Morphologically heterogeneous prostate cancers that behave clinically like small-cell prostate cancers (SCPC) share their chemotherapy responsiveness. We asked whether these clinically defined, ...morphologically diverse, "aggressive variant prostate cancer (AVPC)" also share molecular features with SCPC.
Fifty-nine prostate cancer samples from 40 clinical trial participants meeting AVPC criteria, and 8 patient-tumor derived xenografts (PDX) from 6 of them, were stained for markers aberrantly expressed in SCPC. DNA from 36 and 8 PDX was analyzed by Oncoscan for copy number gains (CNG) and losses (CNL). We used the AVPC PDX to expand observations and referenced publicly available datasets to arrive at a candidate molecular signature for the AVPC.
Irrespective of morphology, Ki67 and Tp53 stained ≥10% cells in 80% and 41% of samples, respectively. RB1 stained <10% cells in 61% of samples and AR in 36%. MYC (surrogate for 8q) CNG and RB1 CNL showed in 54% of 44 samples each and PTEN CNL in 48%. All but 1 of 8 PDX bore Tp53 missense mutations. RB1 CNL was the strongest discriminator between unselected castration-resistant prostate cancer (CRPC) and the AVPC. Combined alterations in RB1, Tp53, and/or PTEN were more frequent in the AVPC than in unselected CRPC and in The Cancer Genome Atlas samples.
Clinically defined AVPC share molecular features with SCPC and are characterized by combined alterations in RB1, Tp53, and/or PTEN.
The solution to the job shop scheduling problem (JSSP) is of great significance for improving resource utilization and production efficiency of enterprises. In this paper, in view of its ...non-deterministic polynomial properties, a multi-agent genetic algorithm based on tabu search (MAGATS) is proposed to solve JSSPs under makespan constraints. Firstly, a multi-agent genetic algorithm (MAGA) is proposed. During the process, a multi-agent grid environment is constructed based on characteristics of multi-agent systems and genetic algorithm (GA), and a corresponding neighbor interaction operator, a mutation operator based on neighborhood structure and a self-learning operator are designed. Then, combining tabu search algorithm with a MAGA, the algorithm MAGATS are presented. Finally, 43 benchmark instances are tested with the new algorithm. Compared with four other algorithms, the optimization performance of it is analyzed based on obtained test results. Effectiveness of the new algorithm is verified by analysis results.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Heavier individuals have higher hip BMD and more robust femur geometry, but it is unclear whether values vary in proportion with body weight in obesity. We studied the variation of hip BMD and ...geometry across categories of body mass index (BMI) in a subset of postmenopausal non‐Hispanic whites (NHWs) from the Women's Health Initiative Observational Cohort (WHI‐OS). The implications on fracture incidence were studied among NHWs in the entire WHI‐OS. Baseline DXA scans of hip and total body from 4642 NHW women were divided into BMI (kg/m2) categories: underweight (<18.5), healthy weight (18.5–24.9), overweight (25–29.9), and mild (30–34.9), moderate (35–39.9), and extreme obesity (>40). Femur BMD and indices of bone axial (cross‐sectional area CSA) and bending strength (section modulus SM) were extracted from DXA scans using the hip structure analysis (HSA) method and compared among BMI categories after adjustment for height, age, hormone use, diabetes, activity level, femur neck‐shaft angle, and neck length. The association between BMI and incident fracture was studied in 78,013 NHWs from the entire WHI‐OS over 8.5 ± 2.6 (SD) yr of follow‐up. Fracture incidence (cases/1000 person‐years) was compared among BMI categories for hip alone, central body (hip, pelvis, spine, ribs, and shoulder girdle), upper extremity (humerus and distal), and lower extremity (femur shaft and distal but not hip). Femur BMD, CSA, and SM were larger in women with higher BMI, but values scaled in proportion to lean and not to fat or total body mass. Women with highest BMI reported more falls in the 12 mo before enrollment, more prevalent fractures, and had lower measures of physical activity and function. Incidence of hip fractures and all central body fractures declined with BMI. Lower extremity fractures distal to the hip trended upward, and upper extremity incidence was independent of BMI. BMD, CSA, and SM vary in proportion to total body lean mass, supporting the view that bones adapt to prevalent muscle loads. Because lean mass is a progressively smaller fraction of total mass in obesity, femur BMD, CSA, and SM decline relative to body weight in higher BMI categories. Traumatic forces increase with body weight, but fracture rates at the hip and central body were less frequent with increasing BMI, possibly because of greater soft tissue padding. There was no evident protective effect in fracture rates at less padded distal extremity sites. Upper extremity fractures showed no variation with BMI, and lower extremity fracture rates were higher only in the overweight (BMI = 25–29.9 kg/m2).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Recycling crushed waste oyster shells (WOS) as a fine aggregate is an attractive method of disposal. However, its use in geopolymer mortar has not been reported. The influence of PVA fibres on the ...engineering properties of the new geopolymer mortar is still unclear. To bridge the gap, this study investigated the influence of various PVA fibre contents (0–1.05 vol%) on the flowability, compressive, flexural strengths, drying shrinkage, sorptivity, chloride resistance, porosity, fibre dispersion, embodied CO2 emissions (ECO2e), and embodied energy (EE) of the geopolymer mortar. The results indicated that the inclusion of 0.15–1.05 vol% of PVA fibres improved the flexural strength by 10.10–42.31% and reduced the drying shrinkage by 13.37–65.79%. The flowability and compressive strength decreased by 10.78–34.28% and 7.50–27.65%, respectively, but they were sufficient for construction. The sorptivity increased by 1.45–15.16%, and the chloride resistance decreased by 15.09–56.35%, but the geopolymer mortar was still classified as low chloride penetrability. In summary, the optimal content of PVA fibres is 0.45 vol%, and the geopolymer mortar has good engineering properties and eco-efficiency. The cost analysis and high-temperature resistance of the geopolymer mortar are neglected in this study, which should be evaluated in future work.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Small-cell prostate carcinoma (SCPC) morphology predicts for a distinct clinical behavior, resistance to androgen ablation, and frequent but short responses to chemotherapy. We sought to develop ...model systems that reflect human SCPC and can improve our understanding of its biology.
We developed a set of castration-resistant prostate carcinomas xenografts and examined their fidelity to their human tumors of origin. We compared the expression and genomic profiles of SCPC and large-cell neuroendocrine carcinoma (LCNEC) xenografts to those of typical prostate adenocarcinoma xenografts. Results were validated immunohistochemically in a panel of 60 human tumors.
The reported SCPC and LCNEC xenografts retain high fidelity to their human tumors of origin and are characterized by a marked upregulation of UBE2C and other mitotic genes in the absence of androgen receptor (AR), retinoblastoma (RB1), and cyclin D1 (CCND1) expression. We confirmed these findings in a panel of samples of CRPC patients. In addition, array comparative genomic hybridization of the xenografts showed that the SCPC/LCNEC tumors display more copy number variations than the adenocarcinoma counterparts. Amplification of the UBE2C locus and microdeletions of RB1 were present in a subset, but none displayed AR nor CCND1 deletions. The AR, RB1, and CCND1 promoters showed no CpG methylation in the SCPC xenografts.
Modeling human prostate carcinoma with xenografts allows in-depth and detailed studies of its underlying biology. The detailed clinical annotation of the donor tumors enables associations of anticipated relevance to be made. Future studies in the xenografts will address the functional significance of the findings.
To ensure bridge safety, the flood risk analysis is significant important. However, due to the small size and large number of piers in the short-distance multi-bridge system, the extremely long ...calculation time and low efficiency of the numerical model are induced by the small mesh size and large mesh number. In this paper, a flood risk assessment model of the multi-bridge system with short distance was established to improve the calculation efficiency based on the finite volume method combined with the Delaunay mesh adaptive refinement method. The calculated water level with refined and non-refined mesh was compared with the experimental data of a partial failure dam break test case and Shukry experiment of open channel bend flow. The calculated water level results are in good agreement with the experimental data. In addition, the mesh refinement model improved the calculation efficiency by more than 73% with ensuring the calculation accuracy. Finally, the flood risk of a real multi-bridge system with short distance was evaluated by using the numerical model. The calculated results shown that, different from the general flow law, the water level in the upstream and downstream channel of Bridge 2 rose with a maximum difference value of 0.326 m while the water level in the far downstream channel of Bridge 2 dropped result from the construction of Bridge 2 on the basis of the Bridges 1, 3 and 4. The construction of Bridge 2 also increased the flow velocity around Bridge 3 with maximum 0.013 m/s. This study provides a new tool and technical reference for flood risk analyses of similar multi-bridge system with short distance.
Due to significant influence on the safety of marine structures, the interaction between extreme waves and structures is a crucial area of study in marine science. This paper focus on the ...verification of a solitary wave meshless SPH model and the application of the model on the interaction between solitary waves and semi-submersible structures. A solitary wave propagation model is established based on the SPH method combined with Rayleigh solitary wave theory, quintic kernel function, artificial viscosity, and Symplectic Method. The accuracy of the model is validated by comparing the calculated wave height with the theoretical value. The calculated results with relative particle spacing
H
0
/
d
0
≥ 20 are in good agreement with the analytical solution. The simulated solitary wave is also quite stable with a maximum
L
2
error 0.016. Therefore, the proposed SPH model can accurately simulate the propagation of the solitary waves. A case study on the interaction between solitary waves and semi-submersible platforms is conducted. The results show that the interaction between solitary waves and semi-submersible causes two double peaks with wave heights of 0.398 m and 0.410 m, respectively, induced by overtopping at the center of the platform. The wave transmission coefficient
K
t
is 0.880 due to that the solitary wave height reduces from 0.498 m to 0.438 m after the solitary wave propagates through the semi-submersible structure. In addition, the solitary wave induces significant vertical wave loads of the structure with a load amplitude of 0.688, while horizontal wave loads are relatively small with a load amplitude of 0.089. The solitary wave arrived the structure induces the upstream and downstream overtopping and forms a hydraulic jump leading to the complex flow field. The maximum velocity at the top and bottom of the structure is 2.2 m/s and 0.8 m/s respectively. Positive or negative vortex are formed at the bottom of the leading edge, top and downstream of the structure with the maximum intensity 28 s
-1
and -40 s
-1
. In a word, the meshless SPH model can conveniently and accurately simulate the propagation of the solitary waves, and be applied to the investigation of the wave height, velocity, vorticity, wave load, and wave breaking of the interaction between solitary waves and structures in ocean engineering.
The effect of the non-uniform bathymetry on the nonlinear wave dynamics for the freak wave is investigated experimentally, with emphasis on the interrelations between different nonlinear behaviors ...resulting from various geometric parameters and spectral analysis. Both the frequency modulation and the nonlinear phase coupling can be provoked by the decreasing water depth and weakened after the top peak of the bar, the nonlinear exhibition for transferring energy to high-frequency contents over shoal supports that frequency modulation can reflect nonlinear phase coupling well. The consistent change of the Hilbert energy spectrum and the bicoherence shows that the main nonlinear interaction in the process of wave propagation in shallowing water is quadratic nonlinearity. In addition, the geometric study is conducted to investigate the effect of the water depth on the parametric variations, the research results show that the mean asymmetry and kurtosis change abruptly when the wave approaches the top peak of the bar. As the wave propagates along the water flume, freak waves can be generated at various locations, however, they appear more frequently as waves propagate close to the shallowest water depth, and the maximum probability of occurrence for a freak wave can be up to about 1%.
By neglecting the viscosity of fluid and rotation in flow, the theory of potential flow cannot accurately predict the hydrodynamic forces on the structures under significant viscous effects. In this ...study, the effects of liquid viscosity on the hydrodynamic forces on a horizontal circular cylinder underwater with a large-amplitude forced oscillation were investigated. The study used a two-dimensional two-phase flow wave tank model based on the viscous fluid theory using the OpenFOAM® package. The numerical calculations were carried out under different types of liquid (i.e., liquid with different viscosities). The liquid viscosity effects are visually shown by comparison of the various frequency components of the hydrodynamic forces on the cylinder, and the magnitude and phase relations of the viscous shear forces and the pressure forces. By analyzing the distribution characteristics of the flow fields around the circular cylinder, the viscous-effect mechanisms are revealed. It is found that the discrepancies of the contributions of viscous shear forces, and the discrepancies of the vortex effects on the phase and magnitude of the pressure forces lead to the obvious differences among the results under different liquid viscosities.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Assessing skeletal muscle mass (SMM) is critical in studying and detecting sarcopenia. Direct measurements by MRI or computerized tomography are expensive or high in radiation exposure. Dual-energy ...X-ray absorptiometry (DXA) is promising for body composition assessments, but the validity of DXA for predicting SMM in the elderly is still under investigation. The objective of this study was to assess the relationship between DXA-derived measurements of lean soft tissue mass (LSTM) and SMM in older women. Study participants were postmenopausal women (n = 101) recruited in southern Arizona. Total and regional body composition was measured using MRI and DXA (QDR4500w). The participants' mean age was 70.7 ± 6.4 y and their mean BMI was 27.4 ± 5.1 kg/m². DXA-derived LSTM was highly correlated with MRI-derived SMM for the whole body (r = 0.94; P < 0.001) and leg region (r = 0.91; P < 0.001). In multivariate models, adjusting for age and DXA-derived percent fat slightly increased the amount of variance in SMM that can be explained by the DXA-derived LSTM assessments for the leg region but not for the total body. In conclusion, although the relationships between DXA measures and MRI-derived SMM vary by region of interest, the overall prediction of SMM by DXA is excellent. We conclude that DXA is a reliable method for cross-sectional assessments of SMM in older women.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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