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Our purpose was to evaluate normal tissue complication probability (NTCP) models for their ability to describe the increase in tolerance as the length of irradiated spinal nerve is reduced in a pig.
Chemoradiation therapy is the standard of care in muscle-invasive bladder cancer (MIBC). Although agents such as gemcitabine can enhance tumor radiosensitivity, their side effects can limit patient eligibility and treatment efficacy. This study investigates ultrasound and microbubbles for targeting gemcitabine delivery to reduce normal-tissue toxicity in a murine orthotopic MIBC model.
Radiation therapy (RT) to the head and neck (H&N) region is critical in the management of various pediatric malignancies; however, it may result in late toxicity. This comprehensive review from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative focused on salivary dysfunction and dental abnormalities in survivors who received RT to the H&N region as children.
Osteoradionecrosis (ORN) of the mandible represents a severe, debilitating complication of radiation therapy (RT) for head and neck cancer (HNC). At present, no normal tissue complication probability (NTCP) models for risk of ORN exist. The aim of this study was to develop a multivariable clinical/dose-based NTCP model for the prediction of ORN any grade (ORN{sub I-IV}) and grade IV (ORN{sub IV}) after RT (±chemotherapy) in patients with HNC.
Preclinical studies using ultra-high dose rate (FLASH) irradiation have demonstrated reduced normal tissue toxicity compared with conventional dose rate (CONV) irradiation, although this finding is not universal. We investigated the effect of temporal pulse structure and average dose rate of FLASH compared with CONV irradiation on acute intestinal toxicity.
Here, the LADTAP II computer code was used to estimate the dose rates to seven nonhuman biota (fish, algae, invertebrate, muskrat, raccoon, heron, and duck) from liquid effluent releases during the normal operations of new light water reactor facilities in the United States. The estimated dose rates to nonhuman biota depended on the nuclear power plant design but were orders of magnitude less than the ‘derived consideration reference levels’ (DCRL) in International Commission on Radiological Protection (ICRP) Publication 108. The estimated dose rates were at least three orders of magnitude lower than the guideline values identified by the International Atomic Energy Agency (IAEA) and the National Council on Radiation Protection and Measurements to cause observable changes in populations of biota. Radionuclides that contributed most of the dose rates for seven nonhuman biota depended on the nuclear power plant design. The differences in the estimated dose rates to seven nonhuman biota calculated from the default bioaccumulation factors used in the LADTAP II computer code and the dose rates calculated from the concentration ratios of radionuclides in the IAEA Technical Report Series (TRS) wildlife handbook were less than one order of magnitude for most default biota in LADTAP. The concentration ratios for some radionuclides in liquid effluent releases from nuclear power plant designs that contributed more than 5% of the internal dose rates for invertebrates (P, and Ru) and algae (La and Pr) were not available in the IAEA TRS wildlife handbook.
To quantify the volumetric effect of delineation variability when using manual versus semiautomated tools to contour the normal bladder on planning computed tomography (CT) and cone beam CT.
High-density fuels have been proposed as a possible replacement for uranium-dioxide as a fuel for light water reactors (LWRs) due to their increased loading of fissionable material. The objectives of this proposal are (1) to increase reactor cycle length and reactor power, and (2) to offset any neutronic penalty associated with advanced cladding systems. Of the high-density fuels under consideration, there is particular interest in triuranium disilicide (U 3 Si 2 ) due to its increased metal density and favorable thermal properties as compared to UO 2 . However, there are concerns regarding the chemical compatibility of U 3 Si 2 with water and steam as used for LWR coolant.This paper summarizes research on fuel-coolant chemical compatibility for UO 2 LWR fuel during a cladding breach and highlights that generally, because of its chemical inertness, UO 2 -coolant reactions are of little consequence to reactor operation. However, the volumetric expansion associated with the reaction of UO 2 and oxygen is a concern for possible conditions encountered during air ingress of dry storage. These same concerns arise for U 3 Si 2 , which exhibits greater volumetric expansion than UO 2 when exposed to water or steam. These reactions ultimately result in increased fuel volume that the cladding must accommodate, as well as additional heat generated as the fuel reacts.The BISON fuel performance code was used to perform a comparative analysis on the behavior of UO 2 and U 3 Si 2 under normal operation. Silicide fuel simulations were then extended to demonstrate how varying thermodynamic and chemical kinetics influence fuel expansion and subsequent cladding performance during a cladding breach. These simulations were further extended to a 3D subsection of a fuel rod to demonstrate the characteristics of the resulting cladding crack.
Some recent studies of rf breakdown physics in cryogenic copper X-band accelerating structures have shown a dramatic increase in the operating gradient while maintaining low breakdown rates. The TOPGUN project, a collaboration between UCLA, SLAC, and INFN, will use this improvement in gradient to create an ultra-high brightness cryogenic normal conducting photoinjector [16]. The brightness is expected to be higher by a factor of 25 relative to the LCLS photogun [9]. This improvement in the brightness will lead to increased performance of X-Ray free electron lasers (FELs) and ultrafast electron diffraction devices [16]. Here, we present the rf design for this S-band photogun, which will be a drop-in replacement for the current LCLS photogun.
High brightness, high repetition rate electron beams are key components for optimizing the performance of next generation scientific instruments, such as MHz-class X-ray Free Electron Laser (XFEL) and Ultra-fast Electron Diffraction/Microscopy (UED/UEM). In the Advanced Photo-injector EXperiment (APEX)at Berkeley Lab, a photoelectron gun based on a 185.7 MHz normal conducting re-entrant RF cavity, has been proven to be a feasible solution to provide high brightness, high repetition rate electron beam for both XFEL and UED/UEM. Based on the success of APEX, a new electron gun system, named APEX2, has been under development to further improve the electron beam brightness. For APEX2, we have designed a new 162.5 MHz two-cell photoelectron gun and achieved a significant increase on the cathode launching field and the beam exit energy. For a fixed charge per bunch, these improvements will allow for the emittance reduction and hence to an increased beam brightness. The design of APEX2 gun cavity is a complex problem with multiple design goals and restrictions, some even competing each other. In conclusion, for a systematic and comprehensive search for the optimized cavity geometry, we have developed and implemented a novel optimization method based on the Multi-Objective Genetic Algorithm (MOGA).
Neutron scattering studies of kinetic processes are often flux limited. For processes which can be repeated many times, this can be mitigated by stroboscopic reintegration. The recorded scattering events are assigned to different time slices of the process and corresponding slices from all repetitions are summed up. The normalization of such data with respect to the incident beam spectrum can be challenging since the incident neutron flux may not necessarily be evenly distributed over all time slices. Here, in this paper, we discuss how this can result in misleading information and we expand on a technique to amend these issues.
Tritiated titanium targets were irradiated by the short-pulse OMEGA EP laser (1.25 kJ, 10 ps) to generate a laser accelerated pulsed beam of tritons by target normal sheath acceleration. Using a Thomson parabola, the beam was found to contain 10 12 tritons per pulse, with a mean energy of 2.2 MeV and an exponential tail reaching up to 10 MeV. In a separate experiment, the triton beam was directed onto a secondary deuterated polyethylene (CD) target to induce deuterium–tritium (D–T) nuclear reactions. Using neutron time-of-flight spectrometers, approximately 10 8 D–T fusion neutrons were observed per laser pulse. Furthermore, this triton beam presents new research opportunities for the study of the 3 H(t, 2n) 4 He reaction and di-neutron transfers to lithium and beryllium that may produce exotic neutron-rich nuclei of interest to basic nuclear science, astrophysics, and inertial confinement fusion technology.
We developed a separation model for deriving the direct normal irradiance (DNI) and the diffuse horizontal irradiance (DHI) from the global tilted irradiance (GTI). The model is based on the DIRINT model, but substitutes the use of the GTI in place of the global horizontal irradiance (GHI) for determining the global clearness index (Kt). Additionally, an iterative method is used to adjust Kt to improve the derived values of the DNI and the DHI. The model is referred to as the GTI-DIRINT model. When using for model input the GTI measured with a pyranometer tilted at a small angle from the horizontal (10°), the deviations between the measured DNI and DHI and the GTI-DIRINT-modeled DNI and DHI were essentially the same as those for the DIRINT model when using the GHI for model input. Increasing the tilt angle from horizontal (as great as 44° for Eugene, Oregon) increased the deviations between the modeled and measured DNI and DHI, but our results were still reasonable. The GTI-DIRINT model provides reasonable values of DNI and DHI from the GTI, and if they are subsequently used with the Perez tilted surface model to model the GTI for orientations within 30° of the azimuth and tilt of the GTI used for model input, the result is as good or better than may be obtained when using a measured DNI and DHI, and without their significant instrumentation cost.
The National Solar Radiation Database (NSRDB) is an extensively used dataset that furnishes satellite-retrieved solar resource data across the United States and an expanding list of other countries. Although the NSRDB uses a physical model to compute global horizontal irradiance (GHI), it currently employs an empirical approach based on surface observations to estimate cloudy-sky direct normal irradiance (DNI). Recently, a new physics-based approach, known as the Fast All-sky Radiation Model for Solar applications with DNI (FARMS-DNI), was developed to improve DNI forecasting. FARMS-DNI integrates direct and scattered solar radiances within the circumsolar region, resulting in improved day-ahead forecasting of DNI by incorporating it into the Weather Research and Forecasting model with Solar extensions (WRF-Solar). This study incorporates FARMS-DNI into the NSRDB algorithm to produce high-spatiotemporal-resolution DNI data from satellite data. The accuracy of the NSRDB based on FARMS-DNI is analyzed using surface observations from 19 sites situated within the National Oceanic and Atmospheric Administration (NOAA) Surface Radiation Budget (SURFRAD) and Solar Radiation (SOLRAD) networks, the University of Oregon (UO) network, the U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) network, and at the National Renewable Energy Laboratory (NREL). The results demonstrate that FARMS-DNI reduces the significant overestimation of DNI in the conventional NSRDB at all surface sites, particularly in cloud overcast conditions classified using both satellite retrievals and surface observations. Consequently, this new model can effectively improve the overall accuracy of the NSRDB. The results also suggest that further improvement of DNI estimates at individual time steps, however, requires advanced satellite techniques and precise identification of clouds and retrieval of cloud properties.
We investigated the associations between environmental exposure to lead and a repertoire of cytokines in seminal plasma of males with normal semen profile according to the WHO criteria. Based on the median lead concentration in seminal plasma, 65 samples were divided into two groups: low (LE) and high exposure to lead (HE). Differences in semen volume and the pH, count, motility and morphology of sperm cells were not observed between the examined groups. The total oxidant status value and the level of protein sulfhydryl groups as well as the activities of manganese superoxide dismutase and catalase were significantly higher in the HE group, whereas the total antioxidant capacity value and the activities of glutathione reductase and glutathione-S-transferase were depressed. IL-7, IL-10, IL-12, and TNF-α levels were significantly higher in the HE group compared with the LE group. Environmental exposure to lead is sufficient to induce oxidative stress in seminal plasma and to modulate antioxidant defense system. - Highlights: • Lead induces oxidative stress in seminal plasma in human. • Lead modulates antioxidant defense system in seminal plasma in human. • Lead does not change a Th1/Th2 imbalance in seminal plasma in human.
Welding fume inhalation causes pulmonary toxicity, including susceptibility to infection. We hypothesized that airway epithelial ion transport is a target of fume toxicity, and investigated the effects of fume particulates from manual metal arc-stainless steel (MMA-SS) and gas metal arc-mild steel (GMA-MS) on ion transport in normal human bronchial epithelium (NHBE) cultured in air-interface. MMA-SS particles, more soluble than GMA-MS particles, contain Cr, Ni, Fe and Mn; GMA-MS particles contain Fe and Mn. MMA-SS or GMA-MS particles (0.0167–166.7 μg/cm{sup 2}) were applied apically to NHBEs. After 18 h transepithelial potential difference (V{sub t}), resistance (R{sub t}), and short circuit current (I{sub sc}) were measured. Particle effects on Na{sup +} and Cl¯ channels and the Na{sup +},K{sup +},2Cl¯-cotransporter were evaluated using amiloride (apical), 5-nitro-2-[(3-phenylpropyl)amino]benzoic acid (NPPB, apical), and bumetanide (basolateral), respectively. MMA-SS (0.0167–16.7 μg/cm{sup 2}) increased basal V{sub t}. Only 16.7 μg/cm{sup 2} GMA-MS increased basal V{sub t} significantly. MMA-SS or GMA-MS exposure potentiated I{sub sc} responses (decreases) to amiloride and bumetanide, while not affecting those to NPPB, GMA-MS to a lesser degree than MMA-SS. Variable effects on R{sub t} were observed in response to amiloride, and bumetanide. Generally, MMA-SS was more potent in altering responses to amiloride and bumetanide than GMA-MS. Hyperpolarization occurred in the absence of LDH release, but decreases in V{sub t}, R{sub t}, and I{sub sc} at higher fume particulate doses accompanied LDH release, to a greater extent for MMA-SS. Thus, Na{sup +} transport and Na{sup +},K{sup +},2Cl¯-cotransport are affected by fume exposure; MMA-MS is more potent than GMA-MS. Enhanced Na{sup +} absorption and decreased airway surface liquid could compromise defenses against infection. - Highlights: • Welding fume particle toxicity was investigated in human bronchial epithelial cells. • MMA-SS fume particles and GMA-MS particles were compared. • Both fumes activated epithelial Na{sup +} channels, MMA-SS more potent than GMA-SS. • MMA-SS is more cytotoxic than GMA-SS with regard to LDH release. • Observed changes may help explain susceptibility to infection in workers.
Hepatitis C virus (HCV) NS5A protein is essential for HCV RNA replication and virus assembly. Here we report the identification of NS5A phosphorylation sites Ser-222, Ser-235 and Thr-348 during an infectious HCV replication cycle and demonstrate that Ser-235 phosphorylation is essential for HCV RNA replication. Confocal microscopy revealed that both phosphoablatant (S235A) and phosphomimetic (S235D) mutants redistribute NS5A to large juxta-nuclear foci that display altered colocalization with known replication complex components. Using electron microscopy (EM) we found that S235D alters virus-induced membrane rearrangements while EM using ‘APEX2’-tagged viruses demonstrated S235D-mediated enrichment of NS5A in irregular membranous foci. Finally, using a customized siRNA screen of candidate NS5A kinases and subsequent analysis using a phospho-specific antibody, we show that phosphatidylinositol-4 kinase III alpha (PI4KIIIα) is important for Ser-235 phosphorylation. We conclude that Ser-235 phosphorylation of NS5A is essential for HCV RNA replication and normal replication complex formation and is regulated by PI4KIIIα. - Highlights: • NS5A residues Ser-222, Ser-235 and Thr-348 are phosphorylated during HCV infection. • Phosphorylation of Ser-235 is essential to HCV RNA replication. • Mutation of Ser-235 alters replication compartment localization and morphology. • Phosphatidylinositol-4 kinase III alpha is important for Ser-235 phosphorylation.
Rap proteins (Rap1, Rap2a, b, c) are small molecular weight GTPases of the Ras family. Rap G proteins mediate diverse cellular events such as cell adhesion, proliferation, and gene activation through various signaling pathways. Activation of Rap signal is regulated tightly by several specific regulatory proteins including guanine nucleotide exchange factors and GTPase-activating proteins. Beyond cell biological studies, increasing attempts have been made in the past decade to define the roles of Rap signal in specific functions of normal tissue systems as well as in cancer. In the immune and hematopoietic systems, Rap signal plays crucial roles in the development and function of essentially all lineages of lymphocytes and hematopoietic cells, and importantly, deregulated Rap signal may lead to unique pathological conditions depending on the affected cell types, including various types of leukemia and autoimmunity. The phenotypical studies have unveiled novel, even unexpected functional aspects of Rap signal in cells from a variety of tissues, providing potentially important clues for controlling human diseases, including malignancy.