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A study of the flowfield of rotor hovers with unstructured meshes is presented. The development of an inviscid flow solver to simulate the flowfield is described. The analysis confirms experimental results.

ABSTRACT In the present study, unsteady flow features and the blade aerodynamic loading of the National Renewable Energy Laboratory phase VI wind turbine rotor, under yawed flow conditions, were numerically investigated by using a three-dimensional incompressible flow solver based on unstructured overset meshes. The effect of turbulence, including laminar-turbulent transition, was accounted for by using a correlation-based transition turbulence model. The calculations were made for an upwind configuration at wind speeds of 7, 10 and 15 m/sec when the turbine rotor was at 30° and 60° yaw angles. The results were compared with measurements in terms of the blade surface pressure and the normal and tangential forces at selected blade radial locations. It was found that under the yawed flow conditions, the blade aerodynamic loading is significantly reduced. Also, because of the wind velocity component aligned tangent to the rotor disk plane, the periodic fluctuation of blade loading is obtained with lower magnitudes at the advancing blade side and higher magnitudes at the retreating side. This tendency is further magnified as the yaw angle becomes larger. At 7 m/sec wind speed, the sectional angle of attack is relatively small, and the flow remains mostly attached to the blade surface. At 10 m/sec wind speed, leading-edge flow separation and strong radial flow are observed at the inboard portion of the retreating blade. As the wind speed is further increased, the flow separation and the radial flow become more pronounced. It was demonstrated that these highly unsteady three-dimensional aerodynamic features are well-captured by the present method. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: An efficient and robust implicit operator for the point Gauss–Seidel method is presented for solving the compressible Euler equations. The new implicit operator was derived by adding a scalar form of artificial dissipation to the upwind implicit side. The amount of artificial dissipation was locally adjusted using a weighting factor based on the solution gradient. For validation, the performance of the new implicit operator was compared in detail with that of several existing implicit operators which have been widely used for solving the flow equations. Numerical experiments showed that the stability and convergence characteristics of the new implicit operator are significantly better than those of other existing implicit operators for calculating flows ranging from subsonic to hypersonic speeds. [Copyright &y& Elsevier]

• Stagnation-point radiative heating of Fire II flight experiment is analyzed. • Non-local absorption is considered in a devised non-Boltzmann radiation calculation. • Proposed set of excitation rates offers improved agreement with the measured data. • Escape factors of strong atomic lines and diatomic nitrogen vacuum ultraviolet systems with non-local absorption effect are proposed. The present work analyzes the stagnation-point radiative heating in the Fire II flight experiment by devising a collisional-radiative model with non-local absorption. In the stagnation-line flow-field calculations, a viscous shock layer method with a thermochemical nonequilibrium model is utilized. In the radiation calculations, a line-by-line method with the non-Boltzmann electronic populations is employed by adopting the quasi-steady state approach of the electronic master equation calculations. In constructing the electronic master equation, the best set of the electron and heavy-particle impact excitation rates is proposed to achieve better agreement with the measured radiative heating flight data. In the flow-radiation coupling procedure, the effect of the non-local absorption is modeled by devising an iterative process between the quasi-steady state electronic master equation and the radiative transfer equation calculations. Escape factors of the strongest atomic lines and the diatomic nitrogen vacuum ultraviolet systems with the non-local absorption effect are also proposed to more efficiently consider the non-local nature of the radiative transition. When compared with the experimental data from the Fire II trajectories, it is found that the present collisional-radiative model with the non-local absorption improves the ability to predict non-Boltzmann radiative heating. [ABSTRACT FROM AUTHOR]

In the present study, a numerical framework for predicting the aerodynamic performance and the aeroelastic behavior of floating offshore wind turbine rotor blades involving platform motion was developed. For this purpose, the aerodynamic and structural analyses were conducted simultaneously in a tightly coupled manner by exchanging the information about the aerodynamic loads and the elastic blade deformations at every time step. The elastic behavior of the turbine rotor blades was described by adopting a structural model based on the Euler-Bernoulli beam. The aerodynamic loads by the rotor blades were evaluated by adopting a blade element momentum theory. The numerical simulations were conducted when the platform of the wind turbine independently moves in each of the six degrees-of-freedom directions consisting of heave, sway, surge, roll, pitch, and yaw. It was observed that flexible blades exhibit complicated vibratory behaviors when they are excited by the aerodynamic, inertia, and gravitational forces simultaneously. It was found that the load variation caused by the platform surge or pitch motion has a significant influence on the flapwise and torsional deformations of the rotor blades. The torsional deformation mainly occurs in the nose-down direction, and results in a reduction of the aerodynamic loads. It was also found that the flapwise root bending moment is mainly influenced by the platform surge and pitch motions. On the other hand, the edgewise bending moment is mostly dictated by the gravitational force, but is not affected much by the platform motion. [ABSTRACT FROM AUTHOR]

In the present study, the narrow-band k -distribution (NBK) model parameters for mixtures of H 2 O, CO 2 , and CO are proposed by utilizing the line-by-line (LBL) calculations with a single mixture gas assumption. For the application of the NBK model to radiative flows, a radiative transfer equation (RTE) solver based on a finite-volume method on unstructured meshes was developed. The NBK model and the RTE solver were verified by solving two benchmark problems including the spectral radiance distribution emitted from one-dimensional slabs and the radiative heat transfer in a truncated conical enclosure. It was shown that the results are accurate and physically reliable by comparing with available data. To examine the applicability of the methods to realistic multi-dimensional problems in non-isothermal and non-homogeneous conditions, radiation in an axisymmetric combustion chamber was analyzed, and then the infrared signature emitted from an aircraft exhaust plume was predicted. For modeling the plume flow involving radiative cooling, a flow-radiation coupled procedure was devised in a loosely coupled manner by adopting a Navier-Stokes flow solver based on unstructured meshes. It was shown that the predicted radiative cooling for the combustion chamber is physically more accurate than other predictions, and is as accurate as that by the LBL calculations. It was found that the infrared signature of aircraft exhaust plume can also be obtained accurately, equivalent to the LBL calculations, by using the present narrow-band approach with a much improved numerical efficiency. [ABSTRACT FROM AUTHOR]

A system for space disposal of the most radioactive component of the spent fuel produced by the nuclear reactors is designed conceptually with an intent of ensuring safety. Unlike the earlier design by NASA, this system is to use a commercially available launch vehicle and be launched from the western Pacific Ocean. It will fly low until it acquires Earth-escape velocity, so that the nuclear package will not fall on land in case of system malfunctioning. The package will be parked in one of the lunar libration points L4 or L5, and kept vigilant by a watch-dog orbital transfer vehicle which will push the package away in case an asteroid approaches. The calculation shows that such a safe system will be feasible and relatively cheap. The details of how the nuclear package is made, how the launch vehicle is made and flown, and how the nuclear package is managed in the final parking orbit are described. [ABSTRACT FROM AUTHOR]

We recently reported that the efficiency of adenoviral gene delivery and virus stability are significantly enhanced when a proteoliposome (PL) containing apolipoprotein (apo) A-I is used in an animal model. In the current study, we tested tumor removal activity of oncolytic adenovirus (Ad) using PL-containing wildtype (WT) or V156K. Oncolytic Ad with or without PL was injected into tumors of zebrafish and nude mice as a Hep3B tumor xenograft model. The V156K-PL-Ad-injected zebrafish, group showed the lowest tumor tissue volume and nucleic acids in the tumor area, whereas injection of Ad alone did not result in adequate removal of tumor activity. Reactive oxygen species (ROS) contents increased two-fold in tumor-bearing zebrafish; however, the V156K-PL-Ad injected group showed a 40% decrease in ROS levels compared to that in normal zebrafish. After reducing the tumor volume with the V156K-PL-Ad injection, the swimming pattern of the zebrafish changed to be more active and energetic. The oncolytic effect of PL-Ad containing either V156K or WT was about two-fold more enhanced in mice than that of Ad alone 34 days after the injection. Immunohistochemical analysis revealed that the PL-Ad-injected groups showed enhanced efficiency of viral delivery with elevated Ad-E1A staining and a diminished number of proliferating tumor cells. Thus, the antitumor effect of oncolytic Ad was strongly enhanced by a PL-containing apoA-I and its mutant (V156K) without causing side effects in mice and zebrafish models. [ABSTRACT FROM AUTHOR]

Abstract: For effective cancer gene therapy, systemic administration of tumor-targeting adenoviral (Ad) complexes is critical for delivery to both primary and metastatic lesions. Electrospinning was used to generate nanocomplexes of Ad, chitosan, poly(ethylene glycol) (PEG), and folic acid (FA) for effective FA receptor-expressing tumor-specific transduction. The chemical structure of the Ad/chitosan–PEG–FA nanocomplexes was characterized by NMR and FT-IR, and the diameter and surface charge were analyzed by dynamic light scattering and zeta potentiometry, respectively. The average size of Ad/chitosan–PEG–FA nanocomplexes was approximately 140nm, and the surface charge was 2.1mV compared to −4.9mV for naked Ad. Electron microscopy showed well-dispersed, individual Ad nanocomplexes without aggregation or degradation. Ad/chitosan nanocomplexes retained biological activity without impairment of the transduction efficiency of naked Ad. The transduction efficiency of Ad/chitosan–PEG–FA was increased as a function of FA ratio in FA receptor-expressing KB cells, but not in FA receptor-negative U343 cells, demonstrating FA receptor-targeted viral transduction. In addition, the transduction efficiency of Ad/chitosan–PEG–FA was 57.2% higher than chitosan-encapsulated Ad (Ad/chitosan), showing the superiority of FA receptor-mediated endocytosis for viral transduction. The production of inflammatory cytokine, IL-6 from macrophages was significantly reduced by Ad/chitosan–PEG–FA nanocomplexes, implying the potential for use in systemic administration. These results clearly demonstrate that cancer cell-targeted viral transduction by Ad/chitosan–PEG–FA nanocomplexes can be used effectively for metastatic tumor treatment with reduced immune reaction against Ad. [ABSTRACT FROM AUTHOR]

Presents a two-dimensional Euler flow solver for the simulation of blade-vortex interaction (BVI) problems on unstructured meshes. Simulation of BVI; Discussion of harmonically oscillating airfoil; Discussion of traveling vortex in a freestream.

In the present study, the effect of crossflow transition on the rotor blade performance in hover was investigated numerically. The simulations were conducted for the Pressure Sensitive Paint (PSP) rotor in hover by using a Reynolds-averaged Navier-Stokes (RANS) solver based on unstructured meshes. The k − ω SST model was used for simulating the turbulent flow fields and for calculating the turbulent eddy viscosity. For predicting the laminar-turbulent onset phenomena involving crossflow-induced transition, the γ − Re θ t − CF + transition model was adopted. For the comparison of the transition locations without considering the crossflow transition effect, simulations were also carried out using the γ − Re θ t transition model. The calculations were made for the PSP rotor at collective pitch angles from four to 12 degrees with an interval of two degrees. To investigate the effect of blade tip Mach number, two blade tip Mach numbers of 0.585 and 0.65 were tested. The predicted results such as the transition onset location and the rotor aerodynamic performance in terms of thrust coefficient, torque coefficient and figure of merit were compared with experimental data. It was found that proper consideration of the effect of crossflow transition is critical for the accurate prediction of the laminar-turbulent transition onset location on rotor blades. The figure of merit also compares better with the experimental data when the effect of laminar-turbulent transition is included. With the addition of the crossflow transition, the figure of merit is slightly decreased, particularly at low thrust levels. [ABSTRACT FROM AUTHOR]

• Quantitative temperature measurement of carbon dioxide. • Detector voltage calculation methodology considering the non-linear sensor characteristics and spectral sensitivity. • Computation efficiency comparison between a random statistical narrow band model and a line-by-line model. • Dominant relationship between the temperature and the detector voltage than the pressure in the high-pressure condition. This paper presents a relatively simple method for temperature measurement of hot carbon dioxide gas using an emission spectroscopy setup. The ν 3 band emission at 4.3 µm is detected using an optical band-pass filter and a mercury cadmium telluride detector. A conversion methodology is introduced that calculates the detector voltage from the spectral radiance considering the spectral sensitivities of the optical components and the non-linear characteristics of the detector. Two radiation models, a line-by-line model and a random statistical narrow band model, are employed to calculate the spectral radiance at given flow conditions. Black body radiation is considered for radiance calculation for optically thick conditions. Temperatures under test conditions in a shock tube are determined using the proposed conversion methodology and are compared with the temperatures obtained from a computational fluid dynamics simulation. The accuracy and efficiency of the temperature measurement using the two radiation models and the black body curve are compared. It is confirmed that the proposed method is a reliable way to determine the temperature while using a relatively simple experimental setup. Detector voltages are presented for a wide range of temperature, pressure, and beam path length for applications under different test conditions. [ABSTRACT FROM AUTHOR]

Temperature determination in a shock tube is one of the most important factors to understand the relevant flow physics inside. In the present study, the reservoir temperature determination in a shock tube using the ultraviolet emission spectra of hydroxyl radical (OH) A-X band was carried out. A radiation model for the OH A-X transition was developed, and it was validated using the benchmark data. Curve fit parameters, such as a peak-to-peak ratio and the absolute peak intensity of the P-branch, are proposed to evaluate the rotational temperature and the OH number density from the measured emission spectra. In the shock tube experiments, humid air from the atmosphere was employed as a test gas, and a small amount of the ultraviolet OH emission was measured behind the reflected shock wave. The measured spectrum was converted to the rotational temperature and the number density using the present model of the OH A-X emission. Then, the evaluated rotational temperature was compared with the calculated values of the reservoir condition behind the reflected shock wave. A good agreement was detected between the measured and the calculated temperatures, which are 4020 ± 290 K and 4110 ± 220 K, respectively. It was recognized that the reservoir temperature behind the reflected shock wave is well described by the present model of the OH A-X ultraviolet emission. [ABSTRACT FROM AUTHOR]

Presents information on a study that examined the surface properties of an underlying silicon substrate after reactive ion etching of SiO[sub2] in CHF[sub3]/C[sub2]F[sub6] gas plasmas. Introduction to reaction ion etching of SiO[sub2] on silicon in a fluorocarbon plasma; Experimental results and discussion; Conclusions.

Although Notch signaling is deregulated in prostate cancer, the role of this pathway in disease development and progression is not fully understood. Here, we analyzed 2 human prostate cancer data sets and found that higher Notch signaling correlates with increased metastatic potential and worse disease survival rates. We used the Pten-null mouse prostate cancer model to investigate the function of Notch signaling in the initiation and progression of prostate cancer. Disruption of the transcription factor RBPJ in Pten-null mice revealed that endogenous canonical Notch signaling is not required for disease initiation and progression. However, augmentation of Notch activity in this model promoted both proliferation and apoptosis of prostate epithelial cells, which collectively reduced the primary tumor burden. The increase in cellular apoptosis was linked to DNA damage-induced p53 activation. Despite a reduced primary tumor burden, Notch activation in Pten-null mice promoted epithelial-mesenchymal transition and FOXC2-dependent tumor metastases but did not confer resistance to androgen deprivation. Notch activation also resulted in transformation of seminal vesicle epithelial cells in Pten-null mice. Our study highlights a multifaceted role for Notch signaling in distinct aspects of prostate cancer biology and supports Notch as a potential therapeutic target for metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Abstract: Cross-linked alginate beads containing adenovirus (Ad) were successfully fabricated using an electrospraying method to achieve the protection and release of Ad in a controlled manner. An aqueous alginate solution containing Ad was electrosprayed into an aqueous phase containing a cross-linking agent (calcium chloride) at different process variables (voltages, alginate concentrations, and flow rates). Alginate beads containing Ad were used for transduction of U343 glioma cells and the transduction efficiency of the alginate beads was measured by quantification of gene expression using a fluorescence-activated cell sorter at different time points. In vitro results of gene expression revealed that the Ad encapsulated in the alginate beads with 0.5wt% of alginate concentration exhibited a high activity for a long period (over 7 days) and was released in a sustained manner from the alginate beads. The Ad-encapsulating alginate beads could be promising materials for local delivery of Ad at a high concentration into target sites. [Copyright &y& Elsevier]

An abstract of the article "Enhanced Cell Killing Effect of E1 Modified Adenoviruses Expressing HSV-TK Suicide Gene," by Yoon-A Kang, Dong Hyun Ko, Jaesung Kim Kim, Young-Sook Lee, Oh-Joon Kwon, Joo Hyuk Sohn, Chae-Ok Yun, Joo-Hang Kim is presented.

Cancer-associated fibroblasts (CAFs) mediate an immunosuppressive effect, but the underlying mechanism remains incompletely defined. Here we show that increasing prostatic stromal Foxf2 suppresses the growth and progression of both syngeneic and autochthonous mouse prostate cancer models in an immunocompetent context. Mechanistically, Foxf2 moderately attenuates the CAF phenotype and transcriptionally downregulates Cxcl5, which diminish the immunosuppressive myeloid cells and enhance T cell cytotoxicity. Increasing prostatic stromal Foxf2 sensitizes prostate cancer to the immune checkpoint blockade therapies. Augmenting lung stromal Foxf2 also mediates an immunosuppressive milieu and inhibits lung colonization of prostate cancer. FOXF2 is expressed higher in the stroma of human transition zone (TZ) than peripheral zone (PZ) prostate. The stromal FOXF2 expression level in primary prostate cancers inversely correlates with the Gleason grade. Our study establishes Foxf2 as a stromal transcription factor modulating the tumor immune microenvironment and potentially explains why cancers are relatively rare and indolent in the TZ prostate., (© 2022. The Author(s).)

Introduction: The Wnt proteins play key roles in the development, homeostasis, and disease progression of many organs including the prostate. However, the spatiotemporal expression patterns of Wnt proteins in prostate cell lineages at different developmental stages and in prostate cancer remain inadequately characterized., Methods: We isolated the epithelial and stromal cells in the developing and mature mouse prostate by flow cytometry and determined the expression levels of Wnt ligands. We used Visium spatial gene expression analysis to determine the spatial distribution of Wnt ligands in the mouse prostatic glands. Using laser-capture microscopy in combination with gene expression analysis, we also determined the expression patterns of Wnt signaling components in stromal and cancer cells in advanced human prostate cancer specimens. To investigate how the stroma-derived Wnt ligands affect prostate development and homeostasis, we used a Col1a2-CreER T2 mouse model to disrupt the Wnt transporter Wntless specifically in prostate stromal cells., Results: We showed that the prostate stromal cells are a major source of several Wnt ligands. Visium spatial gene expression analysis revealed a distinct spatial distribution of Wnt ligands in the prostatic glands. We also showed that Wnt signaling components are highly expressed in the stromal compartment of primary and advanced human prostate cancer. Blocking stromal Wnt secretion attenuated prostate epithelial proliferation and regeneration but did not affect cell survival and lineage maintenance., Discussion: Our study demonstrates a critical role of stroma-derived Wnt ligands in prostate development and homeostasis., (© 2022 Wiley Periodicals LLC.)

Macrophages are increased in human benign prostatic hyperplasia and prostate cancer. We generate a Pb-Csf1 mouse model with prostate-specific overexpression of macrophage colony-stimulating factor (M-Csf/Csf1). Csf1 overexpression promotes immune cell infiltration into the prostate, modulates the macrophage polarity in a lobe-specific manner, and induces senescence and low-grade prostatic intraepithelial neoplasia (PIN). The Pb-Csf1 prostate luminal cells exhibit increased stem cell features and undergo an epithelial-to-mesenchymal transition. Human prostate cancer patients with high CSF-1 expression display similar transcriptional alterations with the Pb-Csf1 model. P53 knockout alleviates senescence but fails to progress PIN lesions. Ablating epithelial Gp130 but not Il1r1 substantially blocks PIN lesion formation. The androgen receptor (AR) is downregulated in Pb-Csf1 mice. ChIP-Seq analysis reveals altered AR binding in 2482 genes although there is no significant widespread change in global AR transcriptional activity. Collectively, our study demonstrates that increased macrophage infiltration causes PIN formation but fails to transform prostate cells., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Prostate adenocarcinoma undergoes neuroendocrine differentiation to acquire resistance toward antihormonal therapies. The underlying mechanisms have been investigated extensively, among which Sox2 has been shown to play a critical role. However, genetic evidence in mouse models for prostate cancer to support the crucial role of Sox2 is missing. The adult mouse prostate luminal cells contain both castration-resistant Sox2-expressing Sca-1 + cells and castration-responsive Sca-1 - cells. We show that both types of the luminal cell are susceptible to oncogenic transformation induced by loss of function of the tumor suppressor Pten. The tumors derived from the Sca-1 + cells are castration resistant and are more inclined to develop castration-induced neuroendocrine differentiation. Genetic ablation of Sox2 suppresses neuroendocrine differentiation but does not impact the castration-resistant property. This study provides direct genetic evidence that Sox2 is necessary for androgen ablation-induced neuroendocrine differentiation of Pten null prostate adenocarcinoma, corroborates that the lineage status of the prostate cancer cells is a determinant for its propensity to exhibit lineage plasticity, and supports that the intrinsic features of cell-of-origin for prostate cancers can dictate their clinical behaviors.

Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that either develops de novo or arises from prostate adenocarcinoma as a result of treatment resistance. Although the prostate basal cells have been shown to directly generate tumor cells with neuroendocrine features when transduced with oncogenic signaling, the identity of the cell-of-origin for de novo NEPC remains unclear. We show that the TACSTD2 high human prostate luminal epithelia cells highly express SOX2 and are relatively enriched in the transition zone prostate. Both TACSTD2 high and TACSTD2 low luminal cells transduced by constitutively activated AKT1 (caAKT1), and c-Myc can form organoids containing versatile clinically relevant tumor cell lineages with regard to the expression of AR and the neuroendocrine cell markers Synaptophysin and Chromogranin A. Tumor organoid cells derived from the TACSTD2 high luminal cells are more predisposed to neuroendocrine differentiation along passaging and are relatively more castration-resistant. Knocking down TACSTD2 and SOX2 both attenuate neuroendocrine differentiation of tumor organoid cells. This study demonstrates de novo neuroendocrine differentiation of the human prostate luminal epithelial cells induced by caAKT1 and c-Myc and reveals an impact of cellular status on initiation of lineage plasticity.

The phenotypic and functional heterogeneity of the mouse prostate epithelial cell lineages remains incompletely characterized. We show that the Sca-1 + luminal cells at the mouse proximal prostate express Sox2. These cells are replicative quiescent, castration resistant, and do not possess secretory function. We use the Probasin-CreER T2 and Sox2-CreER T2 models in concert with a fluorescent reporter line to label the Sca-1 - and Sca-1 + luminal cells, respectively. By a lineage tracing approach, we show that the two luminal cell populations are independently sustained. Sox2 is dispensable for the maintenance of the Sca-1 + luminal cells but is essential for their facultative bipotent differentiation capacity. The Sca-1 + luminal cells share molecular features with the human TACSTD2 + luminal cells. This study corroborates the heterogeneity of the mouse prostate luminal cell lineage and shows that the adult mouse prostate luminal cell lineage is maintained by distinct cellular entities rather than a single progenitor population., (©AlphaMed Press 2020.)

In the present study, three different electronic state-to-state methods are proposed to analyze nonequilibrium air plasma flows behind a strong shock wave. In the first approach representing the conventional method, a two-temperature model combined with the electronic quasi-steady-state assumption is adopted. In the second and the third methods, atomic and molecular electronic master equations are coupled with a conservation equation to describe the electronic state-to-state kinetics. State-of-the-art electronic transition rates for atmospheric gas species are compiled with comparisons of existing data. A prediction of the measured nonequilibrium radiation is made for the flow conditions of recent electric-arc shock tube experiments. In a comparison with the measured spectrum, the present electronic master equation coupling methods are more accurate than the conventional approach when used to estimate the initial rising rate and peak value of the diatomic intensity and small amounts of atomic radiation when the diatomic nonequilibrium condition is dominant. Moreover, the spatial distributions of the intensity and electron number density are more accurately predicted by the present methods when the flow fields are dominated by atomic nonequilibrium.

We perform a single-cell RNA sequencing analysis to investigate the phenotypic and functional heterogeneity of the adult mouse prostate stromal cells. Our analysis identifies three major cell populations representing the smooth muscle cells and two types of fibroblast cells enriched by Sca-1 and CD90. The Sca-1 + CD90 + fibroblast cells are in direct contact with the epithelial cells and express growth factors and genes associated with cell motility, developmental process, and androgen biosynthesis. This suggests that they may regulate epithelial cell survival and growth. The Sca-1 + CD90 -/low myofibroblast-like cells highly express genes associated with the extracellular matrix and cytokine-mediated signaling pathways, indicating a role in tissue repair and immune responses. The Sca-1 + CD90 -/low cells significantly suppress the capacity of the basal cells for bipotent differentiation in the prostate organoid assay. Collectively, we identify the surface markers enabling physical separation of stromal subpopulations and generate the gene expression profiles implying their cellular functions., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Glioblastoma is a highly aggressive and malignant type of cancer that is apoptosis resistant and difficult to cure by conventional cancer therapies. In this regard, an oncolytic adenovirus that selectively targets the tumour tissue and induces tumour cell lysis is a promising treatment option. We designed and constructed a hypoxia-responsive and cancer-specific modified human telomerase reverse transcriptase (H5CmTERT) promoter to drive replication of an oncolytic adenovirus (H5CmTERT-Ad). To enhance the anti-tumour efficacy of H5CmTERT-Ad against malignant glioblastoma, we also generated an H5CmTERT-Ad expressing secretable trimeric tumour necrosis factor-related apoptosis-inducing ligand (H5CmTERT-Ad/TRAIL). H5CmTERT promoter-regulated oncolytic adenoviruses showed cancer-specific and superior cell-killing effect in contrast to a cognate control oncolytic adenovirus replicating under the control of the endogenous adenovirus promoter. The cancer cell-killing effects of H5CmTERT-Ad and H5CmTERT-Ad/TRAIL were markedly higher during hypoxia than normoxia owing to hypoxia responsiveness of the promoter. H5CmTERT-Ad/TRAIL showed more potent anti-tumour efficacy than H5CmTERT-Ad did in a xenograft model of TRAIL-resistant subcutaneous and orthotopic glioblastoma through superior induction of apoptosis and more extensive virus distribution in the tumour tissue. Altogether, our findings show that H5CmTERT-Ad/TRAIL can promote dispersion of an oncolytic adenovirus through robust induction of apoptosis in a highly TRAIL-resistant glioblastoma.

Background and Objectives: The aim of our study was to evaluate postoperative mastoid aeration according to the preoperative middle ear disease and investigate the factors affecting it., Subjects and Methods: We retrospectively reviewed the high-resolution computed tomography (CT) scans of temporal bones that were taken 1 year after surgery. The postoperative mastoid aeration was evaluated according to the preoperative diagnosis, and classified into three groups: grade 1 (complete mastoid aeration), an air-filled epitympanum and mastoid cavity; grade 2 (partial mastoid aeration), an air-filled epitympanum and partially aerated mastoid cavity; and grade 3 (absence of mastoid aeration), no air space in the mastoid cavity., Results: The overall mastoid aeration rate was 55.8%, with adhesive otitis media accounting for 21.2%, attic cholesteatoma 53.8%, and chronic otitis media 75.4%. The rates of postoperative mastoid aeration were significantly higher in the chronic otitis media cases and attic cholesteatoma cases than in the adhesive otitis media cases. There were 14 cases requiring revision operations due to the development of a retraction pocket in the tympanic membrane. All of the revised cases had grade 3 postoperative mastoid aeration, and underwent canal wall down mastoidectomies., Conclusions: The degree of postoperative mastoid aeration is associated with the preoperative middle ear disease. When planning a canal wall up mastoidectomy, the surgeon should contemplate the middle ear disease, because a canal wall down mastoidectomy or mastoid obliteration is recommended if the patient has adhesive otitis media.

Purpose: The aim of our study was to compare the difficulty in performing a posterior tympanotomy in chronic otitis media (COM) versus the same procedure in a normal mastoid., Materials and Methods: The study included 122 patients who underwent tympanomastoidectomy for unilateral chronic otitis media with contralateral normal mastoid pneumatization. We evaluated the anatomical relationships between the mastoid segment and neighboring structures by analyzing axial temporal bone computed tomography scans. A vertical line (line A) was drawn tangential to the most lateral end of the posterior semicircular canal (point A). Three distances were measured: the distance (D1) between the point A and the most lateral end of the mastoid segment of the facial nerve (point B), the distance (D2) between the line A and the point B, and the distance (D3) between the point B and the posterior end of the bony annulus of the external auditory canal., Results: The average measurements of D1 and D3 were 3.79 ± 0.55 and 2.63 ± 0.51 mm, respectively, in the normal mastoid ears and 3.47 ± 0.59 and 2.35 ± 0.44 mm, respectively, in the COM ears. The measurements of D1 and D3 were statistically shorter in the COM ears than in the normal ears., Conclusions: These findings suggest that the facial recess in COM may be narrower than in a normal mastoid and that performing a posterior tympanotomy may be riskier in COM than in a normal mastoid due to the potential for injury to the neighboring structures and the facial nerve.

Although Notch signaling is deregulated in prostate cancer, the role of this pathway in disease development and progression is not fully understood. Here, we analyzed 2 human prostate cancer data sets and found that higher Notch signaling correlates with increased metastatic potential and worse disease survival rates. We used the Pten-null mouse prostate cancer model to investigate the function of Notch signaling in the initiation and progression of prostate cancer. Disruption of the transcription factor RBPJ in Pten-null mice revealed that endogenous canonical Notch signaling is not required for disease initiation and progression. However, augmentation of Notch activity in this model promoted both proliferation and apoptosis of prostate epithelial cells, which collectively reduced the primary tumor burden. The increase in cellular apoptosis was linked to DNA damage-induced p53 activation. Despite a reduced primary tumor burden, Notch activation in Pten-null mice promoted epithelial-mesenchymal transition and FOXC2-dependent tumor metastases but did not confer resistance to androgen deprivation. Notch activation also resulted in transformation of seminal vesicle epithelial cells in Pten-null mice. Our study highlights a multifaceted role for Notch signaling in distinct aspects of prostate cancer biology and supports Notch as a potential therapeutic target for metastatic prostate cancer.

Recent lineage tracing studies showed that the prostate basal and luminal cells in adult mice are two independent lineages under the physiological condition, but basal cells are capable of generating luminal progenies during bacterial infection-induced prostatitis. Because acute bacterial infection in human prostate tissues is relatively rare, the disease relevance of the bacterial infection-induced basal-to-luminal differentiation is uncertain. Herein we employ a high fat diet-induced sterile prostate inflammation model to determine whether basal-to-luminal differentiation can be induced by inflammation irrespective of the underlying etiologies. A K14-CreER model and a fluorescent report line are utilized to specifically label basal cells with the green fluorescent protein. We show that high fat diet promotes immune cell infiltration into the prostate tissues and basal-to-luminal differentiation. Increased cell proliferation accompanies basal-to-luminal differentiation, suggesting a concurrent regulation of basal cell proliferation and differentiation. This study demonstrates that basal-to-luminal differentiation can be induced by different types of prostate inflammation evolved with distinct etiologies. Finally, high fat diet also accelerates initiation and progression of prostatic intraepithelial neoplasia that are originated from basal cells with loss-of-function of the tumor suppressor Pten. Because prostate cancer originated from basal cells tends to be invasive, our study also provides an alternative explanation for the association between obesity and aggressive prostate cancer., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

The classic androgen ablation and replacement experiment demonstrates that prostate epithelia possess extensive regenerative capacities and implies the existence of the prostate stem/progenitor cells. These cells may serve as the cells of origin for prostate cancer and their intrinsic property may dictate the clinical behaviors of the resulting diseases. Therefore, detailed characterization of these cells will potentially benefit disease prevention, diagnosis and prognosis. In this review, we describe several major in vitro and in vivo approaches that have been employed in the studies of the prostate stem cell activities, summarize the major progress that has been made during the last two decades regarding the identity of prostate stem/progenitor cells and their niches, and discuss some remaining outstanding questions in the field.

Background & Aims: Hypoxia-inducible factor-1α (HIF-1α), a key transcription factor in the cellular response to hypoxia, and interleukin 8 (IL-8), a key mediator of angiogenesis, are important in cancerous tumour growth. In this study, we evaluated the effects of HIF-1α and IL-8 knockdown on angiogenesis and tumour growth in hepatocellular carcinoma (HCC)., Methods: Hepatocellular carcinoma cell lines were infected with adenoviruses expressing small-hairpin RNA (shRNA) specific for HIF-1α or IL-8, cultured under hypoxic conditions (1% O2), and examined for their levels of HIF-1α, IL-8, and angiogenesis factors using immunoblot. The effects of adenovirus-mediated shRNA-induced HIF-1α and IL-8 knockdown on tumour growth and angiogenesis were also investigated in a subcutaneous Hep3B-tumour mouse model., Results: Hypoxia-inducible factor-1α knockdown directly repressed tumour growth, whereas IL-8 knockdown indirectly repressed tumour growth. Combined knockdown of HIF-1α and IL-8 increased survival rates of mice. HIF-1α and IL-8 knockdown also decreased microvessel density and tumour volume in vivo. Similarly, HIF-1α and IL-8 knockdown inhibited the angiogenic effects of HCC cell-conditioned media on tube formation and invasion by endothelial cells in vitro., Conclusion: These findings indicate that shRNA-induced HIF-1α and IL-8 knockdown inhibit angiogenesis and tumour growth in HCC. Further development of HIF-1α and IL-8 shRNA technologies could lead to effective therapies for HCC., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)