Cavity flow over a wall-mounted fence

Ventilated cavity flow over a wall mounted fence is experimentally investigated in a cavitation tunnel. The flow over a 2-D fence, attached to the tunnel test section ceiling, is examined for a range of free-stream conditions. The dependence of cavity topology, cavitation number, upstream wall pressure distribution and drag on several parameters, including ventilation rate, fence height based Froude number (Fr), vapour pressure based cavitation number (σv ) and degree of fence immersion in the oncoming wall boundary layer, is investigated. Three different flow regimes are identified throughout the range of cavitation numbers for a particular set of free-stream conditions: shear layer cavitation, fully developed cavity and ‘blocked’ flow. The cavity exhibits a typical re-entrant jet closure and the re-entrant jet intensity is found to be a function of Fr. The high intensity re-entrant jet, present at high Fr, leads to an increase in drag. Drag decreases significantly with an increase in fence immersion in the oncoming boundary layer. Complementary measurements for a naturally cavitating flow are obtained for comparison. A more detailed examination of the topology and unsteady behaviour of ventilated and natural cavity flows over a 2-D wall-mounted fence was undertaken for fixed length cavities with varying free-stream velocity using high-speed and still imaging, X-ray densitometry and dynamic surface pressure measurements in two experimental facilities. Two main unsteady features are observed, the irregular small-scale shedding of structures at the cavity closure and a larger-scale re-entrant jet oscillation. Small-scale cavity break-up was associated with a high-frequency broad-band peak in the wall pressure spectra, found to be governed by the overlying turbulent boundary layer characteristics, similar to observations from single-phase flow over a forward-facing step. A low-frequency peak reflecting the oscillations in size of re-entrant jet, analogous to the ‘flapping’ motion in single-phase flow, was found to be modulated by gravity effects (i.e. a Froude number dependency). Likewise, a significant change in cavity behaviour was observed as the flow underwent transition analogous to the transition from sub- to super- critical regime in open-channel flow. A companion numerical study is undertaken to provide additional insight into particular flow features such as the separated flow region upstream of the fence and to assess the influence of blockage. An implicit unsteady compressible solver is used with a RANS k − ω SST turbulence model and VOF approach to capture the cavity interface. The numerical results are found to compare reasonably with the experimental data, additionally showing a significant influence of blockage on the studied flow. Along with the 2-D fence, a 3-D wall mounted fence, spanning nominally a quarter of the tunnel test section, is investigated. The impact that 3-D effects have on the cavity topology and the relations between the parameters characterizing the flow is observed. The most notable effect of 3-D flow is a change in the closure mechanism observed for low Fr. Following a decrease in Fr the closure topology transforms from a well defined single re-entrant jet regime, through a phase of gradual re-entrant jet widening to a completely split re-entrant jet separated into two branches. Generally, the 2-D and 3-D flows exhibited similar trends with any significant difference attributable to differing levels of flow confinement due to lesser width of 3-D fence

Forprófun á íslenskri útgáfu Sjálfsmatskvarða Becks fyrir börn og unglinga

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenGerð var forprófun á Sjálfsmatskvörðum Becks fyrir börn á aldrinum 7-14 ára til þess að athuga próffræðilega eiginleika íslenskrar útgáfu af kvörðunum. Þátttakendur voru 293 úr 12 grunnskólum í Reykjavík. Próffræðilegir eiginleikar reyndust sambærilegir við erlendar rannsóknir. Innri áreiðanleiki var hár og fylgni atriða við heildarskor hvers kvarða viðunandi. Samleitni kvarða var athugað með þáttagreiningu og niðurstöður sýndu að þunglyndi, kvíði og hegðunarvandi voru einsleitir kvarðar en atriði sjálfsmyndar og reiði mynduðu tvo þætti. Gerð var þáttagreining á öllum 100 atriðum kvarðanna. Niðurstöður sýndu þrjá þætti sem skýrðu 38,6% dreifingar. Fyrsti þáttur samanstóð af þunglyndi, reiði og kvíða. Á annan þátt lögðust þrjú atriði reiði og 18 atriði hegðunarvanda og á þriðja þátt lögðust 18 atriði sjálfsmyndar. Há fylgni reyndist vera milli kvíða, þunglyndis og reiði en það er sambærilegt niðurstöðum erlendra rannsókna. Réttmæti kvarðanna var athugað með þremur spurningum um líðan í skóla og stríðni. Spurning um líðan í frímínútum hafði hæstu fylgni við þunglyndi sem bendir til þess að nemendur sem sýna þunglyndiseinkenni líður frekar illa í frímínútum. Spurning um líðan í kennslustundum hafði hæstu fylgni við hegðunarvanda og reiði og loks var hæst fylgni milli hegðunarvanda og stríðni. Enginn kynja- eða aldursmunur kom fram á kvörðum fyrir þunglyndi, reiði og kvíða. Hins vegar var meðaltal eldri hóps og drengja hærra á kvarða fyrir hegðunarvanda en hjá yngri hóp og stúlkum. Meðaltal á sjálfsmyndarkvarða var lægra í hópi eldri þáttakenda og meiri munur var á milli yngri og eldri stúlkna sem bendir til að sjálfsmynd verði neikvæðari á unglingsárum og sérstaklega hjá stúlkum. Próffræðilegir eiginleikar reyndust í megindráttum góðir en safna þarf meiri gögnum um áreiðanleika og réttmæti kvarðanna áður en hægt er að mæla með almennri notkun þeirra hér á landi.A pilot study of the Beck Youth Inventories (BYI) for children 7-14 years was undertaken to evaluate the psychometric properties of the Icelandic version. Participants were 293 from 12 elementary schools in Reykjavík. Psychometric properties revealed similar findings as other studies abroad have revealed. The internal consistency reliability was high and item total correlation acceptable. A principal axis factor analysis was conducted to evaluate the homogeneity of the BYI. Depression, anxiety and disruptive behavior were unidimensional but self-concept and anger revealed two factors. Additionally a principal axis factor analysis of all items of the inventories indicated three factors explaining 38,6% of variance. Items of depression, anxiety and anger loaded on the first factor. Disruptive behavior and 3 items of anger loaded on the second factor. Items of self-concept loaded on the third factor. Depression, anxiety and anger correlated highly, consistent with studies abroad and the factor analysis results. The scales´ validity was evaluated by three items assesing emotional well being in school and teasing other pupils. The highest correlation was between emotional well being in school breaks and depression, emotional well being in classrooms and disruptive behavior and anger, and between teasing other pupils and disruptive behavior. No significant age and gender differences were found on depression, anxiety and anger. Mean score for boys was higher than for girls on disruptive behavior and older students scored higher than younger students. Older students´ mean score was lower than younger students´ mean on self-concept and this difference was greater for girls than boys. Psychometric properties were good, but additonal studies need to be undertaken on the scales´ reliability and validity before we can recommend general use of the scales for clinical purposes in Iceland

Chemical nature and structure of organic coating of quantum dots is crucial for their application in imaging diagnostics

Rumiana Bakalova1, Zhivko Zhelev1, Daisuke Kokuryo1, Lubomir Spasov2, Ichio Aoki1, Tsuneo Saga11Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; 2Medical Faculty, Sofia University, Sofia, BulgariaBackground: One of the most attractive properties of quantum dots is their potential to extend the opportunities for fluorescent and multimodal imaging in vivo. The aim of the present study was to clarify whether the composition and structure of organic coating of nanoparticles are crucial for their application in vivo.Methods: We compared quantum dots coated with non-crosslinked amino-functionalized polyamidoamine (PAMAM) dendrimers, quantum dots encapsulated in crosslinked carboxyl-functionalized PAMAM dendrimers, and silica-shelled amino-functionalized quantum dots. A multimodal fluorescent and paramagnetic quantum dot probe was also developed and analyzed. The probes were applied intravenously in anesthetized animals for visualization of brain vasculature using two-photon excited fluorescent microscopy and visualization of tumors using fluorescent IVIS® imaging (Caliper Life Sciences, Hopkinton, MA) and magnetic resonance imaging.Results: Quantum dots coated with non-crosslinked dendrimers were cytotoxic. They induced side effects in vivo, including vasodilatation with a decrease in mean arterial blood pressure and heart rate. The quantum dots penetrated the vessels, which caused the quality of fluorescent imaging to deteriorate. Quantum dots encapsulated in crosslinked dendrimers had low cytotoxicity and were biocompatible. In concentrations <0.3 nmol quantum dots/kg bodyweight, these nanoparticles did not affect blood pressure and heart rate, and did not induce vasodilatation or vasoconstriction. PEGylation (PEG [polyethylene glycol]) was an indispensable step in development of a quantum dot probe for in vivo imaging, based on silica-shelled quantum dots. The non-PEGylated silica-shelled quantum dots possessed low colloidal stability in high-salt physiological fluids, accompanied by rapid aggregation in vivo. The conjugation of silica-shelled quantum dots with PEG1100 increased their stability and half-life in the circulation without significant enhancement of their size. In concentrations <2.5 nmol/kg bodyweight, these quantum dots did not affect the main physiological variables. It was possible to visualize capillaries, which makes this quantum dot probe appropriate for investigation of mediators of vasoconstriction, vasodilatation, and brain circulation in intact animals in vivo. The multimodal silica-shelled quantum dots allowed visualization of tumor tissue in an early stage of its development, using magnetic resonance imaging.Conclusion: The present study shows that the type and structure of organic/bioorganic shells of quantum dots determine their biocompatibility and are crucial for their application in imaging in vivo, due to the effects of the shell on the following properties: colloidal stability, solubility in physiological fluids, influence of the basic physiological parameters, and cytotoxicity.Keywords: quantum dot, organic shell, biocompatibility, in vivo imaging, two-photon excited fluorescent microscopy, magnetic resonance imagin

Increased [¹⁸F]FMISO accumulation under hypoxia by multidrug-resistant protein 1 inhibitors

BACKGROUND: [¹⁸F]Fluoromisonidazole ([¹⁸F]FMISO) is a PET imaging probe widely used for the detection of hypoxia. We previously reported that [¹⁸F]FMISO is metabolized to the glutathione conjugate of the reduced form in hypoxic cells. In addition, we found that the [¹⁸F]FMISO uptake level varied depending on the cellular glutathione conjugation and excretion ability such as enzyme activity of glutathione-S-transferase and expression levels of multidrug resistance-associated protein 1 (MRP1, an efflux transporter), in addition to the cellular hypoxic state. In this study, we evaluated whether MRP1 activity affected [¹⁸F]FMISO PET imaging. METHODS: FaDu human pharyngeal squamous cell carcinoma cells were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, incubated with [¹⁸F]FMISO for 4 h under hypoxia, and their radioactivity was then measured. FaDu tumor-bearing mice were intravenously injected with [¹⁸F]FMISO, and PET/CT images were acquired at 4 h post-injection (1st PET scan). Two days later, the same mice were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, and PET/CT images were acquired (2nd PET scan). RESULTS: FaDu cells pretreated with MRP1 inhibitors exhibited significantly higher radioactivity than those without inhibitor treatment (cyclosporine A: 6.91 ± 0.27, lapatinib: 10.03 ± 0.47, MK-571: 10.15 ± 0.44%dose/mg protein, p < 0.01). In the in vivo PET study, the SUVmean ratio in tumors [calculated as after treatment (2nd PET scan)/before treatment of MRP1 inhibitors (1st PET scan)] of the mice treated with MRP1 inhibitors was significantly higher than those of control mice (cyclosporine A: 2.6 ± 0.7, lapatinib: 2.2 ± 0.7, MK-571: 2.2 ± 0.7, control: 1.2 ± 0.2, p < 0.05). CONCLUSION: In this study, we revealed that MRP1 inhibitors increase [¹⁸F]FMISO accumulation in hypoxic cells. This suggests that [¹⁸F]FMISO-PET imaging is affected by MRP1 inhibitors independent of the hypoxic state

Knockdown of COPA, Identified by Loss-of-Function Screen, Induces Apoptosis and Suppresses Tumor Growth in Mesothelioma Mouse Model

AbstractMalignant mesothelioma is a highly aggressive tumor arising from serosal surfaces of the pleura and is triggered by past exposure to asbestos. Currently, there is no widely accepted treatment for mesothelioma. Development of effective drug treatments for human cancers requires identification of therapeutic molecular targets. We therefore conducted a large-scale functional screening of mesothelioma cells using a genome-wide small interfering RNA library. We determined that knockdown of 39 genes suppressed mesothelioma cell proliferation. At least seven of the 39 genes—COPA, COPB2, EIF3D, POLR2A, PSMA6, RBM8A, and RPL18A—would be involved in anti-apoptotic function. In particular, the COPA protein was highly expressed in some mesothelioma cell lines but not in a pleural mesothelial cell line. COPA knockdown induced apoptosis and suppressed tumor growth in a mesothelioma mouse model. Therefore, COPA may have the potential of a therapeutic target and a new diagnostic marker of mesothelioma

Prognostic value of pretreatment FDG PET/CT in uterine cervical cancer according to two major histologic types: squamous cell carcinoma and adenocarcinoma

Objective(s): The aim of this study was to assess the prognostic value of pretreatment Positron emission tomography / computed tomography using 18F-fluorodeoxyglucose (FDG-PET/CT) in cervical cancer according to two major histologic types.Methods: Eighty-three squamous cell carcinoma (SCC) patients and 35 adenocarcinoma (AC) patients who underwent pretreatment FDG-PET/CT were retrospectively analyzed. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor were calculated. Kaplan-Meier analyses were used to compare correlations between each PET parameter and overall survival (OS). The prognostic values of imaging and clinical parameters were assessed using uni- and multivariable Cox proportional hazard models.Results: SUVmax, SUVmean, and TLG were significantly higher in SCC than in AC (p<0.01 each). No significant difference in MTV was seen between the two groups (p=0.10). As for Kaplan-Meier analyses, in SCC, patients with SUVmax, SUVmean, MTV, and TLG exceeding cutoff values tended to show worse OS than patients with lower values (p=0.07, p=0.27, p<0.01, and p=0.01, respectively, for OS). On the other hand, in AC, patients with MTV and TLG exceeding cutoff values showed significantly worse PFS and OS (p<0.01 each for OS), while SUVmax and SUVmean were unrelated to OS (p=0.91 and p=0.83, respectively for OS). As for multivariable analyses, in SCC, TLG was identified as an independent prognostic factor for OS (p=0.01). In AC, MTV was identified as an independent prognostic factor for OS (p=0.02).Conclusion: Our preliminary data suggest that FDG-PET/CT would be useful for predicting prognosis in cervical cancer, although the clinical significance of quantitative values may differ according to histopathological type

A liquid crystalline phase in spermidine-condensed DNA

Over a large range of salt and spermidine concentrations, short DNA fragments precipitated by spermidine (a polyamine) sediment in a pellet from a dilute isotropic supernatant. We report here that the DNA-condensed phase consists of a cholesteric liquid crystal in equilibrium with a more concentrated phase. These results are discussed according to Flory's theory for the ordering of rigid polymers. The liquid crystal described here corresponds to an ordering in the presence of attractive interactions, in contrast with classical liquid crystalline DNA. Polyamines are often used in vitro to study the functional properties of DNA. We suggest that the existence of a liquid crystalline state in spermidine-condensed DNA is relevant to these studies

Denoising approach with deep learning-based reconstruction for neuromelanin-sensitive MRI: image quality and diagnostic performance

[Purpose]Neuromelanin-sensitive MRI (NM-MRI) has proven useful for diagnosing Parkinson’s disease (PD) by showing reduced signals in the substantia nigra (SN) and locus coeruleus (LC), but requires a long scan time. The aim of this study was to assess the image quality and diagnostic performance of NM-MRI with a shortened scan time using a denoising approach with deep learning-based reconstruction (dDLR).[Materials and methods]We enrolled 22 healthy volunteers, 22 non-PD patients and 22 patients with PD who underwentNM-MRI, and performed manual ROI-based analysis. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in ten healthy volunteers were compared among images with a number of excitations (NEX) of 1 (NEX1), NEX1 images with dDLR (NEX1+dDLR) and 5-NEX images (NEX5). Acquisition times for NEX1 and NEX5 were 3 min 12 s and 15 min 58 s, respectively. Diagnostic performances using the contrast ratio (CR) of the SN (CR_SN) and LC (CR_LC) and those by visual assessment for diferentiating PD from non-PD were also compared between NEX1 and NEX1+dDLR.[Results]Image quality analyses revealed that SNRs and CNRs of the SN and LC in NEX1+dDLR were signifcantly higherthan in NEX1, and comparable to those in NEX5. In diagnostic performance analysis, areas under the receiver operating characteristic curve (AUC) using CR_SN and CR_LC of NEX1+dDLR were 0.87 and 0.75, respectively, which had no signifcant diference with those of NEX1. Visual assessment showed improvement of diagnostic performance by applying dDLR.[Conclusion]Image quality for NEX1+dDLR was comparable to that of NEX5. dDLR has the potential to reduce scan time of NM-MRI without degrading image quality. Both 1-NEX NM-MRI with and without dDLR showed high AUCs for diagnosing PD by CR. The results of visual assessment suggest advantages of dDLR. Further tuning of dDLR would be expected to provide clinical merits in diagnosing PD

In Vivo Simultaneous Imaging of Vascular Pool and Hypoxia with a HT-29 Tumor Model: the Application of Dual-Isotope SPECT/PET/CT

Investigation of vascularity and hypoxia in tumors is important in understanding cancer biology to developthe therapeutic strategies in cancer treatment. ------------------------------------------------------------------------ *Corresponding author . Recently, an imaging technology with the VECTor SPECT/PET/CT small-animal scanner (MILabs) has been developed to obtain simultaneous images usingtwodifferent tracers labeled with SPECT and PET nuclides, respectively. In this study, we developed amethod to simultaneously visualize vascularity and hypoxia witha human colon carcinoma HT-29tumor-bearing mouse model with 99mTc-labeled human serum albumin (99mTc-HSA) to detect blood pool, and 64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM) to detect the over-reduced conditionsunder hypoxia, by applying this SPECT/PET/CT technology.Prior to the in vivo experiments, a phantom study was conducted to confirmquantitativity of the 99mTc/64Cu dual-isotope imaging with the SPECT/PET/CT system,by comparing radioactivities detected by SPECT/PET/CT system and those of standards under the conditions of wide range of radioactivities and various content ratios, in our settings. An in vivoimaging study was conducted with HT-29 tumor-bearing mice. Both 64Cu-ATSM (37 MBq) and 99mTc-HSA (18.5 MBq) were intravenously injected into a mouse (n = 4) at 1 h and 10 min, respectively, before scanning for 20 min; the 99mTc/64Cu dual-isotope SPECT/PET/CT images were then obtained.The phantom study demonstrated that this system has high quantitativity, even when 2 isotopes co-existed and the content ratio was changed over a wide range, indicating the feasibility for in vivo experiments. In vivoSPECT/PET/CT imaging with 64Cu-ATSM and 99mTc-HSA visualized the distribution of each probe and showed that 64Cu-ATSM high-uptake regions barely overlapped with 99mTc-HSA high-uptake regions within HT-29 tumors.We developed a method to simultaneously visualize vascularity and hypoxia within HT-29tumors using in vivodual-isotope SPECT/PET/CT imaging. This methodology would be useful for studies oncancer biology with mouse tumor models anddevelopment of the treatment strategies against cancer. Examination of vascularity and hypoxia within in vivotumors is important in understanding the biology of cancer anddevelopmentof the therapeutic strategies in cancer treatment. For hypervascular tumors, antiangiogenic therapy and antivascular therapy are promising approaches. For antiangiogenic therapy, the anti-vascular endothelial growth factor antibody bevacizumab is now clinically used worldwide [1-4], and for antivascular therapy, a clinical trial withcombrestatin A4 phosphate is conducted[5]. For hypovascular tumor, which is usually associated with hypoxia, intensive treatment is necessary, since tumor hypoxia is reportedly resistant to chemotherapy and radiotherapy [6-8]. In recent years, several therapeutic methods have been proposedto damage to hypoxic regions within tumors, such as intensity modulated radiation therapy with hypoxia positron emission tomography (PET) imaging [9, 10], and carbon-ion radiotherapy, which is able to damage tumor cells even in the absence of oxygen by high linear energy transfer beam [11, 12]. However, considering the difficulty of cancer radical cure at the present moment, more effective drugs and treatment methods for antiangiogenic, antivascular, and antihypoxia therapies need to be developed. In addition, combinations of these therapies would be effective approaches, since they can attacktumor vascularity and hypoxia closely linked each other.However, it is still difficult to observe tumor vascularity and hypoxia both coincidently and concisely in in vivo tumor-bearing mouse model. Recently, a technology of single-photon emission computed tomography/positron emission tomography/computed tomography(SPECT/PET/CT) imaging with the VECTor small-animal scanner, launched from MILabs (Utrecht, Netherlands), has been reportedto obtain truly simultaneous images with twotracers labeled with SPECT and PET nuclides, respectively. Conventionally, dual-isotope imaging studies with SPECT and PET have been performed by obtaining each image independently with 2 separate systems [13, 14]. In contrast, the VECTor system is equipped with a clustered pinhole collimator, which dramatically reduces pinhole-edge penetration of high-energy annihilation ?-photons from PET nuclides and enables it to detect high-energy ?-photons derived from PET nuclides, in a manner similar to SPECT nuclides, and to obtain high-resolution images from positron emitters and single-photon emitters at the same time by separating the images based on the photon energy [15, 16]. Thus, this system has a novel concept to make images of PET nuclides, compared to the typical PET system, which measures the coincidence of annihilation ?-photons. Goorden et al. have reported that this system shows high spatial resolution, with 0.8 mm for PET nuclides and 0.5 mm for SPECT nuclides [15]. Miwa et al. also confirmed its performance in simultaneous detection of 99mTc and 18F using this system [17]. In this study, we developed a methodology to easily observe intratumoralvascularity and hypoxia in a simultaneous manner,by applyingthis SPECT/PET/CT technology. We used 99mTc-labeled human serum albumin (99mTc-HSA) labeled with a SPECT nuclide 99mTc (half-life = 6.0 h; 140 keV ?-ray: 89%) to visualize tumor vascularity by detecting blood pool [18]. The 99mTc-HSAhas been reported to detect tumor blood pool in many types of cancer, including colon cancer, renal cell carcinoma, and liver tumor in both preclinical and clinical studies [19-21]. We also used 64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM), labeled with a PET nuclide 64Cu (half-life = 12.7 h; ?+-decay: 17.4%; ??-decay: 38.5%; and electron capture: 43%) [22], to detect tumor hypoxia. The Cu-ATSM, labeled with Cu radioisotopes, such as 60Cu, 62Cu, and 64Cu, has been developed as an imaging agent targeting hypoxic regions in tumors for use with PET [23-26].Many studies have demonstrated that Cu-ATSM accumulation is associated with hypoxic conditions of tumor in vitro and in vivo[26-29]. The mechanism of radiolabeled Cu-ATSM accumulation has been studied: Cu-ATSM has small molecular sizeand high membrane permeability, and thus rapidly diffuses into cells and is reduced and trapped within cells under highly reduced intracellular conditions such as hypoxia [24, 29-31]. A clinical study with 62Cu-ATSM demonstrated that high levels of hypoxia-inducible factor-1? (HIF-1?) expression were found in Cu-ATSM uptake regions in the tumors of patients with glioma [32]. In this study, we performed simultaneous in vivo imaging using a SPECT/PET/CT with 99mTc-HSA and 64Cu-ATSM for detecting tumor vascularity and hypoxia with a HT-29 tumor-bearing mouse model