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At least 361 records · Page 20

The Changing Face of Vascular Interventional Radiology: The Future Role of Pharmacotherapies and Molecular Imaging

Interventional radiology has had to evolve constantly because there is the ever-present competition and threat from other specialties within medicine, surgery, and research. The development of new technologies, techniques, and therapies is vital to broaden the horizon of interventional radiology and to ensure its continued success in the future. In part, this change will be due to improved chronic disease prevention altering what we treat and in whom. The most important of these strategies are the therapeutic use of statins, Beta-blockers, angiotensin-converting enzyme inhibitors, and substances that interfere with mast cell degeneration. Molecular imaging and therapeutic strategies will move away from conventional techniques and nano and microparticle molecular technology, tissue factor imaging, gene therapy, endothelial progenitor cells, and photodynamic therapy will become an important part of interventional radiology of the future. This review looks at these new and exciting technologies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Nascent histamine induces α-synuclein and caspase-3 on human cells

Highlights: • Nascent histamine alters cyclin expression pattern. • Nascent histamine increases expression of α-synuclein. • Nascent histamine activates caspase-3. - Abstract: Histamine (Hia) is the most multifunctional biogenic amine. It is synthetized by histidine decarboxylase (HDC) in a reduced set of mammalian cell types. Mast cells and histaminergic neurons store Hia in specialized organelles until the amine is extruded by exocytosis; however, other immune and cancer cells are able to produce but not store Hia. The intracellular effects of Hia are still not well characterized, in spite of its physiopathological relevance. Multiple functional relationships exist among Hia metabolism/signaling elements and those of other biogenic amines, including growth-related polyamines. Previously, we obtained the first insights for an inhibitory effect of newly synthetized Hia on both growth-related polyamine biosynthesis and cell cycle progression of non-fully differentiated mammalian cells. In this work, we describe progress in this line. HEK293 cells were transfected to express active and inactive versions of GFP-human HDC fusion proteins and, after cell sorting by flow cytometry, the relative expression of a large number of proteins associated with cell signaling were measured using an antibody microarray. Experimental results were analyzed in terms of protein–protein and functional interaction networks. Expression of active HDC induced a cell cycle arrest through the alteration of the levels of several proteins such as cyclin D1, cdk6, cdk7 and cyclin A. Regulation of α-synuclein and caspase-3 was also observed. The analyses provide new clues on the molecular mechanisms underlying the regulatory effects of intracellular newly synthetized Hia on cell proliferation/survival, cell trafficking and protein turnover. This information is especially interesting for emergent and orphan immune and neuroinflammatory diseases.

60 APPLIED LIFE SCIENCES↗

Lysophosphatidylserine suppresses IL-2 production in CD4 T cells through LPS{sub 3}/GPR174

Lysophosphatidylserine (LysoPS) has been shown to have lipid mediator-like actions to induce mast cell degranulation and suppress T lymphocyte proliferation. Recently, three G protein-coupled receptors (GPCRs), LPS{sub 1}/GPR34, LPS{sub 2}/P2Y10, and LPS{sub 3}/GPR174, were found to react specifically with LysoPS, raising the possibility that LysoPS exerts its roles through these receptors. In this study, we show that LPS{sub 3} is expressed in various T cell subtypes and is involved in suppression of Interleukin-2 (IL-2) production in CD4 T cells. We found that LysoPS suppressed the IL-2 production from activated T cells at the mRNA and protein levels. In addition, LysoPS did not have such an effect on the splenocytes and CD4 T cells isolated from LPS{sub 3}-deficient mice. In LPS{sub 3}-deficient splenocytes and CD4 T cells, anti-CD3/anti-CD28-triggered IL-2 production is somewhat increased. Interestingly, LysoPS with various fatty acids was up-regulated upon T cell activation. The present study raised the possibility that LysoPS exerts its immunosuppressive roles by down-regulating IL-2 production through a LysoPS-LPS{sub 3} axis in T cells. - Highlights: • LysoPS suppressed IL-2 production in CD4 T cells via LPS{sub 3}/GPR174. • LPS{sub 3}-deficient T cells showed high IL-2 production capacity. • LysoPS/LPS{sub 3} signaling works in an autocrine manner, since LysoPS level increased in activated T cells.

60 APPLIED LIFE SCIENCES↗

Umbilical cord-derived mesenchymal stem cells alleviated inflammation and inhibited apoptosis in interstitial cystitis via AKT/mTOR signaling pathway

Highlights: • UC-MSCs alleviated inflammation in rat model and cell model of IC. • UC-MSCs promoted proliferation of urothelium. • UC-MSCs inhibited apoptosis of urothelium. • UC-MSCs activated AKT/mTOR signaling pathway to cure IC. Interstitial cystitis (IC) is a bladder syndrome characterized by pelvic pain and urinary frequency without infection or other identifiable pathology. There are no effective treatments to cure IC. This study investigated the effects of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) injection on IC rat model. Furthermore, we used a coculture system to find the possible molecular mechanism on the human uroepithelial cells (SV-HUC-1), which was the cell model of IC. A rat model of IC was established via systemic injection with cyclophosphamide (CYP) and a cell model of IC was induced by being exposed to tumor necrosis factor (TNF)-α (10 ng/ml). After one week, UC-MSCs injection significantly ameliorated the bladder voiding function in IC rat model. And the Histo- and immunohistochemical analyses showed that UC-MSCs can repair impaired bladder, reduce mast cell infiltration and inhibit apoptosis of urothelium. ELISA results showed that UC-MSCs can decrease IL-1β, IL-6 and TNF-α in bladder. In the coculture system, UC-MSCs can promote proliferation of impaired SV-HUC-1 cells, and inhibit apoptosis. However, while knocked down EGF secreted by UC-MSCs with siRNA, the effects would be weaken. Western blot showed that UC-MSCs increase protein expression levels of p-AKT and p-mTOR in SV-HUC-1 cells, and decrease the levels of cleaved caspase-3. Taken together, we provide evidence that UC-MSCs therapy can successfully alleviate IC in a preclinical animal Model and cell model by alleviating inflammation, promoting proliferation and inhibiting apoptosis. In addition, we demonstrate that the AKT/mTOR signaling pathway was activated.

60 APPLIED LIFE SCIENCES↗

The suppressive effect of puerarin on atopic dermatitis-like skin lesions through regulation of inflammatory mediators in vitro and in vivo

Highlights: • Puerarin regulates inflammatory cytokine, such as IL-6, IL-5, and TNF-α in human keratinocyte cell line. • Puerarin attenuates inflammation related protein expression level in human keratinocyte cell line. • Puerarin improves DNCB-induced atopic skin condition by regulating of clinical signs and skin tissue injury. • Oral administration of puerarin recovers inflammatory cytokine secretion in DNCB-induced atopic dermatitis. Atopic dermatitis (AD) is one of the common inflammatory immune disorders. Puerarin is the main isoflavonoid obtained from the root of Pueraria lobata and has been known have ameliorative effects on diverse inflammatory diseases. However, the effects of puerarin on AD have not been uncovered. 2,4-dinitrochlorobenzene (DNCB) was used to induce atopic dermatitis(AD)-like skin lesions on BALB/c mice for 17 days. Further, the BALB/c mice were orally administered puerarin. Puerarin ameliorated DNCB-induced AD-like symptoms in the mice by regulating skin thickness, degranulation of mast cells, and serum immunoglobulin E (IgE). Human keratinocytes (HaCaT cells) were also used to clarify the effects of puerarin on the secretion of pro-inflammatory cytokines. Puerarin inhibited the secretion of inflammatory cytokines and chemokines. The aim of this study was to investigate the protective and alleviative effect of puerarin on AD in vitro and in vivo. The results in this study indicated that puerarin ameliorates AD-like skin lesion and skin inflammation via regulation of various atopic and inflammatory mediators. Therefore, puerarin might be useful in treating AD and other skin diseases.

60 APPLIED LIFE SCIENCES↗

Streptococcus gallolyticus conspires myeloid cells to promote tumorigenesis of inflammatory bowel disease

Highlights: • Streptococcus gallolyticus shows a distinctive enrichment at colonic mucosa in colitis-associated carcinoma. • Introduction of Streptococcus gallolyticus could aggravate the development of colitis-associated carcinoma. • CD11b{sup +} myeloid cells recruitment are initialed by Streptococcus gallolyticus to promote colitis-associated carcinoma progress. Metagenomic analyses indicate that streptococcus gallolyticus is enriched at carcinoma in colitis associated colorectal cancer compared with sporadic colorectal cancer. But the particular mechanism of streptococcus gallolyticus in Inflammatory Bowel Disease malignant progression remains undefined yet. We aim to explore the biological carcinogenesis efficacy of streptococcus gallolyticus and its potential mechanism in azoxymethane and dextran sodium sulphate-induced colitis associated colorectal cancer in mice. Oral pretreatment of streptococcus gallolyticus was adopted to evaluate its detrimental effect. The colorectums of experimental C57BL/6 mice were collected and examined for the degree of tumorigenesis. Comparative 16S rRNA sequencing was carried out to observe streptococcus gallolyticus alterations in abundance. We found that streptococcus gallolyticus are enriched in colonic carcinoma compared to adenoma and healthy mice. Pretreatment of Streptococcus gallolyticus aggravated tumor formation, with more colonic obstruction, larger number and diameter of tumor node. Furthermore, Streptococcus gallolyticus selectively recruits tumor-infiltrating myeloid cells but not mast cells, including marrow-derived suppressor cells, tumor-associated macrophages and dendritic cells, which can inhibit competence of T cells. Moreover, several myeloid-cell-derived proinflammatory cytokines (IL-6, IL-1β, IL-8, CCL2, COX-2, TNF-α) were increased with the formation of carcinoma in IBD. Collectively, these data suggest that, through recruitment of tumor-infiltrating immune cells, Streptococcus gallolyticus generate an immune suppressive microenvironment that is conducive for neoplasia progression of Inflammatory Bowel Disease.

60 APPLIED LIFE SCIENCES↗

Protein 4.1R negatively regulates P815 cells proliferation by inhibiting C-Kit-mediated signal transduction

The proliferation of mast cells (MCs) plays a crucial role in either physiological or pathological progression of human physical. C-Kit-mediated signaling pathway has been confirmed to play a key role in MCs proliferation, and the regulatory mechanisms of C-Kit-mediated MCs proliferation need to be further explored. Our previous study found that protein 4.1R could negatively regulate T cell receptor (TCR) mediated signal pathways in CD4{sup +} T cells. Little is known about the function of 4.1R in C-Kit-mediated proliferation of MCs. In this study, P815-4.1R{sup -/-} cells were constructed by using CRISPR/Cas9 technique. Lack of 4.1R significantly enhanced P815 cells proliferation by accelerating the progression of cell cycle. 4.1R could also significantly alleviate the clinical symptoms of systemic mastocytosis (SM) and improve the overall survival of SM mice. Further study showed that 4.1R could interact directly with C-Kit to inhibit the activation of C-Kit-mediated Ras-Raf-MAPKs and PI3K-AKT signal pathways. Taken together, our findings demonstrate that protein 4.1R, a novel negative regulator, negatively regulates MCs proliferation by inhibiting C-Kit-mediated signal transduction, which maybe provide a potential target to the prevention and treatment of abnormal MCs proliferation-related diseases.

60 APPLIED LIFE SCIENCES↗

Linear stability and nonlinear dynamics of the fishbone mode in spherical tokamaks

Extensive linear and nonlinear simulations have been carried out to investigate the energetic particle-driven fishbone instability in spherical tokamak plasmas with weakly reversed q profile and the q{sub min} slightly above unity. The global kinetic-MHD hybrid code M3D-K is used. Numerical results show that a fishbone instability is excited by energetic beam ions preferentially at higher q{sub min} values, consistent with the observed appearance of the fishbone before the “long-lived mode” in MAST and NSTX experiments. In contrast, at lower q{sub min} values, the fishbone tends to be stable. In this case, the beam ion effects are strongly stabilizing for the non-resonant kink mode. Nonlinear simulations show that the fishbone saturates with strong downward frequency chirping as well as radial flattening of the beam ion distribution. An (m, n) = (2, 1) magnetic island is found to be driven nonlinearly by the fishbone instability, which could provide a trigger for the (2, 1) neoclassical tearing mode sometimes observed after the fishbone instability in NSTX.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Fast ion transport induced by saturated infernal mode

Tokamak discharges with extended weak-shear central core are known to suffer from infernal modes when the core safety factor approaches the mode ratio. These modes can cause an outward convection of the well-passing energetic ions deposited in the core by fusion reactions and/or neutral beam injection. Convection mechanism consists in collisional slowing down of energetic ions trapped in the Doppler-precession resonance with a finite-amplitude infernal mode. Convection velocity can reach a few m/s in modern spherical tori. Possible relation of this transport with the enhanced fast ion losses in the presence of “long lived modes” in the MAST tokamak [I. T. Chapman et al., Nucl. Fusion 50, 045007 (2010)] is discussed.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Synthetic aperture microwave imaging with active probing for fusion plasma diagnostics

A Synthetic Aperture Microwave Imaging (SAMI) system has been designed and built to obtain 2-D images at several frequencies from fusion plasmas. SAMI uses a phased array of linearly polarised antennas. The array configuration has been optimised to achieve maximum synthetic aperture beam efficiency. The signals received by antennas are down-converted to the intermediate frequency range and then recorded in a full vector form. Full vector signals allow beam focusing and image reconstruction in both real time and a post-processing mode. SAMI can scan over 16 pre-programmed frequencies in the range of 10-35GHz with a switching time of 300ns. The system operates in 2 different modes simultaneously: both a 'passive' imaging of plasma emission and also an 'active' imaging of the back-scattered signal of the radiation launched by one of the antennas from the same array. This second mode is similar to so-called Doppler backscattering (DBS) reflectometry with 2-D resolution of the propagation velocity of turbulent structures. Both modes of operation show good performance in fusion plasma experiments on Mega Amp Spherical Tokamak (MAST). We have obtained the first ever 2-D images of BXO mode conversion windows. With active probing, first ever turbulence velocity maps have been obtained. We present an overview of the diagnostic and discuss recent results. In contrast to quasi-optical microwave imaging systems SAMI requires neither big aperture viewing ports nor large 2-D detector arrays to achieve the desired imaging resolution. The number of effective 'pixels' of the synthesized image is proportional to the number of receiving antennas squared. Thus only a small number of optimised antennas is sufficient for the majority of applications. Possible implementation of SAMI on ITERand DEMO is discussed.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

High power heating of magnetic reconnection in merging tokamak experiments

Significant ion/electron heating of magnetic reconnection up to 1.2 keV was documented in two spherical tokamak plasma merging experiment on MAST with the significantly large Reynolds number R∼10{sup 5}. Measured 1D/2D contours of ion and electron temperatures reveal clearly energy-conversion mechanisms of magnetic reconnection: huge outflow heating of ions in the downstream and localized heating of electrons at the X-point. Ions are accelerated up to the order of poloidal Alfven speed in the reconnection outflow region and are thermalized by fast shock-like density pileups formed in the downstreams, in agreement with recent solar satellite observations and PIC simulation results. The magnetic reconnection efficiently converts the reconnecting (poloidal) magnetic energy mostly into ion thermal energy through the outflow, causing the reconnection heating energy proportional to square of the reconnecting (poloidal) magnetic field B{sub rec}{sup 2} ∼ B{sub p}{sup 2}. The guide toroidal field B{sub t} does not affect the bulk heating of ions and electrons, probably because the reconnection/outflow speeds are determined mostly by the external driven inflow by the help of another fast reconnection mechanism: intermittent sheet ejection. The localized electron heating at the X-point increases sharply with the guide toroidal field B{sub t}, probably because the toroidal field increases electron confinement and acceleration length along the X-line. 2D measurements of magnetic field and temperatures in the TS-3 tokamak merging experiment also reveal the detailed reconnection heating mechanisms mentioned above. The high-power heating of tokamak merging is useful not only for laboratory study of reconnection but also for economical startup and heating of tokamak plasmas. The MAST/TS-3 tokamak merging with B{sub p} > 0.4 T will enables us to heat the plasma to the alpha heating regime: T{sub i} > 5 keV without using any additional heating facility.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

The appearance and propagation of filaments in the private flux region in Mega Amp Spherical Tokamak

The transport of particles via intermittent filamentary structures in the private flux region (PFR) of plasmas in the MAST tokamak has been investigated using a fast framing camera recording visible light emission from the volume of the lower divertor, as well as Langmuir probes and IR thermography monitoring particle and power fluxes to plasma-facing surfaces in the divertor. The visible camera data suggest that, in the divertor volume, fluctuations in light emission above the X-point are strongest in the scrape-off layer (SOL). Conversely, in the region below the X-point, it is found that these fluctuations are strongest in the PFR of the inner divertor leg. Detailed analysis of the appearance of these filaments in the camera data suggests that they are approximately circular, around 1–2 cm in diameter, but appear more elongated near the divertor target. The most probable toroidal quasi-mode number is between 2 and 3. These filaments eject plasma deeper into the private flux region, sometimes by the production of secondary filaments, moving at a speed of 0.5–1.0 km/s. Probe measurements at the inner divertor target suggest that the fluctuations in the particle flux to the inner target are strongest in the private flux region, and that the amplitude and distribution of these fluctuations are insensitive to the electron density of the core plasma, auxiliary heating and whether the plasma is single-null or double-null. It is found that the e-folding width of the time-average particle flux in the PFR decreases with increasing plasma current, but the fluctuations appear to be unaffected. At the outer divertor target, the fluctuations in particle and power fluxes are strongest in the SOL.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

First access to ELM-free negative triangularity at low aspect ratio

A plasma scenario with negative triangularity (NT) shaping is achieved on MAST-U for the first time. While edge localized modes (ELMs) are eventually suppressed as the triangularity is decreased below δ ≲ –0.06, an extended period of H-mode operation with Type-III ELMs is sustained at less negative δ even through access to the second stability region for ideal ballooning modes is closed. This documents a qualitative difference from the ELM-free access conditions documented in NT scenarios on conventional aspect ratio machines. The electron temperature at the pedestal top drops across the transition to ELM-free operation, but a steady rise in core temperature as δ is decreased allows for similar normalized β in the ELM-free NT and H-mode positive triangularity shapes.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Systematic multi-machine analysis of the exhaust time-dependent behavior in tokamaks

The understanding of the time-scales and associated transient behavior of fusion exhaust plasmas plays a crucial role in its dynamic modeling and its control. This work presents an overview of experimental investigations of the exhaust dynamics in TCV, MAST-U, ASDEX-Upgrade, WEST, DIII-D, and JET. From the presented experiments, a clear picture arises on properties of the exhaust dynamics across machines. Particularly, we observe that the scrape-off layer equilibrates on fast time-scales ($>$ 70 Hz) and that exhaust dynamics measured in response to gas valve modulations mostly behave smoothly and linearly, with similarities across devices, across scenarios (H-mode, L-mode), injected species, and injection locations. The measurements presented have formed the basis for systematic exhaust control on the considered devices. We now present this database for the essential validation of dynamic exhaust models for reactor design and control.

control↗

Graphite Waste Tank Cleanup and Decontamination under the Marcoule UP1 D and D Program - 13166

The UP1 plant in Marcoule reprocessed nearly 20,000 tons of used natural uranium gas cooled reactor fuel coming from the first generation of civil nuclear reactors in France. During more than 40 years, the decladding operations produced thousands of tons of processed waste, mainly magnesium and graphite fragments. In the absence of a French repository for the graphite waste, the graphite sludge content of the storage pits had to be retrieved and transferred into a newer and safer pit. After an extensive R and D program, the equipment and process necessary for retrieval operations were designed, built and tested. The innovative process is mainly based on the use of two pumps (one to capture and the other one to transfer the sludge) working one after the other and a robotic arm mounted on a telescopic mast. A dedicated process was also set up for the removal of the biggest fragments. The retrieval of the most irradiating fragments was a challenge. Today, the first pit is totally empty and its stainless steel walls have been decontaminated using gels. In the second pit, the sludge retrieval and transfer operations have been almost completed. Most of the non-pumpable graphite fragments has been removed and transferred to a new storage pit. After more than 6 years of operations in sludge retrieval, a lot of experience was acquired from which important 'lessons learned' could be shared. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Visible/near-infrared spectral diversity from in situ observations of the Bagnold Dune Field sands in Gale Crater, Mars

As part of the Bagnold Dune campaign conducted by Mars Science Laboratory rover Curiosity, visible/near–infrared reflectance spectra of dune sands were acquired using Mast Camera (Mastcam) multispectral imaging (445–1013 nm) and Chemistry and Camera (ChemCam) passive point spectroscopy (400–840 nm). By comparing spectra from pristine and rover–disturbed ripple crests and troughs within the dune field, and through analysis of sieved grain size fractions, constraints on mineral segregation from grain sorting could be determined. In general, the dune areas exhibited low relative reflectance, a weak ~530 nm absorption band, an absorption band near 620 nm, and a spectral downturn after ~685 nm consistent with olivine–bearing sands. The finest grain size fractions occurred within ripple troughs and in the subsurface and typically exhibited the strongest ~530 nm bands, highest relative reflectances, and weakest red/near–infrared ratios, consistent with a combination of crystalline and amorphous ferric materials. Coarser–grained samples were the darkest and bluest and exhibited weaker ~530 nm bands, lower relative reflectances, and stronger downturns in the near–infrared, consistent with greater proportions of mafic minerals such as olivine and pyroxene. These grains were typically segregated along ripple crests and among the upper surfaces of grain flows in disturbed sands. Sieved dune sands exhibited progressive decreases in reflectance with increasing grain size, as observed in laboratory spectra of olivine size separates. In conclusion, the continuum of spectral features observed between the coarse– and fine–grained dune sands suggests that mafic grains, ferric materials, and air fall dust mix in variable proportions depending on aeolian activity and grain sorting.

79 ASTRONOMY AND ASTROPHYSICS↗

Factors influencing pregnancy, litter size, and reproductive parameters of invasive wild pigs

Abstract Reproduction is the most energetically expensive life stage with the demands of productivity representing a balance between physiological requirements and environmental conditions. Wild pigs ( Sus scrofa ) throughout most of North America are genetic hybrids of feral domestic pigs and wild boar and have the highest reproductive potential of any wild ungulate. The phenology of reproduction, extent of multiple reproductive events per year, how individual and extrinsic factors contribute to variability in productivity, and impact of genetic lineage on these parameters is not well understood in wild pigs. We quantified reproductive parameters in wild pigs relative to a suite of individual and environmental attributes across seasons and multiple years in South Carolina, USA, from March 2017 and May 2020. We hypothesized that individual attributes (mass, age class, number of teats, rump fat, relative genetic association to wild boar vs. domestic pigs) and extrinsic factors (mast availability) would influence probability of pregnancy and fetal litter size. Wild pigs produced offspring throughout all months with peaks in conception corresponding to a seasonal pulse in food availability. The likelihood of pregnancy was influenced by female mass and nutritional condition and was greatest during years with abundant resources. Similarly, litter size increased with female mass and age, implying larger and older females represent the most important group for population recruitment. In evaluating the relationship between reproductive output and ancestral associations to domestic pigs versus wild boar, the proportion of wild boar ancestry was not an important influence on productivity in our population. We determined juveniles reach a physiological threshold of sexual maturity at approximately 30 kg. Average litter size was comparable to other populations, and wild pigs maintain an average fetal litter size of 5.43 offspring despite 13.6% embryonic mortality. A thorough understanding of biotic and extrinsic factors influencing reproduction are important for realistic population models, which are necessary for identifying areas to focus management needs and implementation.

59 BASIC BIOLOGICAL SCIENCES↗