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In this paper, we propose a nonreflecting outlet boundary condition (NROBC) for particle-based fluid simulation as a combination of inflow/outflow algorithm and periodic boundary condition. We assume to use δ-SPH scheme for weakly compressible flows. In the inflow/outflow algorithm, the domain is divided into four zones: fluid, wall, inflow and outflow zones. The NROBC proposed in this paper inherits the advantage of the periodic boundary condition in the sense that the number of particles is constant. This property contributes to conservation of total mass and insertion of inflow particles without rearranging process. The physical quantities such as density and velocity at the inflow zone are unknown depending on the situation. Our boundary condition supports both cases, prescribed and non-prescribed, and the loss of the accuracy is small even if the quantities are non-prescribed at the inflow zone. In addition, tensile instability is effectively reduced by particle shifting technique. Several simulations are presented to validate and demonstrate the applicability and versatility of the proposed technique. Comparisons between numerical results and analytical solutions are provided with very low Mean Square Error Percent (MSEP) in both test cases.

To examine the dynamics of circulating tumour cells (CTCs) in pancreatic cancer (PC), new mouse CTC models from human PC xenografts were developed.Orthotopic (pancreas) and heterotopic (subcutaneous) transplantation models using GFP-tagged SUIT-2 PC cells were prepared. Using a cytology-based CTC detection platform, CTCs and metastasis were compared.The two types of orthotopic models, including the surgical transplantation model and the intraperitoneal injection model, showed a similar pattern of initial pancreatic tumour formation and subsequent development of peritoneal and hematogenous lung metastases. In the heterotopic model, only hematogenous lung metastasis was observed, and the number of CTCs and lung metastases was higher than that of the orthotopic model. Furthermore, KRAS mutation (G12D) was detected in CTCs.These orthotopic and heterotopic models clearly differ in terms of the pattern of metastasis and CTCs and therefore, would be useful PC models to investigate the effect of drug-therapy on CTCs and the role of KRAS mutation.

Metabolic reprogramming leading to aerobic glycolysis, termed the "Warburg effect," is a critical property of cancer cells. However, the precise mechanisms underlying this phenomenon are not fully understood. A growing body of evidence indicates that γ-glutamylcyclotransferase (GGCT), an enzyme involved in glutathione homeostasis that is highly expressed in many types of cancer, represents a promising therapeutic target. In this study, we identified GGCT as a novel regulator of hypoxia-inducible factor-1α (HIF-1α), a transcription factor that plays a role in hypoxia adaptation promoting aerobic glycolysis. In multiple human cancer cell lines, depletion of GGCT downregulated HIF-1α at the mRNA and protein levels. Conversely, in NIH3T3 mouse fibroblasts, overexpression of GGCT upregulated HIF-1α under normoxia. Moreover, depletion of GGCT downregulated HIF-1α downstream target genes involved in glycolysis, whereas overexpression of GGCT upregulated those genes. Metabolomic analysis revealed that modulation of GGCT expression induced a metabolic switch from the citric acid cycle to glycolysis under normoxia. In addition, we found that GGCT regulates expression of HIF-1α protein via the AMPK-mTORC1-4E-BP1 pathway in PC3 cells. Thus GGCT regulates the expression of HIF-1α in cancer cells, causing a switch to glycolysis.

Background: Phase-III ASPECCT and randomised phase-II WJOG6510G trials demonstrated the noninferiority of panitumumab, when compared with cetuximab, for overall survival in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer. Methods: The subgroup that received bevacizumab either prior to panitumumab or cetuximab monotherapy (ASPECCT) or in combination with irinotecan (WJOG6510G) was included. Multivariate Cox models were created, including the treatment arms as covariates together with patient, disease and treatment characteristics. Results: We included 185 and 189 patients in the panitumumab and cetuximab arms, respectively. The median overall survival was 12.8 and 10.1 months [p = 0.0031; log-rank test, stratified by trial; hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.58–0.90], and the median progression-free survival was 4.7 and 4.1 months, in the panitumumab and cetuximab arms, respectively (p = 0.0207; HR, 0.79; 95% CI, 0.64–0.97). The treatment regimen was an independent prognostic factor of overall survival (adjusted HR, 0.69; 95% CI, 0.54–0.87; p = 0.0013). Conclusions: Panitumumab significantly prolonged the overall survival and progression-free survival, when compared with cetuximab in the cohort that previously received bevacizumab in the included studies. Clinical Trial Registration: ASPECCT trial registered with ClinicalTrials.gov (NCT01001377) and WJOG6510G trial registered with UMIN-CTR (UMIN000006643).

Microglia, the primary immune cells in the brain, sense pathogens and tissue damage, stimulate cytokine production, and phagocytosis to maintain homeostasis. Accumulation of amyloid-β peptides (Aβ) in the brain triggers the onset of Alzheimer's disease (AD). Accordingly, promotion of Aβ clearance represents a promising strategy for AD therapy. We previously demonstrated that primary-cultured rat microglia phagocytose Aβ, and that transplantation of these cells ameliorates the Aβ burden in brains of Aβ-injected rats. In this study, we demonstrate that stimulation with colony-stimulating factor-1 efficiently differentiates mouse bone marrow cells into bone marrow-derived microglia-like (BMDML) cells that express markers for microglia, including the recently identified transmembrane protein 119. BMDML cells effectively phagocytose Aβ in vitro, with effects comparable to primary-cultured mouse microglia and greater than peritoneal macrophages. RT-qPCR analysis for cytokine mRNA levels revealed that BMDML cells polarize to a relatively anti-inflammatory state under non-stimulated and inflammatory conditions but exert a pro-inflammatory reaction after lipopolysaccharide treatment. Moreover, BMDML cells hippocampally injected into a mouse model of AD are morphologically similar to the ramified and amoeboid types of residential microglia. Comparisons with simulations assuming a uniform distribution of cells suggest that BMDML cells migrate directionally toward Aβ plaques. We also detected Aβ phagocytosis by BMDML cells, concomitant with a reduction in the number and area of Aβ plaques. Finally, we observed amelioration of cognitive impairment in a mouse model of AD after hippocampal injection of BMDML cells. Our results suggest that BMDML cells have potential as a cell-based disease-modifying therapy against AD.

This paper presents an improved method for applying smoothed particle hydrodynamics within a nested Lagrangian domain of fluid particles. In our previous implementation, ghost particles, generated ...

Previous studies show that gamma-glutamylcyclotransferase (GGCT) is expressed at high levels in various cancer tissues and that its knockdown inhibits MCF7 cancer cell growth via upregulation of p21WAF1/CIP1 (p21). However, the detailed underlying mechanism is unclear. Here, we used yeast two-hybrid screening and co-immunoprecipitation to identify Prohibitin-2 (PHB2) as a novel protein that interacts with GGCT. We also show that nuclear expression of PHB2 in MCF7 cells falls upon GGCT knockdown, and that overexpression of PHB2 inhibits p21 upregulation. A chromatin immunoprecipitation assay revealed that nuclear PHB2 proteins bind to the p21 promoter, and that this interaction is abrogated by GGCT knockdown. Moreover, knockdown of PHB2 alone led to significant upregulation of p21 and mimicked the cellular events induced by GGCT depletion, including G0/G1 arrest, cellular senescence, and growth inhibition, in a p21 induction-dependent manner. Taken together, the results indicate that PHB2 plays a central role in p21 upregulation following GGCT knockdown and as such may promote deregulated proliferation of cancer cells by suppressing p21.

The variable preconditioned (VP) Krylov subspace method with communication avoiding (CA) technique is adopted for the solver of a linear system obtained from electromagnetic analysis, and the numerical features are investigated. A massive communication time between processing units (PUs) or graphics PU/many integrated core is a big issue for parallelization efficiency that needs to be solved. Although k-skip Krylov subspace method is one solution for the issue, convergence property of the method is becoming worse. For this reason, we adopt the k-skip Krylov subspace method as inner-loop solver of the VP Krylov subspace method. The result of computation shows that the VP Krylov subspace method with CA technique is very effective for the linear system obtained from electromagnetic analysis.

Multiple myeloma (MM) is characterized by the clonal proliferation of neoplastic plasma cells. Despite a stream of new molecular targets based on better understanding of the disease, MM remains incurable. Epigenomic abnormalities contribute to the pathogenesis of MM. bromodomain 4 (BRD4), a member of the bromodomain and extraterminal (BET) family, binds to acetylated histones during M/G1 transition in the cell cycle promoting progression to S phase. In this study, we investigated the effects of a novel BET inhibitor CG13250 on MM cells. CG13250 inhibited ligand binding to BRD4 in a dose-dependent manner and with an IC50 value of 1.1 μM. It inhibited MM proliferation in a dose-dependent manner and arrested cells in G1, resulting in the induction of apoptosis through caspase activation. CG13250 inhibited the binding of BRD4 to c-MYC promoter regions suppressing the transcription of the c-MYC gene. Administered in vivo, CG13250 significantly prolonged survival of an orthotopic MM-bearing mice. In conclusion, CG13250 is a novel bromodomain inhibitor that is a promising molecular targeting agent against MM.

We develop improved boundary conditions for particle-based fluid simulation with implicit surfaces. The implicit surfaces are well suited to represent complex obstacles, specifically, when the shape of the obstacles is smooth or varies with time. In existing particle-based fluid simulation with implicit surfaces, an artificially defined force is applied. Although this artificial force successfully enforces non-penetration boundary conditions to the obstacles, some stability and low-accuracy issues remain. The instability of stacking and clustering, and low-accuracy pressure fields occur because of the artificially defined force and incompatibility of the effective radius when using particle methods. This study presents an improved boundary treatment for implicit surfaces. The proposed boundary conditions follow only the formulation of particle-based methods and do not require any artificial force. When we apply the discretization techniques of particle-based methods, the governing equations are also considered on implicit surfaces. Given that the proposed treatment of boundary conditions is applicable to any particle-based method, we adapted our formulation to both explicit and implicit schemes. The results of the test show that our method does not suffer from instability near the boundary in comparison with existing methods. Moreover, the proposed method can also produce better pressure fields than the existing ones.

Trastuzumab is the only clinically approved targeted therapy for HER2 gene-amplified gastric cancer at present. However, the clinical significance of multi-targeting tyrosine kinase inhibitors (TKIs) in HER2-positive gastric cancer remains unclear.We examined the anti-tumor activity of lapatinib and afatinib, that are reversible and irreversible TKIs, in HER2 gene-amplified trastuzumab-sensitive and - resistant gastric cancer cells (GLM-1 and GLM-1HerR2) in vitro and in vivo.Afatinib inhibited the growth of GLM-1 and GLM-1HerR2 cells in vitro more efficiently than lapatinib by inducing GAfatinib could be a potential new molecular-targeted therapy for trastuzumab-sensitive and trastuzumab-resistant HER2 gene-amplified gastric cancers.

γ-Glutamylcyclotransferase (GGCT), which is one of the major enzymes involved in glutathione metabolism, is upregulated in a wide range of cancers—glioma, breast, lung, esophageal, gastric, colorectal, urinary bladder, prostate, cervical, ovarian cancers and osteosarcoma—and promotes cancer progression; its depletion leads to the suppression of proliferation, invasion, and migration of cancer cells. It has been demonstrated that the suppression or inhibition of GGCT has an antitumor effect in cancer-bearing xenograft mice. Based on these observations, GGCT is now recognized as a promising therapeutic target in various cancers. This review summarizes recent advances on the mechanisms of the antitumor activity of GGCT inhibition.

Many Japanese animation products benefit from the techniques of computer graphics. In the animation process, three-dimensional (3D) characters are often rendered so that the characters move according to a Japanese traditional animation style called limited animation or anime. The hair of the characters is modeled as a set of bunches and the motion of each bunch should also be defined in the manner of limited animation, which is different from its physically correct motion. We present a method to produce a hair motion for 3D characters that is appropriate for limited animation under the assumptions that the hair motion is periodic and other objects, including the camera, remain stationary. We present a mathematical formulation of this hair motion based on a typical technique used in traditional hand-drawn anime and apply the motion to each bunch of hair of an example 3D character.

The emergence of new molecular targeting agents has improved the prognosis of patients with multiple myeloma (MM). However, MM remains incurable because MM stem cells are likely resistant to these agents. Thus, it is important to further investigate the biology of MM stem cells, which reside in the hypoxic bone marrow niche. In this study, we established and investigated the characteristics of hypoxia-adapted MM (HA-MM) cells, which could proliferate for more than six months under hypoxic conditions (1% O2). The G0 fraction of HA-MM cells was larger than that of parental MM cells under normoxic conditions (20% O2). HA-MM cells possess enhanced tumorigenicity in primary and secondary transplantation studies. HA-MM cells also exhibited increased mRNA levels of stem cell markers and an enhanced self-renewal ability, and thus demonstrated characteristics of MM stem cells. These cells overexpressed phosphorylated Smad2, and treatment with a transforming growth factor (TGF)-β/Smad signaling inhibitor decreased their clonogenicity in a replating assay. In conclusion, MM cells adapted to long-exposure of hypoxia exhibit stem cell characters with TGF-β/Smad pathway activation.

Previous studies show that gamma-glutamylcyclotransferase (GGCT) is expressed at high levels in various cancer tissues and that its knockdown inhibits MCF7 cancer cell growth via upregulation of p21

γ-Glutamylcyclotransferase (GGCT) depletion inhibits cancer cell proliferation. However, whether the enzymatic activity of GGCT is critical for the regulation of cancer cell growth remains unclear. In this study, a novel diester-type cell-permeable prodrug, pro-GA, was developed based on the structure of N-glutaryl-l-alanine (GA), by structure optimization using temporary fluorophore-tagged prodrug candidates. The antiproliferative activity of pro-GA was demonstrated using GGCT-overexpressing NIH-3T3 cells and human cancer cells including MCF7, HL-60, and PC3 cells. By contrast, normal cells were not significantly affected by pro-GA treatment. Moreover, pro-GA administration exhibited anticancer effects in a xenograft model using immunocompromised mice inoculated with PC3 cells. These results indicate that the enzymatic activity of GGCT accelerates tumor growth and that GGCT inhibition is a promising therapeutic strategy for the treatment of GGCT-overexpressing tumors.

Background Glioblastoma multiforme (GBM) is a malignant brain tumor with an extremely poor prognosis. GBM tissues frequently express mesenchymal-epithelial transition factor (MET), which induces cell division, growth and migration. In addition, angiogenesis is a significant feature of GBM, attributable to the overexpression of vascular endothelial growth factor (VEGF). Although the VEGF inhibitor bevacizumab was recently highlighted as the second-line drug for GBM treatment, GBMs often recur even with bevacizumab therapy. Based on these findings, we hypothesized that inhibition of both MET and VEGF would exhibit a synergistic effect on MET-overexpressing GBM. Materials and methods As we observed MET expression at high levels in some patients with GBM, we designed GL261 murine glioma-based experiments. GL261 cells were transfected with siRNAs specific for MET and VEGF in vitro, and the cell growth ratios were evaluated. Simultaneously, transfected GL261 cells were transplanted into the brain of C57BL/6 mice, and their survival was monitored. Results GBM tissues frequently overexpressed MET protein at high levels compared with lower-grade gliomas. These GBMs at first responded to bevacizumab, but often eventually recurred. When GL261 cells were co-transfected with both MET-specific siRNA and VEGF-specific siRNA, the in vitro tumor cell growth significantly decelerated compared to single siRNA transfection. Consistently, when mice were transplanted with co-transfected GL261 cells, their survival was significantly prolonged compared to those given cells transfected with single siRNA. Conclusion The current data indicate that the inhibition of both MET and VEGF exhibits efficient therapeutic effects of GBM-bearing hosts.

clinical indications of the EOS device include management of venous (eg, varicocele, ovarian varices, varicose veins) and arterial (eg, emergency arterial embolization in trauma patients) conditions. As no late imaging was obtained in the present case, durable occlusion with the EOS device could be assessed in future studies. To conclude, the EOS may provide a safe and reliable method of immediate vessel occlusion in the peripheral arterial circulation. Its shortand long-term clinical efficacy in patients remains a subject for future research.

The large-scale simulation of the electromagnetic wave propagation using meshless time domain method (MTDM) is numerically investigated. Moreover, compute unified device architecture (CUDA) and OpenMP is adopted for parallelization technique to reduce the computation time. The results of computation show that the execution time of the time evolution calculation on GPU is 8.8 time faster than that of CPU. In addition, the execution time of the shape function generation procedure can be speedup about 7842 times by proposed scheme and OpenMP.

Glioblastoma multiforme (GBM) is the most frequent and the most malignant tumor among adult brain tumors. Previous reports led us to hypothesize that the proto-oncogene mesenchymal-epithelial transition (MET) expressed in glioma stem cell-like cells (GSCs) would be a potent therapeutic target for GBM.To address this question, we analyzed 113 original samples of tumors from patients based on immunohistochemistry. During this process, we were able to establish GSC lines from patients with GBM that were MET-positive and MET-negative. Using these cells, we tested the therapeutic impact of a MET inhibitor, crizotinib, both in vitro and in vivo.Patients with MET-positive GBM exhibited poor survival. GSC-based experiments revealed that treatment with crizotinib, both in vitro and in vivo, exhibited therapeutic efficacy particularly against MET-positive GSCs.Based on these findings, we conclude that MET expressed in GSCs might be a potent therapeutic target for GBM.

In various types of cancers including glioblastoma, accumulating evidence show the existence of cancer stem-like cells (CSCs), characterized by stem cell marker expression, capability of differentiation and self-renewal, and high potential for tumor propagation in vivo. LGR5, whose expression is positively regulated by the Wnt signaling pathway, is a stem cell marker in intestinal mucosa and hair follicle in the skin. As Wnt signaling is also involved in brain development, the function of LGR5 in the maintenance of brain CSCs is to be assessed. Our study showed that the LGR5 transcript level was increased in CSCs. Co-immunofluorescence staining demonstrated the co-localization of CD133- and LGR5-positive cells in glioblastoma tissue sections. Functionally, silencing of LGR5 by lentiviral shRNA-mediated knockdown induced apoptosis in brain CSCs. Moreover, LGR5 depletion led to a downregulation of L1 cell adhesion molecule expression. In line with an important function in glioma tumorigenesis, LGR5 expression increased with glioma progression and correlated with an adverse outcome. Our findings suggest that LGR5 plays a role in maintenance and/or survival of brain CSCs.

The variable preconditioned (VP) Krylov subspace method with mixed precision is implemented on graphics processing unit (GPU) using compute unified device architecture (CUDA), and the linear system obtained from the edge element is solved by means of the method. The VPGCR method has the sufficient condition for the convergence. This sufficient condition leads us that the residual equation for the preconditioned procedure of VPGCR can be solved in the range of single precision. To stretch the sufficient condition, we propose the hybrid scheme of VP Krylov subspace method that uses single and double precision operations. The results of computations show that VPCG with mixed precision on GPU demonstrated significant achievement than that of CPU. Especially, VPCG-JOR on GPU with mixed precision is 41.853 times faster than that of VPCG-CG on CPU.

This paper presents a new technique for real-time isosurface visualization of three-dimensional smooth fields. This technique enables direct isosurface rendering of smoothly defined fields without generating intermediate polygon models as used in the marching-cube algorithm, a standard technique for isosurface extraction. We developed a parallel algorithm that is suitable for effective computation on graphics hardware by converting any field to a set of polynomials, enabling the detection of intersections between rays and isosurfaces at arbitrary isovalue with small computational cost. In addition, the isovalue to be rendered can be changed in real time, because the algorithm is not restricted to a specific isovalue. The technique can also be applied to the problem of the direct rendering of implicit surfaces that are defined as isosurfaces of smoothly defined fields.

The concept of cancer stem-like cells (CSCs) has gained considerable attention in various solid tumors including glioblastoma, the most common primary brain tumor. This sub-population of tumor cells has been intensively investigated and their role in therapy resistance as well as tumor recurrence has been demonstrated. In that respect, development of therapeutic strategies that target CSCs (and possibly also the tumor bulk) appears a promising approach in patients suffering from primary brain tumors. In the present study, we utilized RNA interference (RNAi) to screen the complete human kinome and phosphatome (682 and 180 targets, respectively) in order to identify genes and pathways relevant for the survival of brain CSCs and thereby potential therapeutical targets for glioblastoma. We report of 46 putative candidates including known survival-related kinases and phosphatases. Interestingly, a number of genes identified are involved in metabolism, especially glycolysis, such as PDK1 and PKM2 and, most prominently PFKFB4. In vitro studies confirmed an essential role of PFKFB4 in the maintenance of brain CSCs. Furthermore, high PFKFB4 expression was associated with shorter survival of primary glioblastoma patients. Our findings support the importance of the glycolytic pathway in the maintenance of malignant glioma cells and brain CSCs and imply tumor metabolism as a promising therapeutic target in glioblastoma.

This study provides a parallel algorithm for meshfree analysis based on the radial point interpolation method. This algorithm is designed to suit graphics hardware that support compute unified device architecture, NVIDIA's software development environment on graphics processing units (GPUs). The radial point interpolation method is a meshfree method that enables strict imposition of Dirichlet boundary conditions, and it mainly consists of two steps: the process for assembly of the discrete linear system and the process for solving the linear system. This paper shows that both the processes can be performed effectively on the GPU by applying our parallel algorithm and at the same time, the costs for data transfer to and from the GPU can be reduced, because the processes related to the discrete linear system are performed independently on the GPU. Our numerical tests confirm that the algorithm performed on the GPU accelerates the computations by a factor of maximum 15.

Summary Aims In colorectal cancer (CRC), CD133 expression is an independent prognostic marker associated with adverse clinical outcome. The CD133 epitope AC133 allowed isolating stem cells from normal and cancerous tissues, although its use in colon was questioned. We aimed to identify differences between AC133 hi and AC133 - cells. Methods We analysed the gene expression profiles of EpCAM + /CEA + /AC133 hi and EpCAM + /CEA + /AC133 - cells from primary CRC and liver metastasis tissues (n = 5). Immunohistochemistry confirmed these results in a validation set. Results We identified 68 genes differentially expressed between both populations, including genes of notorious importance in CRC pathogenesis, and several candidates not previously shown to play a major role in CRC. Notably, EGR1 belonged to the most highly expressed genes in AC133 hi cells. In the validation set, the presence of EGR1 and CD133 correlated (r = 0.625). Since EGR1 regulates Wnt through up-regulation of TCF4, which induces stem cell marker LGR5, the potential association between LGR5, EGR1 and CD133 was investigated. The presence of LGR5 correlated with the presence of EGR1 and CD133. Strong signals for LGR5 were detected throughout tumour invasion fronts. Conclusions The study suggests a connection between CD133 and EGR1 and emphasises the importance of the EGR1/TCF4/CD133/LGR5 network in CRC.

Volume graphics is a key technology in fields such as fluid dynamics and medical science. The visualization of volume data requires the creation of a continuous scalar field to exactly or approximately interpolate scalar values assigned to the discrete voxels. In the present paper, we propose a method that we refer to as the volumic version of the multi-level partition of unity (volumic MPU). The method approximately interpolates the scalar values with good precision to generate a scalar field that is continuous up to second-order differentiation. The volumic MPU, being independent of grid structures of input volume data, is applicable to both irregular-grid data and regular grid data. The volumic MPU can also be used as an effective data-compression technique. The speed to evaluate the created scalar field is almost as high as that of trilinear interpolation.

Meshfree methods are effective tools for solving partial differential equations. The radial point interpolation method, a partial differential equation solver based on a meshfree approach, enables accurate imposition of displacement boundary conditions and has been successfully applied to elastostatic analysis of various kinds of three-dimensional solids. In this method, stiffness matrix construction accounts for the majority of CPU time required for the entire process, resulting in high computational costs, especially when higher-order numerical integration is applied for accurate matrix construction. An alternative method, modified radial point interpolation, was proposed to overcome this shortcoming and has accomplished fast computation of elastostatic solid analysis. The purpose of this study is to develop an algorithm for time-dependent simulation of three-dimensional elastic solids. We show that the modified radial point interpolation method also accelerates the construction of the mass matrix required for time-dependent analysis in addition to that of the stiffness matrix. In our approach, the problem domain is assumed to have an implicit function representation that can be constructed from a set of surface points measured using a three-dimensional scanning system. Several numerical tests for elastodynamic analysis of complex shape models are presented.

We propose a method of sampling regular and irregular-grid volume data for visualization. The method is based on the Metropolis algorithm that is a type of Monte Carlo technique. Our method enables "importance sampling" of local regions of interest in the visualization by generating sample points intensively in regions where a user-specified transfer function takes the peak values. The generated sample-point distribution is independent of the grid structure of the given volume data. Therefore, our method is applicable to irregular grids as well as regular grids. We demonstrate the effectiveness of our method by applying it to regular cubic grids and irregular tetrahedral grids with adaptive cell sizes. We visualize volume data by projecting the generated sample points onto the 2D image plane. We tested our sampling with three rendering models: an X-ray model, a simple illuminant particle model, and an illuminant particle model with light-attenuation effects. The grid-independency and the efficiency in the parallel processing mean that our method is suitable for visualizing large-scale volume data. The former means that the required number of sample points is proportional to the number of 2D pixels, not the number of 3D voxels. The latter means that our method can be easily accelerated on the multiple-CPU and/or GPU platforms. We also show that our method can work with adaptive space partitioning of volume data, which also enables us to treat large-scale/complex volume data easily.

Podoplanin is distinctively overexpressed in oral squamous cell carcinoma than oral benign neoplasms and plays a crucial role in the pathogenesis and metastasis of oral squamous cell carcinoma but its diagnostic application is quite limited. Here, we report a new near-infrared fluorescence imaging method using an indocyanine green (ICG)-labeled anti-podoplanin antibody and a desktop/a handheld ICG detection device for the visualization of oral squamous cell carcinoma-xenografted tumors in nude mice. Both near-infrared imaging methods using a desktop (in vivo imaging system: IVIS) and a handheld device (photodynamic eye: PDE) successfully detected oral squamous cell carcinoma tumors in nude mice in a podoplanin expression-dependent manner with comparable sensitivity. Of these 2 devices, only near-infrared imaging methods using a handheld device visualized oral squamous cell carcinoma xenografts in mice in real time. Furthermore, near-infrared imaging methods using the handheld device (PDE) could detect smaller podoplanin-positive oral squamous cell carcinoma tumors than a non-near-infrared, autofluorescence-based imaging method. Based on these results, a near-infrared imaging method using an ICG-labeled anti-podoplanin antibody and a handheld detection device (PDE) allows the sensitive, semiquantitative, and real-time imaging of oral squamous cell carcinoma tumors and therefore represents a useful tool for the detection and subsequent monitoring of malignant oral neoplasms in both preclinical and some clinical settings.

This paper explores a method for creating large-scale urban 3D models using Historical GIS data. The method is capable of automatically generating realistic VR models based on GIS data at a low cost. 3D models of houses are created from polygon data, fences from line data, and pedestrians and trees from point data. The method is applied to the Virtual Kyoto Project in which the landscape of the whole city of Kyoto of the early Edo era (ca 17C) is reconstructed.

We propose a stochastic method to visualize intersection curves of complex implicit surfaces. Our method performs a stochastic 'uniform search' on an implicit surface to visualize its intersection curves, which scatter over the whole surface disconnectedly. The method also offers the capability to perform an efficient 'intensive search' that enables quick investigation of only a part of interest on an implicit surface. The method generates high-density points on intersection curves. This realizes precise visualization of the curves with point-based graphics. The visualization precision realized by our method is higher than that of the conventional intersection-finding/visualizing methods, e.g., the marching methods. Our method is also applicable to precise visualization of contours based on general curvilinear coordinates. This can help our visual understanding of rough/fine structures of complex implicit surfaces. To demonstrate effectiveness of the method, we apply it to complex implicit surfaces that approximate data sets of 10^5 or 10^6 3D points.

application/pdf, Let a physical body in 2 or 3 be given. Assume that the electric conductivity distribution inside consists of conductive inclusions in a known smooth background. Further, assume that a subset is available for boundary measurements. It is proved using hyperbolic geometry that certain information about the location of the inclusions can be exactly recovered from static electric measurements on . More precisely: given a ball B with center outside the convex hull of and satisfying ( ) , boundary measurements on with explicitly given Dirichlet data are enough to determine whether B intersects the inclusion. An approximate detection algorithm is introduced based on the theory. Numerical experiments in dimension two with simulated noisy data suggest that the algorithm finds the inclusion-free domain near and is robust against measurement noise.

複雑な陰関数曲面の高品位な可視化のためには，陰関数曲面を正三角形に近いポリゴン・メッシュに分割することが必要である．そのためには，ポリゴンの頂点となる陰関数曲面上のサンプル点群において，隣接点間の距離を一様にする必要がある．隣接点間距離を一様にするための有効な方法としては，粒子拡散法が知られている．Meyerらは粒子拡散法に効率的な反発力を適用した．しかしながら，彼らの手法は高密度・大量点群に適用された場合には計算の効率が悪い．本論文の目的は，高密度・大量点群に対する新しい反発力を提案し，これにより正三角形に近いポリゴンを生成することである．数値実験の結果は，提案手法を適用した場合，Meyerらの手法と比較して，正三角形に近いポリゴンが多数生成されることを示している．さらに，提案手法はより高速に点群を分布させることも可能である．

We develop a combination of evolution strategy (ES) and fuzzy control (FC) to optimize and simplify an existing dynamic scripting (DS) AI called CodeMonkey for fighting game FightingICE, recently used as a platform in international game AI competitions. One of the major issues in DS is that the user has to decide a lot of parameters whose process is not simple. In addition, a complex user-defined-action-rule set for DS is required. The purpose of our work is to automate this troublesome process and improve the performance of the DS technique. We apply (1+1)-ES with the one-fifth rule for tuning parameters and FC for easing definition of additional action rules. We verify our AI's performance in FightingICE. The test results show that although the proposed AI does not require complex parameter and rule setting by the user, it defeats the original CodeMonkey.

15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), the terminal derivative of the PGJ series, is emerging as a potent antineoplastic agent among cyclopentenone prostaglandins derivatives and also known as the endogenous ligand of peroxisome proliferator-activated receptor γ (PPARγ). On the other hand, death receptor 5 (DR5) is a specific receptor for tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), which is one of the most promising candidates for new cancer therapeutics. Here, we report that 15d-PGJ2 induces DR5 expression at both mRNA and protein levels, resulting in the synergistic sensitization of TRAIL-induced apoptosis in human neoplastic cells, such as Jurkat human leukemia cells or PC3 human prostate cancer cells. 15d-PGJ2 significantly increased DR5 mRNA stability, whereas it did not activate DR5 promoter activity. Synthetic PPARγ agonists, such as pioglitazone or rosiglitazone, did not mimic the DR5-inducing effects of 15d-PGJ2, and a potent PPARγ inhibitor GW9662 failed to block DR5 induction by 15d-PGJ2, suggesting PPARγ-independent mechanisms. Cotreatment with 15d-PGJ2 and TRAIL enhanced the sequential activation of caspase-8, caspase-10, caspase-9, caspase-3, and Bid. DR5/Fc chimera protein, zVAD-fmk pancaspase inhibitor, and caspase-8 inhibitor efficiently blocked the activation of these apoptotic signal mediators and the induction of apoptotic cell death enhanced by cotreatment with 15d-PGJ2 and TRAIL. Moreover, a double-stranded small interfering RNA targeting DR5 gene, which suppressed DR5 up-regulation by 15d-PGJ2, significantly attenuated apoptosis induced by cotreatment with 15d-PGJ2 and TRAIL. These results suggest that 15d-PGJ2 is a potent sensitizer of TRAIL-mediated cancer therapeutics through DR5 up-regulation. [Mol Cancer Ther 2006;5(7):1827–35]