structure and coding homology that the two plastin genes have diverged from a common ancestor gene. L- and T-plastin genes were also mapped to chromosomes 13 and X, respectively, using polymerase chain reaction amplification with isoform-specific probes. An expanded survey of normal cell types and 50 tumor cell lines, demonstrated that 68% of carcinomas and 53% of other solid tumors of nonepithelial origin exhibited L-plastin expression, whereas the normal stem cell progenitors did not. Fibrosarcomas (n = 4), ovarian carcinomas (n = 9), breast carcinomas (n = 4), and choriocarcinomas (n = 2) combined exhibited the highest frequency and levels of L-plastin expression (95% frequency). In addition, 4 tumor cell lines that were L-plastin-negative exhibited evidence of defective T-plastin expression increasing the apparent co-incidence of plastin abnormalities associated with human tumorigenesis to 71%. Evidence is presented in support of a trans-activation mechanism for activation of L-plastin synthesis accompanying tumorigenesis. The induction of L-plastin expression accompanying SV40-mediated transformation of human embryonic lung MRC-5 fibroblasts was also confirmed. Finally, we present evidence that fimbrin is a third distinct plastin isoform which is specifically expressed at high levels in the small intestine.

Plastins are a family of human actin-binding proteins (isoforms) which are abundantly expressed in all normal replicating mammalian cells. One isoform, L-plastin, is constitutively expressed at high levels in hemopoietic cell types while T-plastin is constitutively expressed in all non-hemopoietic cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). L-plastin is, however, constitutively synthesized in many types of malignant human cells of solid tissues suggesting that its expression is induced during tumorigenesis. The frequency of L-plastin induction in some cancers of the steroid-regulated female reproductive tract (breast, ovary, uterus, and placenta) appears to be especially high (79% in a limited survey). To learn the mechanism of L-plastin gene activation accompanying tumorigenesis, we have begun to characterize the promoter and regulatory elements of the L-plastin gene. Transcription initiation from this promoter was found to occur at multiple sites and as near as 10 base pairs from the 3'-side of the TATAAA box. The promoter and its flanking DNA were cloned and sequenced to identify potential regulatory elements that participate in the induction of the L-plastin gene in neoplastic cells. Examination of upstream sequences revealed the existence of two potential progesterone, one potential estrogen, and four potential Ets-1 responsive elements flanking the promoter. A 315-base pair fragment spanning the TATAAA box and a potential Sp1-binding site exhibited maximum promoter activity using CAT as a reporter while longer promoter fragments extending into upstream flanking sequences spanning the hormone receptor-response elements exhibited reduced promoter activity. An expression vector, pHLPPr-1-neo, was constructed using a 5.1-kilobase pair EcoRI-HindIII fragment of the L-plastin gene that contained the potential upstream regulatory elements, the TATAAA box, and part of the first exon. This promoter could direct the constitutive expression of the reporter beta-galactosidase at high frequency in transfected colonies of transformed cells that express L-plastin constitutively; by contrast, this promoter was virtually inactive in transfected colonies of normal fibroblasts and it exhibited a low frequency of constitutive activation in transfected colonies of in vitro SV40-transformed fibroblasts which did not exhibit L-plastin expression. The utility of this recombinant promoter in determining the mechanism(s) that leads to activation of the L-plastin gene in tumor cells is discussed. The potential significance of regulation of the L-plastin gene by reproductive hormones in cancers arising in hormone-responsive tissues is also discussed.

In order to reveal the mechanical behavior of recycled aggregate concrete-filled circle steel tube column under axial compression loading. 22 specimens were designed for test. The specimens parameters are recycled coarse aggregate replacement percentage and steel confine coefficient. According to the test, the failure process and patterns were obtained, the whole process curve of stress- strain and secant modulus-stress were measured, and some important parameters, such as the peak stress and peak strain were analyzed, the study indicates that the recycled aggregate concrete-filled circular steel tube columns' failure patterns are similar to ordinary concrete-filled steel tube column. With the recycled coarse aggregate replacement percentage increasing, the peak stress has slightly increased. In the end, the bearing capacity calculation method is discussed.

According to the experimental studies on 11 specimens of recycled aggregate concrete (RAC) filled square steel tube column under axial compression loading. The failure patterns, mechanical behavior of RAC-filled square steel tube such as the loading-displacement curves, loading capacity, peak stress and strain, rigidity degradation and energy dissipation are obtained. Study results show that failure mode of RAC filled square steel tube is similar to ordinary concrete filled square steel tube; with the recycled coarse aggregate replacement percentage increasing, the bearing capacity have slightly increased.

Several three-dimensional vascular models have been developed to study the effects of adding equations for large blood vessels to the traditional bioheat transfer equation of Pennes when simulating tissue temperature distributions. These vascular models include “transiting” vessels, “supplying” arteries, and “draining” veins, for all of which the mean temperature of the blood in the vessels is calculated along their lengths. For the supplying arteries this spatially variable temperature is then used as the arterial temperature in the bioheat transfer equation. The different vascular models produce significantly different locations for both the maximum tumor and the maximum normal tissue temperatures for a given power deposition pattern. However, all of the vascular models predict essentially the same cold regions in the same locations in tumors: one set at the tumors’ corners and another around the inlets of the large blood vessels to the tumor. Several different power deposition patterns have been simulated in an attempt to eliminate these cold regions; uniform power in the tumor, annular power in the tumor, preheating of the blood in the vessels while they are traversing the normal tissue, and an “optimal” power pattern which combines the best features of the above approaches. Although the calculations indicate that optimal power deposition patterns (which improve the temperature distributions) exist for all of the vascular models, none of the heating patterns studied eliminated all of the cold regions. Vasodilation in the normal tissue is also simulated to see its effects on the temperature fields. This technique can raise the temperatures around the inlet of the large blood vessles to the tumor (due to the higher power deposition rates possible), but on the other hand, normal tissue vasodilation makes the temperatures at the tumor corners slightly colder.

A general three-dimensional planning program has been developed for hyperthermia treatments for cancer.1 In this study, the program is used to analyze the three-dimensional temperature distributions generated by interstitial ferromagnetic implants. An empirical power absorption formula developed by Haider2 for thermally self-regulating nickel-silicon ferromagnetic seeds has been used to calculate the seed power absorption as a function of seed temperature. By properly choosing the seed type (Curie point of seeds), and by using appropriate seed spacing, this heating modality can generate desirable three-dimensional temperature distributions for many different situations over a fairly large range of blood perfusion values. Detailed information regarding the choice of the Curie points of the seeds and the seed spacing for certain blood perfusions is also given as a quantitative guide for treatment planning.

In order to reveal the mechanical behavior of solid steel reinforced concrete special-shaped columns, 5 specimens were designed for low cyclic reversed loading test. The failure patterns, loading-displacement hysteretic curves, displacement ductility, ultimate rotation capacity, energy dissipation capacity were obtained from the test. Experimental study results shown that solid steel reinforced concrete special-shaped columns have strong bearing capacity, displacement ductility good, large ultimate rotation capacity, full hysteretic loop, excellent seismic energy dissipation ability. In the end, the calculation formula about normal section bearing capacity and shear capacity are given. the calculating results are in good agreement with test .All of this may be help for engineering designation and construction.

Differentiation of mouse neuroblastoma cells has been shown to be accompanied by changes in polyamine metabolism and a decrease in polyamine content. We have previously shown that α-difluoromethyl ornithine, a suicide inhibitor of ornithine decar☐ylase (ODC, EC 4.1.1.17) and suboptimal concentrations of dibutyryl cAMP (0.1 to 0.2 mM) are effective in inducing the differentiation of mouse Neuro-2a (N2a) neuroblastoma cells. Exogenously added putrescine or spermidine can block the action of DFMO and dibutyryl cAMP, suggesting that polyamines may play a regulatory role in neuroblastoma differentiation. We have now isolated from N2a cells a clonal variant line, DF-40, whose ODC gene has been amplified by 40-fold. The DF-40 cells overproduced the ODC enzyme and contained very high levels of putrescine, spermidine and spermine. Treatment of DF-40 cells with dibutyryl cAMP or DFMO/dibutyryl cAMP led to a more than 80% reduction in polyamine content. Such a decrease did not cause the DF-40 cells to differentiate. Polyamine content in the treated DF-40 cells was still comparable or higher than that in the undifferentiated N2a cells. In contrast, serum-deprivation induced full differentiation of DF-40 cells. Levels of polyamine in the differentiated DF-40 cells, however, were also found to be comparable to that in the undifferentiated N2a cells. Exogenously added polyamines could not block the differentiation of DF-40 cells induced by serum-deprivation, suggesting that the action of polyamines in regulating neuroblastoma differentiation may depend on the presence of serum factors.

An empirical power absorption formula developed by Haider et al. (1991) for thermally self-regulating nickel-silicon ferromagnetic seeds has been incorporated into a three-dimensional patient treatment planning programme to calculate the seed power absorption as a function of seed temperature. The programme has been used to evaluate systematically the accuracy of two-versus three-dimensional simulations for ferromagnetic implant hyperthermia. The results show that two-dimensional simulations can significantly overestimate temperatures. Consequently, three-dimensional simulations are necessary for accurate hyperthermia treatment planning.

Deoxyhypusine synthase is the key enzyme for modifying a lysine residue to hypusine in the cellular protein eukaryotic initiation factor 5A (eIF-5A). Deletion of the deoxyhypusine synthase or the eIF-5A gene in yeast produces lethal phenotype. Inhibition of deoxyhypusine synthase by 1-guanidino-7-aminoheptane (GC7) suppresses tumor cell growth. Hypusine formation represents one of the most specific polyamine-dependent biochemical reactions. In view of the importance of polyamines in growth regulation and cancer biology, deoxyhypusine synthase has been considered to be a good target for chemotherapeutic drug design. Using GC7 as a prototype we have synthesized and tested three classes of diamine analogs, namely, guanidino-, pyrimidino-, and hydroxamate derivatives, as potential inhibitors for deoxyhypusine synthase. Our study shows that (i) among all the compounds tested, GC7 remained to be the most potent inhibitor for deoxyhypusine synthase; (ii) N,N'-bispyrimidino-1, 9-diaminononane, although a poor inhibitor of deoxyhypusine synthase, was a potent growth inhibitor; and (iii) one of the hydroxamate derivatives, 6-aminohexanoic hydroxamate (HC6), prominently induced the differentiation of mouse neuroblastoma cells at sub-millimolar concentrations. Interestingly, other hydroxamates with different chain length were not nearly as effective as HC6 in inducing neuroblastoma cell differentiation. The effect of HC6 was also unique in that it could induce neurite outgrowth and the expression of neuron-specific genes such as synapsin I and MAP-2 in neuroblastoma cells in the absence of other promoting agents such as cAMP. The effect of HC6 on neuroblastoma cell differentiation was comparable with, or better than that of N(6),O(2)'-dibutyryl cAMP (Bt(2)cAMP), a standard reagent commonly used for inducing the differentiation of mouse and human neuroblastoma cells in culture.

(-)-Epigallocatechin gallate (EGCG), a catechin polyphenol compound, represents the main ingredient of green tea extract. Although EGCG has been shown to be growth inhibitory in a number of tumor cell lines, it is not clear whether the effect is cancer-specific. In this study we compared the effect of EGCG on the growth of SV40 virally transformed WI38 human fibroblasts (WI38VA) with that of normal WI38 cells. The IC50 value of EGCG was estimated to be 120 and 10 microM for WI38 and WI38VA cells, respectively. Thus, EGCG at 40 microM completely inhibited the growth of WI38VA cells, but had little or no inhibitory effect on the growth of WI38 cells. Similar differential growth inhibition was also observed between a human colorectal cancer cell line (Caco-2), a breast cancer cell line (Hs578T) and their respective normal counterparts. EGCG at a concentration range of 40-200 microM induced a significant amount of apoptosis in WI38VA cultures, but not in WI38 cultures, as determined by terminal deoxynucleotidyl transferase assay. After exposure to EGCG at 200 microM for 8 h, more than 50% of WI38VA cells in a confluent culture became apoptotic. In contrast, less than 1% of WI38 cells displayed apoptotic labeling under the same condition. EGCG did not affect the serum-induced expression of c-fos and c-myc genes in normal WI38 cells. However, it significantly enhanced their expression in transformed W138VA cells. It is possible that differential modulation of certain genes, such as c-fos and c-myc, may cause differential effects of EGCG on the growth and death of cancer cells.

Hypusine formation on the eukaryotic initiation factor 5A (eIF-5A) precursor is ubiquitously present in eukaryotic cells and archebacteria. In this reaction, deoxyhypusine synthase catalyzes the conversion of one unique lysine residue on eIF-5A to deoxyhypusine using spermidine as the substrate. Hydroxylation of the deoxyhypusine residue completes hypusine formation on eIF-5A. Hypusine formation activity can be measured by an in vitro labeling technique in polyamine-depleted cells. In addition, an in vitro cross-labeling assay can be employed to measure simultaneously the relative deoxyhypusine synthase activity and protein substrate amount. Using these approaches, together with Western blot analysis, we showed that hypusine formation activity is serum-responsive and significantly elevated in Ras oncogene transfected NIH3T3 cells as compared to NIH3T3 cells. The large difference, >30-fold, in hypusine formation activity between these two cells is mainly due to difference in the amount of newly synthesized eIF-5A precursor rather than deoxyhypusine synthase. The deoxyhypusine synthase activity is about three-fold higher in Ras-3T3 cells than in 3T3 cells, and remains constant throughout serum stimulation in both cells. Despite the significant difference in eIF-5A protein amounts, the eIF-5A mRNA levels in 3T3 cells and in Ras-3T3 cells are almost identical. Furthermore, unlike serum-dependent increase in eIF-5A precursor protein, the eIF-5A mRNA in both cells is constitutively expressed after serum stimulation, suggesting that eIF-5A gene is regulated at posttranscriptional/translational level during serum stimulation and cell transformation.

Deoxyhypusine synthase catalyzes the conversion of lysine to deoxyhypusine residue on the eukaryotic initiation factor 5A (eIF-5A) precursor using spermidine as the substrate. Subsequent hydroxylation of the deoxyhypusine residue completes hypusine formation on eIF-5A. Polyamines (putrescine, spermidine, and spermine) have been implicated in tumor growth and differentiation. Because deoxyhypusine/hypusine formation is one of the most specific polyamine-dependent biochemical events, we decided to use N1-guanyl-1,7-diaminoheptane (GC7), a potent inhibitor for deoxyhypusine synthase, to assess the role of hypusine formation on tumor growth and differentiation. GC7 suppressed the growth of N2a mouse neuroblastoma cells and DS19 murine erythroleukemia cells at micromolar concentrations. However, within a narrow concentration range, GC7 could promote the differentiation of mouse neuroblastoma cells in the presence of suboptimal amount of dibutyryl cAMP. In contrast, GC7 blocked the differentiation of DS19 cells induced with hexamethylene bisacetamide. Polyamine depletion by difluoromethyl ornithine (DFMO) has previously been shown to promote differentiation of neuroblastoma cells but inhibits erythrodifferentiation. Since our studies demonstrated that GC7 mimics the action of DFMO on tumor differentiation, it is likely that the effect of DFMO on tumor differentiation is mediated by hypusine formation and that GC7 represents a more specific inhibitor that can alter the differentiation program in certain tumor cells.

The complete cDNA sequence of human intestine-specific plastin (I-plastin) was determined from a clone derived by PCR. It consists of a 97-bp 5' untranslated region, a 1,887-bp coding region, and a 1,655-bp 3' untranslated region. The coding region predicts a 629-residue polypeptide whose sequence displays 86, 75, and 73% identities with chicken intestine fimbrin, human T-plastin, and human L-plastin, respectively. Recombinant I-plastin cross-linked actin filaments into bundles in the absence but not in the presence of calcium. The I-plastin gene was mapped by PCR to human chromosome 3; the L- and T-plastin genes were previously mapped to chromosomes 13 and X, respectively. I-plastin mRNA was detected in the small intestine, colon, and kidneys; relatively lower levels of expression were detected in the lungs and stomach. In contrast, L-plastin expression was restricted to the spleen and other lymph node-containing organs, while T-plastin was expressed in a variety of organs, including muscle, brain, uterus, and esophagus. In contrast to the situation for the intestine, high levels of L- and T-plastin mRNAs were detected in Caco-2, a human colon-derived cell line. Immunofluorescence microscopy detected I-plastin in the brush border of the small intestine and colon. These results identify I-plastin as the human homolog of chicken intestine fimbrin and as a third plastin isoform in humans.

An analytical, cylindrical coordinate formula for the thermal resistance around small cylindrical objects has been incorporated into finite difference equations in Cartesian coordinates to improve the accuracy of the numerical simulations of hyperthermia cancer treatments. This is done by introducing a circular finite difference control volume which is centered on the cylindrical object. The temperature distributions calculated from this new formulation and from the formulation obtained from a conventional, rectangular control volume are compared to the predictions from an analytical solution. The results show that for a given Cartesian grid spacing, the new method is superior to the conventional one. This will allow more accurate numerical solutions to be obtained at larger grid spacings when the effect of blood vessels or other cylindrical objects, such as ferromagnetic implants, hot water tubes, etc., are being investigated.

A simulation program to study the three-dimensional temperature distributions produced by hyperthermia in anatomically realistic inhomogenous tissue models has been developed using the bioheat transfer equation. The anatomical data for the inhomogeneous tissues of the human body are entered on a digitizing tablet from serial computed tomography (CT) scans. Power deposition patterns from various heating modalities must be calculated independently. The program has been used to comparatively evaluate two- and three-dimensional simulations in a series of parametric calculations based on a simple inhomogeneous tissue model for uniform power deposition. The conclusions are that two-dimensional simulations always lead to significant errors at the ends of tumors (up to tens of degrees). However, they can give valid results for the central region of large tumors, but only with tumor blood perfusions greater than approximately 1 kg/m3/s. These conclusions from the geometrically simple model are substantiated by the results obtained using the full three-dimensional model for actual patient anatomical simulations. In summary, three-dimensional simulations will be necessary for accurate patient treatment planning. The effect of the thermal conductivity, used in the models, on the temperature field has also been studied. The results show that using any thermal conductivity value in the range of 0.4 to 0.6 W/m/degrees C sufficiently characterizes most soft tissues, especially in the presence of high blood perfusion. However, bone (thermal conductivity of 1.16 W/m/degrees C) and fat (thermal conductivity of 0.2 W/m/degrees C) do not fit this generalization and significant errors result if soft tissue values are used.