FAS Death Receptor: A Breast Cancer Subtype-Specific Radiation Response Biomarker and Potential Therapeutic Target

PubMed Central

Horton, Janet K.; Siamakpour-Reihani, Sharareh; Lee, Chen-Ting; Zhou, Ying; Chen, Wei; Geradts, Joseph; Fels, Diane R.; Hoang, Peter; Ashcraft, Kathleen A.; Groth, Jeff; Kung, Hsiu-Ni; Dewhirst, Mark W.; Chi, Jen-Tsan A.

2015-01-01

Although a standardized approach to radiotherapy has been used to treat breast cancer, regardless of subtype (e.g., luminal, basal), recent clinical data suggest that radiation response may vary significantly among subtypes. We hypothesized that this clinical variability may be due, in part, to differences in cellular radiation response. In this study, we utilized RNA samples for microarray analysis from two sources: 1. Paired pre- and postirradiation breast tumor tissue from 32 early-stage breast cancer patients treated in our unique preoperative radiation Phase I trial; and 2. Sixteen biologically diverse breast tumor cell lines exposed to 0 and 5 Gy irradiation. The transcriptome response to radiation exposure was derived by comparing gene expression in samples before and after irradiation. Genes with the highest coefficient of variation were selected for further evaluation and validated at the RNA and protein level. Gene editing and agonistic antibody treatment were performed to assess the impact of gene modulation on radiation response. Gene expression in our cohort of luminal breast cancer patients was distinctly different before and after irradiation. Further, two distinct patterns of gene expression were observed in our biologically diverse group of breast cancer cell lines pre- versus postirradiation. Cell lines that showed significant change after irradiation were largely luminal subtype, while gene expression in the basal and HER2+ cell lines was minimally impacted. The 100 genes with the most significant response to radiation in patients were identified and analyzed for differential patterns of expression in the radiation-responsive versus nonresponsive cell lines. Fourteen genes were identified as significant, including FAS, a member of the tumor necrosis factor receptor family known to play a critical role in programed cell death. Modulation of FAS in breast cancer cell lines altered radiation response phenotype and enhanced radiation sensitivity in

An evaluation of early countermeasures to reduce the risk of internal radiation exposure after the Fukushima nuclear incident in Japan.

PubMed

Nomura, Shuhei; Tsubokura, Masaharu; Gilmour, Stuart; Hayano, Ryugo S; Watanabe, Yuni N; Kami, Masahiro; Kanazawa, Yukio; Oikawa, Tomoyoshi

2016-05-01

After a radiation-release incident, intake of radionuclides in the initial stage immediately following the incident may be the major contributor to total internal radiation exposure for individuals in affected areas. However, evaluation of early internal contamination risk is greatly lacking. This study assessed the relationship between initial stage evacuation/indoor sheltering and internal radiation contamination levels 4 months after the 2011 Fukushima nuclear incident in Japan and estimated potential pathways of the contamination. The study population comprised 525 participants in the internal radiation screening program at Minamisoma Municipal General Hospital, 23 km north of the Fukushima nuclear plant. The analysed dataset included the results of a screening performed in July 2011, 4 months after the incident, and of a questionnaire on early-incident response behaviours, such as sheltering indoors and evacuations, completed by participants. Association between such early countermeasures and internal contamination levels of cesium-134 were assessed using Tobit multiple regression analyses. Our study shows that individuals who evacuated to areas outside Fukushima Prefecture had similar contamination levels of cesium-134 to individuals who stayed in Fukushima (relative risk: 0.86; 95% confidence interval: 0.74-0.99). Time spent outdoors had no significant relationship with contamination levels. The effects of inhalation from radiological plumes released from the nuclear plant on total internal radiation contamination might be so low as to be undetectable by the whole-body counting unit used to examine participants. Given the apparent limited effectiveness of evacuation and indoor sheltering on internal contamination, the decision to implement such early responses to a radiation-release incident should be made by carefully balancing their potential benefits and health risks. © The Author 2015. Published by Oxford University Press. All rights reserved. For

Early caregiving and physiological stress responses.

PubMed

Luecken, Linda J; Lemery, Kathryn S

2004-05-01

Inadequate early caregiving has been associated with risks of stress-related psychological and physical illness over the life span. Dysregulated physiological stress responses may represent a mechanism linking early caregiving to health outcomes. This paper reviews evidence linking early caregiving to physiological responses that can increase vulnerability to stress-related illness. A number of high-risk family characteristics, including high conflict, divorce, abuse, and parental psychopathology, are considered in the development of stress vulnerability. Three theoretical pathways linking caregiving to physiological stress responses are outlined: genetic, psychosocial, and cognitive-affective. Exciting preliminary evidence suggests that early caregiving can impact long-term physiological stress responses. Directions for future research in this area are suggested.

Minimally Invasive Radiation Biodosimetry and Evaluation of Organ Responses

DTIC Science & Technology

2016-10-01

radiation exposure, potentially leading to Acute Radiation Syndromes (ARS) and Delayed Effects of Acute ...underlying conditions and inherent variations. 2. KEYWORDS Radiation Biodosimetry, Radiation Biomarkers, microRNA, Acute Radiation Syndromes ... syndromes and delayed effects of acute radiation exposure. We expect to identify the circulating miRNA biomarkers as early predictors of late effects

Dynamics of Cellular Responses to Radiation

PubMed Central

Wodarz, Dominik; Sorace, Ron; Komarova, Natalia L.

2014-01-01

Understanding the consequences of exposure to low dose ionizing radiation is an important public health concern. While the risk of low dose radiation has been estimated by extrapolation from data at higher doses according to the linear non-threshold model, it has become clear that cellular responses can be very different at low compared to high radiation doses. Important phenomena in this respect include radioadaptive responses as well as low-dose hyper-radiosensitivity (HRS) and increased radioresistance (IRR). With radioadaptive responses, low dose exposure can protect against subsequent challenges, and two mechanisms have been suggested: an intracellular mechanism, inducing cellular changes as a result of the priming radiation, and induction of a protected state by inter-cellular communication. We use mathematical models to examine the effect of these mechanisms on cellular responses to low dose radiation. We find that the intracellular mechanism can account for the occurrence of radioadaptive responses. Interestingly, the same mechanism can also explain the existence of the HRS and IRR phenomena, and successfully describe experimentally observed dose-response relationships for a variety of cell types. This indicates that different, seemingly unrelated, low dose phenomena might be connected and driven by common core processes. With respect to the inter-cellular communication mechanism, we find that it can also account for the occurrence of radioadaptive responses, indicating redundancy in this respect. The model, however, also suggests that the communication mechanism can be vital for the long term survival of cell populations that are continuously exposed to relatively low levels of radiation, which cannot be achieved with the intracellular mechanism in our model. Experimental tests to address our model predictions are proposed. PMID:24722167

Tissue responses to low protracted doses of high let radiations or photons: Early and late damage relevant to radio-protective countermeasures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ainsworth, E.J.; Afzal, S.M.J.; Crouse, D.A.

1988-01-01

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for ..gamma..-radiation. When total doses of 96 or 247 cGy of neutrons or ..gamma.. rays were givenmore » as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and ..gamma..-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. 63 refs., 6 figs., 7 tabs.« less

Biophysical modelling of early and delayed radiation damage at chromosome level

NASA Astrophysics Data System (ADS)

Andreev, S.; Eidelman, Y.

Exposure by ionising radiation increases cancer risk in human population Cancer is thought to originate from an altered expression of certain number of specific genes It is now widely recognised that chromosome aberrations CA are involved in stable change in expression of genes by gain or loss of their functions Thus CA can contribute to initiation or progression of cancer Therefore understanding mechanisms of CA formation in the course of cancer development might be valuable tool for quantification and prognosis of different stages of radiation carcinogenesis Early CA are defined as aberrations induced in first post-irradiation mitotic cycle The present work describes the original biophysical technique for early CA modelling It includes the following simulation steps the ionising particle track structure the structural organisation of all chromosomes in G 0 G 1 cell nucleus spatial distribution of radiation induced DNA double-strand breaks dsb within chromosomes dsb rejoining and misrejoining modelling cell cycle taking into account mitotic delay which results in complex time dependence of aberrant cells in first mitosis The results on prediction of dose-response curves for simple and complex CA measured in cells undergoing first division cycle are presented in comparison with recent experimental data There is increasing evidence that CA are also observed in descendents of irradiated cells many generations after direct DNA damage These delayed CA or chromosome instability CI are thought to be a manifestation of genome

Activation of Protease Activated Receptor 2 by Exogenous Agonist Exacerbates Early Radiation Injury in Rat Intestine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Junru; Boerma, Marjan; Kulkarni, Ashwini

2010-07-15

Purpose: Protease-activated receptor-2 (PAR{sub 2}) is highly expressed throughout the gut and regulates the inflammatory, mitogenic, fibroproliferative, and nociceptive responses to injury. PAR{sub 2} is strikingly upregulated and exhibits increased activation in response to intestinal irradiation. We examined the mechanistic significance of radiation enteropathy development by assessing the effect of exogenous PAR{sub 2} activation. Methods and Materials: Rat small bowel was exposed to localized single-dose radiation (16.5 Gy). The PAR{sub 2} agonist (2-furoyl-LIGRLO-NH{sub 2}) or vehicle was injected intraperitoneally daily for 3 days before irradiation (before), for 7 days after irradiation (after), or both 3 days before and 7 daysmore » after irradiation (before-after). Early and delayed radiation enteropathy was assessed at 2 and 26 weeks after irradiation using quantitative histologic examination, morphometry, and immunohistochemical analysis. Results: The PAR{sub 2} agonist did not elicit changes in the unirradiated (shielded) intestine. In contrast, in the irradiated intestine procured 2 weeks after irradiation, administration of the PAR{sub 2} agonist was associated with more severe mucosal injury and increased intestinal wall thickness in all three treatment groups (p <.05) compared with the vehicle-treated controls. The PAR{sub 2} agonist also exacerbated the radiation injury score, serosal thickening, and mucosal inflammation (p <.05) in the before and before-after groups. The short-term exogenous activation of PAR{sub 2} did not affect radiation-induced intestinal injury at 26 weeks. Conclusion: The results of the present study support a role for PAR{sub 2} activation in the pathogenesis of early radiation-induced intestinal injury. Pharmacologic PAR{sub 2} antagonists might have the potential to reduce the intestinal side effects of radiotherapy and/or as countermeasures in radiologic accidents or terrorism scenarios.« less

Modeling Early Galaxies Using Radiation Hydrodynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

This simulation uses a flux-limited diffusion solver to explore the radiation hydrodynamics of early galaxies, in particular, the ionizing radiation created by Population III stars. At the time of this rendering, the simulation has evolved to a redshift of 3.5. The simulation volume is 11.2 comoving megaparsecs, and has a uniform grid of 10243 cells, with over 1 billion dark matter and star particles. This animation shows a combined view of the baryon density, dark matter density, radiation energy and emissivity from this simulation. The multi-variate rendering is particularly useful because is shows both the baryonic matter ("normal") and darkmore » matter, and the pressure and temperature variables are properties of only the baryonic matter. Visible in the gas density are "bubbles", or shells, created by the radiation feedback from young stars. Seeing the bubbles from feedback provides confirmation of the physics model implemented. Features such as these are difficult to identify algorithmically, but easily found when viewing the visualization. Simulation was performed on Kraken at the National Institute for Computational Sciences. Visualization was produced using resources of the Argonne Leadership Computing Facility at Argonne National Laboratory.« less

AN ORIENTATIONAL RESPONSE TO WEAK GAMMA RADIATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, F.A. Jr.

1963-10-01

The common planarian worm, Duesia dorotocephsla, displays a significant orientational response to increase in Cs/sup 137/ gamma radiation when the increase is no greater than six times background. The worms are able to distinguish the direction of the weak gamma source, turning away from it, whether it is presented on the right or left side. The response sign is, therefore, the same as that of the response of these negatively phototactic worms to visible light. There is a clear compass-directional relationship of the responsiveness to the experimental gamma radiation. A conspicuous negative response is present when the worms are travelingmore » northward or southward in the earth's field with the gamma change in an east-west axis. No statistically significant mean turning response to the gamma radiation is found when the worms are traveling eastward or westward in the earth's field with the gamma change in a north-south axis. The previously observed annual fluctuation in the character of the monthly orientational rhythm of north-directed worms has been confirmed in an additional year of study. During colder months, the rhythm is monthly; during warmer months it is semi-monthly. There is a semi-monthly fluctuation in the response of Dugesia to weak gamma radiation during mid-morning hours, the worms turning away from the source for four days prior to new end full moon, and toward it for two days following new and full moon. The stronger the field strength, up to 9 times backgound, the larger the amplitude of the rhythm. There is a direct relationship between intensities of gamma radiation between that of background and nine times backgound, and the strength of the negative response of the worms. Evidence suggests that the negative response of Dugesia to a gamma source may be modified by experimental alteration of the natural ambient electrostatic field. Some possible biological significances of this remarkable responsiveness to gamma radiation, and its particular

New Modeling Approaches to Investigate Cell Signaling in Radiation Response

NASA Technical Reports Server (NTRS)

Plante, Ianik; Cucinotta, Francis A.; Ponomarev, Artem L.

2011-01-01

Ionizing radiation damages individual cells and tissues leading to harmful biological effects. Among many radiation-induced lesions, DNA double-strand breaks (DSB) are considered the key precursors of most early and late effects [1] leading to direct mutation or aberrant signal transduction processes. In response to damage, a flow of information is communicated to cells not directly hit by the radiation through signal transduction pathways [2]. Non-targeted effects (NTE), which includes bystander effects and genomic instability in the progeny of irradiated cells and tissues, may be particularly important for space radiation risk assessment [1], because astronauts are exposed to a low fluence of heavy ions and only a small fraction of cells are traversed by an ion. NTE may also have important consequences clinical radiotherapy [3]. In the recent years, new simulation tools and modeling approaches have become available to study the tissue response to radiation. The simulation of signal transduction pathways require many elements such as detailed track structure calculations, a tissue or cell culture model, knowledge of biochemical pathways and Brownian Dynamics (BD) propagators of the signaling molecules in their micro-environment. Recently, the Monte-Carlo simulation code of radiation track structure RITRACKS was used for micro and nano-dosimetry calculations [4]. RITRACKS will be used to calculate the fraction of cells traversed by an ion and delta-rays and the energy deposited in cells in a tissue model. RITRACKS also simulates the formation of chemical species by the radiolysis of water [5], notably the .OH radical. This molecule is implicated in DNA damage and in the activation of the transforming growth factor beta (TGF), a signaling molecule involved in NTE. BD algorithms for a particle near a membrane comprising receptors were also developed and will be used to simulate trajectories of signaling molecules in the micro-environment and characterize autocrine

Stomatal Blue Light Response Is Present in Early Vascular Plants.

PubMed

Doi, Michio; Kitagawa, Yuki; Shimazaki, Ken-ichiro

2015-10-01

Light is a major environmental factor required for stomatal opening. Blue light (BL) induces stomatal opening in higher plants as a signal under the photosynthetic active radiation. The stomatal BL response is not present in the fern species of Polypodiopsida. The acquisition of a stomatal BL response might provide competitive advantages in both the uptake of CO2 and prevention of water loss with the ability to rapidly open and close stomata. We surveyed the stomatal opening in response to strong red light (RL) and weak BL under the RL with gas exchange technique in a diverse selection of plant species from euphyllophytes, including spermatophytes and monilophytes, to lycophytes. We showed the presence of RL-induced stomatal opening in most of these species and found that the BL responses operated in all euphyllophytes except Polypodiopsida. We also confirmed that the stomatal opening in lycophytes, the early vascular plants, is driven by plasma membrane proton-translocating adenosine triphosphatase and K(+) accumulation in guard cells, which is the same mechanism operating in stomata of angiosperms. These results suggest that the early vascular plants respond to both RL and BL and actively regulate stomatal aperture. We also found three plant species that absolutely require BL for both stomatal opening and photosynthetic CO2 fixation, including a gymnosperm, C. revoluta, and the ferns Equisetum hyemale and Psilotum nudum. © 2015 American Society of Plant Biologists. All Rights Reserved.

The radiative heating response to climate change

NASA Astrophysics Data System (ADS)

Maycock, Amanda

2016-04-01

The structure and magnitude of radiative heating rates in the atmosphere can change markedly in response to climate forcings; diagnosing the causes of these changes can aid in understanding parts of the large-scale circulation response to climate change. This study separates the relative drivers of projected changes in longwave and shortwave radiative heating rates over the 21st century into contributions from radiatively active gases, such as carbon dioxide, ozone and water vapour, and from changes in atmospheric and surface temperatures. Results are shown using novel radiative diagnostics applied to timeslice experiments from the UM-UKCA chemistry-climate model; these online estimates are compared to offline radiative transfer calculations. Line-by-line calculations showing spectrally-resolved changes in heating rates due to different gases will also be presented.

Comparison of the early response of human embryonic stem cells and human induced pluripotent stem cells to ionizing radiation.

PubMed

Suchorska, Wiktoria Maria; Augustyniak, Ewelina; Łukjanow, Magdalena

2017-04-01

Despite the well-demonstrated efficacy of stem cell (SC) therapy, this approach has a number of key drawbacks. One important concern is the response of pluripotent SCs to treatment with ionizing radiation (IR), given that SCs used in regenerative medicine will eventually be exposed to IR for diagnostic or treatment‑associated purposes. Therefore, the aim of the present study was to examine and compare early IR‑induced responses of pluripotent SCs to assess their radioresistance and radiosensitivity. In the present study, 3 cell lines; human embryonic SCs (hESCs), human induced pluripotent SCs (hiPSCs) and primary human dermal fibroblasts (PHDFs); were exposed to IR at doses ranging from 0 to 15 gray (Gy). Double strand breaks (DSBs), and the gene expression of the following DNA repair genes were analyzed: P53; RAD51; BRCA2; PRKDC; and XRCC4. hiPSCs demonstrated greater radioresistance, as fewer DSBs were identified, compared with hESCs. Both pluripotent SC lines exhibited distinct gene expression profiles in the most common DNA repair genes that are involved in homologous recombination, non‑homologous end‑joining and enhanced DNA damage response following IR exposure. Although hESCs and hiPSCs are equivalent in terms of capacity for pluripotency and differentiation into 3 germ layers, the results of the present study indicate that these 2 types of SCs differ in gene expression following exposure to IR. Consequently, further research is required to determine whether hiPSCs and hESCs are equally safe for application in clinical practice. The present study contributes to a greater understanding of DNA damage response (DDR) mechanisms activated in pluripotent SCs and may aid in the future development of safe SC‑based clinical protocols.

Accelerated hematopoietic syndrome after radiation doses bridging hematopoietic (H-ARS) and gastrointestinal (GI-ARS) acute radiation syndrome: early hematological changes and systemic inflammatory response syndrome in minipig.

PubMed

Moroni, Maria; Elliott, Thomas B; Deutz, Nicolaas E; Olsen, Cara H; Owens, Rossitsa; Christensen, Christine; Lombardini, Eric D; Whitnall, Mark H

2014-05-01

To characterize acute radiation syndrome (ARS) sequelae at doses intermediate between the bone marrow (H-ARS) and full gastrointestinal (GI-ARS) syndrome. Male minipigs, approximately 5 months old, 9-12 kg in weight, were irradiated with Cobalt-60 (total body, bilateral gamma irradiation, 0.6 Gy/min). Endpoints were 10-day survival, gastrointestinal histology, plasma citrulline, bacterial translocation, vomiting, diarrhea, vital signs, systemic inflammatory response syndrome (SIRS), febrile neutropenia (FN). We exposed animals to doses (2.2-5.0 Gy) above those causing H-ARS (1.6-2.0 Gy), and evaluated development of ARS. Compared to what was observed during H-ARS (historical data: Moroni et al. 2011a , 2011c ), doses above 2 Gy produced signs of increasingly severe pulmonary damage, faster deterioration of clinical conditions, and faster increases in levels of C-reactive protein (CRP). In the range of 4.6-5.0 Gy, animals died by day 9-10; signs of the classic GI syndrome, as measured by diarrhea, vomiting and bacterial translocation, did not occur. At doses above 2 Gy we observed transient reduction in circulating citrulline levels, and animals exhibited earlier depletion of blood elements and faster onset of SIRS and FN. An accelerated hematopoietic subsyndrome (AH-ARS) is observed at radiation doses between those producing H-ARS and GI-ARS. It is characterized by early onset of SIRS and FN, and greater lung damage, compared to H-ARS.

Early Cenozoic radiations in the Antarctic marine realm and their evolutionary implications

NASA Astrophysics Data System (ADS)

Crame, Alistair

2014-05-01

The extensive and very well exposed Late Cretaceous - Early Paleogene sedimentary succession of Seymour Island, NE Antarctic Peninsula presents a unique opportunity to examine Early Cenozoic evolutionary radiations in a variety of macrofaunal taxa. Building on the extensive pioneer studies by US and Argentinian palaeontologists, recent investigations have focused on refining litho-, bio- and chronostratigraphies, and taxonomic revisions to a number of key groups. Within the numerically dominant Mollusca, the balance of faunas changes significantly across the Cretaceous/Paleogene boundary, with gastropods becoming numerically dominant for the first time in the Early Paleocene Sobral Formation (SF). At this level seven of the 31 gastropod genera present (= 23%) can be referred to modern Southern Ocean taxa and the same figure is maintained in the Early Eocene La Meseta Formation (LMF) where 21 of 63 genera are modern. A major reason for the rise of the gastropods in the earliest Cenozoic of Antarctica is a significant radiation of the Neogastropoda, which today forms one of the largest clades in the sea. 50% of the SF gastropod fauna and 53% of the LMF at the species level are neogastropods. This important burst of speciation is linked to a major pulse of global warming from ~63 - 43Ma when warm temperate conditions prevailed for long intervals of time at 65ºS. The marked Early Paleogene radiation of neogastropods in Antarctica represents a distinct pulse of southern high-latitude taxa that was coeval with similar tropical/subtropical radiations in localities such as the US Gulf Coast and NW Europe. Thus it would appear that the Early Cenozoic radiation of this major taxon was truly global in scale and not just confined to one latitudinal belt. Whereas it is possible to regard a significant proportion of the modern bivalve fauna as relicts, and thus Antarctica as an evolutionary refugium, or sink, it is much less easy to do so for the Neogastropoda. At least in the

Information Needs of Older Women With Early-Stage Breast Cancer When Making Radiation Therapy Decisions.

PubMed

Wang, Shi-Yi; Kelly, Gabrielle; Gross, Cary; Killelea, Brigid K; Mougalian, Sarah; Presley, Carolyn; Fraenkel, Liana; Evans, Suzanne B

2017-07-15

To identify the information older women with early-stage breast cancer need when making radiation therapy decisions, and who patients identify as the main decision maker. We surveyed (through face-to-face interview, telephone, or mail) women aged ≥65 years who received lumpectomy and were considering or receiving adjuvant radiation therapy for early-stage breast cancer. The survey instrument was constructed with input from patient and professional advisory committees, including breast cancer survivors, advocates of breast cancer care and aging, clinicians, and researchers. Participants rated the importance (on a 4-point scale) of 24 statements describing the benefits, side effects, impact on daily life, and other issues of radiation therapy in relation to radiation therapy decision making. Participants also designated who was considered the key decision maker. The response rate was 56.4% (93 of 165). Mean age was 72.5 years, ranging from 65 to 93 years. More than 96% of participants indicated they were the main decision maker on receiving radiation therapy. There was wide variation in information needs regarding radiation therapy decision making. Participants rated a mean of 18 (range, 3-24) items as "essential." Participants rated items related to benefits highest, followed by side effects. Participants who were older than 75 years rated 13.9 questions as essential, whereas participants aged ≤74 years rated 18.7 as essential (P=.018). Older women desire information and have more agency and input in the decision-making process than prior literature would suggest. The variation in information needs indicates that future decision support tools should provide options to select what information would be of interest to the participants. Copyright © 2017 Elsevier Inc. All rights reserved.

Radiation Dose-Response Relationships and Risk Assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strom, Daniel J.

The notion of a dose-response relationship was probably invented shortly after the discovery of poisons, the invention of alcoholic beverages, and the bringing of fire into a confined space in the forgotten depths of ancient prehistory. The amount of poison or medicine ingested can easily be observed to affect the behavior, health, or sickness outcome. Threshold effects, such as death, could be easily understood for intoxicants, medicine, and poisons. As Paracelsus (1493-1541), the 'father' of modern toxicology said, 'It is the dose that makes the poison.' Perhaps less obvious is the fact that implicit in such dose-response relationships is alsomore » the notion of dose rate. Usually, the dose is administered fairly acutely, in a single injection, pill, or swallow; a few puffs on a pipe; or a meal of eating or drinking. The same amount of intoxicants, medicine, or poisons administered over a week or month might have little or no observable effect. Thus, before the discovery of ionizing radiation in the late 19th century, toxicology ('the science of poisons') and pharmacology had deeply ingrained notions of dose-response relationships. This chapter demonstrates that the notion of a dose-response relationship for ionizing radiation is hopelessly simplistic from a scientific standpoint. While useful from a policy or regulatory standpoint, dose-response relationships cannot possibly convey enough information to describe the problem from a quantitative view of radiation biology, nor can they address societal values. Three sections of this chapter address the concepts, observations, and theories that contribute to the scientific input to the practice of managing risks from exposure to ionizing radiation. The presentation begins with irradiation regimes, followed by responses to high and low doses of ionizing radiation, and a discussion of how all of this can inform radiation risk management. The knowledge that is really needed for prediction of individual risk is

3D-MR Spectroscopic Imaging at 3Tesla for Early Response Assessment of Glioblastoma Patients during External Beam Radiation Therapy

PubMed Central

Muruganandham, Manickam; Clerkin, Patrick P; Smith, Brian J; Anderson, Carryn M; Morris, Ann; Capizzano, Aristides A; Magnotta, Vincent; McGuire, Sarah M; Smith, Mark C; Bayouth, John E; Buatti, John M

2014-01-01

Purpose To evaluate the utility of 3D-MR proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Methods and Materials Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium enhanced MR images at simulation and at boost treatment planning after 17-20 fractions of radiotherapy. All patients received standard radiotherapy with temozolomide and follow-up with every two month MR scans. Progression free survival was defined using MacDonald criteria. MRSI images obtained at initial simulation were analyzed for choline / N-acetylaspartate ratios (Cho/NAA) on a voxel by voxel basis with abnormal activity defined as Cho/NAA ≥ 2. These images were compared on anatomically matched MRSI data collected after 3 weeks of radiotherapy. Changes in Cho/NAA between pre-therapy and 3rd week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression free survival, radiation dose and location of recurrence using Cox proportional hazards regression. Results After 8.6 months (median follow-up), 50% of patients had progressed based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (p< 0.01). Patients with an increase in mean or median Cho/NAA values at the 3rd week RT scan had a significantly greater chance of early progression (p <0.01). An increased Cho/NAA at the 3rd week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval 1.10-6.71, p= 0.03). Most patients received the prescription dose of RT to the Cho/NAA ≥ 2 volume, which was where recurrence most often occurred. Conclusion Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested. PMID:24986746

[Early mobilization. Competencies, responsibilities, milestones].

PubMed

Nydahl, P; Dewes, M; Dubb, R; Filipovic, S; Hermes, C; Jüttner, F; Kaltwasser, A; Klarmann, S; Klas, K; Mende, H; Rothaug, O; Schuchhardt, D

2016-03-01

Early mobilization is an evident, interprofessional concept to improve the outcome of intensive care patients. It reduces psychocognitive deficits and delirium and attenuates a general deconditioning, including atrophy of the respiratory pump and skeletal muscles. In this regard the interdisciplinary approach of early mobilization, taking into account different levels of mobilization, appears to be beneficial. The purpose of this study was to explore opinions on collaboration and tasks between different professional groups. During the 25th Bremen Conference on Intensive Medicine and Nursing on 20 February 2015, a questionnaire survey was carried out among the 120 participants of the German Early Mobilization Network meeting. In all, 102 questionnaires were analyzed. Most participants reported on the interdisciplinarity of the approach, but none of the tasks and responsibilities concerning early mobilization can be assigned to a single professional group. The practical implementation of mobilizing orally intubated patients may require two registered nurses as well as a physical therapist. Implementation in daily practice seems to be heterogeneous. There is no consensus regarding collaboration, competencies, and responsibilities with respect to early mobilization of intensive care patients. The approach to date has been characterized by a lack of interprofessional communication, which may lead to an inefficient use of the broad and varied base of knowledge and experienceof the different professions.

Diurnal changes in CN metabolism and response of rice seedlings to UV-B radiation.

PubMed

Yun, Hyejin; Lim, Sunhyung; Kim, Yangmin X; Lee, Yejin; Lee, Seulbi; Lee, Deogbae; Park, Keewoong; Sung, Jwakyung

2018-03-13

Plants regulate a number of primary metabolites, including carbohydrates, organic acids, and amino acids, in response to UV-B radiation. Therefore, it is essential to understand the time-dependent response of rice plants to UV-B stress. This study focused on the response of plants to UV-B at different leaf developmental phases (emerging, growing, and maturing) in an attempt to fully comprehend the metabolic shift. We analyzed the expression levels of genes related to starch/sucrose metabolism in the leaf blades of rice seedlings (Oryza sativa L. "Saechuchenog") exposed to UV-B irradiation for short (1 day) and long terms (5 days) using quantitative real-time polymerase chain reaction. We also examined the diurnal variations in the contents of primary metabolites using an established GCTOF-MS (gas chromatography time of flight-mass spectrometry) method. The results showed that the levels of primary metabolites were largely dependent upon the diurnal rhythm and leaf developmental phase. The young leaves (sink) produced and accumulated starch rather than sucrose. The short-term (4 h, 1 day) UV-B exposure inhibited sucrose synthesis, which could be the first target of UV-B radiation. Following short- and long-term (5 days) exposure to UV-B radiation, the dynamic response of primary metabolites was evaluated. It was found that the content of carbohydrates decreased throughout the period of exposure to UV-B stress, especially in terms of sucrose concentration. However, the content of the majority of amino acids increased after an early decrease. Our data revealed that the metabolic response, as well as the gene expression, differed with the period (intensity) of exposure to UV-B radiation and with the phase of leaf development. These findings provide new insights for a better understanding of the metabolic response of a variety of plant species exposed to a wide range of UV-B radiation. Copyright © 2018. Published by Elsevier GmbH.

Interplay of space radiation and microgravity in DNA damage and DNA damage response.

PubMed

Moreno-Villanueva, María; Wong, Michael; Lu, Tao; Zhang, Ye; Wu, Honglu

2017-01-01

In space, multiple unique environmental factors, particularly microgravity and space radiation, pose constant threat to the DNA integrity of living organisms. Specifically, space radiation can cause damage to DNA directly, through the interaction of charged particles with the DNA molecules themselves, or indirectly through the production of free radicals. Although organisms have evolved strategies on Earth to confront such damage, space environmental conditions, especially microgravity, can impact DNA repair resulting in accumulation of severe DNA lesions. Ultimately these lesions, namely double strand breaks, chromosome aberrations, micronucleus formation, or mutations, can increase the risk for adverse health effects, such as cancer. How spaceflight factors affect DNA damage and the DNA damage response has been investigated since the early days of the human space program. Over the years, these experiments have been conducted either in space or using ground-based analogs. This review summarizes the evidence for DNA damage induction by space radiation and/or microgravity as well as spaceflight-related impacts on the DNA damage response. The review also discusses the conflicting results from studies aimed at addressing the question of potential synergies between microgravity and radiation with regard to DNA damage and cellular repair processes. We conclude that further experiments need to be performed in the true space environment in order to address this critical question.

Partial breast radiation for early-stage breast cancer.

PubMed

McCormick, Beryl

2012-02-01

This review is to provide an update on the current status of partial breast irradiation (PBI) for women presenting with early-stage breast cancer, as an alternate radiation technique to fractionated, whole breast radiation, following conservation surgery. As more women are asking for and receiving this treatment, both on and off protocols, understanding recent additions to the literature is important to physicians caring for this patient population. Newly published retrospective studies, with follow-up times out to 10 years and the status of both recently completed and still open large prospective phase III trials will be covered, with emphasis on unexpected side effects reported, and some hypothesis-generating radiobiology observations. A recent consensus treatment guideline for PBI use is also discussed. Selected retrospective studies continue to report outcomes matching those achieved with whole breast radiation; however, results from large prospective randomized trials comparing PBI to whole breast radiation have been reported only with short follow-up times, or in two studies, are still pending. A recent consensus guideline is useful at present in selecting patients for discussion of this treatment.

Practice Patterns of Radiation Field Design for Sentinel Lymph Node-Positive Early-Stage Breast Cancer.

PubMed

Azghadi, Soheila; Daly, Megan; Mayadev, Jyoti

2016-10-01

Recent randomized trials have led to decreased use of completion axillary lymph node dissection (ALND) in early-stage breast cancer patients with a positive sentinel lymph node (SLN), causing controversy surrounding radiotherapy coverage of the axilla. We investigated the practice variation among radiation oncologists for regional nodal coverage for clinicopathologic scenarios and evaluated axillary field design decision-making processes. A customized, web-based questionnaire was e-mailed to 983 community (n = 617) and academic (n = 366) radiation oncologists with a breast cancer subspecialty practicing in the United States. The survey consisted of 18 multiple-choice questions evaluating general clinical preferences surrounding radiation therapy (RT) field design for patients with early-stage breast cancer and a positive SLN. Seven case scenarios were developed to investigate the field design in the setting of specific clinical and pathologic risk factors. Nodal coverage was classified as standard tangents (STs), high tangents (HTs), STs and a supraclavicular field (SCF), or STs and full axillary coverage (AX). A total of 145 evaluable responses were collected, with a response rate of 15.0%. Of the respondents, 12 (8.3%) reported using completion ALND for patients with 1 to 3 positive SLNs without extracapsular extension (ECE) and 66 (45.5%) performed ALND with 1 to 3 positive SLNs with ECE. For micrometastatic SLNs, with no lymphovascular system invasion, 115 (87.1%) used STs or HTs. The use of neoadjuvant chemotherapy (NAC) influenced RT field design for patients with a positive SLN without ECE, with 64 (48.5%) using STs and SCF or STs and AX treatment without NAC and 94 (70.7%) using SCF and AX after NAC. With macrometastatic SLN involvement, most respondents preferred SCF (45.27%) and AX (45.66%). In contrast, for micrometastatic involvement, HTs (43.61%) were frequently chosen. Forty (27.8%) reported using online predictive nomograms to predict further

Tissue responses to low protracted doses of high let radiations or photons - Early and late damage relevant to radio-protective countermeasures

NASA Technical Reports Server (NTRS)

Ainsworth, E. J.; Afzal, S. M. J.; Crouse, D. A.; Hanson, W. R.; Fry, R. J. M.

1989-01-01

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

Stress induction in the bacteria Shewanella oneidensis and Deinococcus radiodurans in response to below-background ionizing radiation.

PubMed

Castillo, Hugo; Schoderbek, Donald; Dulal, Santosh; Escobar, Gabriela; Wood, Jeffrey; Nelson, Roger; Smith, Geoffrey

2015-01-01

The 'Linear no-threshold' (LNT) model predicts that any amount of radiation increases the risk of organisms to accumulate negative effects. Several studies at below background radiation levels (4.5-11.4 nGy h(-1)) show decreased growth rates and an increased susceptibility to oxidative stress. The purpose of our study is to obtain molecular evidence of a stress response in Shewanella oneidensis and Deinococcus radiodurans grown at a gamma dose rate of 0.16 nGy h(-1), about 400 times less than normal background radiation. Bacteria cultures were grown at a dose rate of 0.16 or 71.3 nGy h(-1) gamma irradiation. Total RNA was extracted from samples at early-exponential and stationary phases for the rt-PCR relative quantification (radiation-deprived treatment/background radiation control) of the stress-related genes katB (catalase), recA (recombinase), oxyR (oxidative stress transcriptional regulator), lexA (SOS regulon transcriptional repressor), dnaK (heat shock protein 70) and SOA0154 (putative heavy metal efflux pump). Deprivation of normal levels of radiation caused a reduction in growth of both bacterial species, accompanied by the upregulation of katB, recA, SOA0154 genes in S. oneidensis and the upregulation of dnaK in D. radiodurans. When cells were returned to background radiation levels, growth rates recovered and the stress response dissipated. Our results indicate that below-background levels of radiation inhibited growth and elicited a stress response in two species of bacteria, contrary to the LNT model prediction.

Radiation-induced immune responses: mechanisms and therapeutic perspectives.

PubMed

Jeong, Hoibin; Bok, Seoyeon; Hong, Beom-Ju; Choi, Hyung-Seok; Ahn, G-One

2016-09-01

Recent advancement in the radiotherapy technology has allowed conformal delivery of high doses of ionizing radiation precisely to the tumors while sparing large volume of the normal tissues, which have led to better clinical responses. Despite this technological advancement many advanced tumors often recur and they do so within the previously irradiated regions. How could tumors recur after receiving such high ablative doses of radiation? In this review, we outlined how radiation can elicit anti-tumor responses by introducing some of the cytokines that can be induced by ionizing radiation. We then discuss how tumor hypoxia, a major limiting factor responsible for failure of radiotherapy, may also negatively impact the anti-tumor responses. In addition, we highlight how there may be other populations of immune cells including regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that can be recruited to tumors interfering with the anti-tumor immunity. Finally, the impact of irradiation on tumor hypoxia and the immune responses according to different radiotherapy regimen is also delineated. It is indeed an exciting time to see that radiotherapy is being combined with immunotherapy in the clinic and we hope that this review can add an excitement to the field.

SU-F-R-54: CT-Texture Based Early Tumor Treatment Response Assessment During Radiation Therapy Delivery: Small Cell Versus Non-Small Cell Lung Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paul, J; Gore, E; Li, X

Purpose: Tumor treatment response may potentially be assessed during radiation therapy (RT) by analyzing changes in CT-textures. We investigated the different early RT-responses between small cell (SCLC) and non-small cell lung cancer (NSCLC) as assessed by CT-texture. Methods: Daily diagnostic-quality CT acquired during routine CT-guided RT using a CT-on-Rails for 13-NSCLC and 5-SCLC patients were analyzed. These patient had ages ranging from 45–78 and 38–63 years, respectively, for NSCLC and SCLC groups, and tumor-stages ranging from T2-T4, and were treated with either RT or chemotherapy and RT with 45–66Gy/ 20–34 fractions. Gross-tumor volume (GTV) contour was generated on each dailymore » CT by populating GTV contour from simulation to daily CTs with manual editing if necessary. CT-texture parameters, such as Hounsfield Unit (HU) histogram, mean HU, skewness, kurtosis, entropy, and short-run high-gray level emphasis (SRHGLE), were calculated in GTV from each daily CT-set using an in house software tool. Difference in changes of these texture parameters during RT between NSCLC and SCLC was analyzed and compared with GTV volume changes. Results: Radiation-induced changes in CT-texture were different between SCLC and NSCLC. Average changes from first to the last fractions for NSCLC and SCLC in GTV were 28±10(12–44) and 30±15(11–47) HU (mean HU reduction), 12.7% and 18.3% (entropy), 50% and 55% (SRHGLE), 19% and 22% (kurtosis), and 5.2% and 22% (skewness), respectively. Good correlation in kurtosis changes and GTV was seen (R{sup 2}=0.8923) for SCLC, but not for NSCLC (R{sup 2}=0.4748). SCLC had better correlations between GTV volume reduction and entropy (SCLC R{sup 2}=0.847; NSCLC R{sup 2}=0.6485), skewness (SCLC R{sup 2}=0.935; NSCLC R{sup 2}=0.7666), or SRHGLE (SCLC R{sup 2}=0.9619; NSCLC R{sup 2}=0.787). Conclusion: NSCLC and SCLC exhibited different early RT-responses as assessed by CT-texture changes during RT-delivery. The observed larger

Sacramento Regional Response Guide to Radiation Emergencies

DTIC Science & Technology

2006-09-01

emergency operations. Additionally, the utilization of thermo luminescence dosimeters ( TLD ) may be beneficial to track long term exposure for...a radiation area. Stakeholder agency emergency response equipment have been issued electronic dosimeters The purpose of the radiation dosimeter is...Incident.............................................................................84 2. Detection/ Dosimeter Equipment

Monitoring tumor response of prostate cancer to radiation therapy by multi-parametric 1H and hyperpolarized 13C magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Zhang, Vickie Yi

Radiation therapy is one of the most common curative therapies for patients with localized prostate cancer, but despite excellent success rates, a significant number of patients suffer post- treatment cancer recurrence. The accurate characterization of early tumor response remains a major challenge for the clinical management of these patients. Multi-parametric MRI/1H MR spectroscopy imaging (MRSI) has been shown to increase the diagnostic performance in evaluating the effectiveness of radiation therapy. 1H MRSI can detect altered metabolic profiles in cancerous tissue. In this project, the concentrations of prostate metabolites from snap-frozen biopsies of recurrent cancer after failed radiation therapy were correlated with histopathological findings to identify quantitative biomarkers that predict for residual aggressive versus indolent cancer. The total choline to creatine ratio was significantly higher in recurrent aggressive versus indolent cancer, suggesting that use of a higher threshold tCho/Cr ratio in future in vivo 1H MRSI studies could improve the selection and therapeutic planning for patients after failed radiation therapy. Varying radiation doses may cause a diverse effect on prostate cancer micro-environment and metabolism, which could hold the key to improving treatment protocols for individual patients. The recent development and clinical translation of hyperpolarized 13C MRI have provided the ability to monitor both changes in the tumor micro-environment and its metabolism using a multi-probe approach, [1-13C]pyruvate and 13C urea, combined with 1H Multi-parametric MRI. In this thesis, hyperpolarized 13C MRI, 1H dynamic contrast enhancement, and diffusion weighted imaging were used to identify early radiation dose response in a transgenic prostate cancer model. Hyperpolarized pyruvate to lactate metabolism significantly decreased in a dose dependent fashion by 1 day after radiation therapy, prior to any changes observed using 1H DCE and diffusion

Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes.

PubMed

López, Escarlata; Guerrero, Rosario; Núñez, Maria Isabel; del Moral, Rosario; Villalobos, Mercedes; Martínez-Galán, Joaquina; Valenzuela, Maria Teresa; Muñoz-Gámez, José Antonio; Oliver, Francisco Javier; Martín-Oliva, David; Ruiz de Almodóvar, José Mariano

2005-01-01

Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects. Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments. Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects. After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify

Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes

PubMed Central

López, Escarlata; Guerrero, Rosario; Núñez, Maria Isabel; del Moral, Rosario; Villalobos, Mercedes; Martínez-Galán, Joaquina; Valenzuela, Maria Teresa; Muñoz-Gámez, José Antonio; Oliver, Francisco Javier; Martín-Oliva, David; de Almodóvar, José Mariano Ruiz

2005-01-01

Introduction Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects. Methods Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments. Results Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects. Conclusion After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity

Radiation-induced genomic instability: radiation quality and dose response

NASA Technical Reports Server (NTRS)

Smith, Leslie E.; Nagar, Shruti; Kim, Grace J.; Morgan, William F.

2003-01-01

Genomic instability is a term used to describe a phenomenon that results in the accumulation of multiple changes required to convert a stable genome of a normal cell to an unstable genome characteristic of a tumor. There has been considerable recent debate concerning the importance of genomic instability in human cancer and its temporal occurrence in the carcinogenic process. Radiation is capable of inducing genomic instability in mammalian cells and instability is thought to be the driving force responsible for radiation carcinogenesis. Genomic instability is characterized by a large collection of diverse endpoints that include large-scale chromosomal rearrangements and aberrations, amplification of genetic material, aneuploidy, micronucleus formation, microsatellite instability, and gene mutation. The capacity of radiation to induce genomic instability depends to a large extent on radiation quality or linear energy transfer (LET) and dose. There appears to be a low dose threshold effect with low LET, beyond which no additional genomic instability is induced. Low doses of both high and low LET radiation are capable of inducing this phenomenon. This report reviews data concerning dose rate effects of high and low LET radiation and their capacity to induce genomic instability assayed by chromosomal aberrations, delayed lethal mutations, micronuclei and apoptosis.

Influence of ionizing radiation on the immune response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brocadeszaalberg, O.

1974-01-01

The effects of ionizing radiation on the immune response are reviewed. Following an introduction on the function of the immune apparatus, the effect of radiation in the different cell types of the immune system is described. The possible consequences of these effects on the prognosis of radiation victims are discussed. (GRA)

Challenges for Early Responders to a Nuclear / Radiological Terrorism Incident

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wells, M.A.; Stearns, L.J.; Davie, A.D.

2007-07-01

Even in the best of circumstances, most municipalities would face severe challenges in providing effective incident response to a large scale radiation release caused by nuclear terrorism or accident. Compounding obvious complexities, the effectiveness of first and early responders to a radiological emergency may also be hampered by an insufficient distribution of radiation detection and monitoring equipment, local policies concerning triage and field decontamination of critical victims, malfunctioning communications, inadequate inter-agency agility, and the psychological 'fear' impact on early responders. This paper examines several issues impeding the early response to nuclear terrorism incidents with specific consideration given to the on-goingmore » and forward-thinking preparedness efforts currently being developed in the Sacramento, California region. Specific recommendations are provided addressing hot zone protocols, radiation detection and monitoring equipment, hasty patient packaging techniques, vertically and horizontally integrated pre-event training, mitigating psychological fear, and protocols for the effective 'hand-off' from first responders to subsequent early response-recovery teams. (authors)« less

New clade of enigmatic early archosaurs yields insights into early pseudosuchian phylogeny and the biogeography of the archosaur radiation

PubMed Central

2014-01-01

Background The origin and early radiation of archosaurs and closely related taxa (Archosauriformes) during the Triassic was a critical event in the evolutionary history of tetrapods. This radiation led to the dinosaur-dominated ecosystems of the Jurassic and Cretaceous, and the high present-day archosaur diversity that includes around 10,000 bird and crocodylian species. The timing and dynamics of this evolutionary radiation are currently obscured by the poorly constrained phylogenetic positions of several key early archosauriform taxa, including several species from the Middle Triassic of Argentina (Gracilisuchus stipanicicorum) and China (Turfanosuchus dabanensis, Yonghesuchus sangbiensis). These species act as unstable ‘wildcards’ in morphological phylogenetic analyses, reducing phylogenetic resolution. Results We present new anatomical data for the type specimens of G. stipanicicorum, T. dabanensis, and Y. sangbiensis, and carry out a new morphological phylogenetic analysis of early archosaur relationships. Our results indicate that these three previously enigmatic taxa form a well-supported clade of Middle Triassic archosaurs that we refer to as Gracilisuchidae. Gracilisuchidae is placed basally within Suchia, among the pseudosuchian (crocodile-line) archosaurs. The approximately contemporaneous and morphologically similar G. stipanicicorum and Y. sangbiensis may be sister taxa within Gracilisuchidae. Conclusions Our results provide increased resolution of the previously poorly constrained relationships of early archosaurs, with increased levels of phylogenetic support for several key early pseudosuchian clades. Moreover, they falsify previous hypotheses suggesting that T. dabanensis and Y. sangbiensis are not members of the archosaur crown group. The recognition of Gracilisuchidae provides further support for a rapid phylogenetic diversification of crown archosaurs by the Middle Triassic. The disjunct distribution of the gracilisuchid clade in China and

New clade of enigmatic early archosaurs yields insights into early pseudosuchian phylogeny and the biogeography of the archosaur radiation.

PubMed

Butler, Richard J; Sullivan, Corwin; Ezcurra, Martín D; Liu, Jun; Lecuona, Agustina; Sookias, Roland B

2014-06-10

The origin and early radiation of archosaurs and closely related taxa (Archosauriformes) during the Triassic was a critical event in the evolutionary history of tetrapods. This radiation led to the dinosaur-dominated ecosystems of the Jurassic and Cretaceous, and the high present-day archosaur diversity that includes around 10,000 bird and crocodylian species. The timing and dynamics of this evolutionary radiation are currently obscured by the poorly constrained phylogenetic positions of several key early archosauriform taxa, including several species from the Middle Triassic of Argentina (Gracilisuchus stipanicicorum) and China (Turfanosuchus dabanensis, Yonghesuchus sangbiensis). These species act as unstable 'wildcards' in morphological phylogenetic analyses, reducing phylogenetic resolution. We present new anatomical data for the type specimens of G. stipanicicorum, T. dabanensis, and Y. sangbiensis, and carry out a new morphological phylogenetic analysis of early archosaur relationships. Our results indicate that these three previously enigmatic taxa form a well-supported clade of Middle Triassic archosaurs that we refer to as Gracilisuchidae. Gracilisuchidae is placed basally within Suchia, among the pseudosuchian (crocodile-line) archosaurs. The approximately contemporaneous and morphologically similar G. stipanicicorum and Y. sangbiensis may be sister taxa within Gracilisuchidae. Our results provide increased resolution of the previously poorly constrained relationships of early archosaurs, with increased levels of phylogenetic support for several key early pseudosuchian clades. Moreover, they falsify previous hypotheses suggesting that T. dabanensis and Y. sangbiensis are not members of the archosaur crown group. The recognition of Gracilisuchidae provides further support for a rapid phylogenetic diversification of crown archosaurs by the Middle Triassic. The disjunct distribution of the gracilisuchid clade in China and Argentina demonstrates that early

Early and Late Damages in Chromosome 3 of Human Lymphocytes After Radiation Exposure

NASA Technical Reports Server (NTRS)

Sunagawa, Mayumi; Mangala, Lingegowda; Zhang, Ye; Kahdim, Munira; Wilson, Bobby; Cucinotta, Francis A.; Wu, Honglu

2011-01-01

Tumor formation in humans or animals is a multi-step process. An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. GI is defined as elevated or persistent genetic damages occurring many generations after the cells are exposed. While early studies have demonstrated radiation-induced GI in several cell types as detected in endpoints such as mutation, apoptosis and damages in chromosomes, the dependence of GI on the quality of radiation remains uncertain. To investigate GI in human lymphocytes induced by both low- and high-LET radiation, we initially exposed white blood cells collected from healthy subjects to gamma rays in vitro, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis post irradiation and at several intervals during the culture period. Among a number of biological endpoints planned for the project, the multi-color banding fluorescent in situ hybridization (mBAND) allows identification of inversions that were expected to be stable. We present here early and late chromosome aberrations detected with mBAND in chromosome 3 after gamma exposure. Comparison of chromosome damages in between human lymphocytes and human epithelial cells is also discussed

Solar Radiation as Driving Force In Early Evolution

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.; Peterson, David L. (Technical Monitor)

2002-01-01

Ultraviolet radiation (UVR) has provided an evolutionary challenge to life on Earth in that it is both an agent of mutation and as well as a selective force. Today surface fluxes of UVR vary diurnally, seasonally, etc. Still, the UVR flux was probably substantially higher during the early phases of evolution, suggesting that its role in evolution was even more prominent during this time. In this presentation, the creative role of UVR in evolution is discussed, specifically in connection with the role that UVR may have played in the evolution of early microbial ecosystems. The presentation will include discussions of the direct influence of UVR on such processes as photosynthesis and genetic damage, as well as the indirect influence of UVR as mediated through the production of reactive oxygen species. These biological effects of UVR will be viewed against the backdrop of the physical nature of the early Earth, surely a very different place then than now.

Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

PubMed Central

Bakkal, B.H.; Gultekin, F.A.; Guven, B.; Turkcu, U.O.; Bektas, S.; Can, M.

2013-01-01

Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage. PMID:23969972

Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer's disease.

PubMed

Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J

2009-01-01

Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy and environmental nuclear contamination as well as for Earth-orbit and space missions. Analyses of transcriptome profiles of mouse brain tissue after whole-body irradiation showed that low-dose exposures (10 cGy) induced genes not affected by high-dose radiation (2 Gy) and that low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues and pathways that were specific for brain tissue. Low-dose genes clustered into a saturated network (P < 10(-53)) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified nine neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose irradiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down-regulated in normal human aging and Alzheimer's disease.

Radiation, Inflammation, and Immune Responses in Cancer

PubMed Central

Multhoff, Gabriele; Radons, Jürgen

2012-01-01

Chronic inflammation has emerged as one of the hallmarks of cancer. Inflammation also plays a pivotal role in modulating radiation responsiveness of tumors. As discussed in this review, ionizing radiation (IR) leads to activation of several transcription factors modulating the expression of numerous mediators in tumor cells and cells of the microenvironment promoting cancer development. Novel therapeutic approaches thus aim to interfere with the activity or expression of these factors, either in single-agent or combinatorial treatment or as supplements of the existing therapeutic concepts. Among them, NF-κB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. A great variety of classical or novel drugs including nutraceuticals such as plant phytochemicals have the capacity to interfere with the inflammatory network in cancer and are considered as putative radiosensitizers. Thus, targeting the inflammatory signaling pathways induced by IR offers the opportunity to improve the clinical outcome of radiation therapy by enhancing radiosensitivity and decreasing putative metabolic effects. Since inflammation and sex steroids also impact tumorigenesis, a therapeutic approach targeting glucocorticoid receptors and radiation-induced production of tumorigenic factors might be effective in sensitizing certain tumors to IR. PMID:22675673

microRNA-451a regulates colorectal cancer proliferation in response to radiation.

PubMed

Ruhl, Rebecca; Rana, Shushan; Kelley, Katherine; Espinosa-Diez, Cristina; Hudson, Clayton; Lanciault, Christian; Thomas, Charles R; Liana Tsikitis, V; Anand, Sudarshan

2018-05-03

Colorectal cancer (CRC) is a leading cause of cancer-related death. The biologic response of CRC to standard of care adjuvant therapies such as chemotherapy and radiation are poorly understood. MicroRNAs (miRs) have been shown to affect CRC progression and metastasis. Therefore, we hypothesized that specific miRs modulate CRC response to chemoradiation. In this study, we used miR expression profiling and discovered a set of microRNAs upregulated rapidly in response to either a single 2 Gy dose fraction or a 10 Gy dose of γ-radiation in mouse colorectal carcinoma models. We used gain and loss-of-function studies in 2D and 3Dcell proliferation assays and colony formation assays to understand the role of the top miR candidate from our profiling. We used Student's T-tests for simple comparisons and two-factor ANOVA for evaluating significance. The most upregulated candidate at early time points in our signature, miR-451a inhibited tumor cell proliferation and attenuated surviving fraction in longer-term cultures. Conversely, inhibition of miR-451a increased proliferation, tumorsphere formation, and surviving fraction of tumor cells. Using a bioinformatics approach, we identified four genes, CAB39, EMSY, MEX3C, and EREG, as targets of miR-451a. Transfection of miR-451a decreased both mRNA and protein levels of these targets. Importantly, we found miR-451a expression was high and CAB39, EMSY levels were low in a small subset of rectal cancer patients who had a partial response to chemoradiation when compared to patients that had no response. Finally, analysis of a TCGA colorectal cancer dataset revealed that CAB39 and EMSY are upregulated at the protein level in a significant number of CRC patients. Higher levels of CAB39 and EMSY correlated with poorer overall survival. Taken together, our data indicates miR-451a is induced by radiation and may influence colorectal carcinoma proliferation via CAB39 and EMSY pathways.

MicroRNA-Related DNA Repair/Cell-Cycle Genes Independently Associated With Relapse After Radiation Therapy for Early Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gee, Harriet E., E-mail: harriet.gee@sydney.edu.au; The Chris O'Brien Lifehouse, Missenden Road, Camperdown, NSW; Central Clinical School, Sydney Medical School, University of Sydney, NSW

Purpose: Local recurrence and distant failure after adjuvant radiation therapy for breast cancer remain significant clinical problems, incompletely predicted by conventional clinicopathologic markers. We had previously identified microRNA-139-5p and microRNA-1274a as key regulators of breast cancer radiation response in vitro. The purpose of this study was to investigate standard clinicopathologic markers of local recurrence in a contemporary series and to establish whether putative target genes of microRNAs involved in DNA repair and cell cycle control could better predict radiation therapy response in vivo. Methods and Materials: With institutional ethics board approval, local recurrence was measured in a contemporary, prospectively collected series ofmore » 458 patients treated with radiation therapy after breast-conserving surgery. Additionally, independent publicly available mRNA/microRNA microarray expression datasets totaling >1000 early-stage breast cancer patients, treated with adjuvant radiation therapy, with >10 years of follow-up, were analyzed. The expression of putative microRNA target biomarkers—TOP2A, POLQ, RAD54L, SKP2, PLK2, and RAG1—were correlated with standard clinicopathologic variables using 2-sided nonparametric tests, and to local/distant relapse and survival using Kaplan-Meier and Cox regression analysis. Results: We found a low rate of isolated local recurrence (1.95%) in our modern series, and that few clinicopathologic variables (such as lymphovascular invasion) were significantly predictive. In multiple independent datasets (n>1000), however, high expression of RAD54L, TOP2A, POLQ, and SKP2 significantly correlated with local recurrence, survival, or both in univariate and multivariate analyses (P<.001). Low RAG1 expression significantly correlated with local recurrence (multivariate, P=.008). Additionally, RAD54L, SKP2, and PLK2 may be predictive, being prognostic in radiation therapy–treated patients but not in untreated

Radiative transfer in CO2-rich atmospheres: 1. Collisional line mixing implies a colder early Mars

NASA Astrophysics Data System (ADS)

Ozak, N.; Aharonson, O.; Halevy, I.

2016-06-01

Fast and accurate radiative transfer methods are essential for modeling CO2-rich atmospheres, relevant to the climate of early Earth and Mars, present-day Venus, and some exoplanets. Although such models already exist, their accuracy may be improved as better theoretical and experimental constraints become available. Here we develop a unidimensional radiative transfer code for CO2-rich atmospheres, using the correlated k approach and with a focus on modeling early Mars. Our model differs from existing models in that it includes the effects of CO2 collisional line mixing in the calculation of the line-by-line absorption coefficients. Inclusion of these effects results in model atmospheres that are more transparent to infrared radiation and, therefore, in colder surface temperatures at radiative-convective equilibrium, compared with results of previous studies. Inclusion of water vapor in the model atmosphere results in negligible warming due to the low atmospheric temperatures under a weaker early Sun, which translate into climatically unimportant concentrations of water vapor. Overall, the results imply that sustained warmth on early Mars would not have been possible with an atmosphere containing only CO2 and water vapor, suggesting that other components of the early Martian climate system are missing from current models or that warm conditions were not long lived.

Oligodendroglial response to ionizing radiation: Dose and dose-rate response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levy, R.P.

1991-12-01

An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute {gamma}-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DICmore » 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain.« less

Oligodendroglial response to ionizing radiation: Dose and dose-rate response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levy, Richard P.

1991-12-01

An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute γ-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DICmore » 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain.« less

Radiation environment and shielding for early manned Mars missions

NASA Technical Reports Server (NTRS)

Hall, Stephen B.; Mccann, Michael E.

1986-01-01

The problem of shielding a crew during early manned Mars missions is discussed. Requirements for shielding are presented in the context of current astronaut exposure limits, natural ionizing radiation sources, and shielding inherent in a particular Mars vehicle configuration. An estimated range for shielding weight is presented based on the worst solar flare dose, mission duration, and inherent vehicle shielding.

Exploratory Investigation of Early Biomarkers for Chronic Fatigue in Prostate Cancer Patients Following Radiation Therapy

PubMed Central

Feng, Li Rebekah; Wolff, Brian S.; Lukkahatai, Nada; Espina, Alexandra; Saligan, Leorey N.

2016-01-01

Background Fatigue is one of the most debilitating side effects of cancer therapy. Identifying biomarkers early during cancer therapy may help us understand the biologic underpinnings of the persistence of fatigue following therapy. Objective We aimed to identify early biomarkers of fatigue by examining correlations of levels of cytokines during external beam radiation therapy (EBRT) with persistence of fatigue one year following treatment completion in men with non-metastatic prostate cancer (NM-PC). Methods A sample of 34 men with NM-PC scheduled to receive EBRT were followed at baseline (T1), midpoint of EBRT (T2), and one year following EBRT (T3). Demographic and clinical data were obtained by chart review. The Functional Assessment of Cancer Therapy-Fatigue (FACT-F) was administered to measure fatigue levels. Plasma cytokine levels were determined at T1 and T2 using the Bio-Rad Bio-Plex Cytokine Assay Kits. Results Significant correlations were observed between levels of IL-3, IL-8, IL-9, IL-10, IL-16, IP10, IFNα2, IFNγ, and SDF1α at T2 with worsening of fatigue from T1 to T3. Conclusions Immunological changes prior to chronic fatigue development may reflect the long term response to radiation therapy-induced damage. Implications for Practice Early biomarkers for chronic fatigue related to cancer therapy will help advance our understanding of the etiology of this distressing symptom and will help nurses identify patients at risk for developing chronic fatigue after cancer treatment. This information will also aide in patient education, as well as symptom management. PMID:27105468

SU-E-J-274: Responses of Medulloblastoma Cells to Radiation Dosimetric Parameters in Intensity-Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, J; Molecular Imaging Program at Stanford, Stanford, CA; Bio-X Program, Stanford, CA

2015-06-15

Purpose: To evaluate radiation responses of the medulloblastoma cell line Daoy in intensity-modulated radiation therapy (IMRT), quantitative variations to variable radiation dosimetic parameters were tracked by bioluminescent images (BLIs). Methods: The luciferase and green fluorescent protein positive Daoy cells were cultured on dishes. The medulloblastoma cells irradiated to different dose rate, interval of fractionated doses, field margin and misalignment, and dose uniformity in IMRT were monitored using bioluminescent images. The cultured cells were placed into a dedicated acrylic phantom to deliver intensity-modulated fluences and calculate accurate predicted dose distribution. The radiation with dose rate from 0.5 Gy/min to 15 Gy/minmore » was irradiated by adjusting monitor unit per minute and source-to-surface distances. The intervals of fractionated dose delivery were changed considering the repair time of double strand breaks (DSB) revealed by straining of gamma-H2AX.The effect of non-uniform doses on the cells were visualized by registering dose distributions and BLIs. The viability according to dosimetric parameters was correlated with bioluminescent intensities for cross-check of radiation responses. Results: The DSB and cell responses due to the first fractionated dose delivery significantly affected final tumor control rather than other parameters. The missing tumor volumes due to the smaller field margin than the tumor periphery or field misalignment caused relapse of cell responses on BLIs. The dose rate and gradient had effect on initial responses but could not bring out the distinguishable killing effect on cancer cells. Conclusion: Visualized and quantified bioluminescent images were useful to correlate the dose distributions with spatial radiation effects on cells. This would derive the effective combination of dose delivery parameters and fractionation. Radiation responses in particular IMRT configuration could be reflected to image based

MOSFET and MOS capacitor responses to ionizing radiation

NASA Technical Reports Server (NTRS)

Benedetto, J. M.; Boesch, H. E., Jr.

1984-01-01

The ionizing radiation responses of metal oxide semiconductor (MOS) field-effect transistors (FETs) and MOS capacitors are compared. It is shown that the radiation-induced threshold voltage shift correlates closely with the shift in the MOS capacitor inversion voltage. The radiation-induced interface-state density of the MOSFETs and MOS capacitors was determined by several techniques. It is shown that the presence of 'slow' states can interfere with the interface-state measurements.

Effects of gamma radiation on the early developmental stages of Zebrafish (Danio rerio).

PubMed

Praveen Kumar, M K; Shyama, S K; Kashif, Shamim; Dubey, S K; Avelyno, D'costa; Sonaye, B H; Kadam Samit, B; Chaubey, R C

2017-08-01

The zebrafish is gaining importance as a popular vertebrate model organism and is widely employed in ecotoxicological studies, especially for the biomonitoring of pollution in water bodies. There is limited data on the genetic mechanisms governing the adverse health effects in regards to an early developmental exposure to gamma radiation. In the present study zebrafish (Danio rerio) embryos were exposed to 1, 2.5, 5, 7.5 and 10Gy of gamma radiation at 3h post fertilization (hpf). Different developmental toxicity endpoints were investigated. Further, expression of genes associated with the development and DNA damage i.e. (sox2 sox19a and p53) were evaluated using Quantitative PCR (qPCR). The significant changes in the expression of sox2 sox19a and p53 genes were observed. This data was supported the developmental defects observed in the zebrafish embryo exposed to gamma radiation such as i.e. increased DNA damage, decreased hatching rate, increase in median hatching time, decreased body length, increased mortality rate, increased morphological deformities. Further, study shows that the potential ecotoxicological threat of gamma radiation on the early developmental stages of zebrafish. Further, it revealed that the above parameters can be used as predictive biomarkers of gamma radiation exposure. Copyright © 2017. Published by Elsevier Inc.

Neutron responsive self-powered radiation detector

DOEpatents

Brown, Donald P.; Cannon, Collins P.

1978-01-01

An improved neutron responsive self-powered radiation detector is disclosed in which the neutron absorptive central emitter has a substantially neutron transmissive conductor collector sheath spaced about the emitter and the space between the emitter and collector sheath is evacuated.

The Response of Human Skin Commensal Bacteria as a Reflection of UV Radiation: UV-B Decreases Porphyrin Production

PubMed Central

Wang, Yanhan; Zhu, Wenhong; Shu, Muya; Jiang, Yong; Gallo, Richard L.; Liu, Yu-Tsueng; Huang, Chun-Ming

2012-01-01

Recent global radiation fears reflect the urgent need for a new modality that can simply determine if people are in a radiation risk of developing cancer and other illnesses. Ultraviolet (UV) radiation has been thought to be the major risk factor for most skin cancers. Although various biomarkers derived from the responses of human cells have been revealed, detection of these biomarkers is cumbersome, probably requires taking live human tissues, and varies significantly depending on human immune status. Here we hypothesize that the reaction of Propionibacterium acnes (P. acnes), a human resident skin commensal, to UV radiation can serve as early surrogate markers for radiation risk because the bacteria are immediately responsive to radiation. In addition, the bacteria can be readily accessible and exposed to the same field of radiation as human body. To test our hypothesis, P. acnes was exposed to UV-B radiation. The production of porphyrins in P. acnes was significantly reduced with increasing doses of UV-B. The porphyrin reduction can be detected in both P. acnes and human skin bacterial isolates. Exposure of UV-B to P. acnes- inoculated mice led to a significant decrease in porphyrin production in a single colony of P. acnes and simultaneously induced the formation of cyclobutane pyrimidine dimers (CPD) in the epidermal layers of mouse skin. Mass spectrometric analysis via a linear trap quadrupole (LTQ)-Orbitrap XL showed that five peptides including an internal peptide (THLPTGIVVSCQNER) of a peptide chain release factor 2 (RF2) were oxidized by UV-B. Seven peptides including three internal peptides of 60 kDa chaperonin 1 were de-oxidized by UV-B. When compared to UV-B, gamma radiation also decreased the porphyrin production of P. acnes in a dose-dependent manner, but induced a different signature of protein oxidation/de-oxidation. We highlight that uncovering response of skin microbiome to radiation will facilitate the development of pre-symptomatic diagnosis

The response of human skin commensal bacteria as a reflection of UV radiation: UV-B decreases porphyrin production.

PubMed

Wang, Yanhan; Zhu, Wenhong; Shu, Muya; Jiang, Yong; Gallo, Richard L; Liu, Yu-Tsueng; Huang, Chun-Ming

2012-01-01

Recent global radiation fears reflect the urgent need for a new modality that can simply determine if people are in a radiation risk of developing cancer and other illnesses. Ultraviolet (UV) radiation has been thought to be the major risk factor for most skin cancers. Although various biomarkers derived from the responses of human cells have been revealed, detection of these biomarkers is cumbersome, probably requires taking live human tissues, and varies significantly depending on human immune status. Here we hypothesize that the reaction of Propionibacterium acnes (P. acnes), a human resident skin commensal, to UV radiation can serve as early surrogate markers for radiation risk because the bacteria are immediately responsive to radiation. In addition, the bacteria can be readily accessible and exposed to the same field of radiation as human body. To test our hypothesis, P. acnes was exposed to UV-B radiation. The production of porphyrins in P. acnes was significantly reduced with increasing doses of UV-B. The porphyrin reduction can be detected in both P. acnes and human skin bacterial isolates. Exposure of UV-B to P. acnes- inoculated mice led to a significant decrease in porphyrin production in a single colony of P. acnes and simultaneously induced the formation of cyclobutane pyrimidine dimers (CPD) in the epidermal layers of mouse skin. Mass spectrometric analysis via a linear trap quadrupole (LTQ)-Orbitrap XL showed that five peptides including an internal peptide (THLPTGIVVSCQNER) of a peptide chain release factor 2 (RF2) were oxidized by UV-B. Seven peptides including three internal peptides of 60 kDa chaperonin 1 were de-oxidized by UV-B. When compared to UV-B, gamma radiation also decreased the porphyrin production of P. acnes in a dose-dependent manner, but induced a different signature of protein oxidation/de-oxidation. We highlight that uncovering response of skin microbiome to radiation will facilitate the development of pre-symptomatic diagnosis

Observations from Juno's Radiation Monitoring Investigation during Juno's Early Orbits

NASA Astrophysics Data System (ADS)

Becker, Heidi N.; Jorgensen, John L.; Adriani, Alberto; Mura, Alessandro; Connerney, John E. P.; Santos-Costa, Daniel; Bolton, Scott J.; Levin, Steven M.; Alexander, James W.; Adumitroaie, Virgil; Manor-Chapman, Emily A.; Daubar, Ingrid J.; Lee, Clifford; Benn, Mathias; Denver, Troelz; Sushkova, Julia; Cicchetti, Andrea; Noschese, Raffaella; Thorne, Richard M.

2017-04-01

Juno's Radiation Monitoring (RM) Investigation profiles Jupiter's >10-MeV electron environment throughout unexplored regions of the Jovian magnetosphere. RM's measurement approach involves active retrieval of the characteristic noise signatures from penetrating radiation in images obtained by Juno's heavily shielded star cameras and science instruments. Collaborative observation campaigns of "radiation image" collection and penetrating particle counts are conducted at targeted opportunities within the magnetosphere during each of Juno's perijove passes using the spacecraft Stellar Reference Unit, the Magnetic Field Investigation's Advanced Stellar Compass Imagers, and the JIRAM infrared imager. Simultaneous observations gathered from these very different instruments provide comparative spectral information due to substantial differences in instrument shielding. Juno's orbit provides a unique sampling of energetic particles within Jupiter's innermost radiation belts and polar regions. We present a survey of observations of the high energy radiation environment made by Juno's SRU and ASC star cameras and the JIRAM infrared imager during Juno's early perijove passes on August 27 and December 11, 2016; and February 2 and March 27, 2017. The JPL author's copyright for this publication is held by the California Institute of Technology. Government Sponsorship acknowledged.

Radiation-induced genomic instability and bystander effects: related inflammatory-type responses to radiation-induced stress and injury? A review.

PubMed

Lorimore, S A; Wright, E G

2003-01-01

To review studies of radiation responses in the haemopoietic system in the context of radiation-induced genomic instability, bystander effects and inflammatory-type processes. There is considerable evidence that cells that themselves are not exposed to ionizing radiation but are the progeny of cells irradiated many cell divisions previously may express a high frequency of gene mutations, chromosomal aberrations and cell death. These effects are collectively known as radiation-induced genomic instability. A second untargeted effect results in non-irradiated cells exhibiting responses typically associated with direct radiation exposure but occurs as a consequence of contact with irradiated cells or by receiving soluble signals from irradiated cells. These effects are collectively known as radiation-induced bystander effects. Reported effects include increases or decreases in damage-inducible and stress-related proteins; increases or decreases in reactive oxygen species, cell death or cell proliferation, and induction of mutations and chromosome aberrations. This array of responses is reminiscent of effects mediated by cytokines and other similar regulatory factors that may involve, but do not necessarily require, gap junction-mediated transfer, have multiple inducers and a variety of context-dependent consequences in different cell systems. That chromosomal instability in haemopoietic cells can be induced by an indirect bystander-type mechanism both in vitro and in vivo provides a potential link between these two untargeted effects and there are radiation responses in vivo consistent with the microenvironment contributing secondary cell damage as a consequence of an inflammatory-type response to radiation-induced injury. Intercellular signalling, production of cytokines and free radicals are features of inflammatory responses that have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. The

Linear response theory for annealing of radiation damage in semiconductor devices

NASA Technical Reports Server (NTRS)

Litovchenko, Vitaly

1988-01-01

A theoretical study of the radiation/annealing response of MOS ICs is described. Although many experiments have been performed in this field, no comprehensive theory dealing with radiation/annealing response has been proposed. Many attempts have been made to apply linear response theory, but no theoretical foundation has been presented. The linear response theory outlined here is capable of describing a broad area of radiation/annealing response phenomena in MOS ICs, in particular, both simultaneous irradiation and annealing, as well as short- and long-term annealing, including the case when annealing is nearing completion. For the first time, a simple procedure is devised to determine the response function from experimental radiation/annealing data. In addition, this procedure enables us to study the effect of variable temperature and dose rate, effects which are of interest in spaceflight. In the past, the shift in threshold potential due to radiation/annealing has usually been assumed to depend on one variable: the time lapse between an impulse dose and the time of observation. While such a suggestion of uniformity in time is certainly true for a broad range of radiation annealing phenomena, it may not hold for some ranges of the variables of interest (temperature, dose rate, etc.). A response function is projected which is dependent on two variables: the time of observation and the time of the impulse dose. This dependence on two variables allows us to extend the theory to the treatment of a variable dose rate. Finally, the linear theory is generalized to the case in which the response is nonlinear with impulse dose, but is proportional to some impulse function of dose. A method to determine both the impulse and response functions is presented.

Plant response to solar ultraviolet radiation

NASA Technical Reports Server (NTRS)

Caldwell, M. M.

1981-01-01

Plant reactions and mechanisms of reaction to solar UV radiation are reviewed, along with characteristics of plants which enhance UV tolerance. Wavelength regions to which proteins are particularly sensitive are examined and the possibility of synergistic effects from photoreactions to multiple wavelengths is considered, along with available evidence of nonadditive plant spectral responses to UV radiation. Decreases in atmospheric ozone content are explored in terms of UV wavelengths which would increase with the ozone decreases, particularly for UV-B, which depresses photosynthesis and would increase 1% with a 16% reduction of stratospheric ozone. Higher elevations are projected to display effects of increased UV incident flux first, and global distributions of UV increases due to atmospheric inhomogeneity and water surface clarity are examined. Finally, the response of plant nucleic acids, DNA, chlorophyll to enhanced UV are described, along with repair, avoidance, and optical mechanisms which aid plant survival

Predicted levels of human radiation tolerance extrapolated from clinical studies of radiation effects

NASA Technical Reports Server (NTRS)

Lushbaugh, C. C.

1972-01-01

Results of clinical studies of radiation effects on man are used to evaluate space radiation hazards encountered during manned space travel. Considered are effects of photons as well as of mixed fission neutrons and gamma irradiations in establishing body radiosensitivity and tolerance levels. Upper and lower dose-response-time relations for acute radiation syndromes in patients indicate that man is more than sufficiently radioresistant to make the risks of an early radiation effect during one short space mission intangibly small in relation to the other nonradiation risks involved.

Mechanisms and biological importance of photon-induced bystander responses: do they have an impact on low-dose radiation responses

PubMed Central

Tomita, Masanori; Maeda, Munetoshi

2015-01-01

Abstract Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or γ-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced bystander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect. PMID:25361549

Radiation-induced bystander effect and adaptive response in mammalian cells

NASA Technical Reports Server (NTRS)

Zhou, H.; Randers-Pehrson, G.; Waldren, C. A.; Hei, T. K.

2004-01-01

Two conflicting phenomena, bystander effect and adaptive response, are important in determining the biological responses at low doses of radiation and have the potential to impact the shape of the dose-response relationship. Using the Columbia University charged-particle microbeam and the highly sensitive AL cell mutagenic assay, we show here that non-irradiated cells acquire mutagenesis through direct contact with cells whose nuclei have been traversed with a single alpha particle each. Pretreatment of cells with a low dose of X-rays four hours before alpha particle irradiation significantly decreased this bystander mutagenic response. Results from the present study address some of the fundamental issues regarding both the actual target and radiation dose effect and can contribute to our current understanding in radiation risk assessment. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

Cellular Response to Ionizing Radiation: A MicroRNA Story

PubMed Central

Halimi, Mohammad; Asghari, S. Mohsen; Sariri, Reyhaneh; Moslemi, Dariush; Parsian, Hadi

2012-01-01

MicroRNAs (miRNAs) represent a class of small non-coding RNA molecules that regulate gene expression at the post-transcriptional level. They play a crucial role in diverse cellular pathways. Ionizing radiation (IR) is one of the most important treatment protocols for patients that suffer from cancer and affects directly or indirectly cellular integration. Recently it has been discovered that microRNA-mediated gene regulation interferes with radio-related pathways in ionizing radiation. Here, we review the recent discoveries about miRNAs in cellular response to IR. Thoroughly understanding the mechanism of miRNAs in radiation response, it will be possible to design new strategies for improving radiotherapy efficiency and ultimately cancer treatment. PMID:24551775

Individual Human Cell Responses to Low Doses of Chemicals and Radiation Studied by Synchrotron Infrared Spectromicroscopy

NASA Astrophysics Data System (ADS)

Martin, Michael C.; Holman, Hoi-Ying N.; Blakely, Eleanor A.; Goth-Goldstein, Regine; McKinney, Wayne R.

2000-03-01

Vibrational spectroscopy, when combined with synchrotron radiation-based (SR) microscopy, is a powerful new analytical tool with high spatial resolution for detecting biochemical changes in individual living cells. In contrast to other microscopy methods that require fixing, drying, staining or labeling, SR FTIR microscopy probes intact living cells providing a composite view of all of the molecular responses and the ability to monitor the responses over time in the same cell. Observed spectral changes include all types of lesions induced in that cell as well as cellular responses to external and internal stresses. These spectral changes combined with other analytical tools may provide a fundamental understanding of the key molecular mechanisms induced in response to stresses created by low-doses of radiation and chemicals. In this study we used high spatial-resolution SR FTIR vibrational spectromicroscopy at ALS Beamline 1.4.3 as a sensitive analytical tool to detect chemical- and radiation-induced changes in individual human cells. Our preliminary spectral measurements indicate that this technique is sensitive enough to detect changes in nucleic acids and proteins of cells treated with environmentally relevant concentrations of oxidative stresses: bleomycin, hydrogen peroxide, and X-rays. We observe spectral changes that are unique to each exogenous stressor. This technique has the potential to distinguish changes from exogenous or endogenous oxidative processes. Future development of this technique will allow rapid monitoring of cellular processes such as drug metabolism, early detection of disease, bio-compatibility of implant materials, cellular repair mechanisms, self assembly of cellular apparatus, cell differentiation and fetal development.

Metabolic Phenotyping Reveals a Lipid Mediator Response to Ionizing Radiation

PubMed Central

2015-01-01

Exposure to ionizing radiation has dramatically increased in modern society, raising serious health concerns. The molecular response to ionizing radiation, however, is still not completely understood. Here, we screened mouse serum for metabolic alterations following an acute exposure to γ radiation using a multiplatform mass-spectrometry-based strategy. A global, molecular profiling revealed that mouse serum undergoes a series of significant molecular alterations following radiation exposure. We identified and quantified bioactive metabolites belonging to key biochemical pathways and low-abundance, oxygenated, polyunsaturated fatty acids (PUFAs) in the two groups of animals. Exposure to γ radiation induced a significant increase in the serum levels of ether phosphatidylcholines (PCs) while decreasing the levels of diacyl PCs carrying PUFAs. In exposed mice, levels of pro-inflammatory, oxygenated metabolites of arachidonic acid increased, whereas levels of anti-inflammatory metabolites of omega-3 PUFAs decreased. Our results indicate a specific serum lipidomic biosignature that could be utilized as an indicator of radiation exposure and as novel target for therapeutic intervention. Monitoring such a molecular response to radiation exposure might have implications not only for radiation pathology but also for countermeasures and personalized medicine. PMID:25126707

Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

PubMed

Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

2016-08-01

Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome.

Radiation Segmentectomy versus Selective Chemoembolization in the Treatment of Early-Stage Hepatocellular Carcinoma.

PubMed

Biederman, Derek M; Titano, Joseph J; Korff, Ricki A; Fischman, Aaron M; Patel, Rahul S; Nowakowski, Francis S; Lookstein, Robert A; Kim, Edward

2018-01-01

To compare outcomes of radiation segmentectomy (RS) and segmental transarterial chemoembolization in treatment of unresectable, solitary hepatocellular carcinoma (HCC) ≤ 3 cm. From January 2012 to January 2016, 534 and 877 patients were treated with radioembolization and transarterial chemoembolization, respectively. A cohort of 112 (radiation segmentectomy [RS], 55; chemoembolization, 57) locoregional therapy-naïve patients with solitary HCC ≤ 3 cm without vascular invasion or metastasis was retrospectively identified and stratified according to baseline patient demographics, tumor characteristics, and laboratory values. Propensity score matching (PSM) was conducted using a nearest neighbor algorithm (1:1). Outcomes analyzed included laboratory toxicities, imaging response, time to secondary therapy (TTST), and overall survival. Before PSM, complete response (CR) rate was 81.2% for RS and 49.1% for chemoembolization (odds ratio 2.2; 95% confidence interval [CI], 1.4-3.3; P < .001). Median (95% CI) TTST after initial therapy was 246 days (135-250 d) in chemoembolization group and 700 days (308-812 d) in RS group (hazard ratio 0.71; 95% CI, 0.55-0.92; P = .009). Overall survival before PSM was not significantly different between the 2 groups (P = .29). Overall CR rate after PSM was 92.1% in RS group and 52.6% in chemoembolization group (P = .005). Median (95% CI) TTST after matching was 161 days (76-350 d) in chemoembolization group and 812 days (363-812 d) in RS group (P = .001). Overall survival after matching was not significantly different between the 2 groups (P = .71). RS results in improved imaging response and longer TTST compared with transarterial chemoembolization in treatment of early-stage HCC. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

MicroRNAs in Skin Response to UV Radiation

PubMed Central

Syed, Deeba N.; Khan, Mohammad Imran; Shabbir, Maria; Mukhtar, Hasan

2014-01-01

Solar ultraviolet (UV) radiation, an ubiquitous environmental carcinogen, is classified depending on the wave-length, into three regions; short-wave UVC (200–280 nm), mid-wave UVB (280–320 nm), and long-wave UVA (320–400 nm). The human skin, constantly exposed to UV radiation, particularly the UVB and UVA components, is vulnerable to its various deleterious effects such as erythema, photoaging, immunosuppression and cancer. To counteract these and for the maintenance of genomic integrity, cells have developed several protective mechanisms including DNA repair, cell-cycle arrest and apoptosis. The network of damage sensors, signal transducers, mediators, and various effector proteins is regulated through changes in gene expression. MicroRNAs (miRNAs), a group of small non-coding RNAs, act as post-transcriptional regulators through binding to complementary sequences in the 3′-untranslated region of their target genes, resulting in either translational repression or target degradation. Recent studies show that miRNAs add an additional layer of complexity to the intricately controlled cellular responses to UV radiation. This review summarizes our current knowledge of the role of miRNAs in the regulation of the human skin response upon exposure to UV radiation. PMID:23834148

The Sail-Backed Reptile Ctenosauriscus from the Latest Early Triassic of Germany and the Timing and Biogeography of the Early Archosaur Radiation

PubMed Central

Butler, Richard J.; Brusatte, Stephen L.; Reich, Mike; Nesbitt, Sterling J.; Schoch, Rainer R.; Hornung, Jahn J.

2011-01-01

Background Archosaurs (birds, crocodilians and their extinct relatives including dinosaurs) dominated Mesozoic continental ecosystems from the Late Triassic onwards, and still form a major component of modern ecosystems (>10,000 species). The earliest diverse archosaur faunal assemblages are known from the Middle Triassic (c. 244 Ma), implying that the archosaur radiation began in the Early Triassic (252.3–247.2 Ma). Understanding of this radiation is currently limited by the poor early fossil record of the group in terms of skeletal remains. Methodology/Principal Findings We redescribe the anatomy and stratigraphic position of the type specimen of Ctenosauriscus koeneni (Huene), a sail-backed reptile from the Early Triassic (late Olenekian) Solling Formation of northern Germany that potentially represents the oldest known archosaur. We critically discuss previous biomechanical work on the ‘sail’ of Ctenosauriscus, which is formed by a series of elongated neural spines. In addition, we describe Ctenosauriscus-like postcranial material from the earliest Middle Triassic (early Anisian) Röt Formation of Waldhaus, southwestern Germany. Finally, we review the spatial and temporal distribution of the earliest archosaur fossils and their implications for understanding the dynamics of the archosaur radiation. Conclusions/Significance Comprehensive numerical phylogenetic analyses demonstrate that both Ctenosauriscus and the Waldhaus taxon are members of a monophyletic grouping of poposauroid archosaurs, Ctenosauriscidae, characterised by greatly elongated neural spines in the posterior cervical to anterior caudal vertebrae. The earliest archosaurs, including Ctenosauriscus, appear in the body fossil record just prior to the Olenekian/Anisian boundary (c. 248 Ma), less than 5 million years after the Permian–Triassic mass extinction. These earliest archosaur assemblages are dominated by ctenosauriscids, which were broadly distributed across northern Pangea and which

The sail-backed reptile Ctenosauriscus from the latest Early Triassic of Germany and the timing and biogeography of the early archosaur radiation.

PubMed

Butler, Richard J; Brusatte, Stephen L; Reich, Mike; Nesbitt, Sterling J; Schoch, Rainer R; Hornung, Jahn J

2011-01-01

Archosaurs (birds, crocodilians and their extinct relatives including dinosaurs) dominated Mesozoic continental ecosystems from the Late Triassic onwards, and still form a major component of modern ecosystems (>10,000 species). The earliest diverse archosaur faunal assemblages are known from the Middle Triassic (c. 244 Ma), implying that the archosaur radiation began in the Early Triassic (252.3-247.2 Ma). Understanding of this radiation is currently limited by the poor early fossil record of the group in terms of skeletal remains. We redescribe the anatomy and stratigraphic position of the type specimen of Ctenosauriscus koeneni (Huene), a sail-backed reptile from the Early Triassic (late Olenekian) Solling Formation of northern Germany that potentially represents the oldest known archosaur. We critically discuss previous biomechanical work on the 'sail' of Ctenosauriscus, which is formed by a series of elongated neural spines. In addition, we describe Ctenosauriscus-like postcranial material from the earliest Middle Triassic (early Anisian) Röt Formation of Waldhaus, southwestern Germany. Finally, we review the spatial and temporal distribution of the earliest archosaur fossils and their implications for understanding the dynamics of the archosaur radiation. Comprehensive numerical phylogenetic analyses demonstrate that both Ctenosauriscus and the Waldhaus taxon are members of a monophyletic grouping of poposauroid archosaurs, Ctenosauriscidae, characterised by greatly elongated neural spines in the posterior cervical to anterior caudal vertebrae. The earliest archosaurs, including Ctenosauriscus, appear in the body fossil record just prior to the Olenekian/Anisian boundary (c. 248 Ma), less than 5 million years after the Permian-Triassic mass extinction. These earliest archosaur assemblages are dominated by ctenosauriscids, which were broadly distributed across northern Pangea and which appear to have been the first global radiation of archosaurs.

Metformin: A Novel Biological Modifier of Tumor Response to Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koritzinsky, Marianne, E-mail: mkoritzi@uhnresearch.ca

2015-10-01

Over the last decade, evidence has emerged to support a role for the antidiabetic drug metformin in the prevention and treatment of cancer. In particular, recent studies demonstrate that metformin enhances tumor response to radiation in experimental models, and retrospective analyses have shown that diabetic cancer patients treated with radiation therapy have improved outcomes if they take metformin to control their diabetes. Metformin may therefore be of utility for nondiabetic cancer patients treated with radiation therapy. The purpose of this review is to examine the data pertaining to an interaction between metformin and radiation, highlighting the essential steps needed tomore » advance our current knowledge. There is also a focus on key biomarkers that should accompany prospective clinical trials in which metformin is being examined as a modifying agent with radiation therapy. Existing evidence supports that the mechanism underlying the ability of metformin to enhance radiation response is multifaceted, and includes direct radiosensitization as well as a reduction in tumor stem cell fraction, proliferation, and tumor hypoxia. Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers.« less

Fibrinogen deficiency suppresses the development of early and delayed radiation enteropathy

PubMed Central

Wang, Junru; Pathak, Rupak; Garg, Sarita; Hauer-Jensen, Martin

2017-01-01

AIM To determine the mechanistic role of fibrinogen, a key regulator of inflammation and fibrosis, in early and delayed radiation enteropathy. METHODS Fibrinogen wild-type (Fib+/+), fibrinogen heterozygous (Fib+/-), and fibrinogen knockout (Fib-/-) mice were exposed to localized intestinal irradiation and assessed for early and delayed structural changes in the intestinal tissue. A 5-cm segment of ileum of mice was exteriorized and exposed to 18.5 Gy of x-irradiation. Intestinal tissue injury was assessed by quantitative histology, morphometry, and immunohistochemistry at 2 wk and 26 wk after radiation. Plasma fibrinogen level was measured by enzyme-linked immunosorbent assay. RESULTS There was no difference between sham-irradiated Fib+/+ and Fib+/- mice in terms of fibrinogen concentration in plasma and intestinal tissue, intestinal histology, morphometry, intestinal smooth muscle cell proliferation, and neutrophil infiltration. Therefore, Fib+/- mice were used as littermate controls. Unlike sham-irradiated Fib+/+ and Fib+/- mice, no fibrinogen was detected in the plasma and intestinal tissue of sham-irradiated Fib-/- mice. Moreover, fibrinogen level was not elevated after irradiation in the intestinal tissue of Fib-/- mice, while significant increase in intestinal fibrinogen level was noticed in irradiated Fib+/+ and Fib+/- mice. Importantly, irradiated Fib-/- mice exhibited substantially less overall intestinal structural injury (RIS, P = 0.000002), intestinal wall thickness (P = 0.003), intestinal serosal thickness (P = 0.009), collagen deposition (P = 0.01), TGF-β immunoreactivity (P = 0.03), intestinal smooth muscle proliferation (P = 0.046), neutrophil infiltration (P = 0.01), and intestinal mucosal injury (P = 0.0003), compared to irradiated Fib+/+ and Fib+/- mice at both 2 wk and 26 wk. CONCLUSION These data demonstrate that fibrinogen deficiency directly attenuates development of early and delayed radiation enteropathy. Fibrinogen could be a novel target

Warming early Mars with carbon dioxide clouds that scatter infrared radiation.

PubMed

Forget, F; Pierrehumbert, R T

1997-11-14

Geomorphic evidence that Mars was warm enough to support flowing water about 3.8 billion years ago presents a continuing enigma that cannot be explained by conventional greenhouse warming mechanisms. Model calculations show that the surface of early Mars could have been warmed through a scattering variant of the greenhouse effect, resulting from the ability of the carbon dioxide ice clouds to reflect the outgoing thermal radiation back to the surface. This process could also explain how Earth avoided an early irreversible glaciation and could extend the size of the habitable zone on extrasolar planets around stars.

Evaluating average and atypical response in radiation effects simulations

NASA Astrophysics Data System (ADS)

Weller, R. A.; Sternberg, A. L.; Massengill, L. W.; Schrimpf, R. D.; Fleetwood, D. M.

2003-12-01

We examine the limits of performing single-event simulations using pre-averaged radiation events. Geant4 simulations show the necessity, for future devices, to supplement current methods with ensemble averaging of device-level responses to physically realistic radiation events. Initial Monte Carlo simulations have generated a significant number of extremal events in local energy deposition. These simulations strongly suggest that proton strikes of sufficient energy, even those that initiate purely electronic interactions, can initiate device response capable in principle of producing single event upset or microdose damage in highly scaled devices.

Factors modifying the response of large animals to low-intensity radiation exposure

NASA Technical Reports Server (NTRS)

Page, N. P.; Still, E. T.

1972-01-01

In assessing the biological response to space radiation, two of the most important modifying factors are dose protraction and dose distribution to the body. Studies are reported in which sheep and swine were used to compare the hematology and lethality response resulting from radiation exposure encountered in a variety of forms, including acute (high dose-rate), chronic (low dose-rate), combinations of acute and chronic, and whether received as a continuous or as fractionated exposure. While sheep and swine are basically similar in response to acute radiation, their sensitivity to chronic irradiation is markedly different. Sheep remain relatively sensitive as the radiation exposure is protracted while swine are more resistant and capable of surviving extremely large doses of chronic irradiation. This response to chronic irradiation correlated well with changes in radiosensitivity and recovery following an acute, sublethal exposure.

Calculating the Responses of Self-Powered Radiation Detectors.

NASA Astrophysics Data System (ADS)

Thornton, D. A.

Available from UMI in association with The British Library. The aim of this research is to review and develop the theoretical understanding of the responses of Self -Powered Radiation Detectors (SPDs) in Pressurized Water Reactors (PWRs). Two very different models are considered. A simple analytic model of the responses of SPDs to neutrons and gamma radiation is presented. It is a development of the work of several previous authors and has been incorporated into a computer program (called GENSPD), the predictions of which have been compared with experimental and theoretical results reported in the literature. Generally, the comparisons show reasonable consistency; where there is poor agreement explanations have been sought and presented. Two major limitations of analytic models have been identified; neglect of current generation in insulators and over-simplified electron transport treatments. Both of these are developed in the current work. A second model based on the Explicit Representation of Radiation Sources and Transport (ERRST) is presented and evaluated for several SPDs in a PWR at beginning of life. The model incorporates simulation of the production and subsequent transport of neutrons, gamma rays and electrons, both internal and external to the detector. Neutron fluxes and fuel power ratings have been evaluated with core physics calculations. Neutron interaction rates in assembly and detector materials have been evaluated in lattice calculations employing deterministic transport and diffusion methods. The transport of the reactor gamma radiation has been calculated with Monte Carlo, adjusted diffusion and point-kernel methods. The electron flux associated with the reactor gamma field as well as the internal charge deposition effects of the transport of photons and electrons have been calculated with coupled Monte Carlo calculations of photon and electron transport. The predicted response of a SPD is evaluated as the sum of contributions from individual

Molecular stress response in the CNS of mice after systemic exposureto interferon-alpha, ionizing radiation and ketamine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lowe, Xiu R.; Marchetti, Francesco; Lu, Xiaochen

2009-03-03

We previously showed that the expression of troponin T1 (Tnnt 1) was induced in the central nervous system (CNS) of adultmice 30 min after treatment with ketamine, a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist. We hypothesized that Tnnt 1 expression may be an early molecular biomarker of stress response in the CNS of mice. To further evaluate this hypothesis, we investigated the regional expression of Tnnt 1 in the mouse brain using RNA in situ hybridization 4 h after systemic exposure to interferon-a (IFN-a) and gamma ionizing radiation, both of which have be associated with wide ranges of neuropsychiatric complications.more » Adult B6C3F1 male mice were treated with either human IFN-a (a single i.p. injection at 1 x 105 IU/kg) or whole body gamma-radiation (10 cGy or 2 Gy). Patterns of Tnnt 1 transcript expression were compared in various CNS regions after IFN-a, radiation and ketamine treatments (previous study). Tnnt 1 expression was consistently induced in pyramidal neurons of cerebral cortex and hippocampus after all treatment regimens including 10 cGy of ionizing radiation. Regional expression of Tnnt 1 was induced in Purkinje cells of cerebellum after ionizing radiation and ketamine treatment; but not after IFN-a treatment. None of the three treatments induced Tnnt 1 expression in glial cells. The patterns of Tnnt 1 expression in pyramidal neurons of cerebral cortex andhippocampus, which are both known to play important roles in cognitive function, memory and emotion, suggest that the expression of Tnnt 1 may be an early molecular biomarker of induced CNS stress.« less

Biological Bases for Radiation Adaptive Responses in the Lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scott, Bobby R.; Lin, Yong; Wilder, Julie

2015-03-01

Our main research objective was to determine the biological bases for low-dose, radiation-induced adaptive responses in the lung, and use the knowledge gained to produce an improved risk model for radiation-induced lung cancer that accounts for activated natural protection, genetic influences, and the role of epigenetic regulation (epiregulation). Currently, low-dose radiation risk assessment is based on the linear-no-threshold hypothesis, which now is known to be unsupported by a large volume of data.

Blood gene expression profiling of an early acetaminophen response.

PubMed

Bushel, P R; Fannin, R D; Gerrish, K; Watkins, P B; Paules, R S

2017-06-01

Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4 g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing, and 12 genes were detected with expression profiles significantly altered within 24 h. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure, and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration.

Blood Gene Expression Profiling of an Early Acetaminophen Response

PubMed Central

Bushel, Pierre R.; Fannin, Rick D.; Gerrish, Kevin; Watkins, Paul B.; Paules, Richard S.

2018-01-01

Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing and 12 genes were detected with expression profiles significantly altered within 24 hrs. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration. PMID:26927286

Early response to psychological trauma--what GPs can do.

PubMed

Wade, Darryl; Howard, Alexandra; Fletcher, Susan; Cooper, John; Forbes, David

2013-09-01

There is a high prevalence of psychological trauma exposure among primary care patients. General practitioners are well placed to provide appropriate support for patients coping with trauma. This article outlines an evidence-based early response to psychological trauma. Psychological first aid is the preferred approach in providing early assistance to patients who have experienced a traumatic event. General practitioners can be guided by five empirically derived principles in their early response: promoting a sense of safety, calming, self efficacy, connectedness and hope. Structured psychological interventions, including psychological debriefing, are not routinely recommended in the first few weeks following trauma exposure. General practitioner self care is an important aspect of providing post-trauma patient care.

Induction of adaptive response in human blood lymphocytes exposed to radiofrequency radiation.

PubMed

Sannino, Anna; Sarti, Maurizio; Reddy, Siddharth B; Prihoda, Thomas J; Vijayalaxmi; Scarfì, Maria Rosaria

2009-06-01

The incidence of micronuclei was evaluated to assess the induction of an adaptive response to non-ionizing radiofrequency (RF) radiation in peripheral blood lymphocytes collected from five different human volunteers. After stimulation with phytohemagglutinin for 24 h, the cells were exposed to an adaptive dose of 900 MHz RF radiation used for mobile communications (at a peak specific absorption rate of 10 W/kg) for 20 h and then challenged with a single genotoxic dose of mitomycin C (100 ng/ml) at 48 h. Lymphocytes were collected at 72 h to examine the frequency of micronuclei in cytokinesis-blocked binucleated cells. Cells collected from four donors exhibited the induction of adaptive response (i.e., responders). Lymphocytes that were pre-exposed to 900 MHz RF radiation had a significantly decreased incidence of micronuclei induced by the challenge dose of mitomycin C compared to those that were not pre-exposed to 900 MHz RF radiation. These preliminary results suggested that the adaptive response can be induced in cells exposed to non-ionizing radiation. A similar phenomenon has been reported in cells as well as in animals exposed to ionizing radiation in several earlier studies. However, induction of adaptive response was not observed in the remaining donor (i.e., non-responder). The incidence of micronuclei induced by the challenge dose of mitomycin C was not significantly different between the cells that were pre-exposed and unexposed to 900 MHz RF radiation. Thus the overall data indicated the existence of heterogeneity in the induction of an adaptive response between individuals exposed to RF radiation and showed that the less time-consuming micronucleus assay can be used to determine whether an individual is a responder or non-responder.

Role of Interleukin-6 in the Radiation Response of Liver Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Miao-Fen, E-mail: miaofen@adm.cgmh.org.tw; College of Medicine, Chang Gung University, Taiwan; Hsieh, Ching-Chuan

2012-12-01

Purpose: To investigate the role of interleukin (IL)-6 in biological sequelae and tumor regrowth after irradiation for hepatic malignancy, which are critical for the clinical radiation response of liver tumors. Methods and Materials: The Hepa 1-6 murine hepatocellular cancer cell line was used to examine the radiation response by clonogenic assays and tumor growth delay in vivo. After irradiation in a single dose of 6 Gy in vitro or 15 Gy in vivo, biological changes including cell death and tumor regrowth were examined by experimental manipulation of IL-6 signaling. The effects of blocking IL-6 were assessed by cells preincubated inmore » the presence of IL-6-neutralizing antibody for 24 hours or stably transfected with IL-6-silencing vectors. The correlations among tumor responses, IL-6 levels, and myeloid-derived suppressor cells (MDSC) recruitment were examined using animal experiments. Results: Interleukin-6 expression was positively linked to irradiation and radiation resistance, as demonstrated by in vitro and in vivo experiments. Interleukin-6-silencing vectors induced more tumor inhibition and DNA damage after irradiation. When subjects were irradiated with a sublethal dose, the regrowth of irradiated tumors significantly correlated with IL-6 levels and MDSC recruitment in vivo. Furthermore, blocking of IL-6 could overcome irradiation-induced MDSC recruitment and tumor regrowth after treatment. Conclusion: These data demonstrate that IL-6 is important in determining the radiation response of liver tumor cells. Irradiation-induced IL-6 and the subsequent recruitment of MDSC could be responsible for tumor regrowth. Therefore, treatment with concurrent IL-6 inhibition could be a potential therapeutic strategy for increasing the radiation response of tumors.« less

Hypofractionated whole breast radiation and partial breast radiation for early-stage breast cancers: an update on progress.

PubMed

McCormick, Beryl

2012-09-01

This article provides an update of recent progress using partial breast irradiation (PBI) for the treatment of early-stage breast cancer, rather than whole breast radiotherapy (WBRT), which is the standard of care. Several large, prospective, randomized trials are nearing target accrual or have been completed, including the NSABP/RTOG trial, the Milan-based intraoperative radiation trial, and the international TARGIT trial, and the status of each is discussed. The American Society for Radiation Oncology has also published a consensus statement to guide the use of PBI until some of the phase III trials are more mature. Finally, several articles have appeared recently, reporting unexpected adverse effects of PBI in small series, and this information is reviewed. Several recent prospective trials of WBRT are also discussed, with the theme of comparing the standard 25 fractions to a shortened, hypofractionated trial arm delivering equivalent doses of WBRT in approximately 15 treatments, another radiation strategy for a shortened course of treatment after breast-conserving surgery.

The response of the TIMED/SABER O2 nightglow to solar radiation

NASA Astrophysics Data System (ADS)

Gao, Hong; Xu, Jiyao; William, Ward

2015-04-01

The TIMED/SABER O2 nightglow observations between January 2002 and June 2014 are used to study the response of O2 emission to the solar radiation. both the O2 nightglow emission rate and intensity are found to be positively correlated to the solar radiation. The O2 nightglow emission rate/intensity and F10.7 solar flux index can be expressed by a linear relation very well. The response of the O2 global mean nightglow emission rate to the solar radiation is enhanced with increasing altitude from about 80km, reaches its peak around 92 km and then decreases with increasing altitude. The response of the O2 nightglow intensity to F10.7 index changes with latitude with three peaks around 40S/N and the equator. The response of the O2 global mean nightglow intensity to the solar radiation is about 27 kR/100 sfu, corresponding to 24.1%/100 sfu.

Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury

PubMed Central

Acharya, Sanket S.; Fendler, Wojciech; Watson, Jacqueline; Hamilton, Abigail; Pan, Yunfeng; Gaudiano, Emily; Moskwa, Patryk; Bhanja, Payel; Saha, Subhrajit; Guha, Chandan; Parmar, Kalindi; Chowdhury, Dipanjan

2015-01-01

Accidental radiation exposure is a threat to human health that necessitates effective clinical planning and diagnosis. Minimally invasive biomarkers that can predict long-term radiation injury are urgently needed for optimal management after a radiation accident. We have identified serum microRNA (miRNA) signatures that indicate long-term impact of total body irradiation (TBI) in mice when measured within 24 hours of exposure. Impact of TBI on the hematopoietic system was systematically assessed to determine a correlation of residual hematopoietic stem cells (HSCs) with increasing doses of radiation. Serum miRNA signatures distinguished untreated mice from animals exposed to radiation and correlated with the impact of radiation on HSCs. Mice exposed to sublethal (6.5 Gy) and lethal (8 Gy) doses of radiation were indistinguishable for 3 to 4 weeks after exposure. A serum miRNA signature detectable 24 hours after radiation exposure consistently segregated these two cohorts. Furthermore, using either a radioprotective agent before, or radiation mitigation after, lethal radiation, we determined that the serum miRNA signature correlated with the impact of radiation on animal health rather than the radiation dose. Last, using humanized mice that had been engrafted with human CD34+ HSCs, we determined that the serum miRNA signature indicated radiation-induced injury to the human bone marrow cells. Our data suggest that serum miRNAs can serve as functional dosimeters of radiation, representing a potential breakthrough in early assessment of radiation-induced hematopoietic damage and timely use of medical countermeasures to mitigate the long-term impact of radiation. PMID:25972001

[The clinical characteristics of the early manifestations of radiation exposure in children].

PubMed

Evdokimov, I K

1993-11-01

The article substantiates the necessity to conduct the thorough study not only of the remote consequences of the Chernobyl APS disaster, but also of the early clinical manifestations of radiation influence in children, as a most vulnerable group in respect to radiation. Age factor is considered to be one of the dominant features which influence upon the absorptive capacity of thyroid gland in respect to radioiodine, and thus provoking a high vulnerability of children in crisis situations. The authors study hematological peculiarities of radioreactions in children and adults. There are recommendations for preventing the reception of radionuclides by babies during lactation.

Proteomic Analysis of Trypanosoma cruzi Response to Ionizing Radiation Stress

PubMed Central

Vieira, Helaine Graziele Santos; Grynberg, Priscila; Bitar, Mainá; Pires, Simone da Fonseca; Hilário, Heron Oliveira; Macedo, Andrea Mara; Machado, Carlos Renato; de Andrade, Hélida Monteiro; Franco, Glória Regina

2014-01-01

Trypanosoma cruzi, the causative agent of Chagas disease, is extremely resistant to ionizing radiation, enduring up to 1.5 kGy of gamma rays. Ionizing radiation can damage the DNA molecule both directly, resulting in double-strand breaks, and indirectly, as a consequence of reactive oxygen species production. After a dose of 500 Gy of gamma rays, the parasite genome is fragmented, but the chromosomal bands are restored within 48 hours. Under such conditions, cell growth arrests for up to 120 hours and the parasites resume normal growth after this period. To better understand the parasite response to ionizing radiation, we analyzed the proteome of irradiated (4, 24, and 96 hours after irradiation) and non-irradiated T. cruzi using two-dimensional differential gel electrophoresis followed by mass spectrometry for protein identification. A total of 543 spots were found to be differentially expressed, from which 215 were identified. These identified protein spots represent different isoforms of only 53 proteins. We observed a tendency for overexpression of proteins with molecular weights below predicted, indicating that these may be processed, yielding shorter polypeptides. The presence of shorter protein isoforms after irradiation suggests the occurrence of post-translational modifications and/or processing in response to gamma radiation stress. Our results also indicate that active translation is essential for the recovery of parasites from ionizing radiation damage. This study therefore reveals the peculiar response of T. cruzi to ionizing radiation, raising questions about how this organism can change its protein expression to survive such a harmful stress. PMID:24842666

10 CFR 35.24 - Authority and responsibilities for the radiation protection program.

Code of Federal Regulations, 2012 CFR

2012-01-01

... protection program. (a) In addition to the radiation protection program requirements of § 20.1101 of this...) Radiation protection program changes that do not require a license amendment and are permitted under § 35.26... responsible for implementing the radiation protection program. The licensee, through the Radiation Safety...

10 CFR 35.24 - Authority and responsibilities for the radiation protection program.

Code of Federal Regulations, 2014 CFR

2014-01-01

... protection program. (a) In addition to the radiation protection program requirements of § 20.1101 of this...) Radiation protection program changes that do not require a license amendment and are permitted under § 35.26... responsible for implementing the radiation protection program. The licensee, through the Radiation Safety...

10 CFR 35.24 - Authority and responsibilities for the radiation protection program.

Code of Federal Regulations, 2011 CFR

2011-01-01

... protection program. (a) In addition to the radiation protection program requirements of § 20.1101 of this...) Radiation protection program changes that do not require a license amendment and are permitted under § 35.26... responsible for implementing the radiation protection program. The licensee, through the Radiation Safety...

10 CFR 35.24 - Authority and responsibilities for the radiation protection program.

Code of Federal Regulations, 2010 CFR

2010-01-01

... protection program. (a) In addition to the radiation protection program requirements of § 20.1101 of this...) Radiation protection program changes that do not require a license amendment and are permitted under § 35.26... responsible for implementing the radiation protection program. The licensee, through the Radiation Safety...

10 CFR 35.24 - Authority and responsibilities for the radiation protection program.

Code of Federal Regulations, 2013 CFR

2013-01-01

... protection program. (a) In addition to the radiation protection program requirements of § 20.1101 of this...) Radiation protection program changes that do not require a license amendment and are permitted under § 35.26... responsible for implementing the radiation protection program. The licensee, through the Radiation Safety...

RESPONSE OF THE GREEK EARLY WARNING SYSTEM REUTER-STOKES IONIZATION CHAMBERS TO TERRESTRIAL AND COSMIC RADIATION EVALUATED IN COMPARISON WITH SPECTROSCOPIC DATA AND TIME SERIES ANALYSIS.

PubMed

Leontaris, F; Clouvas, A; Xanthos, S; Maltezos, A; Potiriadis, C; Kiriakopoulos, E; Guilhot, J

2018-02-01

The Telemetric Early Warning System Network of the Greek Atomic Energy Commission consists mainly of a network of 24 Reuter-Stokes high-pressure ionization chambers (HPIC) for gamma dose rate measurements and covers all Greece. In the present work, the response of the Reuter-Stokes HPIC to terrestrial and cosmic radiation was evaluated in comparison with spectroscopic data obtained by in situ gamma spectrometry measurements with portable hyper pure Germanium detectors (HPGe), near the Reuter-Stokes detectors and time series analysis. For the HPIC detectors, a conversion factor for the measured absorbed dose rate in air (in nGy h-1) to the total ambient dose equivalent rate Ḣ*(10), due to terrestrial and cosmic component, was deduced by the field measurements. Time series analysis of the mean monthly dose rate (measured by the Reuter-Stokes detector in Thessaloniki, northern Greece, from 2001 to 2016) was performed with advanced statistical methods (Fast Fourier Analysis and Zhao Atlas Marks Transform). Fourier analysis reveals several periodicities (periodogram). The periodogram of the absorbed dose rate in air values was compared with the periodogram of the values measured for the same period (2001-16) and in the same location with a NaI (Tl) detector which in principle is not sensitive to cosmic radiation. The obtained results are presented and discussed. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Radiation response issues for infrared detectors

NASA Technical Reports Server (NTRS)

Kalma, Arne H.

1990-01-01

Researchers describe the most important radiation response issues for infrared detectors. In general, the two key degradation mechanisms in infrared detectors are the noise produced by exposure to a flux of ionizing particles (e.g.; trapped electronics and protons, debris gammas and electrons, radioactive decay of neutron-activated materials) and permanent damage produced by exposure to total dose. Total-dose-induced damage is most often the result of charge trapping in insulators or at interfaces. Exposure to short pulses of ionization (e.g.; prompt x rays or gammas, delayed gammas) will cause detector upset. However, this upset is not important to a sensor unless the recovery time is too long. A few detector technologies are vulnerable to neutron-induced displacement damage, but fortunately most are not. Researchers compare the responses of the new technologies with those of the mainstream technologies of PV HgCdTe and IBC Si:As. One important reason for this comparison is to note where some of the newer technologies have the potential to provide significantly improved radiation hardness compared with that of the mainstream technologies, and thus to provide greater motivation for the pursuit of these technologies.

Health responsibility and workplace health promotion among women: early detection of cancer.

PubMed

Kushnir, T; Rabinowitz, S; Melamed, S; Weisberg, E; Ribak, J

1995-01-01

The importance of health responsibility as one aspect of a health-promoting lifestyle has been emphasized repeatedly. Yet there are only a few empirical studies of its role in preventive behavior. We examined the relationship between health responsibility and early-detection practices for breast and cervical cancer. A group of 253 women employees of a large industrial company participated in a cancer screening program subsidized by the employer. They completed questionnaires assessing health responsibility and reported early-detection practices: frequency of breast self-examination and physician breast examinations, frequency of Pap tests, and time lapsed since last Pap test and breast examinations. Health responsibility was a significant independent predictor of breast examination indicators but not of Pap tests. Education level was an important predictor for Pap tests, and age predicted most early-detection practices. The findings lend some support to the role of health responsibility in initiating breast examinations. Better prediction of early-detection practices could be achieved by adding cognitive and emotional components to the existing responsibility scale and by distinguishing between retrospective and prospective responsibility.

Presence of early stage cancer does not impair the early protein metabolic response to major surgery

PubMed Central

Klimberg, V. Suzanne; Allasia, Arianna; Deutz, Nicolaas EP

2017-01-01

Abstract Background Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. Methods In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post‐absorptive state and net protein anabolic response to a meal. Results Major surgery resulted in an up‐regulation of post‐absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2 = 0.85, P < 0.001) was independent of the presence of non‐cachectic early stage breast cancer or surgery. Conclusions The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the

Presence of early stage cancer does not impair the early protein metabolic response to major surgery.

PubMed

Engelen, Mariëlle P K J; Klimberg, V Suzanne; Allasia, Arianna; Deutz, Nicolaas Ep

2017-06-01

Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post-absorptive state and net protein anabolic response to a meal. Major surgery resulted in an up-regulation of post-absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2  = 0.85, P < 0.001) was independent of the presence of non-cachectic early stage breast cancer or surgery. The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after

Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Appelt, Ane L., E-mail: ane.lindegaard.appelt@slb.regionsyddanmark.dk; University of Southern Denmark, Odense; Ploen, John

2013-01-01

Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from themore » histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D{sub 50,i}, and the normalized dose-response gradient, {gamma}{sub 50,i}. Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D{sub 50,TRG1} = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), {gamma}{sub 50,TRG1} = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D{sub 50,TRG1} and {sub 2} = 72.1 Gy (CI 65.3-94.0 Gy), {gamma}{sub 50,TRG1} and {sub 2} = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.« less

Early induced protein 1 (PrELIP1) and other photosynthetic, stress and epigenetic regulation genes are involved in Pinus radiata D. don UV-B radiation response.

PubMed

Valledor, Luis; Cañal, María Jesús; Pascual, Jesús; Rodríguez, Roberto; Meijón, Mónica

2012-11-01

The continuous atmospheric and environmental deterioration is likely to increase, among others, the influx of ultraviolet B (UV-B) radiation. The plants have photoprotective responses, which are complex mechanisms involving different physiological responses, to avoid the damages caused by this radiation that may lead to plant death. We have studied the adaptive responses to UV-B in Pinus radiata, given the importance of this species in conifer forests and reforestation programs. We analyzed the photosynthetic activity, pigments content, and gene expression of candidate genes related to photosynthesis, stress and gene regulation in needles exposed to UV-B during a 96 h time course. The results reveal a clear increase of pigments under UV-B stress while photosynthetic activity decreased. The expression levels of the studied genes drastically changed after UV-B exposure, were stress related genes were upregulated while photosynthesis (RBCA and RBCS) and epigenetic regulation were downregulated (MSI1, CSDP2, SHM4). The novel gene PrELIP1, fully sequenced for this work, was upregulated and expressed mainly in the palisade parenchyma of needles. This gene has conserved domains related to the dissipation of the UV-B radiation that give to this protein a key role during photoprotection response of the needles in Pinus radiata. Copyright © Physiologia Plantarum 2012.

Cellular response to low dose radiation: Role of phosphatidylinositol-3 kinase like kinases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balajee, A.S.; Meador, J.A.; Su, Y.

It is increasingly realized that human exposure either to an acute low dose or multiple chronic low doses of low LET radiation has the potential to cause different types of cancer. Therefore, the central theme of research for DOE and NASA is focused on understanding the molecular mechanisms and pathways responsible for the cellular response to low dose radiation which would not only improve the accuracy of estimating health risks but also help in the development of predictive assays for low dose radiation risks associated with tissue degeneration and cancer. The working hypothesis for this proposal is that the cellularmore » mechanisms in terms of DNA damage signaling, repair and cell cycle checkpoint regulation are different for low and high doses of low LET radiation and that the mode of action of phosphatidylinositol-3 kinase like kinases (PIKK: ATM, ATR and DNA-PK) determines the dose dependent cellular responses. The hypothesis will be tested at two levels: (I) Evaluation of the role of ATM, ATR and DNA-PK in cellular response to low and high doses of low LET radiation in simple in vitro human cell systems and (II) Determination of radiation responses in complex cell microenvironments such as human EpiDerm tissue constructs. Cellular responses to low and high doses of low LET radiation will be assessed from the view points of DNA damage signaling, DNA double strand break repair and cell cycle checkpoint regulation by analyzing the activities (i.e. post-translational modifications and kinetics of protein-protein interactions) of the key target proteins for PI-3 kinase like kinases both at the intra-cellular and molecular levels. The proteins chosen for this proposal are placed under three categories: (I) sensors/initiators include ATM ser1981, ATR, 53BP1, gamma-H2AX, MDC1, MRE11, Rad50 and Nbs1; (II) signal transducers include Chk1, Chk2, FANCD2 and SMC1; and (III) effectors include p53, CDC25A and CDC25C. The primary goal of this proposal is to elucidate the

Diet-Induced Obesity Modulates Epigenetic Responses to Ionizing Radiation in Mice

PubMed Central

Vares, Guillaume; Wang, Bing; Ishii-Ohba, Hiroko; Nenoi, Mitsuru; Nakajima, Tetsuo

2014-01-01

Both exposure to ionizing radiation and obesity have been associated with various pathologies including cancer. There is a crucial need in better understanding the interactions between ionizing radiation effects (especially at low doses) and other risk factors, such as obesity. In order to evaluate radiation responses in obese animals, C3H and C57BL/6J mice fed a control normal fat or a high fat (HF) diet were exposed to fractionated doses of X-rays (0.75 Gy ×4). Bone marrow micronucleus assays did not suggest a modulation of radiation-induced genotoxicity by HF diet. Using MSP, we observed that the promoters of p16 and Dapk genes were methylated in the livers of C57BL/6J mice fed a HF diet (irradiated and non-irradiated); Mgmt promoter was methylated in irradiated and/or HF diet-fed mice. In addition, methylation PCR arrays identified Ep300 and Socs1 (whose promoters exhibited higher methylation levels in non-irradiated HF diet-fed mice) as potential targets for further studies. We then compared microRNA regulations after radiation exposure in the livers of C57BL/6J mice fed a normal or an HF diet, using microRNA arrays. Interestingly, radiation-triggered microRNA regulations observed in normal mice were not observed in obese mice. miR-466e was upregulated in non-irradiated obese mice. In vitro free fatty acid (palmitic acid, oleic acid) administration sensitized AML12 mouse liver cells to ionizing radiation, but the inhibition of miR-466e counteracted this radio-sensitization, suggesting that the modulation of radiation responses by diet-induced obesity might involve miR-466e expression. All together, our results suggested the existence of dietary effects on radiation responses (especially epigenetic regulations) in mice, possibly in relationship with obesity-induced chronic oxidative stress. PMID:25171162

Biological effects of high ultraviolet radiation on early earth--a theoretical evaluation.

PubMed

Cockell, C S

1998-08-21

The surface of early Earth was exposed to both UVC radiation (< 280 nm) and higher doses of UVB (280-315 nm) compared with the surface of present day Earth. The degree to which this radiation environment acted as a selection pressure on organisms and biological systems has rarely been theoretically examined with respect to the biologically effective irradiances that ancient organisms would receive. Here action spectra for DNA inactivation and isolated chloroplast inhibition are used to estimate biologically effective irradiances on archean Earth. Comparisons are made with present day Earth. The theoretical estimations on the UV radiation screening required to protect DNA on archean Earth compare well with field and laboratory observations on protection strategies found in present day microbial communities. They suggest that many physical and biological methods may have been effective and would have allowed for the radiation of life even under the high UV radiation regimes of archean Earth. Such strategies would also have provided effective reduction of photoinhibition by UV radiation. The data also suggest that the UV regime on the surface of Mars is not a life limiting factor per se, although other environmental factors such as desiccation and low temperatures may contribute towards the apparent lack of a surface biota.

The Dose Response Relationship for Radiation Carcinogenesis

NASA Astrophysics Data System (ADS)

Hall, Eric

2008-03-01

Recent surveys show that the collective population radiation dose from medical procedures in the U.S. has increased by 750% in the past two decades. It would be impossible to imagine the practice of medicine today without diagnostic and therapeutic radiology, but nevertheless the widespread and rapidly increasing use of a modality which is a known human carcinogen is a cause for concern. To assess the magnitude of the problem it is necessary to establish the shape of the dose response relationship for radiation carcinogenesis. Information on radiation carcinogenesis comes from the A-bomb survivors, from occupationally exposed individuals and from radiotherapy patients. The A-bomb survivor data indicates a linear relationship between dose and the risk of solid cancers up to a dose of about 2.5 Sv. The lowest dose at which there is a significant excess cancer risk is debatable, but it would appear to be between 40 and 100 mSv. Data from the occupation exposure of nuclear workers shows an excess cancer risk at an average dose of 19.4 mSv. At the other end of the dose scale, data on second cancers in radiotherapy patients indicates that cancer risk does not continue to rise as a linear function of dose, but tends towards a plateau of 40 to 60 Gy, delivered in a fractionated regime. These data can be used to estimate the impact of diagnostic radiology at the low dose end of the dose response relationship, and the impact of new radiotherapy modalities at the high end of the dose response relationship. In the case of diagnostic radiology about 90% of the collective population dose comes from procedures (principally CT scans) which involve doses at which there is credible evidence of an excess cancer incidence. While the risk to the individual is small and justified in a symptomatic patient, the same is not true of some screening procedures is asymptomatic individuals, and in any case the huge number of procedures must add up to a potential public health problem. In the

The Cosmic Microwave Background Radiation - A Unique Window on the Early Universe

NASA Technical Reports Server (NTRS)

Hinshaw, Gary F.

2009-01-01

The cosmic microwave background radiation is the remnant heat from the Big Bang. It provides us with a unique probe of conditions in the early universe, long before any organized structures had yet formed. The anisotropy in the radiation's brightness yields important clues about primordial structure and additionally provides a wealth of information about the physics of the early universe. Within the framework of inflationary dark matter models, observations of the anisotropy on sub-degree angular scales reveals the signatures of acoustic oscillations of the photon-baryon fluid at a redshift of approx. 1100. Data from the first five years of operation of the Wilkinson Microwave Anisotropy Probe (WMAP) satellite provide detailed full-sky maps of the cosmic microwave background temperature and polarization anisotropy. Together, the data provide a wealth of cosmological information, including the age of the universe, the epoch when the first stars formed, and the overall composition of baryonic matter, dark matter, and dark energy. The results also provide constraints on the period of inflationary expansion in the very first moments of time.

7th International Workshop on Microbeam Probes of Cellular Radiation Response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brenner, David J.

2009-07-21

The extended abstracts that follow present a summary of the Proceedings of the 7th International Workshop: Microbeam Probes of Cellular Radiation Response, held at Columbia University’s Kellogg Center in New York City on March 15–17, 2006. These International Workshops on Microbeam Probes of Cellular Radiation Response have been held regularly since 1993 (1–5). Since the first workshop, there has been a rapid growth (see Fig. 1) in the number of centers developing microbeams for radiobiological research, and worldwide there are currently about 30 microbeams in operation or under development. Single-cell/single-particle microbeam systems can deliver beams of different ionizing radiations withmore » a spatial resolution of a few micrometers down to a few tenths of a micrometer. Microbeams can be used to addressquestions relating to the effects of low doses of radiation (a single radiation track traversing a cell or group of cells), to probe subcellular targets (e.g. nucleus or cytoplasm), and to address questions regarding the propagation of information about DNA damage (for example, the radiation-induced bystander effect). Much of the recent research using microbeams has been to study low-dose effects and ‘‘non-targeted’’ responses such as bystander effects, genomic instability and adaptive responses. This Workshop provided a forum to assess the current state of microbeam technology and current biological applications and to discuss future directions for development, both technological and biological. Over 100 participants reviewed the current state of microbeam research worldwide and reported on new technological developments in the fields of both physics and biology.« less

Rapid response radiation sensors for homeland security applications

NASA Astrophysics Data System (ADS)

Mukhopadhyay, Sanjoy; Maurer, Richard; Guss, Paul

2014-09-01

The National Security Technologies, LLC, Remote Sensing Laboratory is developing a rapid response radiation detection system for homeland security field applications. The intelligence-driven system is deployed only when non-radiological information about the target is verifiable. The survey area is often limited, so the detection range is small; in most cases covering a distance of 10 meters or less suffices. Definitive response is required in no more than 3 seconds and should minimize false negative alarms, but can err on the side of positive false alarms. The detection system is rapidly reconfigurable in terms of size, shape, and outer appearance; it is a plug-and-play system. Multiple radiation detection components (viz., two or more sodium iodide scintillators) are used to independently "over-determine" the existence of the threat object. Rapid response electronic dose rate meters are also included in the equipment suite. Carefully studied threat signatures are the basis of the decision making. The use of Rad-Detect predictive modeling provides information on the nature of the threat object. Rad-Detect provides accurate dose rate from heavily shielded large sources; for example those lost in Mexico were Category 1 radiation sources (~3,000 Ci of 60Co), the most dangerous of five categories defined by the International Atomic Energy Agency. Taken out of their shielding containers, Category 1 sources can kill anyone who is exposed to them at close range for a few minutes to an hour. Whenever possible sub-second data acquisition will be attempted, and, when deployed, the system will be characterized for false alarm rates. Although the radiation detection materials selected are fast (viz., faster scintillators), their speed is secondary to sensitivity, which is of primary importance. Results from these efforts will be discussed and demonstrated.

Short Diffusion Time Diffusion-Weighted Imaging With Oscillating Gradient Preparation as an Early Magnetic Resonance Imaging Biomarker for Radiation Therapy Response Monitoring in Glioblastoma: A Preclinical Feasibility Study.

PubMed

Bongers, Andre; Hau, Eric; Shen, Han

2018-01-04

To investigate a novel alternative diffusion-weighted imaging (DWI) approach using oscillating gradients preparation (OGSE) to obtain much shorter effective diffusion times (Δ eff ) for tumor response monitoring by apparent diffusion coefficient (ADC) mapping in a glioblastoma mouse model. Twenty-four BALB/c nude mice inoculated with U87 glioblastoma cells were randomized into a control group and an irradiation group, which underwent a 15-day fractioned radiation therapy (RT) course with 2 Gy/d. Therapy response was assessed by mapping of ADCs at 6 time points using an in-house implementation of a cos-OGSE DWI sequence with Δ eff  = 1.25 ms and compared with a standard pulsed gradient DWI protocol (PGSE) with typical clinical diffusion time Δ eff  = 18 ms. Longitudinal ADC changes in tumor and contralateral white matter (WM) were statistically assessed using repeated-measures analysis of variance and post hoc (Sidak) testing. On short Δ eff OGSE maps tumor ADC was generally 30%-50% higher than in surrounding WM. Areas correlated well with histology. Tumor identification was generally more difficult on PGSE maps owing to nonsignificant WM/tumor contrast. During RT, OGSE maps also showed significant tumor ADC increase (approximately 15%) in response to radiation, consistently seen after 14-Gy RT dose. The clinical reference (PGSE) showed lower sensitivity to radiation changes, and no significant response across the radiation group and time course could be detected. Our short Δ eff DWI method using OGSE better reflected histologically defined tumor areas and enabled more consistent and earlier detection of microstructural radiation changes than conventional methods. Oscillating gradients preparation offers significant potential as a robust microstructural RT response biomarker, potentially helping to shift important therapy decisions to earlier stages in the RT time course. Copyright © 2018 Elsevier Inc. All rights reserved.

Climate Response of Direct Radiative Forcing of Anthropogenic Black Carbon

NASA Technical Reports Server (NTRS)

Chung, Serena H.; Seinfeld,John H.

2008-01-01

The equilibrium climate effect of direct radiative forcing of anthropogenic black carbon (BC) is examined by 100-year simulations in the Goddard Institute for Space Studies General Circulation Model II-prime coupled to a mixed-layer ocean model. Anthropogenic BC is predicted to raise globally and annually averaged equilibrium surface air temperature by 0.20 K if BC is assumed to be externally mixed. The predicted increase is significantly greater in the Northern Hemisphere (0.29 K) than in the Southern Hemisphere (0.11 K). If BC is assumed to be internally mixed with the present day level of sulfate aerosol, the predicted annual mean surface temperature increase rises to 0.37 K globally, 0.54 K for the Northern Hemisphere, and 0.20 K for the Southern Hemisphere. The climate sensitivity of BC direct radiative forcing is calculated to be 0.6 K W (sup -1) square meters, which is about 70% of that of CO2, independent of the assumption of BC mixing state. The largest surface temperature response occurs over the northern high latitudes during winter and early spring. In the tropics and midlatitudes, the largest temperature increase is predicted to occur in the upper troposphere. Direct radiative forcing of anthropogenic BC is also predicted to lead to a change of precipitation patterns in the tropics; precipitation is predicted to increase between 0 and 20 N and decrease between 0 and 20 S, shifting the intertropical convergence zone northward. If BC is assumed to be internally mixed with sulfate instead of externally mixed, the change in precipitation pattern is enhanced. The change in precipitation pattern is not predicted to alter the global burden of BC significantly because the change occurs predominantly in regions removed from BC sources.

Early life socioeconomic position and immune response to persistent infections among elderly Latinos.

PubMed

Meier, Helen C S; Haan, Mary N; Mendes de Leon, Carlos F; Simanek, Amanda M; Dowd, Jennifer B; Aiello, Allison E

2016-10-01

Persistent infections, such as cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), Helicobacter pylori (H. pylori), and Toxoplasma gondii (T. gondii), are common in the U.S. but their prevalence varies by socioeconomic status. It is unclear if early or later life socioeconomic position (SEP) is a more salient driver of disparities in immune control of these infections. Using data from the Sacramento Area Latino Study on Aging, we examined whether early or later life SEP was the strongest predictor of immune control later in life by contrasting two life course models, the critical period model and the chain of risk model. Early life SEP was measured as a latent variable, derived from parental education and occupation, and food availability. Indicators for SEP in later life included education level and occupation. Individuals were categorized by immune response to each pathogen (seronegative, low, medium and high) with increasing immune response representing poorer immune control. Cumulative immune response was estimated using a latent profile analysis with higher total immune response representing poorer immune control. Structural equation models were used to examine direct, indirect and total effects of early life SEP on each infection and cumulative immune response, controlling for age and gender. The direct effect of early life SEP on immune response was not statistically significant for the infections or cumulative immune response. Higher early life SEP was associated with lower immune response for T. gondii, H. pylori and cumulative immune response through pathways mediated by later life SEP. For CMV, higher early life SEP was both directly associated and partially mediated by later life SEP. No association was found between SEP and HSV-1. Findings from this study support a chain of risk model, whereby early life SEP acts through later life SEP to affect immune response to persistent infections in older age. Copyright © 2016 Elsevier Ltd. All rights

ULTRAVIOLET PROTECTIVE PIGMENTS AND DNA DIMER INDUCTION AS RESPONSES TO ULTRAVIOLET RADIATION

EPA Science Inventory

Life on Earth has evolved adaptations to many environmental stresses over the epochs. One consistent stress has been exposure to ultraviolet (UV) radiation. The most basic effect of UV radiation on biological systems is damage to DNA. In response to UV radiation organisms have ad...

A metabolomics and mouse models approach to study inflammatory and immune responses to radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fornace, Albert J.; Li, Henghong

2013-12-02

The three-year project entitled "A Metabolomics and Mouse Models Approach to Study Inflammatory and Immune Responses to Radiation" was initiated in September 2009. The overall objectives of this project were to investigate the acute and persistent effects of low dose radiation on T cell lymphocyte function and physiology, as well the contributions of these cells to radiation-induced inflammatory responses. Inflammation after ionizing radiation (IR), even at low doses, may impact a variety of disease processes, including infectious disease, cardiovascular disease, cancer, and other potentially inflammatory disorders. There were three overall specific aims: 1. To investigate acute and persistent effects ofmore » low dose radiation on T cell subsets and function; 2. A genetic approach with mouse models to investigate p38 MAPK pathways that are involved in radiation-induced inflammatory signaling; 3. To investigate the effect of radiation quality on the inflammatory response. We have completed the work proposed in these aims.« less

Subtype-Specific Radiation Response and Therapeutic Effect of FAS Death Receptor Modulation in Human Breast Cancer.

PubMed

Lee, Chen-Ting; Zhou, Yingchun; Roy-Choudhury, Kingshuk; Siamakpour-Reihani, Sharareh; Young, Kenneth; Hoang, Peter; Kirkpatrick, John P; Chi, Jen-Tsan A; Dewhirst, Mark W; Horton, Janet K

2017-08-01

Breast cancer is the most common malignancy diagnosed among women and represents a heterogeneous group of subtypes. Radiation therapy is a critical component of treatment for breast cancer patients. However, little is known about radiation response among these intrinsic subtypes. In previous studies, we identified a significant induction of FAS after irradiation in biologically favorable breast cancer patients and breast cancer cell lines. Here, we expanded our study and investigated radiation response in a mouse model of breast cancer. MCF7 (luminal), HCC1954 (HER2 + ) or SUM159 (basal) cells were implanted orthotopically into the dorsal mammary fat pad of nude mice. These mice were then treated with different doses of radiation to assess tumor growth control. We further investigated the therapeutic effect of FAS modulation by silencing FAS in radiation-responsive tumors and injecting FAS agonist antibody into radiation-resistant tumors. Exposure to radiation inhibited MCF7, and to a lesser extent HCC1954 tumor growth in a dose-dependent manner. In contrast, SUM159 tumors were resistant to radiation. The estimated TCD 50 values were 19.3 Gy for MCF7 and 44.9 Gy for SUM159. Radiation induced FAS expression in MCF7 tumors, but not SUM159 tumors. We found that silencing of FAS did not negatively impact radiation response in MCF7 tumors, possibly due to compensation by other apoptotic pathways. On the other hand, FAS activating antibody in combination with radiation treatment delayed SUM159 and HCC1954 tumor growth. However, it did not reach statistical significance compared to radiation treatment alone. Our results suggest that there is intrinsic variation in radiation response among breast cancer subtypes. FAS activation concurrent with radiation slows tumor growth in the radiation-resistant subtypes, but the effect was not significant. Alternative subtype-specific modulators of radiation response are under investigation.

ULTRAVIOLET PROTECTIVE COMPOUNDS AS A RESPONSE TO ULTRAVIOLET RADIATION EXPOSURE

EPA Science Inventory

Life on Earth has evolved adaptations to many environmental stresses over the epochs. One consistent stress has been exposure to ultraviolet radiation. In response to UVR organisms have adapted myriad responses; behavioral, morphological and physiological. Behaviorally, some orga...

Cell phone radiations affect early growth of Vigna radiata (mung bean) through biochemical alterations.

PubMed

Sharma, Ved Parkash; Singh, Harminder Pal; Batish, Daizy Rani; Kohli, Ravinder Kumar

2010-01-01

The indiscriminate use of wireless technologies, particularly of cell phones, has increased the health risks among living organisms including plants. We investigated the impact of cell phone electromagentic field (EMF) radiations (power density, 8.55 microW cm(-2)) on germination, early growth, proteins and carbohydrate contents, and activities of some enzymes in Vigna radiata. Cell phone EMF radiations significantly reduced the seedling length and dry weight of V radiata after exposure for 0.5, 1, 2, and 4 h. Furthermore, the contents of proteins and carbohydrates were reduced in EMF-exposed plants. However, the activities of proteases, alpha-amylases, beta-amylases, polyphenol oxidases, and peroxidases were enhanced in EMF-exposed radicles indicating their role in providing protection against EMF-induced stress. The study concludes that cell phone EMFs impair early growth of V radiata seedlings by inducing biochemical changes.

FLUKA simulation of TEPC response to cosmic radiation.

PubMed

Beck, P; Ferrari, A; Pelliccioni, M; Rollet, S; Villari, R

2005-01-01

The aircrew exposure to cosmic radiation can be assessed by calculation with codes validated by measurements. However, the relationship between doses in the free atmosphere, as calculated by the codes and from results of measurements performed within the aircraft, is still unclear. The response of a tissue-equivalent proportional counter (TEPC) has already been simulated successfully by the Monte Carlo transport code FLUKA. Absorbed dose rate and ambient dose equivalent rate distributions as functions of lineal energy have been simulated for several reference sources and mixed radiation fields. The agreement between simulation and measurements has been well demonstrated. In order to evaluate the influence of aircraft structures on aircrew exposure assessment, the response of TEPC in the free atmosphere and on-board is now simulated. The calculated results are discussed and compared with other calculations and measurements.

Genetic differences in transcript responses to low-dose ionizing radiation identify tissue functions associated with breast cancer susceptibility.

PubMed

Snijders, Antoine M; Marchetti, Francesco; Bhatnagar, Sandhya; Duru, Nadire; Han, Ju; Hu, Zhi; Mao, Jian-Hua; Gray, Joe W; Wyrobek, Andrew J

2012-01-01

High dose ionizing radiation (IR) is a well-known risk factor for breast cancer but the health effects after low-dose (LD, <10 cGy) exposures remain highly uncertain. We explored a systems approach that compared LD-induced chromosome damage and transcriptional responses in strains of mice with genetic differences in their sensitivity to radiation-induced mammary cancer (BALB/c and C57BL/6) for the purpose of identifying mechanisms of mammary cancer susceptibility. Unirradiated mammary and blood tissues of these strains differed significantly in baseline expressions of DNA repair, tumor suppressor, and stress response genes. LD exposures of 7.5 cGy (weekly for 4 weeks) did not induce detectable genomic instability in either strain. However, the mammary glands of the sensitive strain but not the resistant strain showed early transcriptional responses involving: (a) diminished immune response, (b) increased cellular stress, (c) altered TGFβ-signaling, and (d) inappropriate expression of developmental genes. One month after LD exposure, the two strains showed opposing responses in transcriptional signatures linked to proliferation, senescence, and microenvironment functions. We also discovered a pre-exposure expression signature in both blood and mammary tissues that is predictive for poor survival among human cancer patients (p = 0.0001), and a post-LD-exposure signature also predictive for poor patient survival (p<0.0001). There is concordant direction of expression in the LD-exposed sensitive mouse strain, in biomarkers of human DCIS and in biomarkers of human breast tumors. Our findings support the hypothesis that genetic mechanisms that determine susceptibility to LD radiation induced mammary cancer in mice are similar to the tissue mechanisms that determine poor-survival in breast cancer patients. We observed non-linearity of the LD responses providing molecular evidence against the LNT risk model and obtained new evidence that LD responses are strongly

WE-FG-202-02: Exploration of High-Resolution Quantitative Ultrasonic Micro-Vascular Imaging for Early Assessment of Radiotherapy Tumor Response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kasoji, S; Rivera, J; Dayton, P

Purpose: Currently, we cannot predict an individual patient’s response to a given radiotherapy which normally is not detected for weeks to months post-treatment. As a result, precious time is wasted for patients with unresponsive tumors who could have switched to an alternative treatment much earlier. Presently, no early treatment response detection method exists that is effective, low-cost, non-invasive, and safe. We hypothesize that changes in tumor microvasculature predict tumor response to radiotherapy earlier than tumor volume changes. Recent radiobiology research suggests tumors undergo vascular remodeling in response to radiation well before manifesting changes in tumor volume. We propose monitoring tumormore » microvasculature post-radiation using Acoustic Angiography (AA), a novel ultrasound imaging modality developed and patented in-house. In this study, we investigate whether changes in tumor microvasculature, measured using AA, can be an early indicator of high-dose radiotherapy success, compared to changes in tumor volume. Methods: Fibrosarcoma xenograft tumor tissue was subcutaneously implanted into rodent flanks (N=10). Animal tumors (N=8) were irradiated with a single treatment of 15Gy using a clinical LINAC at 100SSD and 2×2cm field size. Two untreated rats were left as tumor controls. AA imaging was performed immediately posttreatment and every third day thereafter for 30 days, or until tumors disappeared. Tumor volumes and vascular densities were measured from anatomical b-mode ultrasound and AA images, respectively. Results: Statistical differences in vascular density between treatment responders and non-responders were observed on Day 10 (p=0.005), whereas statistical differences in tumor volume were not observed until Day 19 (p=0.02). Conclusions: Tumor vascularity differences may be observed substantially earlier than differences in tumor size. In addition, significant early increases in vascular density were observed in non

Radiation impedance of condenser microphones and their diffuse-field responses.

PubMed

Barrera-Figueroa, Salvador; Rasmussen, Knud; Jacobsen, Finn

2010-04-01

The relation between the diffuse-field response and the radiation impedance of a microphone has been investigated. Such a relation can be derived from classical theory. The practical measurement of the radiation impedance requires (a) measuring the volume velocity of the membrane of the microphone and (b) measuring the pressure on the membrane of the microphone. The first measurement is carried out by means of laser vibrometry. The second measurement cannot be implemented in practice. However, the pressure on the membrane can be calculated numerically by means of the boundary element method. In this way, a hybrid estimate of the radiation impedance is obtained. The resulting estimate of the diffuse-field response is compared with experimental estimates of the diffuse-field response determined using reciprocity and the random-incidence method. The different estimates are in good agreement at frequencies below the resonance frequency of the microphone. Although the method may not be of great practical utility, it provides a useful validation of the estimates obtained by other means.

10 CFR 35.2024 - Records of authority and responsibilities for radiation protection programs.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Records of authority and responsibilities for radiation protection programs. 35.2024 Section 35.2024 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Records § 35.2024 Records of authority and responsibilities for radiation protection programs. (a...

10 CFR 35.2024 - Records of authority and responsibilities for radiation protection programs.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Records of authority and responsibilities for radiation protection programs. 35.2024 Section 35.2024 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Records § 35.2024 Records of authority and responsibilities for radiation protection programs. (a...

10 CFR 35.2024 - Records of authority and responsibilities for radiation protection programs.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Records of authority and responsibilities for radiation protection programs. 35.2024 Section 35.2024 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Records § 35.2024 Records of authority and responsibilities for radiation protection programs. (a...

10 CFR 35.2024 - Records of authority and responsibilities for radiation protection programs.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Records of authority and responsibilities for radiation protection programs. 35.2024 Section 35.2024 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Records § 35.2024 Records of authority and responsibilities for radiation protection programs. (a...

10 CFR 35.2024 - Records of authority and responsibilities for radiation protection programs.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Records of authority and responsibilities for radiation protection programs. 35.2024 Section 35.2024 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Records § 35.2024 Records of authority and responsibilities for radiation protection programs. (a...

Response of asymmetric carbon nanotube network devices to sub-terahertz and terahertz radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gayduchenko, I., E-mail: igorandg@gmail.com, E-mail: gefedorov@mail.ru; National Research Centre “Kurchatov Institute,” Moscow 123128; Kardakova, A.

2015-11-21

Demand for efficient terahertz radiation detectors resulted in intensive study of the asymmetric carbon nanostructures as a possible solution for that problem. It was maintained that photothermoelectric effect under certain conditions results in strong response of such devices to terahertz radiation even at room temperature. In this work, we investigate different mechanisms underlying the response of asymmetric carbon nanotube (CNT) based devices to sub-terahertz and terahertz radiation. Our structures are formed with CNT networks instead of individual CNTs so that effects probed are more generic and not caused by peculiarities of an individual nanoscale object. We conclude that the DCmore » voltage response observed in our structures is not only thermal in origin. So called diode-type response caused by asymmetry of the device IV characteristic turns out to be dominant at room temperature. Quantitative analysis provides further routes for the optimization of the device configuration, which may result in appearance of novel terahertz radiation detectors.« less

Radiation response of nanotwinned Cu under multiple-collision cascades

NASA Astrophysics Data System (ADS)

Wu, Lianping; Yu, Wenshan; Hu, Shuling; Shen, Shengping

2018-07-01

In this paper, multiple collision cascades (MCC) of nanotwinned (nt) Cu with three different twin spacings are performed to model the response of nt Cu upon a radiation dose of 1 displacements per atom (dpa). Considering the defects developed with high randomness in the material during a MCC process, each MCC in a nt Cu is conducted for eight times. This enables us to analyze some average properties of defect clusters in the radiated nt Cu with different twin spacings at the different radiation doses. We also analyze the microstructural evolution in the nt Cu during the MCC. Smaller size of defect clusters and lower defect density are seen in the nt Cu with smaller twin spacing. In addition, a number of defect clusters could be removed via their frequent interactions with the coherent twin boundaries (CTBs) during the MCC. This induces either the migration of CTBs or the healing of CTBs. Moreover, the potential formation and elimination mechanisms of stacking fault are found to be due to the climb of Frank partial dislocation and glide of Shockley partial dislocations. This study provides further evidence on the irradiation tolerance of CTBs and the self-healing capability of CTBs in response to radiation.

The response of Galileo aft cover components to laser radiation

NASA Technical Reports Server (NTRS)

Metzger, J. W.

1982-01-01

The aft region of the Galileo probe will be subjected to severe heat transfer rates dominated by the radiation contributions. To assess the response of several vehicle aft region components to thermal radiation, tests employing a 10 KW CO2 laser were conducted. The experiments evaluated the annulus/aft cover interface, the umbilical feedthrough assembly and the mortar cover seal assembly. Experimental evidence of the response of the phenolic nylon heatshield and quantitative measures of its effect on gap geometries of several vehicle components were acquired. In addition, qualitative measures of the survivability of the irradiated components were obtained.

Early-life inflammation, immune response and ageing.

PubMed

Khan, Imroze; Agashe, Deepa; Rolff, Jens

2017-03-15

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. © 2017 The Author(s).

Early-life inflammation, immune response and ageing

PubMed Central

2017-01-01

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. PMID:28275145

Low-Dose Consolidation Radiation Therapy for Early Stage Unfavorable Hodgkin Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Torok, Jordan A., E-mail: jordan.torok@dm.duke.edu; Wu, Yuan; Prosnitz, Leonard R.

Purpose: The German Hodgkin Study Group (GHSG) trial HD11 established 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and 30 Gy of radiation therapy (RT) as a standard for early stage (I, II), unfavorable Hodgkin lymphoma (HL). Additional cycles of ABVD may allow for a reduction in RT dose and improved toxicity profile. Methods and Materials: Patients treated with combined modality therapy at the Duke Cancer Institute for early stage, unfavorable HL by GHSG criteria from 1994 to 2012 were included. Patients who did not undergo post-chemotherapy functional imaging (positron emission tomography or gallium imaging) or who failed to achievemore » a complete response were excluded. Clinical outcomes were estimated using the Kaplan-Meier method. Late effects were also evaluated. Results: A total of 90 patients met inclusion criteria for analysis. Median follow-up was 5 years. Chemotherapy consisted primarily of ABVD (88%) with a median number of 6 cycles. The median dose of consolidation RT was 23.4 Gy. Four patients had relapses, 2 of which were in-field. Ten-year progression-free survival (PFS) and overall survival (OS) were 93% (95% confidence interval [CI]: 0.82-0.97) and 98% (95% CI: 0.92-0.99), respectively. For the subset of patients (n=46) who received 5 to 6 cycles of chemotherapy and ≤24 Gy, the 10-year PFS and OS values were 88% (95% CI: 70%-96%) and 98% (95% CI: 85% - 99%), respectively. The most common late effect was hypothyroidism (20%) with no cardiac complications. Seven secondary malignancies were diagnosed, with only 1 arising within the RT field. Conclusions: Lower doses of RT may be sufficient when combined with more than 4 cycles of ABVD for early stage, unfavorable HL and may result in a more favorable toxicity profile than 4 cycles of ABVD and 30 Gy of RT.« less

Climate Response to Negative Greenhouse Gas Radiative Forcing in Polar Winter

NASA Astrophysics Data System (ADS)

Flanner, M. G.; Huang, X.; Chen, X.; Krinner, G.

2018-02-01

Greenhouse gas (GHG) additions to Earth's atmosphere initially reduce global outgoing longwave radiation, thereby warming the planet. In select environments with temperature inversions, however, increased GHG concentrations can actually increase local outgoing longwave radiation. Negative top of atmosphere and effective radiative forcing (ERF) from this situation give the impression that local surface temperatures could cool in response to GHG increases. Here we consider an extreme scenario in which GHG concentrations are increased only within the warmest layers of winter near-surface inversions of the Arctic and Antarctic. We find, using a fully coupled Earth system model, that the underlying surface warms despite the GHG addition exerting negative ERF and cooling the troposphere in the vicinity of the GHG increase. This unique radiative forcing and thermal response is facilitated by the high stability of the polar winter atmosphere, which inhibit thermal mixing and amplify the impact of surface radiative forcing on surface temperature. These findings also suggest that strategies to exploit negative ERF via injections of short-lived GHGs into inversion layers would likely be unsuccessful in cooling the planetary surface.

Selection towards different adaptive optima drove the early diversification of locomotor phenotypes in the radiation of Neotropical geophagine cichlids.

PubMed

Astudillo-Clavijo, Viviana; Arbour, Jessica H; López-Fernández, Hernán

2015-05-01

Simpson envisaged a conceptual model of adaptive radiation in which lineages diversify into "adaptive zones" within a macroevolutionary adaptive landscape. However, only a handful of studies have empirically investigated this adaptive landscape and its consequences for our interpretation of the underlying mechanisms of phenotypic evolution. In fish radiations the evolution of locomotor phenotypes may represent an important dimension of ecomorphological diversification given the implications of locomotion for feeding and habitat use. Neotropical geophagine cichlids represent a newly identified adaptive radiation and provide a useful system for studying patterns of locomotor diversification and the implications of selective constraints on phenotypic divergence in general. We use multivariate ordination, models of phenotypic evolution and posterior predictive approaches to investigate the macroevolutionary adaptive landscape and test for evidence of early divergence of locomotor phenotypes in Geophagini. The evolution of locomotor phenotypes was characterized by selection towards at least two distinct adaptive peaks and the early divergence of modern morphological disparity. One adaptive peak included the benthic and epibenthic invertivores and was characterized by fishes with deep, laterally compressed bodies that optimize precise, slow-swimming manoeuvres. The second adaptive peak resulted from a shift in adaptive optima in the species-rich ram-feeding/rheophilic Crenicichla-Teleocichla clade and was characterized by species with streamlined bodies that optimize fast starts and rapid manoeuvres. Evolutionary models and posterior predictive approaches favoured an early shift to a new adaptive peak over decreasing rates of evolution as the underlying process driving the early divergence of locomotor phenotypes. The influence of multiple adaptive peaks on the divergence of locomotor phenotypes in Geophagini is compatible with the expectations of an ecologically driven

Diagnostic Biodosimetry Response for Radiation Disasters: Current Research and Service Activities at AFRRI

DTIC Science & Technology

2004-06-01

address the need for triage, based on early physical assessments, bioindicators , and biological assessments, in order to aid clinical management of... bioindicator for radiation exposure, Strahlentherapy Onkol., 166: 688-95. [IAEA] Cytogenetic analysis for radiation dose assessment. A manual...Name: Dr Rios-Tejada (SP) Question: Is there relevance of biodosimetry in air crews who fly high and at high latitudes? Author’s Reply: The

Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

PubMed

Kogawa, T; Doi, A; Shimokawa, M; Fouad, T M; Osuga, T; Tamura, F; Mizushima, T; Kimura, T; Abe, S; Ihara, H; Kukitsu, T; Sumiyoshi, T; Yoshizaki, N; Hirayama, M; Sasaki, T; Kawarada, Y; Kitashiro, S; Okushiba, S; Kondo, H; Tsuji, Y

2015-03-01

Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

Pediatric CT and radiation: our responsibility

NASA Astrophysics Data System (ADS)

Frush, Donald P.

2009-02-01

In order to discuss the cost-benefit ratio of CT examinations in children, one must be familiar with the reasons why CT can provide a high collective or individual dose. The reasons include increasing CT use as well as lack of attention to dose reduction strategies. While those have been substantial efforts for dose reduction, additional work is necessary to prevent unnecessary radiation exposure. This responsibility is shared between science and medicine, industry, regulatory agencies, and patients as well.

In silico nanodosimetry: new insights into nontargeted biological responses to radiation.

PubMed

Kuncic, Zdenka; Byrne, Hilary L; McNamara, Aimee L; Guatelli, Susanna; Domanova, Westa; Incerti, Sébastien

2012-01-01

The long-held view that radiation-induced biological damage must be initiated in the cell nucleus, either on or near DNA itself, is being confronted by mounting evidence to suggest otherwise. While the efficacy of cell death may be determined by radiation damage to nuclear DNA, a plethora of less deterministic biological responses has been observed when DNA is not targeted. These so-called nontargeted responses cannot be understood in the framework of DNA-centric radiobiological models; what is needed are new physically motivated models that address the damage-sensing signalling pathways triggered by the production of reactive free radicals. To this end, we have conducted a series of in silico experiments aimed at elucidating the underlying physical processes responsible for nontargeted biological responses to radiation. Our simulation studies implement new results on very low-energy electromagnetic interactions in liquid water (applicable down to nanoscales) and we also consider a realistic simulation of extranuclear microbeam irradiation of a cell. Our results support the idea that organelles with important functional roles, such as mitochondria and lysosomes, as well as membranes, are viable targets for ionizations and excitations, and their chemical composition and density are critical to determining the free radical yield and ensuing biological responses.

Radiation Exposure and Mortality from Cardiovascular Disease and Cancer in Early NASA Astronauts: Space for Exploration

NASA Technical Reports Server (NTRS)

Elgart, S. R.; Little, M. P.; Campbell, L. J.; Milder, C. M.; Shavers, M. R.; Huff, J. L.; Patel, Z. S.

2018-01-01

Of the many possible health challenges posed during extended exploratory missions to space, the effects of space radiation on cardiovascular disease and cancer are of particular concern. There are unique challenges to estimating those radiation risks; care and appropriate and rigorous methodology should be applied when considering small cohorts such as the NASA astronaut population. The objective of this work was to establish whether there is evidence for excess cardiovascular disease or cancer mortality in an early NASA astronaut cohort and determine if a correlation exists between space radiation exposure and mortality.

THE METABOLIC RESPONSE TO RADIATION IN THE PRIMATE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hunter, C.G.

1959-10-31

At present there is little information available concerning the metabolism of man following exposure to ionizing radiation in the lethal range. Reference is made in vague terms to the maintenance of fluid and electrolytes, the administration of a bland diet, intravenous glucose, salines etc., with little experimental evidence from primate studies to indicate the benefit of these modes of therapy. It is felt, therefore, that results of metabolic studies made in sub-human primates will be of therapeutic interest. Adult monkeys of both sexes were exposed to whole-body irradiation with x and gamma rays. The absorbed doses were in the sub-lethalmore » and lower lethal range for monkeys (400 to 500 r), and were administered at rates varying from 7 to 124 r/min. Observations were made on eleven monkeys that were kept in metabolic cages before and after irradiation. The derangement of metabolism consequent to irradiation was studied. After physioiogical recovery of eight surviving animals, the experiment was repeated using identical dietary intake and experimental technique but omitting irradiation. Comparisons were then raade between the results of the irradiation study and those obtained after physiological recovery. Data are presented on the clinical physiology of representative animals, including data on body weights, food and fluid intakes, urine and faecal outputs, insensible losses, metabolic rates, balances of water, nitrogen and electrolytes, nitrogen utilization, and caloric intakes. It is concluded that the metabolic response to radiation injury in the lethal range does not differ qualitatively in the primate from that of any injury and that the irradiated primate is not at a disadvantage until the time of anabolic response. At that time the tissues responsible for normal reparative processes, themselves injured by the radiation, are no longer able to perform normal restorative functions, the resultant catabolism being in excess of that from equivalent injury

Anomalous response of superconducting titanium nitride resonators to terahertz radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bueno, J., E-mail: j.bueno@sron.nl; Baselmans, J. J. A; Coumou, P. C. J. J.

We present an experimental study of kinetic inductance detectors (KIDs) fabricated of atomic layer deposited TiN films and characterized at radiation frequencies of 350 GHz. The responsivity to radiation is measured and found to increase with the increase in radiation powers, opposite to what is expected from theory and observed for hybrid niobium titanium nitride/aluminium (NbTiN/Al) and all-aluminium (all-Al) KIDs. The noise is found to be independent of the level of the radiation power. The noise equivalent power improves with higher radiation powers, also opposite to what is observed and well understood for hybrid NbTiN/Al and all-Al KIDs. We suggestmore » that an inhomogeneous state of these disordered superconductors should be used to explain these observations.« less

Istanbul Earthquake Early Warning and Rapid Response System

NASA Astrophysics Data System (ADS)

Erdik, M. O.; Fahjan, Y.; Ozel, O.; Alcik, H.; Aydin, M.; Gul, M.

2003-12-01

As part of the preparations for the future earthquake in Istanbul a Rapid Response and Early Warning system in the metropolitan area is in operation. For the Early Warning system ten strong motion stations were installed as close as possible to the fault zone. Continuous on-line data from these stations via digital radio modem provide early warning for potentially disastrous earthquakes. Considering the complexity of fault rupture and the short fault distances involved, a simple and robust Early Warning algorithm, based on the exceedance of specified threshold time domain amplitude levels is implemented. The band-pass filtered accelerations and the cumulative absolute velocity (CAV) are compared with specified threshold levels. When any acceleration or CAV (on any channel) in a given station exceeds specific threshold values it is considered a vote. Whenever we have 2 station votes within selectable time interval, after the first vote, the first alarm is declared. In order to specify the appropriate threshold levels a data set of near field strong ground motions records form Turkey and the world has been analyzed. Correlations among these thresholds in terms of the epicenter distance the magnitude of the earthquake have been studied. The encrypted early warning signals will be communicated to the respective end users by UHF systems through a "service provider" company. The users of the early warning signal will be power and gas companies, nuclear research facilities, critical chemical factories, subway system and several high-rise buildings. Depending on the location of the earthquake (initiation of fault rupture) and the recipient facility the alarm time can be as high as about 8s. For the rapid response system one hundred 18 bit-resolution strong motion accelerometers were placed in quasi-free field locations (basement of small buildings) in the populated areas of the city, within an area of approximately 50x30km, to constitute a network that will enable early

Radiation protection issues on preparedness and response for a severe nuclear accident: experiences of the Fukushima accident.

PubMed

Homma, T; Takahara, S; Kimura, M; Kinase, S

2015-06-01

Radiation protection issues on preparedness and response for a severe nuclear accident are discussed in this paper based on the experiences following the accident at Fukushima Daiichi nuclear power plant. The criteria for use in nuclear emergencies in the Japanese emergency preparedness guide were based on the recommendations of International Commission of Radiological Protection (ICRP) Publications 60 and 63. Although the decision-making process for implementing protective actions relied heavily on computer-based predictive models prior to the accident, urgent protective actions, such as evacuation and sheltering, were implemented effectively based on the plant conditions. As there were no recommendations and criteria for long-term protective actions in the emergency preparedness guide, the recommendations of ICRP Publications 103, 109, and 111 were taken into consideration in determining the temporary relocation of inhabitants of heavily contaminated areas. These recommendations were very useful in deciding the emergency protective actions to take in the early stages of the Fukushima accident. However, some suggestions have been made for improving emergency preparedness and response in the early stages of a severe nuclear accident. © The Chartered Institution of Building Services Engineers 2014.

Observing the Cosmic Microwave Background Radiation: A Unique Window on the Early Universe

NASA Technical Reports Server (NTRS)

Hinshaw, Gary; Fisher, Richard R. (Technical Monitor)

2001-01-01

The cosmic microwave background radiation is the remnant heat from the Big Bang. It provides us with a unique probe of conditions in the early universe, long before any organized structures had yet formed. The anisotropy in the radiation's brightness yields important clues about primordial structure and additionally provides a wealth of information about the physics,of the early universe. Within the framework of inflationary dark matter models observations of the anisotropy on sub-degree angular scales will reveal the signatures of acoustic oscillations of the photon-baryon fluid at a redshift of approx. 1100. The validity of inflationary models will be tested and, if agreement is found, accurate values for most of the key cosmological parameters will result. If disagreement is found, we will need to rethink our basic ideas about the physics of the early universe. I will present an overview of the physical processes at work in forming the anisotropy and discuss what we have already learned from current observations. I will conclude with a brief overview of the recently launched Microwave Anisotropy Probe (MAP) mission which will observe the anisotropy over the full sky with 0.21 degree angular resolution. At the time of this meeting, MAP will have just arrived at the L2 Lagrange point, marking the start of its observing campaign. The MAP hardware is being produced by Goddard in partnership with Princeton University.

Deconvolving the temporal response of photoelectric x-ray detectors for the diagnosis of pulsed radiations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zou, Shiyang; Song, Peng; Pei, Wenbing

2013-09-15

Based on the conjugate gradient method, a simple algorithm is presented for deconvolving the temporal response of photoelectric x-ray detectors (XRDs) to reconstruct the resolved time-dependent x-ray fluxes. With this algorithm, we have studied the impact of temporal response of XRD on the radiation diagnosis of hohlraum heated by a short intense laser pulse. It is found that the limiting temporal response of XRD not only postpones the rising edge and peak position of x-ray pulses but also smoothes the possible fluctuations of radiation fluxes. Without a proper consideration of the temporal response of XRD, the measured radiation flux canmore » be largely misinterpreted for radiation pulses of a hohlraum heated by short or shaped laser pulses.« less

Macrophage and tumor cell responses to repetitive pulsed X-ray radiation

NASA Astrophysics Data System (ADS)

Buldakov, M. A.; Tretyakova, M. S.; Ryabov, V. B.; Klimov, I. A.; Kutenkov, O. P.; Kzhyshkowska, J.; Bol'shakov, M. A.; Rostov, V. V.; Cherdyntseva, N. V.

2017-05-01

To study a response of tumor cells and macrophages to the repetitive pulsed low-dose X-ray radiation. Methods. Tumor growth and lung metastasis of mice with an injected Lewis lung carcinoma were analysed, using C57Bl6. Monocytes were isolated from a human blood, using CD14+ magnetic beads. IL6, IL1-betta, and TNF-alpha were determined by ELISA. For macrophage phenotyping, a confocal microscopy was applied. “Sinus-150” was used for the generation of pulsed X-ray radiation (the absorbed dose was below 0.1 Gy, the pulse repetition frequency was 10 pulse/sec). The irradiation of mice by 0.1 Gy pulsed X-rays significantly inhibited the growth of primary tumor and reduced the number of metastatic colonies in the lung. Furthermore, the changes in macrophage phenotype and cytokine secretion were observed after repetitive pulsed X-ray radiation. Conclusion. Macrophages and tumor cells had a different response to a low-dose pulsed X-ray radiation. An activation of the immune system through changes of a macrophage phenotype can result in a significant antitumor effect of the low-dose repetitive pulsed X-ray radiation.

Response Modeling of Lightweight Charring Ablators and Thermal Radiation Testing Results

NASA Technical Reports Server (NTRS)

Congdon, William M.; Curry, Donald M.; Rarick, Douglas A.; Collins, Timothy J.

2003-01-01

Under NASA's In-Space Propulsion/Aerocapture Program, ARA conducted arc-jet and thermal-radiation ablation test series in 2003 for advanced development, characterization, and response modeling of SRAM-20, SRAM-17, SRAM-14, and PhenCarb-20 ablators. Testing was focused on the future Titan Explorer mission. Convective heating rates (CW) were as high as 153 W/sq cm in the IHF and radiation rates were 100 W/sq cm in the Solar Tower Facility. The ablators showed good performance in the radiation environment without spallation, which was initially a concern, but they also showed higher in-depth temperatures when compared to analytical predictions based on arc-jet thermal-ablation response models. More testing in 2003 is planned in both of these facility to generate a sufficient data base for Titan TPS engineering.

Early feeding and early life housing conditions influence the response towards a noninfectious lung challenge in broilers.

PubMed

Simon, K; de Vries Reilingh, G; Bolhuis, J E; Kemp, B; Lammers, A

2015-09-01

Early life conditions such as feed and water availability immediately post hatch (PH) and housing conditions may influence immune development and therefore immune reactivity later in life. The current study addressed the consequences of a combination of these 2 early life conditions for immune reactivity, i.e., the specific antibody response towards a non-infectious lung challenge. Broiler chicks received feed and water either immediately p.h. or with a 72 h delay and were either reared in a floor or a cage system. At 4 weeks of age, chicks received either an intra-tracheally administered Escherichia coli lipopolysaccharide (LPS)/Human Serum Albumin (HUSA) challenge or a placebo, and antibody titers were measured up to day 14 after administration of the challenge. Chicks housed on the floor and which had a delayed access to feed p.h. showed the highest antibody titers against HuSA. These chicks also showed the strongest sickness response and poorest performance in response to the challenge, indicating that chicks with delayed access to feed might be more sensitive to an environment with higher antigenic pressure. In conclusion, results from the present study show that early life feeding strategy and housing conditions influence a chick's response to an immune challenge later in life. These 2 early life factors should therefore be taken into account when striving for a balance between disease resistance and performance in poultry. © 2015 Poultry Science Association Inc.

Defining Clinical Response Criteria and Early Response Criteria for Precision Oncology: Current State-of-the-Art and Future Perspectives.

PubMed

Subbiah, Vivek; Chuang, Hubert H; Gambhire, Dhiraj; Kairemo, Kalevi

2017-02-15

In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for "go" versus "no go" decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords "response assessment" and various known response assessment criteria published up to 2016. In this article we review the commonly used response assessment criteria. We present a decision tree to facilitate selection of appropriate criteria. We also suggest methods for standardization of various response assessment criteria. The relevant response assessment criteria were further studied for rational of development, key features, proposed use and acceptance by various entities. We also discuss early response evaluation and provide specific case studies of early response to targeted therapy. With high-throughput, advanced computing programs and digital data-mining it is now possible to acquire vast amount of high quality imaging data opening up a new field of "omics in radiology"-radiomics that complements genomics for personalized medicine. Radiomics is rapidly evolving and is still in the research arena. This cutting-edge technology is poised to move soon to the mainstream clinical arena. Novel agents with new mechanisms of action require advanced molecular imaging as imaging biomarkers. There is an urgent need for development of standardized early response assessment criteria for evaluation of response to precision therapy.

Monitoring early response to chemoradiotherapy with 18F-FMISO dynamic PET in head and neck cancer.

PubMed

Grkovski, Milan; Lee, Nancy Y; Schöder, Heiko; Carlin, Sean D; Beattie, Bradley J; Riaz, Nadeem; Leeman, Jonathan E; O'Donoghue, Joseph A; Humm, John L

2017-09-01

There is growing recognition that biologic features of the tumor microenvironment affect the response to cancer therapies and the outcome of cancer patients. In head and neck cancer (HNC) one such feature is hypoxia. We investigated the utility of 18 F-fluoromisonidazole (FMISO) dynamic positron emission tomography (dPET) for monitoring the early microenvironmental response to chemoradiotherapy in HNC. Seventy-two HNC patients underwent FMISO dPET scans in a customized immobilization mask (0-30 min dynamic acquisition, followed by 10 min static acquisitions starting at ∼95 min and ∼160 min post-injection) at baseline and early into treatment where patients have already received one cycle of chemotherapy and anywhere from five to ten fractions of 2 Gy per fraction radiation therapy. Voxelwise pharmacokinetic modeling was conducted using an irreversible one-plasma two-tissue compartment model to calculate surrogate biomarkers of tumor hypoxia (k 3 and Tumor-to-Blood Ratio (TBR)), perfusion (K 1 ) and FMISO distribution volume (DV). Additionally, Tumor-to-Muscle Ratios (TMR) were derived by visual inspection by an experienced nuclear medicine physician, with TMR > 1.2 defining hypoxia. One hundred and thirty-five lesions in total were analyzed. TBR, k 3 and DV decreased on early response scans, while no significant change was observed for K 1 . The k 3 -TBR correlation decreased substantially from baseline scans (Pearson's r = 0.72 and 0.76 for mean intratumor and pooled voxelwise values, respectively) to early response scans (Pearson's r = 0.39 and 0.40, respectively). Both concordant and discordant examples of changes in intratumor k 3 and TBR were identified; the latter partially mediated by the change in DV. In 13 normoxic patients according to visual analysis (all having lesions with TMR = 1.2), subvolumes were identified where k 3 indicated the presence of hypoxia. Pharmacokinetic modeling of FMISO dynamic PET reveals a more detailed

PLANT PROTECTIVE RESPONSE TO ENHANCED UV-B RADIATION UNDER FIELD CONDITIONS: LEAF OPTICAL PROPERTIES AND PHOTOSYNTHESIS

EPA Science Inventory

Plants of Vicia faba were grown in the field during early to midsummer while receiving two levels of supplemental UV-B radiation. Light-saturated photosynthesis and stomatal diffusive conductance of intact leaves did not show any indications of UV-radiation damage. Supplemental U...

Radiation response and electrical properties of polymer energy storage capacitors: PVF2, Polysulfone, and Mylar

NASA Technical Reports Server (NTRS)

Edwards, L. R.

1981-01-01

Efforts were made to develop a polymer film capacitor that is tolerant to radiation. The capacitors are to be utilized in a high voltage pulse discharge application. Radiation response data at high dose/dose rate levels are presented for polyvinylidene fluoride (PVF2), polysulfone, and Mylar. The results show that PVF2 is the most radiation tolerant while Mylar is the least tolerant. The data also show that the radiation response is quite dependent on operating electric stress.

Different responses of tumor and normal cells to low-dose radiation

PubMed Central

Liu, Ning; Wang, Hao; Shang, Qingjun; Jiang, Peng; Zhang, Yuanmei

2013-01-01

Aim of the study We demonstrated stimulation of both erythrocyte immune function and superoxide dismutase activity in tumor-bearing mice in response to whole-body 75 mGy X-rays. In addition, we enhanced the chemotherapeutic effect by exposing tumor-bearing mice to low-dose radiation (LDR). This study aims to investigate the different responses of tumor cells and normal cells to LDR. Material and methods Survival fraction, micronucleus frequency, and cell cycle of Lewis cells and primary human fibroblast AG01522 cells were measured. S180 sarcoma cells were implanted in mice, and tumor sizes were measured in vivo. Results In response to LDR exposure in vitro, a stimulating effect was observed in AG01522 cells but not in Lewis cells. Low-dose radiation did not cause an adaptive response in the Lewis cell cycle. Lack of an LDR-induced radioadaptive response in tumor cells was observed in tumor-bearing mouse models. Furthermore, a higher apoptotic effect and lower expression of the anti-apoptosis gene Bcl-2 were found in tumor cells of tumor-bearing mice exposed to D1 + D2 than those in tumor cells of tumor-bearing mice exposed to D2 alone. Conclusions Different responses of tumor cells and normal cells to LDR were found. Low-dose radiation was found to stimulate the growth of normal cells but not of tumor cells in vitro and in vivo, which is a very important and clinically relevant phenomenon. PMID:24592123

Role of Stereotactic Body Radiation Therapy Before Orthotopic Liver Transplantation: Retrospective Evaluation of Pathologic Response and Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mannina, Edward Michael, E-mail: emmannina@gmail.com; Cardenes, Higinia Rosa; Lasley, Foster D.

Purpose: To analyze the results of stereotactic body radiation therapy (SBRT) in patients with early-stage, localized hepatocellular carcinoma who underwent definitive orthotopic liver transplantation (OLT). Methods and Materials: The subjects of this retrospective report are 38 patients diagnosed with hepatocellular carcinoma who underwent SBRT per institutional phase 1 to 2 eligibility criteria, before definitive OLT. Pre-OLT radiographs were compared with pathologic gold standard. Analysis of treatment failures and deaths was undertaken. Results: With median follow-up of 4.8 years from OLT, 9 of 38 patients (24%) recurred, whereas 10 of 38 patients (26%) died. Kaplan-Meier estimates of 3-year overall survival and disease-free survivalmore » are 77% and 74%, respectively. Sum longest dimension of tumors was significantly associated with disease-free survival (hazard ratio 1.93, P=.026). Pathologic response rate (complete plus partial response) was 68%. Radiographic scoring criteria performed poorly; modified Response Evaluation Criteria in Solid Tumors produced highest concordance (κ = 0.224). Explants revealed viable tumor in 74% of evaluable patients. Treatment failures had statistically larger sum longest dimension of tumors (4.0 cm vs 2.8 cm, P=.014) and non–statistically significant higher rates of lymphovascular space invasion (44% vs 17%), cT2 disease (44% vs 21%), ≥pT2 disease (67% vs 34%), multifocal tumors at time of SBRT (44% vs 21%), and less robust mean α-fetoprotein response (−25 IU/mL vs −162 IU/mL). Conclusions: Stereotactic body radiation therapy before to OLT is a well-tolerated treatment providing 68% pathologic response, though 74% of explants ultimately contained viable tumor. Radiographic response criteria poorly approximate pathology. Our data suggest further stratification of patients according to initial disease burden and treatment response.« less

Plant Responses to Increased UV-B Radiation: A Research Project

NASA Technical Reports Server (NTRS)

DAntoni, H. L.; Skiles, J. W.; Armstrong, R.; Coughlan, J.; Daleo, G.; Mayoral, A.; Lawless, James G. (Technical Monitor)

1994-01-01

Ozone decrease implies more ultraviolet-B (UV-B) radiation reaching the surface of the Earth. Increased UV-B radiation triggers responses by living organisms. Despite the large potential impacts on vegetation, little is known about UV-B effects on terrestrial ecosystems. Long-term ecological studies are needed to quantify the effects of increased UV radiation on terrestrial ecosystems, asses the risks, and produce reliable data for prediction. Screening pigments are part of one of the protective mechanism in plants. Higher concentrations of screening pigments in leaves may be interpreted as a response to increased UV radiation. If the screening effect is not sufficient, important molecules will be disturbed by incoming radiation. Thus, genetics, photosynthesis, growth, plant and leaf shape and size, and pollen grains may be affected. This will have an impact on ecosystem dynamics, structure and productivity. It is necessary to monitor selected terrestrial ecosystems to permit detection and interpretation of changes attributable to global climate change and depleted ozone shield. The objectives of this project are: (1) To identify and measure indicators of the effects of increased solar UV-B radiation on terrestrial plants; (2) to select indicators with the greatest responses to UV-B exposure; (3) to test, adapt or create ecosystem models that use the information gathered by this project for prediction and to enhance our understanding of the effects of increased UV-B radiation on terrestrial ecosystems. As a first step to achieve these objectives we propose a three-year study of forest and steppe vegetation on the North slope of the Brooks Range (within the Arctic circle, in Alaska), in the Saguaro National Monument (near Tucson, Arizona) and in the forests and steppes of Patagonia (Argentina). We selected (1) vegetation north of the Polar Circle because at 70N there is 8% risk of plant damage due to increased UV-B radiation; (2) the foothills of Catalina Mountains

Precipitation Response to Regional Radiative Forcing

NASA Technical Reports Server (NTRS)

Shindell, D. T.; Voulgarakis, A.; Faluvegi, G.; Milly, G.

2012-01-01

Precipitation shifts can have large impacts on human society and ecosystems. Many aspects of how inhomogeneous radiative forcings influence precipitation remain unclear, however. Here we investigate regional precipitation responses to various forcings imposed in different latitude bands in a climate model. We find that several regions show strong, significant responses to most forcings, but that the magnitude and even the sign depends upon the forcing location and type. Aerosol and ozone forcings typically induce larger responses than equivalent carbon dioxide (CO2) forcing, and the influence of remote forcings often outweighs that of local forcings. Consistent with this, ozone and especially aerosols contribute greatly to precipitation changes over the Sahel and South and East Asia in historical simulations, and inclusion of aerosols greatly increases the agreement with observed trends in these areas, which cannot be attributed to either greenhouse gases or natural forcings. Estimates of precipitation responses derived from multiplying our Regional Precipitation Potentials (RPP; the response per unit forcing relationships) by historical forcings typically capture the actual response in full transient climate simulations fairly well, suggesting that these relationships may provide useful metrics. The strong sensitivity to aerosol and ozone forcing suggests that although some air quality improvements may unmask greenhouse gas-induced warming, they have large benefits for reducing regional disruption of the hydrologic cycle.

Radiation Exposure and Mortality from Cardiovascular Disease and Cancer in Early NASA Astronauts.

PubMed

Elgart, S Robin; Little, Mark P; Chappell, Lori J; Milder, Caitlin M; Shavers, Mark R; Huff, Janice L; Patel, Zarana S

2018-05-31

Understanding space radiation health effects is critical due to potential increased morbidity and mortality following spaceflight. We evaluated whether there is evidence for excess cardiovascular disease or cancer mortality in early NASA astronauts and if a correlation exists between space radiation exposure and mortality. Astronauts selected from 1959-1969 were included and followed until death or February 2017, with 39 of 73 individuals still alive at that time. Calculated standardized mortality rates for tested outcomes were significantly below U.S. white male population rates, including all-cardiovascular disease (n = 7, SMR = 33; 95% CI, 14-65) and all-cancer (n = 7, SMR = 43; 95% CI, 18-83), as anticipated in a healthy worker population. Space radiation doses for cohort members ranged from 0-78 mGy. No significant associations between space radiation dose and mortality were found using logistic regression with an internal reference group, adjusting for medical radiation. Statistical power of the logistic regression was <6%, remaining <12% even when expected risk level or observed deaths were assumed to be 10 times higher than currently reported. While no excess radiation-associated cardiovascular or cancer mortality risk was observed, findings must be tempered by the statistical limitations of this cohort; notwithstanding, this small unique cohort provides a foundation for assessment of astronaut health.

Comparison between the early cellular response to electron radiation and the production of tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sinclair, Ian P.

1972-11-01

The aim of the study is to quantitate radiation-induced cell population changes in various epithelial components of rat skin and to correlate them, if possible with the subsequent production of tumors.

The origin and early radiation of dinosaurs

NASA Astrophysics Data System (ADS)

Brusatte, Stephen L.; Nesbitt, Sterling J.; Irmis, Randall B.; Butler, Richard J.; Benton, Michael J.; Norell, Mark A.

2010-07-01

Dinosaurs were remarkably successful during the Mesozoic and one subgroup, birds, remain an important component of modern ecosystems. Although the extinction of non-avian dinosaurs at the end of the Cretaceous has been the subject of intense debate, comparatively little attention has been given to the origin and early evolution of dinosaurs during the Late Triassic and Early Jurassic, one of the most important evolutionary radiations in earth history. Our understanding of this keystone event has dramatically changed over the past 25 years, thanks to an influx of new fossil discoveries, reinterpretations of long-ignored specimens, and quantitative macroevolutionary analyses that synthesize anatomical and geological data. Here we provide an overview of the first 50 million years of dinosaur history, with a focus on the large-scale patterns that characterize the ascent of dinosaurs from a small, almost marginal group of reptiles in the Late Triassic to the preeminent terrestrial vertebrates of the Jurassic and Cretaceous. We provide both a biological and geological background for early dinosaur history. Dinosaurs are deeply nested among the archosaurian reptiles, diagnosed by only a small number of characters, and are subdivided into a number of major lineages. The first unequivocal dinosaurs are known from the late Carnian of South America, but the presence of their sister group in the Middle Triassic implies that dinosaurs possibly originated much earlier. The three major dinosaur lineages, theropods, sauropodomorphs, and ornithischians, are all known from the Triassic, when continents were joined into the supercontinent Pangaea and global climates were hot and arid. Although many researchers have long suggested that dinosaurs outcompeted other reptile groups during the Triassic, we argue that the ascent of dinosaurs was more of a matter of contingency and opportunism. Dinosaurs were overshadowed in most Late Triassic ecosystems by crocodile-line archosaurs and

Potential pre-cataractous markers induced by low-dose radiation effects in cultured human lens cells

NASA Astrophysics Data System (ADS)

Blakely, E.; McNamara, M.; Bjornstad, K.; Chang, P.

The human lens is one of the most radiosensitive organs of the body. Cataract, the opacification of the lens, is a late-appearing response to radiation damage. Recent evidence indicates that exposure to relatively low doses of space radiation are associated with an increased incidence and early appearance of human cataracts (Cucinotta et al., Radiat. Res. 156:460-466, 2001). Basic research in this area is needed to integrate the early responses of various late-responding tissues into our understanding and estimation of radiation risk for space travel. In addition, these studies may contribute to the development of countermeasures for the early lenticular changes, in order to prevent the late sequelae. Radiation damage to the lens is not life threatening but, if severe, can affect vision unless surgically corrected with synthetic lens replacement. The lens, however, may be a sensitive detector of radiation effects for other cells of ectodermal origin in the body for which there are not currently clear endpoints of low-dose radiation effects. We have investigated the dose-dependent expression of several radiation-responsive endpoints using our in vitro model of differentiating human lens epithelial cells (Blakely et al., Investigative Ophthalmology &Visual Sciences, 41(12):3898-3907, 2000). We have investigated radiation effects on several gene families that include, or relate to, DNA damage, cytokines, cell-cycle regulators, cell adhesion molecules, cell cytoskeletal function and apoptotic cell death. In this paper we will summarize some of our dose-dependent data from several radiation types, and describe the model of molecular and cellular events that we believe may be associated with precataractous events in the human lens after radiation exposure. This work was supported by NASA Grant #T-965W.

Radiation induces an antitumour immune response to mouse melanoma.

PubMed

Perez, Carmen A; Fu, Allie; Onishko, Halina; Hallahan, Dennis E; Geng, Ling

2009-12-01

Irradiation of cancer cells can cause immunogenic death. We used mouse models to determine whether irradiation of melanoma can enhance the host antitumour immune response and function as an effective vaccination strategy, and investigated the molecular mechanisms involved in this radiation-induced response. For in vivo studies, C57BL6/J mice and the B16F0 melanoma cell line were used in a lung metastasis model, intratumoural host immune activation assays, and tumour growth delay studies. In vitro studies included a dendritic cell (DC) phagocytosis assay, detection of cell surface exposure of the protein calreticulin (CRT), and small interfering RNA (siRNA)-mediated depletion of CRT cellular levels. Irradiation of cutaneous melanomas prior to their resection resulted in more than 20-fold reduction in lung metastases after systemic challenge with untreated melanoma cells. A syngeneic vaccine derived from irradiated melanoma cells also induced adaptive immune response markers in irradiated melanoma implants. Our data indicate a trend for radiation-induced increase in melanoma cell surface exposure of CRT, which is involved in the enhanced phagocytic activity of DC against irradiated melanoma cells (VIACUC). The present study suggests that neoadjuvant irradiation of cutaneous melanoma tumours prior to surgical resection can stimulate an endogenous anti-melanoma host immune response.

Auditory-neurophysiological responses to speech during early childhood: Effects of background noise

PubMed Central

White-Schwoch, Travis; Davies, Evan C.; Thompson, Elaine C.; Carr, Kali Woodruff; Nicol, Trent; Bradlow, Ann R.; Kraus, Nina

2015-01-01

Early childhood is a critical period of auditory learning, during which children are constantly mapping sounds to meaning. But learning rarely occurs under ideal listening conditions—children are forced to listen against a relentless din. This background noise degrades the neural coding of these critical sounds, in turn interfering with auditory learning. Despite the importance of robust and reliable auditory processing during early childhood, little is known about the neurophysiology underlying speech processing in children so young. To better understand the physiological constraints these adverse listening scenarios impose on speech sound coding during early childhood, auditory-neurophysiological responses were elicited to a consonant-vowel syllable in quiet and background noise in a cohort of typically-developing preschoolers (ages 3–5 yr). Overall, responses were degraded in noise: they were smaller, less stable across trials, slower, and there was poorer coding of spectral content and the temporal envelope. These effects were exacerbated in response to the consonant transition relative to the vowel, suggesting that the neural coding of spectrotemporally-dynamic speech features is more tenuous in noise than the coding of static features—even in children this young. Neural coding of speech temporal fine structure, however, was more resilient to the addition of background noise than coding of temporal envelope information. Taken together, these results demonstrate that noise places a neurophysiological constraint on speech processing during early childhood by causing a breakdown in neural processing of speech acoustics. These results may explain why some listeners have inordinate difficulties understanding speech in noise. Speech-elicited auditory-neurophysiological responses offer objective insight into listening skills during early childhood by reflecting the integrity of neural coding in quiet and noise; this paper documents typical response properties

Altered Evoked Gamma-Band Responses Reveal Impaired Early Visual Processing in ADHD Children

ERIC Educational Resources Information Center

Lenz, Daniel; Krauel, Kerstin; Flechtner, Hans-Henning; Schadow, Jeanette; Hinrichs, Hermann; Herrmann, Christoph S.

2010-01-01

Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90 ms after visual stimulation in human EEG, have…

Development and Verification of Enclosure Radiation Capabilities in the CHarring Ablator Response (CHAR) Code

NASA Technical Reports Server (NTRS)

Salazar, Giovanni; Droba, Justin C.; Oliver, Brandon; Amar, Adam J.

2016-01-01

With the recent development of multi-dimensional thermal protection system (TPS) material response codes, the capability to account for surface-to-surface radiation exchange in complex geometries is critical. This paper presents recent efforts to implement such capabilities in the CHarring Ablator Response (CHAR) code developed at NASA's Johnson Space Center. This work also describes the different numerical methods implemented in the code to compute geometric view factors for radiation problems involving multiple surfaces. Verification of the code's radiation capabilities and results of a code-to-code comparison are presented. Finally, a demonstration case of a two-dimensional ablating cavity with enclosure radiation accounting for a changing geometry is shown.

Early effects of 16O radiation on neuronal morphology and cognition in a murine model

NASA Astrophysics Data System (ADS)

Carr, Hannah; Alexander, Tyler C.; Groves, Thomas; Kiffer, Frederico; Wang, Jing; Price, Elvin; Boerma, Marjan; Allen, Antiño R.

2018-05-01

Astronauts exposed to high linear energy transfer radiation may experience cognitive injury. The pathogenesis of this injury is unknown but may involve glutamate receptors or modifications to dendritic structure and/or dendritic spine density and morphology. Glutamate is the major excitatory neurotransmitter in the central nervous system, where it acts on ionotropic and metabotropic glutamate receptors located at the presynaptic terminal and in the postsynaptic membrane at synapses in the hippocampus. Dendritic spines are sites of excitatory synaptic transmission, and changes in spine structure and dendrite morphology are thought to be morphological correlates of altered brain function associated with hippocampal-dependent learning and memory. The aim of the current study is to assess whether behavior, glutamate receptor gene expression, and dendritic structure in the hippocampus are altered in mice after early exposure to 16O radiation in mice. Two weeks post-irradiation, animals were tested for hippocampus-dependent cognitive performance in the Y-maze. During Y-maze testing, mice exposed to 0.1 Gy and 0.25 Gy radiation failed to distinguish the novel arm, spending approximately the same amount of time in all 3 arms during the retention trial. Exposure to 16O significantly reduced the expression of Nr1 and GluR1 in the hippocampus and modulated spine morphology in the dentate gyrus and cornu Ammon 1 within the hippocampus. The present data provide evidence that 16O radiation has early deleterious effects on mature neurons that are associated with hippocampal learning and memory.

The radiation response of human dermal fibroblasts

NASA Astrophysics Data System (ADS)

Mitchell, Stephen Andrew

A clinically reliable predictive assay based on normal-tissue radiosensitivity may lead to improved tumour control through individualised dose prescriptions. In-vitro fibroblast radiosensitivity has been shown, in several studies, to correlate with late radiation morbidity. The aim of this study was to investigate some of the cellular mechanisms underlying the normal-tissue response. In this study, seventeen primary fibroblast strains were established by enzymatic disaggregation of skin biopsies obtained from patients. These comprised seven who experienced acute tissue reactions to radiotherapy, four patients with a normal response and six non-cancer volunteers. An AT cell line was included as a positive control for radiosensitivity. In-vitro radiosensitivity was measured using a clonogenic assay at both high (HDR: 1.6 Gymin-1) and low dose rate (LDR: 0.01 Gymin-1). The radiation parameter HDR SF2 was the most sensitive in discriminating the seven sensitive patients from the remaining ten normal patients (range 0.11-0.19 sensitive patients compared with 0.17-0.34 control patients: p<0.0001). Neither the use of an internal control or LDR radiation protocol increased this discrimination. Pulsed-field gel electrophoresis (PFGE) was used to measure the level of initial and residual double-strand breaks following irradiation. No correlation was found between HDR SF2 and initial DNA damage. However, a strong correlation was found between clonogenic survival and both residual DNA damage (measured over 10-70 Gy, allowing 4 h repair, correlation coefficient: 0.90, <0.0001) and the ratio of residual/initial DNA damage, with the sensitive cell lines generally showing a higher level of residual DNA damage. Cell-cycle delays were found in all 18 cell strains in response to 2 Gy irradiation, but were not found to discriminate between sensitive and normal patients. Associated studies found no mutations of the ATM gene in the five radiosensitive patients studied. However, a coding

CT Perfusion Imaging as an Early Biomarker of Differential Response to Stereotactic Radiosurgery in C6 Rat Gliomas

PubMed Central

Yeung, Timothy Pok Chi; Kurdi, Maher; Wang, Yong; Al-Khazraji, Baraa; Morrison, Laura; Hoffman, Lisa; Jackson, Dwayne; Crukley, Cathie; Lee, Ting-Yim; Bauman, Glenn; Yartsev, Slav

2014-01-01

Background The therapeutic efficacy of stereotactic radiosurgery for glioblastoma is not well understood, and there needs to be an effective biomarker to identify patients who might benefit from this treatment. This study investigated the efficacy of computed tomography (CT) perfusion imaging as an early imaging biomarker of response to stereotactic radiosurgery in a malignant rat glioma model. Methods Rats with orthotopic C6 glioma tumors received either mock irradiation (controls, N = 8) or stereotactic radiosurgery (N = 25, 12 Gy in one fraction) delivered by Helical Tomotherapy. Twelve irradiated animals were sacrificed four days after stereotactic radiosurgery to assess acute CT perfusion and histological changes, and 13 irradiated animals were used to study survival. Irradiated animals with survival >15 days were designated as responders while those with survival ≤15 days were non-responders. Longitudinal CT perfusion imaging was performed at baseline and regularly for eight weeks post-baseline. Results Early signs of radiation-induced injury were observed on histology. There was an overall survival benefit following stereotactic radiosurgery when compared to the controls (log-rank P<0.04). Responders to stereotactic radiosurgery showed lower relative blood volume (rBV), and permeability-surface area (PS) product on day 7 post-stereotactic radiosurgery when compared to controls and non-responders (P<0.05). rBV and PS on day 7 showed correlations with overall survival (P<0.05), and were predictive of survival with 92% accuracy. Conclusions Response to stereotactic radiosurgery was heterogeneous, and early selection of responders and non-responders was possible using CT perfusion imaging. Validation of CT perfusion indices for response assessment is necessary before clinical implementation. PMID:25329655

The skin: its structure and response to ionizing radiation.

PubMed

Hopewell, J W

1990-04-01

The response of the skin to ionizing radiation has important implications both for the treatment of malignant disease by radiation and for radiological protection. The structural organization of human skin is described and compared with that of the pig, with which it shows many similarities, in order that the response of the skin to ionizing radiation may be more fully understood. Acute radiation damage to the skin is primarily a consequence of changes in the epidermis; the timing of the peak of the reaction is related to the kinetic organization of this layer. The rate of development of damage is independent of the radiation dose, since this is related to the natural rate of loss of cells from the basal layer of the epidermis. Recovery of the epidermis occurs as a result of the proliferation of surviving clonogenic basal cells from within the irradiated area. The presence of clonogenic cells in the canal of the hair follicle is important, particularly after non-uniform irradiation from intermediate energy beta-emitters. The migration of viable cells from the edges of the irradiated site is also significant when small areas of skin are irradiated. Late damage to the skin is primarily a function of radiation effects on the vasculature; this produces a wave of dermal atrophy after 16-26 weeks. Dermal necrosis develops at this time after high doses. A second phase of dermal thinning is seen to develop after greater than 52 weeks, and this later phase of damage is associated with the appearance of telangiectasia. Highly localized irradiation of the skin, either to a specific layer (as may result from exposure to very low energy beta-emitters) or after exposure to small highly radioactive particles, 'hot particles', produces gross effects that become visibly manifest within 2 weeks of exposure. These changes result from the direct killing of the cells of the skin in interphase after doses greater than 100 Gy. Dose-effect curves have been established for the majority of

Environmental standards for ionizing radiation: theoretical basis for dose-response curves.

PubMed Central

Upton, A C

1983-01-01

The types of injury attributable to ionizing radiation are subdivided, for purposes of risk assessment and radiological protection, into two broad categories: stochastic effects and nonstochastic effects. Stochastic effects are viewed as probablistic phenomena, varying in frequency but not severity as a function of the dose, without any threshold; nonstochastic effects are viewed as deterministic phenomena, varying in both frequency and severity as a function of the dose, with clinical thresholds. Included among stochastic effects are heritable effects (mutations and chromosome aberrations) and carcinogenic effects. Both types of effects are envisioned as unicellular phenomena which can result from nonlethal injury of individual cells, without the necessity of damage to other cells. For the induction of mutations and chromosome aberrations in the low-to-intermediate dose range, the dose-response curve with high-linear energy transfer (LET) radiation generally conforms to a linear nonthreshold relationship and varies relatively little with the dose rate. In contrast, the curve with low-LET radiation generally conforms to a linear-quadratic relationship, rising less steeply than the curve with high-LET radiation and increasing in slope with increasing dose and dose rate. The dose-response curve for carcinogenic effects varies widely from one type of neoplasm to another in the intermediate-to-high dose range, in part because of differences in the way large doses of radiation can affect the promotion and progression of different neoplasms. Information about dose-response relations for low-level irradiation is fragmentary but consistent, in general, with the hypothesis that the neoplastic transformation may result from mutation, chromosome aberration or genetic recombination in a single susceptible cell. PMID:6653536

Assessment of tumor response to radiation and vascular targeting therapy in mice using quantitative ultrasound spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

El Kaffas, Ahmed; Sadeghi-Naini, Ali; Falou, Omar

Purpose: It is now recognized that the tumor vasculature is in part responsible for regulating tumor responses to radiation therapy. However, the extent to which radiation-based vascular damage contributes to tumor cell death remains unknown. In this work, quantitative ultrasound spectroscopy (QUS) methods were used to investigate the acute responses of tumors to radiation-based vascular treatments. Methods: Tumor xenografts (MDA-MB-231) were treated with single radiation doses of 2 or 8 Gy alone, or in combination with pharmacological agents that modulate vascular radiosensitivity. The midband fit, the slope, and the 0-MHz intercept QUS parameters were obtained from a linear-regression fit tomore » the averaged power spectrum of frequency-dependent ultrasound backscatter and were used to quantify acute tumor responses following treatment administration. Power spectrums were extracted from raw volumetric radio-frequency ultrasound data obtained before and 24 h following treatment administration. These parameters have previously been correlated to tumor cell death. Staining using in situ end labeling, carbonic anhydrase 9 and cluster of differentiation 31 of tumor sections were used to assess cell death, oxygenation, and vasculature distributions, respectively. Results: Results indicate a significant midband fit QUS parameter increases of 3.2 ± 0.3 dBr and 5.4 ± 0.5 dBr for tumors treated with 2 and 8 Gy radiation combined with the antiangiogenic agent Sunitinib, respectively. In contrast, tumors treated with radiation alone demonstrated a significant midband fit increase of 4.4 ± 0.3 dBr at 8 Gy only. Preadministration of basic fibroblast growth factor, an endothelial radioprotector, acted to minimize tumor response following single large doses of radiation. Immunohistochemical analysis was in general agreement with QUS findings; an R{sup 2} of 0.9 was observed when quantified cell death was correlated with changes in midband fit. Conclusions: Results from QUS

Early Change in Stroke Size Performs Best in Predicting Response to Therapy.

PubMed

Simpkins, Alexis Nétis; Dias, Christian; Norato, Gina; Kim, Eunhee; Leigh, Richard

2017-01-01

Reliable imaging biomarkers of response to therapy in acute stroke are needed. The final infarct volume and percent of early reperfusion have been used for this purpose. Early fluctuation in stroke size is a recognized phenomenon, but its utility as a biomarker for response to therapy has not been established. This study examined the clinical relevance of early change in stroke volume and compared it with the final infarct volume and percent of early reperfusion in identifying early neurologic improvement (ENI). Acute stroke patients, enrolled between 2013 and 2014 with serial magnetic resonance imaging (MRI) scans (pretreatment baseline, 2 h post, and 24 h post), who received thrombolysis were included in the analysis. Early change in stroke volume, infarct volume at 24 h on diffusion, and percent of early reperfusion were calculated from the baseline and 2 h MRI scans were compared. ENI was defined as ≥4 point decrease in National Institutes of Health Stroke Scales within 24 h. Logistic regression models and receiver operator characteristics analysis were used to compare the efficacy of 3 imaging biomarkers. Serial MRIs of 58 acute stroke patients were analyzed. Early change in stroke volume was significantly associated with ENI by logistic regression analysis (OR 0.93, p = 0.048) and remained significant after controlling for stroke size and severity (OR 0.90, p = 0.032). Thus, for every 1 mL increase in stroke volume, there was a 10% decrease in the odds of ENI, while for every 1 mL decrease in stroke volume, there was a 10% increase in the odds of ENI. Neither infarct volume at 24 h nor percent of early reperfusion were significantly associated with ENI by logistic regression. Receiver-operator characteristic analysis identified early change in stroke volume as the only biomarker of the 3 that performed significantly different than chance (p = 0.03). Early fluctuations in stroke size may represent a more reliable biomarker for response to therapy than the

In Vitro Studies on Space Radiation-Induced Delayed Genetic Responses: Shielding Effects

NASA Technical Reports Server (NTRS)

Kadhim, Munira A.; Green, Lora M.; Gridley, Daila S.; Murray, Deborah K.; Tran, Da Thao; Andres, Melba; Pocock, Debbie; Macdonald, Denise; Goodhead, Dudley T.; Moyers, Michael F.

2003-01-01

Understanding the radiation risks involved in spaceflight is of considerable importance, especially with the long-term occupation of ISS and the planned crewed exploration missions. Several independent causes may contribute to the overall risk to astronauts exposed to the complex space environment, such as exposure to GCR as well as SPES. Protons and high-Z energetic particles comprise the GCR spectrum and may exert considerable biological effects even at low fluence. There are also considerable uncertainties associated with secondary particle effects (e.g. HZE fragments, neutrons etc.). The interaction of protons and high-LET particles with biological materials at all levels of biological organization needs to be investigated fully in order to establish a scientific basis for risk assessment. The results of these types of investigation will foster the development of appropriately directed countermeasures. In this study, we compared the biological responses to proton irradiation presented to the target cells as a monoenergetic beam of particles of complex composition delivered to cells outside or inside a tissue phantom head placed in the United States EVA space suit helmet. Measurements of chromosome aberrations, apoptosis, and the induction of key proteins were made in bone marrow from CBA/CaJ and C57BL/6 mice at early and late times post exposure to radiation at 0, 0.5, 1 and 2 Gy while inside or outside of the helmet. The data showed that proton irradiation induced transmissible chromosomal/genomic instability in haematopoietic stem cells in both strains of mice under both irradiation conditions and especially at low doses. Although differences were noted between the mouse strains in the degree and kinetics of transforming growth factor-beta 1 and tumor necrosis factor-alpha secretion, there were no significant differences observed in the level of the induced instability under either radiation condition, or for both strains of mice. Consequently, when

Radiation Response of Emerging High Gain, Low Noise Detectors

NASA Technical Reports Server (NTRS)

Becker, Heidi N.; Farr, William H; Zhu, David Q.

2007-01-01

Data illustrating the radiation response of emerging high gain, low noise detectors are presented. Ionizing dose testing of silicon internal discrete avalanche photodiodes, and 51-MeV proton testing of InGaAs/InAlAs avalanche photodiodes operated in Geiger mode are discussed.

Indirect macrophage responses to ionizing radiation: implications for genotype-dependent bystander signaling.

PubMed

Coates, Philip J; Rundle, Jana K; Lorimore, Sally A; Wright, Eric G

2008-01-15

In addition to the directly mutagenic effects of energy deposition in DNA, ionizing radiation is associated with a variety of untargeted and delayed effects that result in ongoing bone marrow damage. Delayed effects are genotype dependent with CBA/Ca mice, but not C57BL/6 mice, susceptible to the induction of damage and also radiation-induced acute myeloid leukemia. Because macrophages are a potential source of ongoing damaging signals, we have determined their gene expression profiles and we show that bone marrow-derived macrophages show widely different intrinsic expression patterns. The profiles classify macrophages derived from CBA/Ca mice as M1-like (pro-inflammatory) and those from C57BL/6 mice as M2-like (anti-inflammatory); measurements of NOS2 and arginase activity in normal bone marrow macrophages confirm these findings. After irradiation in vivo, but not in vitro, C57BL/6 macrophages show a reduction in NOS2 and an increase in arginase activities, indicating a further M2 response, whereas CBA/Ca macrophages retain an M1 phenotype. Activation of specific signal transducer and activator of transcription signaling pathways in irradiated hemopoietic tissues supports these observations. The data indicate that macrophage activation is not a direct effect of radiation but a tissue response, secondary to the initial radiation exposure, and have important implications for understanding genotype-dependent responses and the mechanisms of the hemotoxic and leukemogenic consequences of radiation exposure.

Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

PubMed Central

Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

2014-01-01

The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initial control of MCMV, although at later time points, CD70-/- mice became more susceptible to MCMV infection. The heightened cytokine response during the early phase of MCMV infection in CD70-/- mice was paralleled by a reduction in regulatory T cells (Treg). Treg from naïve CD70-/- mice were not as efficient at suppressing T cell proliferation compared to Treg from naïve WT mice and depletion of Treg during MCMV infection in Foxp3-DTR mice or in WT mice recapitulated the phenotype observed in CD70-/- mice. Our study demonstrates that while CD70 is required for the activation of the antiviral adaptive response, it has a regulatory role in early cytokine responses to viruses such as MCMV, possibly through maintenance of Treg survival and function. PMID:24913981

The biobehavioral and neuroimmune impact of low-dose ionizing radiation

PubMed Central

York, Jason M; Blevins, Neil A; Meling, Daryl D; Peterlin, Molly B; Gridley, Daila S; Cengel, Keith A; Freund, Gregory G

2011-01-01

In the clinical setting, repeated exposures (10–30) to low-doses of ionizing radiation (≤ 200 cGy), as seen in radiotherapy for cancer, causes fatigue. Almost nothing is known, however, about the fatigue inducing effects of a single exposure to environmental low-dose ionizing radiation that might occur during high-altitude commercial air flight, a nuclear reactor accident or a solar particle event (SPE). To investigate the short-term impact of low-dose ionizing radiation on mouse biobehaviors and neuroimmunity, male CD-1 mice were whole body irradiated with 50 cGy or 200 cGy of gamma or proton radiation. Gamma radiation was found to reduce spontaneous locomotor activity by 35% and 36%, respectively, 6 h post irradiation. In contrast, the motivated behavior of social exploration was un-impacted by gamma radiation. Examination of pro-inflammatory cytokine gene transcripts in the brain demonstrated that gamma radiation increased hippocampal TNF-α expression as early as 4 h post-irradiation. This was coupled to subsequent increases in IL-1RA (8 h and 12 h post irradiation) in the cortex and hippocampus and reductions in activity-regulated cytoskeleton-associated protein (Arc) (24 h post irradiation) in the cortex. Finally, restraint stress was a significant modulator of the neuroimmune response to radiation blocking the ability of 200 cGy gamma radiation from impairing locomotor activity and altering the brain-based inflammatory response to irradiation. Taken together, these findings indicate that low-dose ionizing radiation rapidly activates the neuroimmune system potentially causing early onset fatigue-like symptoms in mice. PMID:21958477

Radiative feedback and cosmic molecular gas: the role of different radiative sources

NASA Astrophysics Data System (ADS)

Maio, Umberto; Petkova, Margarita; De Lucia, Gabriella; Borgani, Stefano

2016-08-01

We present results from multifrequency radiative hydrodynamical chemistry simulations addressing primordial star formation and related stellar feedback from various populations of stars, stellar spectral energy distributions (SEDs) and initial mass functions. Spectra for massive stars, intermediate-mass stars and regular solar-like stars are adopted over a grid of 150 frequency bins and consistently coupled with hydrodynamics, heavy-element pollution and non-equilibrium species calculations. Powerful massive Population III stars are found to be able to largely ionize H and, subsequently, He and He+, causing an inversion of the equation of state and a boost of the Jeans masses in the early intergalactic medium. Radiative effects on star formation rates are between a factor of a few and 1 dex, depending on the SED. Radiative processes are responsible for gas heating and photoevaporation, although emission from soft SEDs has minor impacts. These findings have implications for cosmic gas preheating, primordial direct-collapse black holes, the build-up of `cosmic fossils' such as low-mass dwarf galaxies, the role of active galactic nuclei during reionization, the early formation of extended discs and angular-momentum catastrophe.

Monitoring early tumor response to drug therapy with diffuse optical tomography

NASA Astrophysics Data System (ADS)

Flexman, Molly L.; Vlachos, Fotios; Kim, Hyun Keol; Sirsi, Shashank R.; Huang, Jianzhong; Hernandez, Sonia L.; Johung, Tessa B.; Gander, Jeffrey W.; Reichstein, Ari R.; Lampl, Brooke S.; Wang, Antai; Borden, Mark A.; Yamashiro, Darrell J.; Kandel, Jessica J.; Hielscher, Andreas H.

2012-01-01

Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy--thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

Radiation exposure and disease questionnaires of early entrants after the Hiroshima bombing.

PubMed

Imanaka, Tetsuji; Endo, Satoru; Kawano, Noriyuki; Tanaka, Kenichi

2012-03-01

It is popularly known that people who entered into the ground-zero area shortly after the atomic bombings in Hiroshima and Nagasaki suffered from various syndromes similar to acute radiation effects. External exposures from neutron-induced radionuclides in soil have recently been reassessed based on DS02 calculations as functions of both distance from the hypocentres and elapsed time after the explosions. Significant exposure due to induced radiation can be determined for those who entered the area within 1000 m from the hypocentres shortly after the bombing. Although it was impossible to track the action of each of the survivors over the days or weeks following the bombings in order to make reliable dose estimates for their exposures to soil activation or fallout, four individuals among those early entrants were investigated here to describe useful information of what happened shortly after the bombing.

The Molecular and Physiological Responses of Physcomitrella patens to Ultraviolet-B Radiation1[W][OA

PubMed Central

Wolf, Luise; Rizzini, Luca; Stracke, Ralf; Ulm, Roman; Rensing, Stefan A.

2010-01-01

Ultraviolet-B (UV-B) radiation present in sunlight is an important trigger of photomorphogenic acclimation and stress responses in sessile land plants. Although numerous moss species grow in unshaded habitats, our understanding of their UV-B responses is very limited. The genome of the model moss Physcomitrella patens, which grows in sun-exposed open areas, encodes signaling and metabolic components that are implicated in the UV-B response in flowering plants. In this study, we describe the response of P. patens to UV-B radiation at the morphological and molecular levels. We find that P. patens is more capable of surviving UV-B stress than Arabidopsis (Arabidopsis thaliana) and describe the differential expression of approximately 400 moss genes in response to UV-B radiation. A comparative analysis of the UV-B response in P. patens and Arabidopsis reveals both distinct and conserved pathways. PMID:20427465

Children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood.

PubMed

Leppert, Katherine A; Kushner, Marissa; Smith, Victoria C; Lemay, Edward P; Dougherty, Lea R

2016-12-01

This study examined the stability of children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood. Ninety-six children (51 males) completed stress-inducing laboratory tasks and provided five salivary cortisol samples in early (W1) and middle (W2) childhood. Although W1 cortisol responses did not predict W2 cortisol responses, children's cortisol responses demonstrated change: compared to their W1 cortisol responses, children's W2 cortisol responses demonstrated an increased slope and more negative quadratic curvature. Furthermore, child psychiatric symptoms at W1 moderated the stability of children's cortisol responses. Children with fewer preschool psychiatric symptoms demonstrated greater inter-individual and intra-individual stability, whereas children with higher preschool psychiatric symptoms and comorbidity demonstrated systematic inter-individual and intra-individual instability in cortisol responses over time. Findings suggest a developmental shift toward increasing cortisol stress responses from early to middle childhood and highlight preschool psychopathology as a moderator of stability in children's cortisol responses over time. © 2016 Wiley Periodicals, Inc.

Frameworks for Response to Intervention in Early Childhood: Description and Implications

ERIC Educational Resources Information Center

Communication Disorders Quarterly, 2014

2014-01-01

In February, 2013, the Division of Early Childhood, the National Association for the Education of Young Children, and the National Head Start Association released a collaborative paper to provide clarification and assistance regarding the relationship of response to intervention (RTI) with the field of early childhood (EC). In addition to…

Epidermal Homeostasis and Radiation Responses in a Multiscale Tissue Modeling Framework

NASA Technical Reports Server (NTRS)

Hu, Shaowen; Cucinotta, Francis A.

2013-01-01

The surface of skin is lined with several thin layers of epithelial cells that are maintained throughout life time by a small population of stem cells. High dose radiation exposures could injure and deplete the underlying proliferative cells and induce cutaneous radiation syndrome. In this work we propose a multiscale computational model for skin epidermal dynamics that links phenomena occurring at the subcellular, cellular, and tissue levels of organization, to simulate the experimental data of the radiation response of swine epidermis, which is closely similar to human epidermis. Incorporating experimentally measured histological and cell kinetic parameters, we obtain results of population kinetics and proliferation indexes comparable to observations in unirradiated and acutely irradiated swine experiments. At the sub-cellular level, several recently published Wnt signaling controlled cell-cycle models are applied and the roles of key components and parameters are analyzed. Based on our simulation results, we demonstrate that a moderate increase of proliferation rate for the survival proliferative cells is sufficient to fully repopulate the area denuded by high dose radiation, as long as the integrity of underlying basement membrane is maintained. Our work highlights the importance of considering proliferation kinetics as well as the spatial organization of tissues when conducting in vivo investigations of radiation responses. This integrated model allow us to test the validity of several basic biological rules at the cellular level and sub-cellular mechanisms by qualitatively comparing simulation results with published research, and enhance our understanding of the pathophysiological effects of ionizing radiation on skin.

Residual fluctuations in the matter and radiation distribution after the decoupling epoch. [of early universe

NASA Technical Reports Server (NTRS)

Silk, J.; Wilson, M. L.

1980-01-01

The residual spectra of matter and radiation fluctuations in the early universe are investigated, and the evolution of primordial adiabatic and isothermal fluctuations through the decoupling epoch is studied. Amplification of adiabatic density fluctuations during decoupling, or velocity 'overshoot', is largely suppressed by Compton drag. Consequently, the amplitude of density fluctuations entering the horizon prior to decoupling is larger than hitherto assumed in the adiabatic theory. Damping of primordial adiabatic density fluctuations by an order of magnitude occurs on mass-scales of 3 x 10 to the 13th solar masses (Omega = 1) or 10 to the 14th solar masses (Omega = 0.2). Comparison of the residual radiation fluctuations with observational limits indicates that the adiabatic theory is only acceptable if re-ionization of the intergalactic medium results in additional scattering of the radiation after decoupling. Primordial isothermal fluctuations are found to yield radiation fluctuations which are insensitive to the assumed spectrum and lie a factor of about 5 below current limits

Optimal imaging surveillance after stereotactic ablative radiation therapy for early-stage non-small cell lung cancer: Findings of an International Delphi Consensus Study.

PubMed

Nguyen, Timothy K; Senan, Suresh; Bradley, Jeffery D; Franks, Kevin; Giuliani, Meredith; Guckenberger, Matthias; Landis, Mark; Loo, Billy W; Louie, Alexander V; Onishi, Hiroshi; Schmidt, Heidi; Timmerman, Robert; Videtic, Gregory M M; Palma, David A

Imaging after stereotactic ablative radiation therapy (SABR) for early-stage non-small cell lung cancer can detect recurrences and second primary lung cancers; however, the optimal follow-up practice of these patients remains unclear. We sought to establish consensus recommendations for surveillance after SABR. International opinion leaders in thoracic radiation oncology and radiology were invited to participate (n = 31), with 11 accepting (9 radiation oncologists, 2 radiologists). Consensus-building was achieved using a 3-round Delphi process. Participants rated their agreement/disagreement with statements using a 5-point Likert scale. An a priori threshold of ≥75% agreement/disagreement was required for consensus. A 100% response rate was achieved and final consensus statements were approved by all participants. The consensus statements were: (1.1) thoracic computed tomography (CT) scans should be ordered routinely in follow-up; (1.2) if there is a suspicion for local recurrence (LR), fludeoxyglucose positron emission tomography/CT scans are strongly recommended. Otherwise, there is limited evidence to guide routine use of fludeoxyglucose positron emission tomography /CT; (1.3) CT imaging is not recommended at 6 weeks, but is recommended at months 3, 6, and 12 in year 1 and then every 6 months in year 2 and annually in years 3 through 5; (1.4) after 5 years, CT imaging should continue, although no consensus was reached regarding the frequency. (2.1) Response Evaluation Criteria in Solid Tumors 1.1 criteria are not sufficient for detecting LR; (2.2) a formal scoring system, informed by validated data, should be used to classify high-risk imaging features predictive of LR; (2.3) CT findings suspicious for LR include: infiltration into adjacent structures, bulging margins, sustained growth, mass-like growth, spherical growth, craniocaudal growth, and loss of air bronchograms. (3) Salvage therapy without pathologic confirmation of recurrence is acceptable if

Early improvements in anxiety, depression, and anger/hostility symptoms and response to antidepressant treatment.

PubMed

Farabaugh, Amy; Sonawalla, Shamsah; Johnson, Daniel P; Witte, Janet; Papakostas, George I; Goodness, Tracie; Clain, Alisabet; Baer, Lee; Mischoulon, David; Fava, Maurizio; Harley, Rebecca

2010-08-01

The purpose of this study was to examine whether treatment response to fluoxetine by depressed outpatients was predicted by early improvement on any of 3 subscales (Anxiety, Depression, and Anger/Hostility) of the Symptom Questionnaire (SQ). We evaluated 169 depressed outpatients (52.6% female) between ages 18 and 65 (mean age, 40.3 +/- 10.6 years) meeting DSM-IIIR criteria for major depressive disorder (MDD). All patients completed the SQ at baseline (week 0) and at weeks 2, 4, and 8 of treatment with fluoxetine 20 mg/d. We defined treatment response as a > or= 50% reduction in score on the 17-item Hamilton Rating Scale for Depression, and early improvement on 3 SQ subscales (Anxiety, Depression, and Anger/Hostility) as a >30% reduction in score by week 2. The percentage of patients with significant early improvement in anger was significantly greater than the percentage of those with early improvements in anxiety or depression. When early improvement on the Anxiety, Depression, and Anger/Hostility subscales of the SQ were assessed independently by logistic regression, all 3 subscales were predictors of response to treatment. Early improvement in anger, anxiety, and depressive symptoms may predict response to antidepressant treatment among outpatients with MDD.

Early Twentieth Century Responses to the Drug Problem.

ERIC Educational Resources Information Center

Pfennig, Dennis Joseph

1991-01-01

Describes early twentieth-century responses to the drug problem in the United States. Discusses pressure from the media and reformers to control the availability of drugs such as opium and cocaine that were widely available in over-the-counter medications. Focuses on New York State, which took the lead in enacting drug control legislation. (DK)

Solar ultraviolet radiation is necessary to enhance grapevine fruit ripening transcriptional and phenolic responses.

PubMed

Carbonell-Bejerano, Pablo; Diago, Maria-Paz; Martínez-Abaigar, Javier; Martínez-Zapater, José M; Tardáguila, Javier; Núñez-Olivera, Encarnación

2014-07-09

Ultraviolet (UV) radiation modulates secondary metabolism in the skin of Vitis vinifera L. berries, which affects the final composition of both grapes and wines. The expression of several phenylpropanoid biosynthesis-related genes is regulated by UV radiation in grape berries. However, the complete portion of transcriptome and ripening processes influenced by solar UV radiation in grapes remains unknown. Whole genome arrays were used to identify the berry skin transcriptome modulated by the UV radiation received naturally in a mid-altitude Tempranillo vineyard. UV radiation-blocking and transmitting filters were used to generate the experimental conditions. The expression of 121 genes was significantly altered by solar UV radiation. Functional enrichment analysis of altered transcripts mainly pointed out that secondary metabolism-related transcripts were induced by UV radiation including VvFLS1, VvGT5 and VvGT6 flavonol biosynthetic genes and monoterpenoid biosynthetic genes. Berry skin phenolic composition was also analysed to search for correlation with gene expression changes and UV-increased flavonols accumulation was the most evident impact. Among regulatory genes, novel UV radiation-responsive transcription factors including VvMYB24 and three bHLH, together with known grapevine UV-responsive genes such as VvMYBF1, were identified. A transcriptomic meta-analysis revealed that genes up-regulated by UV radiation in the berry skin were also enriched in homologs of Arabidopsis UVR8 UV-B photoreceptor-dependent UV-B -responsive genes. Indeed, a search of the grapevine reference genomic sequence identified UV-B signalling pathway homologs and among them, VvHY5-1, VvHY5-2 and VvRUP were up-regulated by UV radiation in the berry skin. Results suggest that the UV-B radiation-specific signalling pathway is activated in the skin of grapes grown at mid-altitudes. The biosynthesis and accumulation of secondary metabolites, which are appreciated in winemaking and

Quantitative correlational study of microbubble-enhanced ultrasound imaging and magnetic resonance imaging of glioma and early response to radiotherapy in a rat model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Chen; Lee, Dong-Hoon; Zhang, Kai

Purpose: Radiotherapy remains a major treatment method for malignant tumors. Magnetic resonance imaging (MRI) is the standard modality for assessing glioma treatment response in the clinic. Compared to MRI, ultrasound imaging is low-cost and portable and can be used during intraoperative procedures. The purpose of this study was to quantitatively compare contrast-enhanced ultrasound (CEUS) imaging and MRI of irradiated gliomas in rats and to determine which quantitative ultrasound imaging parameters can be used for the assessment of early response to radiation in glioma. Methods: Thirteen nude rats with U87 glioma were used. A small thinned skull window preparation was performedmore » to facilitate ultrasound imaging and mimic intraoperative procedures. Both CEUS and MRI with structural, functional, and molecular imaging parameters were performed at preradiation and at 1 day and 4 days postradiation. Statistical analysis was performed to determine the correlations between MRI and CEUS parameters and the changes between pre- and postradiation imaging. Results: Area under the curve (AUC) in CEUS showed significant difference between preradiation and 4 days postradiation, along with four MRI parameters, T{sub 2}, apparent diffusion coefficient, cerebral blood flow, and amide proton transfer-weighted (APTw) (all p < 0.05). The APTw signal was correlated with three CEUS parameters, rise time (r = − 0.527, p < 0.05), time to peak (r = − 0.501, p < 0.05), and perfusion index (r = 458, p < 0.05). Cerebral blood flow was correlated with rise time (r = − 0.589, p < 0.01) and time to peak (r = − 0.543, p < 0.05). Conclusions: MRI can be used for the assessment of radiotherapy treatment response and CEUS with AUC as a new technique and can also be one of the assessment methods for early response to radiation in glioma.« less

Quantitative correlational study of microbubble-enhanced ultrasound imaging and magnetic resonance imaging of glioma and early response to radiotherapy in a rat model.

PubMed

Yang, Chen; Lee, Dong-Hoon; Mangraviti, Antonella; Su, Lin; Zhang, Kai; Zhang, Yin; Zhang, Bin; Li, Wenxiao; Tyler, Betty; Wong, John; Wang, Ken Kang-Hsin; Velarde, Esteban; Zhou, Jinyuan; Ding, Kai

2015-08-01

Radiotherapy remains a major treatment method for malignant tumors. Magnetic resonance imaging (MRI) is the standard modality for assessing glioma treatment response in the clinic. Compared to MRI, ultrasound imaging is low-cost and portable and can be used during intraoperative procedures. The purpose of this study was to quantitatively compare contrast-enhanced ultrasound (CEUS) imaging and MRI of irradiated gliomas in rats and to determine which quantitative ultrasound imaging parameters can be used for the assessment of early response to radiation in glioma. Thirteen nude rats with U87 glioma were used. A small thinned skull window preparation was performed to facilitate ultrasound imaging and mimic intraoperative procedures. Both CEUS and MRI with structural, functional, and molecular imaging parameters were performed at preradiation and at 1 day and 4 days postradiation. Statistical analysis was performed to determine the correlations between MRI and CEUS parameters and the changes between pre- and postradiation imaging. Area under the curve (AUC) in CEUS showed significant difference between preradiation and 4 days postradiation, along with four MRI parameters, T2, apparent diffusion coefficient, cerebral blood flow, and amide proton transfer-weighted (APTw) (all p < 0.05). The APTw signal was correlated with three CEUS parameters, rise time (r = - 0.527, p < 0.05), time to peak (r = - 0.501, p < 0.05), and perfusion index (r = 458, p < 0.05). Cerebral blood flow was correlated with rise time (r = - 0.589, p < 0.01) and time to peak (r = - 0.543, p < 0.05). MRI can be used for the assessment of radiotherapy treatment response and CEUS with AUC as a new technique and can also be one of the assessment methods for early response to radiation in glioma.

The Origin and Early Radiation of Archosauriforms: Integrating the Skeletal and Footprint Record.

PubMed

Bernardi, Massimo; Klein, Hendrik; Petti, Fabio Massimo; Ezcurra, Martín D

2015-01-01

We present a holistic approach to the study of early archosauriform evolution by integrating body and track records. The ichnological record supports a Late Permian-Early Triassic radiation of archosauriforms not well documented by skeletal material, and new footprints from the Upper Permian of the southern Alps (Italy) provide evidence for a diversity not yet sampled by body fossils. The integrative study of body fossil and footprint data supports the hypothesis that archosauriforms had already undergone substantial taxonomic diversification by the Late Permian and that by the Early Triassic archosauromorphs attained a broad geographical distribution over most parts of Pangea. Analysis of body size, as deduced from track size, suggests that archosauriform average body size did not change significantly from the Late Permian to the Early Triassic. A survey of facies yielding both skeletal and track record indicate an ecological preference for inland fluvial (lacustrine) environments for early archosauromorphs. Finally, although more data is needed, Late Permian chirotheriid imprints suggest a shift from sprawling to erect posture in archosauriforms before the end-Permian mass extinction event. We highlight the importance of approaching palaeobiological questions by using all available sources of data, specifically through integrating the body and track fossil record.

The Origin and Early Radiation of Archosauriforms: Integrating the Skeletal and Footprint Record

PubMed Central

Bernardi, Massimo; Klein, Hendrik; Petti, Fabio Massimo; Ezcurra, Martín D.

2015-01-01

We present a holistic approach to the study of early archosauriform evolution by integrating body and track records. The ichnological record supports a Late Permian–Early Triassic radiation of archosauriforms not well documented by skeletal material, and new footprints from the Upper Permian of the southern Alps (Italy) provide evidence for a diversity not yet sampled by body fossils. The integrative study of body fossil and footprint data supports the hypothesis that archosauriforms had already undergone substantial taxonomic diversification by the Late Permian and that by the Early Triassic archosauromorphs attained a broad geographical distribution over most parts of Pangea. Analysis of body size, as deduced from track size, suggests that archosauriform average body size did not change significantly from the Late Permian to the Early Triassic. A survey of facies yielding both skeletal and track record indicate an ecological preference for inland fluvial (lacustrine) environments for early archosauromorphs. Finally, although more data is needed, Late Permian chirotheriid imprints suggest a shift from sprawling to erect posture in archosauriforms before the end-Permian mass extinction event. We highlight the importance of approaching palaeobiological questions by using all available sources of data, specifically through integrating the body and track fossil record. PMID:26083612

Oligodendroglial response to ionizing radiation: Dose and dose-rate response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levy, R.P.

1991-01-01

An in vitro system using neuroglia from neonatal rat brain was developed to examining the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute [gamma]-radiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DICmore » 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. It was concluded that oligodendrocytes in irradiated cultures had significantly lower functional capacity than did unirradiated controls. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. At DIC 14, the group irradiated in a single fraction had significantly lower oligodendrocyte counts than any group given split doses; all irradiated cultures had marked depression of MBP synthesis, but to significant differences referable to time interval between doses. At DIC 21, cultures irradiated at intervals of 0 h to 2 h had similar oligodendrocyte counts to one another, but these counts were significantly lower than in cultures irradiated at intervals of 4 h to 6 h; MBP levels remained depressed at DIC 21 for all irradiated cultures. The oligodendrocyte response to dose rate (0.03 to 1.97 Gy/min) was evaluated at DIC 14 and DIC 21. Exposure at 0.03 Gy/min suppressed oligodendrocyte counts at DIC 21 less than did higher dose rates in 5-Gy irradiated cultures.« less

Protracted low-dose radiation priming and response of liver to acute gamma and proton radiation.

PubMed

Gridley, D S; Mao, X W; Cao, J D; Bayeta, E J M; Pecaut, M J

2013-10-01

This study evaluated liver from C57BL/6 mice irradiated with low-dose/low-dose-rate (LDR) γ-rays (0.01 Gy, 0.03 cGy/h), with and without subsequent exposure to acute 2 Gy gamma or proton radiation. Analyses were performed on day 56 post-exposure. Expression patterns of apoptosis-related genes were strikingly different among irradiated groups compared with 0 Gy (p < 0.05). Two genes were affected in the Gamma group, whereas 10 were modified in the LDR + Gamma group. In Proton and LDR + Proton groups, there were six and 12 affected genes, respectively. Expression of genes in the Gamma (Traf3) and Proton (Bak1, Birc2, Birc3, Mcl1) groups was no longer different from 0 Gy control group when mice were pre-exposed to LDR γ-rays. When each combined regimen was compared with the corresponding group that received acute radiation alone, two genes in the LDR + Gamma group and 17 genes in the LDR + Proton group were modified; greatest effect was on Birc2 and Nol3 (> 5-fold up-regulated by LDR + Protons). Oxygen radical production in livers from the LDR + Proton group was higher in LDR, Gamma, and LDR + Gamma groups (p < 0.05 vs. 0 Gy), but there were no differences in phagocytosis of E. coli. Sections stained with hematoxylin and eosin (H&E) suggested more inflammation, with and without necrosis, in some irradiated groups. The data demonstrate that response to acute radiation is dependent on radiation quality and regimen and that some LDR γ-ray-induced modifications in liver response were still evident nearly 2 months after exposure.

Surface effects on the radiation response of nanoporous Au foams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, E. G.; Caro, M.; Wang, Y. Q.

2012-11-05

We report on an experimental and simulation campaign aimed at exploring the radiation response of nanoporous Au (np-Au) foams. We find different defect accumulation behavior by varying radiation dose-rate in ion-irradiated np-Au foams. Stacking fault tetrahedra are formed when np-Au foams are irradiated at high dose-rate, but they do not seem to be formed in np-Au at low dose-rate irradiation. A model is proposed to explain the dose-rate dependent defect accumulation based on these results.

Early response in cognitive-behavior therapy for syndromes of medically unexplained symptoms.

PubMed

Kleinstäuber, Maria; Lambert, Michael J; Hiller, Wolfgang

2017-05-25

Early dramatic treatment response suggests a subset of patients who respond to treatment before most of it has been offered. These early responders tend to be over represented among those who are well at termination and at follow-up. Early response patterns in psychotherapy have been investigated only for a few of mental disorders so far. The main aim of the current study was to examine early response after five therapy-preparing sessions of a cognitive behavior therapy (CBT) for syndromes of medically unexplained symptoms (MUS). In the context of a randomized, waiting-list controlled trial 48 patients who suffered from ≥3 MUS over ≥6 months received 5 therapy-preparing sessions and 20 sessions of CBT for somatoform disorders. They completed self-report scales of somatic symptom severity (SOMS-7 T), depression (BDI-II), anxiety (BSI), illness anxiety and behavior (IAS) at pre-treatment, after 5 therapy-preparing sessions (FU-5P) and at therapy termination (FU-20 T). The current analyses are based on data from the treatment arm only. Repeated measure ANOVAs revealed a significant decrease of depression (d = 0.34), anxiety (d = 0.60), illness anxiety (d = 0.38) and illness behavior (d = 0.42), but no change of somatic symptom severity (d = -0.03) between pre-treatment and FU-5P. Hierarchical linear multiple regression analyses showed that symptom improvements between pre-treatment and FU-5P predict a better outcome at therapy termination for depression and illness anxiety, after controlling for pre-treatment scores. Mixed-effect ANOVAs revealed significant group*time interaction effects indicating differences in the course of symptom improvement over the therapy between patients who fulfilled a reliable change (i.e., early response) during the 5 therapy-preparing sessions and patients who did not reach an early reliable change. Demographic or clinical variables at pre-treatment were not significantly correlated with differential scores between pre

Radiation hazards of radio frequency waves on the early embryonic development of Zebrafish

NASA Astrophysics Data System (ADS)

Harkless, Ryan; Al-Quraishi, Muntather; Vagula, Mary C.

2014-06-01

With the growing use of wireless devices in almost all day-to-day activities, exposure to radio-frequency radiation has become an immediate health concern. It is imperative that the effects of such radiation not only on humans, but also on other organisms be well understood. In particular, it is critical to understand if RF radiation has any bearing on the gene expression during embryonic development, as this is a crucial and delicate phase for any organism. Owing to possible effects that RF radiation may have on gene expression, it is essential to explore the carcinogenic or teratogenic properties that it may show. This study observed the effects of RF radiation emitted from a cellular telephone on the embryonic development of zebra fish. The expression of the gene shha plays a key role in the early development of the fish. This gene has homologs in humans as well as in other model organisms. Additionally, several biomarkers indicative of cell stress were examined: including lactate dehydrogenase (LDH), superoxide dismutase (SOD), and lipid peroxidation (LPO). Results show a significant decrease in the expression of shha, a significant decrease in LDH activity. There was no significant increase in SOD and LPO activity. No morphological abnormalities were observed in the developing embryos. At present, these results indicate that exposure to cell phone radiation may have a suppressive effect on expression of shha in D. rerio, though such exposure does not appear to cause morphological detriments. More trials are underway to corroborate these results.

The Response of a Spectral General Circulation Model to Refinements in Radiative Processes.

NASA Astrophysics Data System (ADS)

Ramanathan, V.; Pitcher, Eric J.; Malone, Robert C.; Blackmon, Maurice L.

1983-03-01

We present here results and analyses of a series of numerical experiments performed with a spectral general circulation model (GCM). The purpose of the GCM experiments is to examine the role of radiation/cloud processes in the general circulation of the troposphere and stratosphere. The experiments were primarily motivated by the significant improvements in the GCM zonal mean simulation as refinements were made in the model treatment of clear-sky radiation and cloud-radiative interactions. The GCM with the improved cloud/radiation model is able to reproduce many observed features, such as: a clear separation between the wintertime tropospheric jet and the polar night jet; winter polar stratospheric temperatures of about 200 K; interhemispheric and seasonal asymmetries in the zonal winds.In a set of sensitivity experiments, we have stripped the cloud/radiation model of its improvements, the result being a significant degradation of the zonal mean simulations by the GCM. Through these experiments we have been able to identify the processes that are responsible for the improved GCM simulations: (i) careful treatment of the upper boundary condition for O3 solar heating; (ii) temperature dependence of longwave cooling by CO2 15 m bands., (iii) vertical distribution of H2O that minimizes the lower stratospheric H2O longwave cooling; (iv) dependence of cirrus emissivity on cloud liquid water content.Comparison of the GCM simulations, with and without the cloud/radiation improvements, reveals the nature and magnitude of the following radiative-dynamical interactions: (i) the temperature decrease (due to errors in radiative heating) within the winter polar stratosphere is much larger than can be accounted for by purely radiative adjustment; (ii) the role of dynamics in maintaining the winter polar stratosphere thermal structure is greatly diminished in the GCM with the degraded treatment of radiation; (iii) the radiative and radiative-dynamical response times of the

Ultraviolet radiation and the photobiology of earth's early oceans.

PubMed

Cockell, C S

2000-10-01

During the Archean era (3.9-2.5 Ga ago) the earth was dominated by an oceanic lithosphere. Thus, understanding how life arose and persisted in the Archean oceans constitutes a major challenge in understanding early life on earth. Using a radiative transfer model of the late Archean oceans, the photobiological environment of the photic zone and the surface microlayer is explored at the time before the formation of a significant ozone column. DNA damage rates might have been approximately three orders of magnitude higher in the surface layer of the Archean oceans than on the present-day oceans, but at 30 m depth, damage may have been similar to the surface of the present-day oceans. However at this depth the risk of being transported to surface waters in the mixed layer was high. The mixed layer may have been inhabited by a low diversity UV-resistant biota. But it could have been numerically abundant. Repair capabilities similar to Deinococcus radiodurans would be sufficient to survive in the mixed layer. Diversity may have been greater in the region below the mixed layer and above the light compensation point corresponding to today's 'deep chlorophyll maximum'. During much of the Archean the air-water interface was probably an uninhabitable extreme environment for neuston. The habitability of some regions of the photic zone is consistent with the evidence embodied in the geologic record, which suggests an oxygenated upper layer in the Archean oceans. During the early Proterozoic, as ozone concentrations increased to a column abundance above 1 x 10(17) cm-2, UV stress would have been reduced and possibly a greater diversity of organisms could have inhabited the mixed layer. However, nutrient upwelling from newly emergent continental crusts may have been more significant in increasing total planktonic abundance in the open oceans and coastal regions than photobiological factors. The phohobiological environment of the Archean oceans has implications for the potential

Alectinib induced CNS radiation necrosis in an ALK+NSCLC patient with a remote (7 years) history of brain radiation.

PubMed

Ou, Sai-Hong Ignatius; Weitz, Michael; Jalas, John R; Kelly, Daniel F; Wong, Vanessa; Azada, Michele C; Quines, Oliver; Klempner, Samuel J

2016-06-01

Alectinib is a second generation ALK inhibitor that has significant clinical activity in central nervous system (CNS) metastases in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Pseudoprogression (PsP) due to radiation necrosis during alecitnib treatment of central nervous system (CNS) metastases from ALK-rearranged NSCLC as been reported. Hence, distinguishing radiation-related PsP from alectinib-induced radiographic changes is important to avoid erroneous early trial discontinuation and abandonment of an effective treatment. However, it remains difficult to assess casuality of radiation necrosis is related to recent direct radiation or induced by alectinib treatment or both. It is also unknown how long from previous radiation can alectinib still induce radiation necrosis. Here we reported a crizotinib-refractory ALK-positive NSCLC patient who develop radiation necrosis in one of his metastatic CNS lesions after approximately 12 months of alectinib treatment who otherwise had on-going CNS response on alectinib. His most recent radiation to his CNS metastases was 7 years prior to the start of alectinib. This case illustrates that in the setting of pror CNS radiation, given the significant clinical activity of alectinib in CNS metastases in ALK-positive NSCLC patients the risk of CNS radiation necrosis remains long after previous radiation to the CNS metastases has been completed and can occur after durable response of treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Early urinary diversion with ileal conduit and vesicovaginostomy in the treatment of radiation cystitis due to carcinoma cervix: a study from a tertiary care hospital in South India.

PubMed

Banerji, John Samuel; Devasia, Antony; Kekre, Nitin Sudhakar; Chacko, Ninan

2015-10-01

To study the magnitude of radiation cystitis following radiation therapy for carcinoma cervix, and propose an algorithm to decide on early diversion, with or without vesicovaginostomy. Women who developed radiation cystitis following radiotherapy for carcinoma cervix from January 1998 to December 2011 were included in this retrospective study. Electronic hospital records were analysed to document the presence of radiation cystitis. All women who developed evidence of radiation-induced cystitis, according to the common toxicity and Radiation Therapy Oncology Group criteria, were included in the study. We looked at transfusion requirements, number of hospital admissions, quality of life and cost involved. Chi-square tests were done where applicable. SPSS version 16 was used for analysis. Of the 902 patients who received radiation for carcinoma cervix in the 13-year period, 62 (6.87%) developed grade 3/4 cystitis. Twenty-eight of them underwent ileal conduit diversion, with 18 undergoing concomitant vesicovaginostomy. When compared with the patients who did not have diversion, the transfusion requirements, number of hospital admissions and quality of life had a statistically significant difference. Cost analysis of early diversion too showed a marginal benefit with early diversion. The limitation of the study was that it was retrospective in nature. In radiation cystitis, multiple hospital admissions and consequential increase in cost is the norm. In severe disease, early diversion is a prudent, cost-effective approach with good quality of life and early return to normal activity. © 2014 Royal Australasian College of Surgeons.

Synergizing Radiation Therapy and Immunotherapy for Curing Incurable Cancers: Opportunities and Challenges

PubMed Central

Hodge, James W.; Guha, Chandan; Neefjes, Jacques; Gulley, James L.

2012-01-01

The combination of radiation therapy and immunotherapy holds particular promise as a strategy for cancer therapeutics. There is evidence that immunotherapy is most beneficial alone when employed early in the disease process or in combination with standard therapies (e.g., radiation) later in the disease process. Indeed, radiation may act synergistically with immunotherapy to enhance immune responses, inhibit immunosuppression, and/or alter the phenotype of tumor cells, thus rendering them more susceptible to immune-mediated killing. Furthermore, as monotherapies, both immunotherapy and radiation may be insufficient to eliminate tumor masses. However, following immunization with a cancer vaccine, the destruction of even a small percentage of tumor cells by radiation could result in cross-priming and presentation of tumor antigens to the immune system, thereby potentiating antitumor responses. Learning how to exploit radiation-induced changes to tumor-cell antigens, and how to induce effective immune responses to these cumulatively immunogenic stimuli, is an exciting frontier in cancer therapy research. This review examines a) mechanisms by which many forms of radiation therapy can induce or augment antitumor immune responses and b) preclinical systems that demonstrate that immunotherapy can be effectively combined with radiation therapy. Finally, we review current clinical trials where standard-of-care radiation therapy is being combined with immunotherapy. PMID:18777956

On-orbit characterizations of Earth Radiation Budget Experiment broadband shortwave active cavity radiometer sensor responses

NASA Astrophysics Data System (ADS)

Lee, Robert B., III; Wilson, Robert S.; Smith, G. Louis; Bush, Kathryn A.; Thomas, Susan; Pandey, Dhirendra K.; Paden, Jack

2004-12-01

The NASA Earth Radiation Budget Experiment (ERBE) missions were designed to monitor long-term changes in the earth radiation budget components which may cause climate changes. During the October 1984 through September 2004 period, the NASA Earth Radiation Budget Satellite (ERBS)/ERBE nonscanning active cavity radiometers (ACR) were used to monitor long-term changes in the earth radiation budget components of the incoming total solar irradiance (TSI), earth-reflected TSI, and earth-emitted outgoing longwave radiation (OLR). The earth-reflected total solar irradiances were measured using broadband shortwave fused, waterless quartz (Suprasil) filters and ACR"s that were covered with a black paint absorbing surface. Using on-board calibration systems, 1984 through 1999, long-term ERBS/ERBE ACR sensor response changes were determined from direct observations of the incoming TSI in the 0.2-5 micrometer shortwave broadband spectral region. During the October 1984 through September 1999 period, the ERBS shortwave sensor responses were found to decrease as much as 8.8% when the quartz filter transmittances decreased due to direct exposure to TSI. On October 6, 1999, the on-board ERBS calibration systems failed. To estimate the 1999-2004, ERBS sensor response changes, the 1984-1997 NOAA-9, and 1986-1995 NOAA-10 Spacecraft ERBE ACR responses were used to characterize response changes as a function of exposure time. The NOAA-9 and NOAA-10 ACR responses decreased as much as 10% due to higher integrated TSI exposure times. In this paper, for each of the ERBS, NOAA-9, and NOAA-10 Spacecraft platforms, the solar calibrations of the ERBE sensor responses are described as well as the derived ERBE sensor response changes as a function of TSI exposure time. For the 1984-2003 ERBS data sets, it is estimated that the calibrated ERBE earth-reflected TSI measurements have precisions approaching 0.2 Watts-per-squared-meter at satellite altitudes.

Genetic background modulates lncRNA-coordinated tissue response to low dose ionizing radiation

DOE PAGES

Tang, Jonathan; Huang, Yurong; Nguyen, David H.; ...

2015-02-04

Long noncoding RNAs (lncRNAs) are emerging as key regulators of diverse cell functions and processes. However, the relevance of lncRNAs in the cell and tissue response to ionizing radiation has not yet been characterized. Here we used microarray profiling to determine lncRNA and mRNA expression in mammary glands of BALB/c and SPRET/EiJ mice after low-dose ionizing radiation (LDIR) exposure. We found that unirradiated mammary tissues of these strains differed significantly in baseline expressions of 290 lncRNAs. LDIR exposure (10 cGy) induced a significant change in the expression of many lncRNAs. The vast majority of lncRNAs identified to be differentially expressed aftermore » LDIR in either BALB/c or SPRET/EiJ had a significantly correlated expression pattern with at least one LDIR responsive mRNA. Functional analysis revealed that the response to LDIR in BALB/c mice is highly dynamic with enrichment for genes involved in tissue injury, inflammatory responses, and mammary gland development at 2, 4, and 8 weeks after LDIR, respectively. Our study demonstrates that genetic background strongly influences the expression of lncRNAs and their response to radiation and that lncRNAs may coordinate the tissue response to LDIR exposure via regulation of coding mRNAs.« less

Genetic background modulates lncRNA-coordinated tissue response to low dose ionizing radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Jonathan; Huang, Yurong; Nguyen, David H.

Long noncoding RNAs (lncRNAs) are emerging as key regulators of diverse cell functions and processes. However, the relevance of lncRNAs in the cell and tissue response to ionizing radiation has not yet been characterized. Here we used microarray profiling to determine lncRNA and mRNA expression in mammary glands of BALB/c and SPRET/EiJ mice after low-dose ionizing radiation (LDIR) exposure. We found that unirradiated mammary tissues of these strains differed significantly in baseline expressions of 290 lncRNAs. LDIR exposure (10 cGy) induced a significant change in the expression of many lncRNAs. The vast majority of lncRNAs identified to be differentially expressed aftermore » LDIR in either BALB/c or SPRET/EiJ had a significantly correlated expression pattern with at least one LDIR responsive mRNA. Functional analysis revealed that the response to LDIR in BALB/c mice is highly dynamic with enrichment for genes involved in tissue injury, inflammatory responses, and mammary gland development at 2, 4, and 8 weeks after LDIR, respectively. Our study demonstrates that genetic background strongly influences the expression of lncRNAs and their response to radiation and that lncRNAs may coordinate the tissue response to LDIR exposure via regulation of coding mRNAs.« less

The biobehavioral and neuroimmune impact of low-dose ionizing radiation.

PubMed

York, Jason M; Blevins, Neil A; Meling, Daryl D; Peterlin, Molly B; Gridley, Daila S; Cengel, Keith A; Freund, Gregory G

2012-02-01

In the clinical setting, repeated exposures (10-30) to low-doses of ionizing radiation (≤200 cGy), as seen in radiotherapy for cancer, causes fatigue. Almost nothing is known, however, about the fatigue inducing effects of a single exposure to environmental low-dose ionizing radiation that might occur during high-altitude commercial air flight, a nuclear reactor accident or a solar particle event (SPE). To investigate the short-term impact of low-dose ionizing radiation on mouse biobehaviors and neuroimmunity, male CD-1 mice were whole body irradiated with 50 cGy or 200 cGy of gamma or proton radiation. Gamma radiation was found to reduce spontaneous locomotor activity by 35% and 36%, respectively, 6 h post irradiation. In contrast, the motivated behavior of social exploration was un-impacted by gamma radiation. Examination of pro-inflammatory cytokine gene transcripts in the brain demonstrated that gamma radiation increased hippocampal TNF-α expression as early as 4 h post-irradiation. This was coupled to subsequent increases in IL-1RA (8 and 12 h post irradiation) in the cortex and hippocampus and reductions in activity-regulated cytoskeleton-associated protein (Arc) (24 h post irradiation) in the cortex. Finally, restraint stress was a significant modulator of the neuroimmune response to radiation blocking the ability of 200 cGy gamma radiation from impairing locomotor activity and altering the brain-based inflammatory response to irradiation. Taken together, these findings indicate that low-dose ionizing radiation rapidly activates the neuroimmune system potentially causing early onset fatigue-like symptoms in mice. Copyright © 2011 Elsevier Inc. All rights reserved.

Energy response of diamond sensor to beta radiation.

PubMed

Tchouaso, Modeste Tchakoua; Kasiwattanawut, Haruetai; Prelas, Mark A

2018-04-26

This paper demonstrates the ability of diamond sensors to respond to beta radiation. A Chemical Vapor Deposition (CVD) single crystal diamond was used in this work. The diamond crystal has a dimension of 4.5×4.5 by 0.5 mm thick. Metal contacts were fabricated on both sides of the diamond using titanium and palladium metals with thicknesses of 50 nm and 150 nm, respectively. The energy response of the diamond sensor was experimentally measured using three beta isotopes that cover the entire range of beta energy: 147 Pm, a weak beta radiation with a maximum energy of 0.225 MeV, 2 ° 4 Tl, a medium energy beta radiation with a maximum energy of 0.763 MeV, and 9 °Sr/ 9 °Y, with both a medium energy beta radiation with a maximum energy of 0.546 MeV, and a high energy beta radiation with a maximum energy of 2.274 MeV. The beta measurements indicate that diamond sensors are sensitive to beta radiation and are suitable for beta spectroscopy. This is important in estimating dose since diamond is tissue equivalent, and the absorbed dose is easily determined from the energy and the mass of the active volume. The high energy betas from 2 ° 4 Tl and 90 Sr/ 90 Y penetrates the sensor without depositing sufficient energy in the active area because their range is larger than the thickness of sensor. The sensitivity of the detector is limited because of its small volume and can be improved by combining smaller area sensors since growing large size diamond is currently a challenge. Copyright © 2018 Elsevier Ltd. All rights reserved.

Response of dosemeters in the radiation field generated by a TW-class laser system.

PubMed

Olšovcová, V; Klír, D; Krása, J; Krůs, M; Velyhan, A; Zelenka, Z; Rus, B

2014-10-01

State-of-the-art laser systems are able to generate ionising radiation of significantly high energies by focusing ultra-short and intense pulses onto targets. Thus, measures ensuring the radiation protection of both working personnel and the general public are required. However, commercially available dosemeters are primarily designed for measurement in continuous fields. Therefore, it is important to explore their response to very short pulses. In this study, the responses of dosemeters in a radiation field generated by iodine high-power and Ti:Sapphire laser systems are examined in proton and electron acceleration experiments. Within these experiments, electron bunches of femtosecond pulse duration and 100-MeV energy and proton bunches with sub-nanosecond pulse duration and energy of several megaelectronvolts were generated in single-shot regimes. Responses of typical detectors (TLD, films and electronic personal dosemeter) were analysed and compared. Further, a first attempt was carried out to characterise the radiation field generated by TW-class laser systems. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Evidence-Based Early Reading Practices within a Response to Intervention System

ERIC Educational Resources Information Center

Bursuck, Bill; Blanks, Brooke

2010-01-01

Many students who experience reading failure are inappropriately placed in special education. A promising response to reducing reading failure and the overidentification of students for special education is Response to Intervention (RTI), a comprehensive early detection and prevention system that allows teachers to identify and support struggling…

The Cosmic Microwave Background Radiation - A Unique Window on the Early Universe

NASA Technical Reports Server (NTRS)

Hinshaw, Gary F.

2009-01-01

The cosmic microwave background radiation is the remnant heat from the Big Bang. It provides us with a unique probe of conditions in the early universe, long before any organized structures had yet formed. The anisotropy in the radiation's brightness yields important clues about primordial structure and additionally provides a wealth of information about the physics of the early universe. Within the framework of inflationary dark matter models, observations of the anisotropy on sub-degree angular scales reveals the signatures of acoustic oscillations of the photon-baryon fluid at a redshift of approximately 1100. Data from the first five years of operation of the Wilkinson Microwave Anisotropy Probe (WMAP) satellite provide detailed full-sky maps of the cosmic microwave background temperature and polarization anisotropy. Together, the data provide a wealth of cosmological information, including the age of the universe, the epoch when the first stars formed, and the overall composition of baryonic matter, dark matter, and dark energy. The results also provide constraints on the period of inflationary expansion in the very first moments of time. WMAP, part of NASA's Explorers program, was launched on June 30, 2001. The WMAP satellite was produced in a partnership between the Goddard Space Flight Center and Princeton University. The WMAP team also includes researchers at the Johns Hopkins University; the Canadian Institute of Theoretical Astrophysics; University of Texas; Oxford University; University of Chicago; Brown University; University of British Columbia; and University of California, Los Angeles.

The Cosmic Microwave Background Radiation - A Unique Window on the Early Universe

NASA Technical Reports Server (NTRS)

Hinshaw, Gary F.

2008-01-01

The cosmic microwave background radiation is the remnant heat from the Big Bang. It provides us with a unique probe of conditions in the early universe, long before any organized structures had yet formed. The anisotropy in the radiation's brightness yields important clues about primordial structure and additionally provides a wealth of information about the physics of the early universe. Within the framework of inflationary dark matter models, observations of the anisotropy on sub-degree angular scales reveals the signatures of acoustic oscillations of the photon-baryon fluid at a redshift of approximately 1100. Data from the first five years of operation of the Wilkinson Microwave Anisotropy Probe (WMAP) satellite provide detailed full-sky maps of the cosmic microwave background temperature and polarization anisotropy. Together, the data provide a wealth of cosmological information, including the age of the universe, the epoch when the first stars formed, and the overall composition of baryonic matter, dark matter, and dark energy. The results also provide constraints on the period of inflationary expansion in the very first moments of time. WMAP, part of NASA's Explorers program, was launched on June 30, 2001. The WMAP satellite was produced in a partnership between the Goddard Space Flight Center and Princeton University. The WMAP team also includes researchers at Johns Hopkins University; the Canadian Institute of Theoretical Astrophysics; University of Texas; Oxford University; University of Chicago; Brown university; University of British Columbia; and University of California, Los Angeles.

The Cosmic Microwave Background Radiation-A Unique Window on the Early Universe

NASA Technical Reports Server (NTRS)

Hinshaw, Gary

2010-01-01

The cosmic microwave background radiation is the remnant heat from the Big Bang. It provides us with a unique probe of conditions in the early universe, long before any organized structures had yet formed. The anisotropy in the radiation's brightness yields important clues about primordial structure and additionally provides a wealth of information about the physics of the early universe. Within the framework of inflationary dark matter models, observations of the anisotropy on sub-degree angular scales reveals the signatures of acoustic oscillations of the photon-baryon fluid at a redshift of 11 00. Data from the first seven years of operation of the Wilkinson Microwave Anisotropy Probe (WMAP) satellite provide detailed full-sky maps of the cosmic microwave background temperature and polarization anisotropy. Together, the data provide a wealth of cosmological information, including the age of the universe, the epoch when the first stars formed, and the overall composition of baryonic matter, dark matter, and dark energy. The results also provide constraints on the period of inflationary expansion in the very first moments of time. WMAP, part of NASA's Explorers program, was launched on June 30, 2001. The WMAP satellite was produced in a partnership between the Goddard Space Flight Center and Princeton University. The WMAP team also includes researchers at the Johns Hopkins University; the Canadian Institute of Theoretical Astrophysics; University of Texas; Oxford University; University of Chicago; Brown University; University of British Columbia; and University of California, Los Angeles.

Raman spectroscopy identifies radiation response in human non-small cell lung cancer xenografts

NASA Astrophysics Data System (ADS)

Harder, Samantha J.; Isabelle, Martin; Devorkin, Lindsay; Smazynski, Julian; Beckham, Wayne; Brolo, Alexandre G.; Lum, Julian J.; Jirasek, Andrew

2016-02-01

External beam radiation therapy is a standard form of treatment for numerous cancers. Despite this, there are no approved methods to account for patient specific radiation sensitivity. In this report, Raman spectroscopy (RS) was used to identify radiation-induced biochemical changes in human non-small cell lung cancer xenografts. Chemometric analysis revealed unique radiation-related Raman signatures that were specific to nucleic acid, lipid, protein and carbohydrate spectral features. Among these changes was a dramatic shift in the accumulation of glycogen spectral bands for doses of 5 or 15 Gy when compared to unirradiated tumours. When spatial mapping was applied in this analysis there was considerable variability as we found substantial intra- and inter-tumour heterogeneity in the distribution of glycogen and other RS spectral features. Collectively, these data provide unique insight into the biochemical response of tumours, irradiated in vivo, and demonstrate the utility of RS for detecting distinct radiobiological responses in human tumour xenografts.

Cortisol Response to Psychosocial Stress in Chinese Early Puberty Girls: Possible Role of Depressive Symptoms.

PubMed

Sun, Ying; Deng, Fang; Liu, Yang; Tao, Fang-Biao

2015-01-01

Objective. The present study aimed at investigating unique patterns of salivary cortisol reactivity and recovery in response to a social stressor among girls with early puberty and exploring possible role of depressive symptom in this association. Design. Case-control study. Patients. Fifty-six girls with early puberty and age- and body mass index- (BMI-) matched normal puberty controls (n = 56) were selected. Measurements. Salivary cortisol was measured in response to the Groningen Social Stress Test for Children. Results. Girls with early puberty had higher cortisol concentration at the end of the GSST (C3), cortisol concentration 20 min after the end of the GSST (C4), and AUC increment (AUCi) compared to non-early puberty girls. Depressive symptoms correlated with blunted HPA reactivity among girls with early puberty. Conclusion. This study demonstrated the disturbance effect of objectively examined early pubertal timing on HPA axis responses. It also suggested that stress reactivity might be blunted for individuals with depressive symptoms.

Development, Verification and Validation of Enclosure Radiation Capabilities in the CHarring Ablator Response (CHAR) Code

NASA Technical Reports Server (NTRS)

Salazar, Giovanni; Droba, Justin C.; Oliver, Brandon; Amar, Adam J.

2016-01-01

With the recent development of multi-dimensional thermal protection system (TPS) material response codes including the capabilities to account for radiative heating is a requirement. This paper presents the recent efforts to implement such capabilities in the CHarring Ablator Response (CHAR) code developed at NASA's Johnson Space Center. This work also describes the different numerical methods implemented in the code to compute view factors for radiation problems involving multiple surfaces. Furthermore, verification and validation of the code's radiation capabilities are demonstrated by comparing solutions to analytical results, to other codes, and to radiant test data.

Oxidative Stress and Autophagy Responses of Osteocytes Exposed to Spaceflight-like Radiation.

NASA Technical Reports Server (NTRS)

Tahimic, Candice; Rael, Victoria E.; Globus, Ruth K.

2015-01-01

Weightlessness and radiation, two of the unique elements of the space environment, causes a profound decrement in bone mass that mimics aging. This bone loss is thought to result from increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. Our current understanding of the signaling factors and mechanisms underlying bone loss is incomplete. However, it is known that oxidative stress, characterized by the excess production of free radicals, is elevated during radiation exposure. The goals of this study is to examine the response of osteocytes to spaceflight-like radiation and to identify signaling processes that may be targeted to mitigate bone loss in scenarios of space exploration, earth-based radiotherapy and accidental radiation exposure. We hypothesize that (1) oxidative stress, as induced by radiation, decreases osteocyte survival and increases pro-osteoclastogenic signals and that (2) autophagy is one of the key cellular defenses against oxidative stress. Autophagy is the process by which cellular components including organelles and proteins are broken down and recycled. To test our hypothesis, we exposed the osteocyte-like cell line, MLO-Y4, to 0.5, 1, and 2 Gy of simulated space radiation (Iron-56 radiation at 600 MeV/n) and assessed cell numbers, cell growth-associated molecules as well as markers of autophagy and oxidative stress at various time points post-irradiation. We observed a reduction in cell numbers in the groups exposed to 1 and 2 Gy of Iron-56 radiation. Collectively, flow cytometry and gene expression analysis revealed that radiation caused a shift in cell cycle distribution consistent with growth arrest. Compared to sham-treatment, 2 Gy of Iron-56 increased FoxO3, SOD1, and RANKL gene expression yet unexpectedly decreased LC3B-II protein levels at 4 and 24 hours post-IR. Taken together, these findings suggest that simulated space radiation invoke

Predictors of Responsiveness to Early Literacy Intervention: A 10-Year Update

ERIC Educational Resources Information Center

Lam, Elizabeth A.; McMaster, Kristen L.

2014-01-01

The purpose of this review was to update previous reviews on factors related to students' responsiveness to early literacy intervention. The 14 studies in this synthesis used experimental designs, provided small-group or one-on-one reading interventions, and analyzed factors related to responsiveness to those interventions. Participants were…

Cortisol Stress Response Variability in Early Adolescence Attachment, Affect and Sex

PubMed Central

Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J.; Wynne-Edwards, Katherine; Wright, Joan M.; Weinberg, Joanne

2017-01-01

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic–pituitary–adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents. PMID:27468997

Cortisol Stress Response Variability in Early Adolescence: Attachment, Affect and Sex.

PubMed

Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J; Wynne-Edwards, Katherine; Wright, Joan M; Weinberg, Joanne

2017-01-01

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic-pituitary-adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents.

Exposures involving perturbations of the EM field have non-linear effects on radiation response and can alter the expression of radiation induced bystander effects

NASA Astrophysics Data System (ADS)

Mothersill, Carmel; Seymour, Colin

2012-07-01

Our recent data suggest there is a physical component to the bystander signal induced by radiation exposure and that alternative medicine techniques such as Reiki and acupuncture or exposures to weak EM fields alter the response of cells to direct irradiation and either altered bystander signal production or altered the response of cells receiving bystander signals. Our proposed mechanism to explain these findings is that perturbation of electromagnetic (EM) fields is central to the induction of low radiation dose responses especially non-targeted bystander effects. In this presentation we review the alternative medicine data and other data sets from our laboratory which test our hypothesis that perturbation of bio-fields will modulate radiation response in the low dose region. The other data sets include exposure to MRI, shielding using lead and or Faraday cages, the use of physical barriers to bystander signal transmission and the use of membrane channel blockers. The data taken together strongly suggest that EM field perturbation can modulate low dose response and that in fact the EM field rather than the targeted deposition of ionizing energy in the DNA may be the key determinant of dose response in a cell or organism The results also lead us to suspect that at least when chemical transmission is blocked, bystander signals can be transmitted by other means. Our recent experiments suggest light signals and volatiles are not likely. We conclude that alternative medicine and other techniques involving electromagnetic perturbations can modify the response of cells to low doses of ionizing radiation and can induce bystander effects similar to those seen in medium transfer experiments. In addition to the obvious implications for mechanistic studies of low dose effects, this could perhaps provide a novel target to exploit in space radiation protection and in optimizing therapeutic gain during radiotherapy.

Effects of epidermal growth factor receptor kinase inhibition on radiation response in canine osteosarcoma cells.

PubMed

Mantovani, Fernanda B; Morrison, Jodi A; Mutsaers, Anthony J

2016-05-31

Radiation therapy is a palliative treatment modality for canine osteosarcoma, with transient improvement in analgesia observed in many cases. However there is room for improvement in outcome for these patients. It is possible that the addition of sensitizing agents may increase tumor response to radiation therapy and prolong quality of life. Epidermal growth factor receptor (EGFR) expression has been documented in canine osteosarcoma and higher EGFR levels have been correlated to a worse prognosis. However, effects of EGFR inhibition on radiation responsiveness in canine osteosarcoma have not been previously characterized. This study examined the effects of the small molecule EGFR inhibitor erlotinib on canine osteosarcoma radiation responses, target and downstream protein expression in vitro. Additionally, to assess the potential impact of treatment on tumor angiogenesis, vascular endothelial growth factor (VEGF) levels in conditioned media were measured. Erlotinib as a single agent reduced clonogenic survival in two canine osteosarcoma cell lines and enhanced the impact of radiation in one out of three cell lines investigated. In cell viability assays, erlotinib enhanced radiation effects and demonstrated single agent effects. Erlotinib did not alter total levels of EGFR, nor inhibit downstream protein kinase B (PKB/Akt) activation. On the contrary, erlotinib treatment increased phosphorylated Akt in these osteosarcoma cell lines. VEGF levels in conditioned media increased after erlotinib treatment as a single agent and in combination with radiation in two out of three cell lines investigated. However, VEGF levels decreased with erlotinib treatment in the third cell line. Erlotinib treatment promoted modest enhancement of radiation effects in canine osteosarcoma cells, and possessed activity as a single agent in some cell lines, indicating a potential role for EGFR inhibition in the treatment of a subset of osteosarcoma patients. The relative radioresistance of

Infrared response measurements on radiation-damaged Si/Li/ detectors.

NASA Technical Reports Server (NTRS)

Sher, A. H.; Liu, Y. M.; Keery, W. J.

1972-01-01

The improved infrared response (IRR) technique has been used to qualitatively compare radiation effects on Si(Li) detectors with energy levels reported for silicon in the literature. Measurements have been made on five commercial silicon detectors and one fabricated in-house, both before and after irradiation with fast neutrons, 1.9-MeV protons, and 1.6-MeV electrons. Effects dependent upon the extent of radiation damage have been observed. It seems likely that the photo-EMF, or photo-voltage, effect is the basic mechanism for the observation of IRR in p-i-n diodes with a wide i-region. Experimental characteristics of the IRR measurement are in agreement with those of the photovoltage effect.

Early stage response problem for post-disaster incidents

NASA Astrophysics Data System (ADS)

Kim, Sungwoo; Shin, Youngchul; Lee, Gyu M.; Moon, Ilkyeong

2018-07-01

Research on evacuation plans for reducing damages and casualties has been conducted to advise defenders against threats. However, despite the attention given to the research in the past, emergency response management, designed to neutralize hazards, has been undermined since planners frequently fail to apprehend the complexities and contexts of the emergency situation. Therefore, this study considers a response problem with unique characteristics for the duration of the emergency. An early stage response problem is identified to find the optimal routing and scheduling plan for responders to prevent further hazards. Due to the complexity of the proposed mathematical model, two algorithms are developed. Data from a high-rise building, called Central City in Seoul, Korea, are used to evaluate the algorithms. Results show that the proposed algorithms can procure near-optimal solutions within a reasonable time.

Prospective study to determine early hypertrophy of the contra-lateral liver lobe after unilobar, Yttrium-90, selective internal radiation therapy in patients with hepatocellular carcinoma.

PubMed

Teo, Jin Yao; Allen, John Carson; Ng, David Chee Eng; Abdul Latiff, Julianah Bee; Choo, Su Pin; Tai, David Wai-Meng; Low, Albert Su Chong; Cheah, Foong Koon; Chang, Jason Pik Eu; Kam, Juinn Huar; Lee, Victor T W; Chung, Alexander Yaw Fui; Chan, Chung Yip; Chow, Pierce Kah Hoe; Goh, Brian K P

2018-05-01

Liver resection is a major curative option in patients presenting with hepatocellular carcinoma. An inadequate functional liver remnant is a major limiting factor precluding liver resection. In recent years, hypertrophy of the functional liver remnant after selective internal radiation therapy hypertrophy has been observed, but the degree of hypertrophy in the early postselective internal radiation therapy period has not been well studied. We conducted a prospective study on patients undergoing unilobar, Yttrium-90 selective internal radiation therapy for hepatocellular carcinoma to evaluate early hypertrophy at 4-6 weeks and 8-12 weeks after selective internal radiation therapy. In the study, 24 eligible patients were recruited and had serial volumetric measurements performed. The median age was 66 years (38-75 years). All patients were either Child-Pugh Class A or B, and 6/24 patients had documented, clinically relevant portal hypertension; 15 of the 24 patients were hepatitis B positive. At 4-6 weeks, modest hypertrophy was seen (median 3%; range -12 to 42%) and this increased at 8-12 weeks (median 9%; range -12 to 179%). No preprocedural factors predictive of hypertrophy were identified. Hypertrophy of the functional liver remnant after selective internal radiation therapy with Yttrium-90 occurred in a subset of patients but was modest and unpredictable in the early stages. Selective internal radiation therapy cannot be recommended as a standard treatment modality to induce early hypertrophy for patients with hepatocellular carcinoma. (Surgery 2017;160:XXX-XXX.). Copyright © 2017 Elsevier Inc. All rights reserved.

The Pattern of Use of Hypofractionated Radiation Therapy for Early-Stage Breast Cancer in New South Wales, Australia, 2008 to 2012

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delaney, Geoff P., E-mail: Geoff.delaney@swsahs.nsw.gov.au; Collaboration for Cancer Outcomes Research and Evaluation, University of New South Wales, Sydney; Ingham Health and Medical Research Institute, Sydney

Purpose: Increasing phase 3 evidence has been published about the safety and efficacy of hypofractionated radiation therapy, in comparison with standard fractionation, in early-stage, node-negative breast cancer. However, uptake of hypofractionation has not been universal. The aim of this study was to investigate the hypofractionation regimen variations in practice across public radiation oncology facilities in New South Wales (NSW). Methods and Materials: Patients with early breast cancer registered in the NSW Clinical Cancer Registry who received radiation therapy for early-stage breast cancer in a publicly funded radiation therapy department between 2008 and 2012 were identified. Data extracted and analyzed includedmore » dose and fractionation type, patient age at first fraction, address (for geocoding), year of diagnosis, year of treatment, laterality, and department of treatment. A logistic regression model was used to identify factors associated with fractionation type. Results: Of the 5880 patients fulfilling the study criteria, 3209 patients (55%) received standard fractionation and 2671 patients (45%) received hypofractionation. Overall, the use of hypofractionation increased from 37% in 2008 to 48% in 2012 (range, 7%-94% across departments). Treatment facility and the radiation oncologist prescribing the treatment were the strongest independent predictors of hypofractionation. Weaker associations were also found for age, tumor site laterality, year of treatment, and distance to facility. Conclusions: Hypofractionated regimens of whole breast radiation therapy have been variably administered in the adjuvant setting in NSW despite the publication of long-term trial results and consensus guidelines. Some factors that predict the use of hypofractionation are not based on guideline recommendations, including lower rates of left-sided treatment and increasing distance from a treatment facility.« less

Dynamic skin changes of acute radiation dermatitis revealed by in vivo reflectance confocal microscopy.

PubMed

Vano-Galvan, S; Fernandez-Lizarbe, E; Truchuelo, M; Diaz-Ley, B; Grillo, E; Sanchez, V; Ríos-Buceta, L; Paoli, J; Sancho, S; Montero, A; Hernanz, R; Ramos, A; Jaen, P; Gonzalez, S

2013-09-01

A better knowledge of the dynamic biological changes that the skin undergoes in response to ionizing radiation is advisable to improve the management of radiation dermatitis, allowing selection of patients needing treatment or close monitoring. To describe the evolution of the skin in response to ionizing radiation through the reflectance confocal microscopy (RCM) features of acute radiation dermatitis. In this prospective descriptive study, six women (median age, 55 years; range, 45-80 years) diagnosed with breast cancer in stages IA-IB undergoing adjuvant radiotherapy were included in the study through consecutive sampling. Clinical, dermoscopic and RCM evaluation of the skin were performed prior to treatment and on days 1, 15, 30 and 45 after radiotherapy. While clinical features of radiation dermatitis emerged after 30 days on average, histopathological changes were detectable by RCM after a mean time of 15 days. The main RCM features included initial appearance of spongiosis, exocytosis and inflammatory cells followed by the presence of dendritic-shaped cells, 'streaming-like figures', 'broken geographic papillae', epidermal architectural disarray, effacement of rete ridges, melanophages and, finally, hyperpigmentation of the basal layer. RCM may safely detect the dynamic biological changes that the skin undergoes in response to ionizing radiation, even before than clinical onset of acute radiation dermatitis. Therefore, RCM may be useful to make an early and non-invasive diagnosis of radiation dermatitis during radiotherapy, allowing an early selection of patients needing treatment or close monitoring and avoiding skin biopsies. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

WHO-REMPAN for global health security and strengthening preparedness and response to radiation emergencies.

PubMed

Carr, Zhanat

2010-06-01

In response to the changing global environment and emerging new issues related to health security, the World Health Organization (WHO) is putting in place new tools for collective defense, such as the revised International Health Regulations (IHR) (2005). The new framework puts additional responsibilities on both Member States and WHO itself in order to effectively implement the IHR (2005) and react effectively in case of public health emergency events of any nature. Since its establishment in 1987, the Radiation Emergency Medical Preparedness and Assistance Network of WHO (WHO-REMPAN) has become an important asset for the organization's capacity to respond to radiation emergencies and to assist its Member States to strengthen their own response capacities. The paper describes in detail the framework for the WHO's role in preparedness and response to radiation emergencies, including Emergency Conventions and IHR (2005), and how the WHO-REMPAN, through its activities (i.e., technical guidelines development, training, education, research, and information sharing), provides a significant contribution to the organization's program of work towards achievement of the global health security goal.

Assessment of Early Toxicity and Response in Patients Treated With Proton and Carbon Ion Therapy at the Heidelberg Ion Therapy Center Using the Raster Scanning Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rieken, Stefan; Habermehl, Daniel; Nikoghosyan, Anna

2011-12-01

Puropose: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center. Patients and Methods: Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility. Results: In all 118 patients, few side effects were observed,more » in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. Conclusions: Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility.« less

Assessment of early toxicity and response in patients treated with proton and carbon ion therapy at the Heidelberg ion therapy center using the raster scanning technique.

PubMed

Rieken, Stefan; Habermehl, Daniel; Nikoghosyan, Anna; Jensen, Alexandra; Haberer, Thomas; Jäkel, Oliver; Münter, Marc W; Welzel, Thomas; Debus, Jürgen; Combs, Stephanie E

2011-12-01

PUROPOSE: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center. Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility. In all 118 patients, few side effects were observed, in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility. Copyright © 2011 Elsevier Inc. All rights reserved.

Applications in Bioastronautics and Bioinformatics: Early Radiation Cataracts Detected by Noninvasive, Quantitative, and Remote Means

NASA Technical Reports Server (NTRS)

Ansari, Rafat R.; King, James F.; Giblin, Frank J.

2000-01-01

Human exploration of Mars is a key goal in NASA's exploration planning in the next 20 years. Maintaining crew health and good vision is certainly an important aspect of achieving a successful mission. Continuous radiation exposure is a risk factor for radiation-induced cataracts in astronauts because radiation exposure in space travel has the potential of accelerating the aging process (ref. 1). A patented compact device (ref. 2) based on the technique of dynamic light scattering (DLS) was designed for monitoring an astronaut's ocular health during long-duration space travel. This capability of early diagnosis, unmatched by any other clinical technique in use today, may enable prompt initiation of preventive/curative therapy. An Internet web-based system integrating photon correlation data and controlling the hardware to monitor cataract development in vivo at a remote site in real time (teleophthalmology) is currently being developed. The new technology detects cataracts very early (at the molecular level). Cataract studies onboard the International Space Station will be helpful in quantifying any adverse effect of radiation to ocular health. The normal lens in a human eye, situated behind the cornea, is a transparent tissue. It contains 35 wt % protein and 65 wt % water. Aging, disease (e.g., diabetes), smoking, dehydration, malnutrition, and exposure to ultraviolet light and ionizing radiation can cause agglomeration of the lens proteins. Protein aggregation can take place anywhere in the lens, causing lens opacity. The aggregation and opacification could produce nuclear (central portion of the lens) or cortical (peripheral) cataracts. Nuclear and posterior subcapsular (the membrane's capsule surrounds the whole lens) cataracts, being on the visual optical axis of the eye, cause visual impairment that can finally lead to blindness. The lens proteins, in their native state, are small in size. As a cataract develops, this size grows from a few nanometers

Arsenic and Immune Response to Infection During Pregnancy and Early Life.

PubMed

Attreed, Sarah E; Navas-Acien, Ana; Heaney, Christopher D

2017-06-01

Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity-including the specific mechanisms in humans-is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines.

A 3-dimensional DTI MRI-based model of GBM growth and response to radiation therapy.

PubMed

Hathout, Leith; Patel, Vishal; Wen, Patrick

2016-09-01

Glioblastoma (GBM) is both the most common and the most aggressive intra-axial brain tumor, with a notoriously poor prognosis. To improve this prognosis, it is necessary to understand the dynamics of GBM growth, response to treatment and recurrence. The present study presents a mathematical diffusion-proliferation model of GBM growth and response to radiation therapy based on diffusion tensor (DTI) MRI imaging. This represents an important advance because it allows 3-dimensional tumor modeling in the anatomical context of the brain. Specifically, tumor infiltration is guided by the direction of the white matter tracts along which glioma cells infiltrate. This provides the potential to model different tumor growth patterns based on location within the brain, and to simulate the tumor's response to different radiation therapy regimens. Tumor infiltration across the corpus callosum is simulated in biologically accurate time frames. The response to radiation therapy, including changes in cell density gradients and how these compare across different radiation fractionation protocols, can be rendered. Also, the model can estimate the amount of subthreshold tumor which has extended beyond the visible MR imaging margins. When combined with the ability of being able to estimate the biological parameters of invasiveness and proliferation of a particular GBM from serial MRI scans, it is shown that the model has potential to simulate realistic tumor growth, response and recurrence patterns in individual patients. To the best of our knowledge, this is the first presentation of a DTI-based GBM growth and radiation therapy treatment model.

Can early host responses to mycobacterial infection predict eventual disease outcomes?

PubMed

de Silva, Kumudika; Begg, Douglas J; Plain, Karren M; Purdie, Auriol C; Kawaji, Satoko; Dhand, Navneet K; Whittington, Richard J

2013-11-01

Diagnostic tests used for Johne's disease in sheep either have poor sensitivity and specificity or only detect disease in later stages of infection. Predicting which of the infected sheep are likely to become infectious later in life is currently not feasible and continues to be a major hindrance in disease control. We conducted this longitudinal study to investigate if a suite of diagnostic tests conducted in Mycobacterium avium subspecies paratuberculosis (MAP) exposed lambs at 4 months post infection can accurately predict their clinical status at 12 months post infection. We tracked cellular and humoral responses and quantity of MAP shedding for up to 12 months post challenge in 20 controls and 37 exposed sheep. Infection was defined at necropsy by tissue culture and disease spectrum by lesion type. Data were analysed using univariable and multivariable logistic regression models and a subset of variables from the earliest period post inoculation (4 months) was selected for predicting disease outcomes later on (12 months). Sensitivity and specificity of tests and their combinations in series and parallel were determined. Early elevation in faecal MAP DNA quantity and a lower interferon gamma (IFNγ) response were significantly associated with sheep becoming infectious as well as progressing to severe disease. Conversely, early low faecal MAP DNA and higher interleukin-10 responses were significantly associated with an exposed animal developing protective immunity. Combination of early elevated faecal MAP DNA or lower IFNγ response had the highest sensitivity (75%) and specificity (81%) for identifying sheep that would become infectious. Collectively, these results highlight the potential for combined test interpretation to aid in the early prediction of sheep susceptibility to MAP infection. Copyright © 2013 Elsevier B.V. All rights reserved.

Negative affective spillover from daily events predicts early response to cognitive therapy for depression.

PubMed

Cohen, Lawrence H; Gunthert, Kathleen C; Butler, Andrew C; Parrish, Brendt P; Wenze, Susan J; Beck, Judith S

2008-12-01

This study evaluated the predictive role of depressed outpatients' (N = 62) affective reactivity to daily stressors in their rates of improvement in cognitive therapy (CT). For 1 week before treatment, patients completed nightly electronic diaries that assessed daily stressors and negative affect (NA). The authors used multilevel modeling to compute each patient's within-day relationship between daily stressors and daily NA (within-day reactivity), as well as the relationship between daily stressors and next-day NA (next-day reactivity; affective spillover). In growth model analyses, the authors evaluated the predictive role of patients' NA reactivity in their early (Sessions 1-4) and late (Sessions 5-12) response to CT. Within-day NA reactivity did not predict early or late response to CT. However, next-day reactivity predicted early response to CT, such that patients who had greater NA spillover in response to negative events had a slower rate of symptom change during the first 4 sessions. Affective spillover did not influence later response to CT. The findings suggest that depressed patients who have difficulty bouncing back the next day from their NA reactions to a relative increase in daily negative events will respond less quickly to the early sessions of CT.

Early cosmology constrained

NASA Astrophysics Data System (ADS)

Verde, Licia; Bellini, Emilio; Pigozzo, Cassio; Heavens, Alan F.; Jimenez, Raul

2017-04-01

We investigate our knowledge of early universe cosmology by exploring how much additional energy density can be placed in different components beyond those in the ΛCDM model. To do this we use a method to separate early- and late-universe information enclosed in observational data, thus markedly reducing the model-dependency of the conclusions. We find that the 95% credibility regions for extra energy components of the early universe at recombination are: non-accelerating additional fluid density parameter ΩMR < 0.006 and extra radiation parameterised as extra effective neutrino species 2.3 < Neff < 3.2 when imposing flatness. Our constraints thus show that even when analyzing the data in this largely model-independent way, the possibility of hiding extra energy components beyond ΛCDM in the early universe is seriously constrained by current observations. We also find that the standard ruler, the sound horizon at radiation drag, can be well determined in a way that does not depend on late-time Universe assumptions, but depends strongly on early-time physics and in particular on additional components that behave like radiation. We find that the standard ruler length determined in this way is rs = 147.4 ± 0.7 Mpc if the radiation and neutrino components are standard, but the uncertainty increases by an order of magnitude when non-standard dark radiation components are allowed, to rs = 150 ± 5 Mpc.

Early cosmology constrained

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verde, Licia; Jimenez, Raul; Bellini, Emilio

We investigate our knowledge of early universe cosmology by exploring how much additional energy density can be placed in different components beyond those in the ΛCDM model. To do this we use a method to separate early- and late-universe information enclosed in observational data, thus markedly reducing the model-dependency of the conclusions. We find that the 95% credibility regions for extra energy components of the early universe at recombination are: non-accelerating additional fluid density parameter Ω{sub MR} < 0.006 and extra radiation parameterised as extra effective neutrino species 2.3 < N {sub eff} < 3.2 when imposing flatness. Our constraintsmore » thus show that even when analyzing the data in this largely model-independent way, the possibility of hiding extra energy components beyond ΛCDM in the early universe is seriously constrained by current observations. We also find that the standard ruler, the sound horizon at radiation drag, can be well determined in a way that does not depend on late-time Universe assumptions, but depends strongly on early-time physics and in particular on additional components that behave like radiation. We find that the standard ruler length determined in this way is r {sub s} = 147.4 ± 0.7 Mpc if the radiation and neutrino components are standard, but the uncertainty increases by an order of magnitude when non-standard dark radiation components are allowed, to r {sub s} = 150 ± 5 Mpc.« less

THE DEPRESSANT EFFECT OF CONTINUOUS COBALT-60 RADIATION ON THE SECONDARY TETANUS ANTITOXIN RESPONSE IN MICE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoner, R.D.; Hale, W.M.

1958-05-01

The radiosensitivity of the secondary tetanus antitoxin response in mice was demonstrated after rather low doses of continuous gamma -radiation given at a dose rate of 4 rep/hr. Accumulated doses of 48 to 288 rep depressed antitoxin formation. Comparable doses of acute gamma radiation did not depress antitoxin production. Acute doses of 350 to 650 rep sharply depressed the secondary antibody response, however. Extended periods of continuous gamma -radiation from 10 to 28 days to accumulated doses of 960 to 2688 rep markedly depressed the secondary antibody response. An accumulated dose of 2688 rep was needed to depress antitoxin formationmore » to the level observed after an acute dose of 650 rep. When the secondary stimulus of fluid tetanus toxoid was given prior to 10 days of continuous exposure to an accumulated dose of 860 rep, the secondary antibody respense was not depressed. Irradiated mice recovered the ability to produce a normal secondary antitoxin response during the second week after an accumulated dose of 1248 rep. The secondary antitoxin response was depressed in mice given long-continued gamma -radiation at a dose rate of 1 rep/hr. (auth)« less

A Finite-Element Method Model of Soft Tissue Response to Impulsive Acoustic Radiation Force

PubMed Central

Palmeri, Mark L.; Sharma, Amy C.; Bouchard, Richard R.; Nightingale, Roger W.; Nightingale, Kathryn R

2010-01-01

Several groups are studying acoustic radiation force and its ability to image the mechanical properties of tissue. Acoustic radiation force impulse (ARFI) imaging is one modality using standard diagnostic ultrasound scanners to generate localized, impulsive, acoustic radiation forces in tissue. The dynamic response of tissue is measured via conventional ultrasonic speckle-tracking methods and provides information about the mechanical properties of tissue. A finite-element method (FEM) model has been developed that simulates the dynamic response of tissues, with and without spherical inclusions, to an impulsive acoustic radiation force excitation from a linear array transducer. These FEM models were validated with calibrated phantoms. Shear wave speed, and therefore elasticity, dictates tissue relaxation following ARFI excitation, but Poisson’s ratio and density do not significantly alter tissue relaxation rates. Increased acoustic attenuation in tissue increases the relative amount of tissue displacement in the near field compared with the focal depth, but relaxation rates are not altered. Applications of this model include improving image quality, and distilling material and structural information from tissue’s dynamic response to ARFI excitation. Future work on these models includes incorporation of viscous material properties and modeling the ultrasonic tracking of displaced scatterers. PMID:16382621

Radiation protection program for early detection of breast cancer in a mammography facility

NASA Astrophysics Data System (ADS)

Villagomez Casimiro, Mariana; Ruiz Trejo, Cesar; Espejo Fonseca, Ruby

2014-11-01

Mammography is the best tool for early detection of Breast Cancer. In this diagnostic radiology modality it is necessary to establish the criteria to ensure the proper use and operation of the equipment used to obtain mammographic images in order to contribute to the safe use of ionizing radiation. The aim of the work was to implement at FUCAM-AC the radiation protection program which must be established for patients and radiation workers according to Mexican standards [1-4]. To achieve this goal, radiation protection and quality control manuals were elaborated [5]. Furthermore, a quality control program (QCP) in the mammography systems (analog/digital), darkroom included, has been implemented. Daily sensitometry, non-variability of the image quality, visualizing artifacts, revision of the equipment mechanical stability, compression force and analysis of repetition studies are some of the QCP routine tests that must be performed by radiological technicians of this institution as a set of actions to ensure the protection of patients. Image quality and patients dose assessment were performed on 4 analog equipment installed in 2 mobile units. In relation to dose assessment, all equipment passed the acceptance criteria (<3 mGy per projection). The image quality test showed that most images (70%)- presented artifacts. A brief summary of the results of quality control tests applied to the equipment and film processor are presented. To maintain an adequate level of quality and safety at FUCAM-AC is necessary that the proposed radiation protection program in this work is applied.

Radiation protection program for early detection of breast cancer in a mammography facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mariana, Villagomez Casimiro, E-mail: marjim10-66@ciencias.unam.mx, E-mail: cesar@fisica.unam.mx; Cesar, Ruiz Trejo, E-mail: marjim10-66@ciencias.unam.mx, E-mail: cesar@fisica.unam.mx; Ruby, Espejo Fonseca

Mammography is the best tool for early detection of Breast Cancer. In this diagnostic radiology modality it is necessary to establish the criteria to ensure the proper use and operation of the equipment used to obtain mammographic images in order to contribute to the safe use of ionizing radiation. The aim of the work was to implement at FUCAM-AC the radiation protection program which must be established for patients and radiation workers according to Mexican standards [1–4]. To achieve this goal, radiation protection and quality control manuals were elaborated [5]. Furthermore, a quality control program (QCP) in the mammography systemsmore » (analog/digital), darkroom included, has been implemented. Daily sensitometry, non-variability of the image quality, visualizing artifacts, revision of the equipment mechanical stability, compression force and analysis of repetition studies are some of the QCP routine tests that must be performed by radiological technicians of this institution as a set of actions to ensure the protection of patients. Image quality and patients dose assessment were performed on 4 analog equipment installed in 2 mobile units. In relation to dose assessment, all equipment passed the acceptance criteria (<3 mGy per projection). The image quality test showed that most images (70%)– presented artifacts. A brief summary of the results of quality control tests applied to the equipment and film processor are presented. To maintain an adequate level of quality and safety at FUCAM-AC is necessary that the proposed radiation protection program in this work is applied.« less

NCI–RTOG Translational Program Strategic Guidelines for the Early-Stage Development of Radiosensitizers

PubMed Central

2013-01-01

The addition of chemotherapeutic agents to ionizing radiation has improved survival in many malignancies. Cure rates may be further improved by adding novel targeted agents to current radiotherapy or radiochemotherapy regimens. Despite promising laboratory data, progress in the clinical development of new drugs with radiation has been limited. To define and address the problems involved, a collaborative effort between individuals within the translational research program of the Radiation Oncology Therapy Group and the National Cancer Institute was established. We discerned challenges to drug development with radiation including: 1) the limited relevance of preclinical work, 2) the pharmaceutical industry’s diminished interest, and 3) the important individual skills and institutional commitments required to ensure a successful program. The differences between early-phase trial designs with and without radiation are noted as substantial. The traditional endpoints for early-phase clinical trials—acute toxicity and maximum-tolerated dose—are of limited value when combining targeted agents with radiation. Furthermore, response rate is not a useful surrogate marker of activity in radiation combination trials.Consequently, a risk-stratified model for drug-dose escalation with radiation is proposed, based upon the known and estimated adverse effects. The guidelines discuss new clinical trial designs, such as the time-to-event continual reassessment method design for phase I trials, randomized phase II “screening” trials, and the use of surrogate endpoints, such as pathological response. It is hoped that by providing a clear pathway, this article will accelerate the rate of drug development with radiation. PMID:23231975

Bcl2-independent chromatin cleavage is a very early event during induction of apoptosis in mouse thymocytes after treatment with either dexamethasone or ionizing radiation.

PubMed

Hahn, Peter J; Lai, Zhi-Wei; Nevaldine, Barbara; Schiff, Ninel; Fiore, Nancy C; Silverstone, Allen E

2003-11-01

We have quantified the emergence of early chromatin breaks during the signal transduction phase of apoptosis in mouse thymocytes after treatment with either ionizing radiation or dexamethasone. Dexamethasone at 1 microM can induce significant levels of DNA breaks (equivalent to the amount induced directly by 7.5 Gy ionizing radiation) within 0.5 h of treatment. The execution phase of apoptosis was not observed until 4-6 h after the same treatment. The presence of the Bcl2 transgene under the control of the p56lck promoter almost completely inhibited apoptosis up to 24 h after treatment, but it had virtually no effect on the early chromatin cleavage occurring in the first 6 h. Ionizing radiation induced chromatin cleavage both directly by damaging DNA and indirectly with kinetics similar to the induction of chromatin cleavage by dexamethasone. The presence of the Bcl2 transgene had no effect on the direct or indirect radiation-induced cleavage in the first 6 h, but after the first 6 h, the Bcl2 gene inhibited further radiation-induced chromatin cleavage. These results suggest that endonucleases are activated within minutes of treatment with either dexamethasone or ionizing radiation as part of the very early signal transduction phase of apoptosis, and prior to the irreversible commitment to cell death.

Radiation-Related New Primary Solid Cancers in the Childhood Cancer Survivor Study: Comparative Radiation Dose Response and Modification of Treatment Effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inskip, Peter D., E-mail: inskippeter@gmail.com; Sigurdson, Alice J.; Veiga, Lene

Objectives: The majority of childhood cancer patients now achieve long-term survival, but the treatments that cured their malignancy often put them at risk of adverse health outcomes years later. New cancers are among the most serious of these late effects. The aims of this review are to compare and contrast radiation dose–response relationships for new solid cancers in a large cohort of childhood cancer survivors and to discuss interactions among treatment and host factors. Methods: This review is based on previously published site-specific analyses for subsequent primary cancers of the brain, breast, thyroid gland, bone and soft tissue, salivary glands,more » and skin among 12,268 5-year childhood cancer survivors in the Childhood Cancer Survivor Study. Analyses included tumor site–specific, individual radiation dose reconstruction based on radiation therapy records. Radiation-related second cancer risks were estimated using conditional logistic or Poisson regression models for excess relative risk (ERR). Results: Linear dose–response relationships over a wide range of radiation dose (0-50 Gy) were seen for all cancer sites except the thyroid gland. The steepest slopes occurred for sarcoma, meningioma, and nonmelanoma skin cancer (ERR/Gy > 1.00), with glioma and cancers of the breast and salivary glands forming a second group (ERR/Gy = 0.27-0.36). The relative risk for thyroid cancer increased up to 15-20 Gy and then decreased with increasing dose. The risk of thyroid cancer also was positively associated with chemotherapy, but the chemotherapy effect was not seen among those who also received very high doses of radiation to the thyroid. The excess risk of radiation-related breast cancer was sharply reduced among women who received 5 Gy or more to the ovaries. Conclusions: The results suggest that the effect of high-dose irradiation is consistent with a linear dose–response for most organs, but they also reveal important organ-specific and host

Radiometric and Radiation Response of Visible FPAs

NASA Technical Reports Server (NTRS)

Hubbs, John

2007-01-01

The readout integrated circuit (ROIC) used in these devices was originally developed for use in space based infrared systems operating at deep cryogenic temperatures and was selected because of its proven tolerance to total ionizing radiation? The detectors are a 128 x 128 array of 60 pm x 60 pm pixel elements that have been anti-reflection (AR) coated to improve the response at very short wavelengths. These visible focal plane arrays were operated at -40 C (233 K). Two focal planes were characterized using cobalt-60 radiation to produce ionizing total dose damage in the VFPAs. Both operational and performance data were obtained as functions of total dose. The first device tested showed no appreciable change in responsivity or noise up to 300 krad(Si). However, at the next dose level of 600 krad(Si), the readout was non-operational due to failure in the digital circuitry. The second device was characterized to a total dose of 750 krad(Si) with no observed change in responsivity. An increase dark current was observed in both devices, and in the second device, the dark current caused an increase in noise at low irradiance at 400 krad(Si) and above. The increase in dark current was somewhat un-expected for visible PIN detectors. The median dark current increased more than two orders of magnitude at 300 krad(Si) for the first device and a factor of 350 at 750 krad(Si) for pixels near the edge for the second device. The dark current was found to be a strong function of detector bias, with pixels near the edge of the array showing a greater increase in dark current with bias than those near the center. Since the optical response was not a function of bias, it is hypothesized that the dark current is a surface effect and that the variation in dark current with location is due to a variation in pixel bias, caused by a voltage drop across the pixel common lead. As the total dose increased, the dark current and the voltage drop increased

Parkin regulates translesion DNA synthesis in response to UV radiation.

PubMed

Zhu, Xuefei; Ma, Xiaolu; Tu, Yingfeng; Huang, Min; Liu, Hongmei; Wang, Fengli; Gong, Juanjuan; Wang, Jiuqiang; Li, Xiaoling; Chen, Qian; Shen, Hongyan; Zhu, Shu; Wang, Yun; Liu, Yang; Guo, Caixia; Tang, Tie-Shan

2017-05-30

Deficiency of Parkin is a major cause of early-onset Parkinson's disease (PD). Notably, PD patients also exhibit a significantly higher risk in melanoma and other skin tumors, while the mechanism remains largely unknown. In this study, we show that depletion of Parkin causes compromised cell viability and genome stability after ultraviolet (UV) radiation. We demonstrate that Parkin promotes efficient Rad18-dependent proliferating cell nuclear antigen (PCNA) monoubiquitination by facilitating the formation of Replication protein A (RPA)-coated ssDNA upon UV radiation. Furthermore, Parkin is found to physically interact with NBS1 (Nijmegen breakage syndrome 1), and to be required for optimal recruitment of NBS1 and DNA polymerase eta (Polη) to UV-induced damage sites. Consequently, depletion of Parkin leads to increased UV-induced mutagenesis. These findings unveil an important role of Parkin in protecting genome stability through positively regulating translesion DNA synthesis (TLS) upon UV damage, providing a novel mechanistic link between Parkin deficiency and predisposition to skin cancers in PD patients.

Response of GaAs charge storage devices to transient ionizing radiation

NASA Astrophysics Data System (ADS)

Hetherington, D. L.; Klem, J. F.; Hughes, R. C.; Weaver, H. T.

Charge storage devices in which non-equilibrium depletion regions represent stored charge are sensitive to ionizing radiation. This results since the radiation generates electron-hole pairs that neutralize excess ionized dopant charge. Silicon structures, such as dynamic RAM or CCD cells are particularly sensitive to radiation since carrier diffusion lengths in this material are often much longer than the depletion width, allowing collection of significant quantities of charge from quasi-neutral sections of the device. For GaAs the situation is somewhat different in that minority carrier diffusion lengths are shorter than in silicon, and although mobilities are higher, we expect a reduction of radiation sensitivity as suggested by observations of reduced quantum efficiency in GaAs solar cells. Dynamic memory cells in GaAs have potential increased retention times. In this paper, we report the response of a novel GaAs dynamic memory element to transient ionizing radiation. The charge readout technique is nondestructive over a reasonable applied voltage range and is more sensitive to stored charge than a simple capacitor.

MO-DE-303-03: Session on quantitative imaging for assessment of tumor response to radiation therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowen, S.

This session will focus on quantitative imaging for assessment of tumor response to radiation therapy. This is a technically challenging method to translate to practice in radiation therapy. In the new era of precision medicine, however, delivering the right treatment, to the right patient, and at the right time, can positively impact treatment choices and patient outcomes. Quantitative imaging provides the spatial sensitivity required by radiation therapy for precision medicine that is not available by other means. In this Joint ESTRO -AAPM Symposium, three leading-edge investigators will present specific motivations for quantitative imaging biomarkers in radiation therapy of esophageal, headmore » and neck, locally advanced non-small cell lung cancer, and hepatocellular carcinoma. Experiences with the use of dynamic contrast enhanced (DCE) MRI, diffusion- weighted (DW) MRI, PET/CT, and SPECT/CT will be presented. Issues covered will include: response prediction, dose-painting, timing between therapy and imaging, within-therapy biomarkers, confounding effects, normal tissue sparing, dose-response modeling, and association with clinical biomarkers and outcomes. Current information will be presented from investigational studies and clinical practice. Learning Objectives: Learn motivations for the use of quantitative imaging biomarkers for assessment of response to radiation therapy Review the potential areas of application in cancer therapy Examine the challenges for translation, including imaging confounds and paucity of evidence to date Compare exemplary examples of the current state of the art in DCE-MRI, DW-MRI, PET/CT and SPECT/CT imaging for assessment of response to radiation therapy Van der Heide: Research grants from the Dutch Cancer Society and the European Union (FP7) Bowen: RSNA Scholar grant.« less

Radiation Therapy Induces Macrophages to Suppress Immune Responses Against Pancreatic Tumors in Mice

PubMed Central

Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Ly, Nancy Ngoc Giao; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R.; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

2016-01-01

Background & Aims The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcome, compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of pre-invasive foci. Methods We investigated the effects of radiation in p48Cre;LSL-KrasG12D (KC) and p48Cre;LSLKrasG12D;LSL-Trp53R172H (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2–12 Gy and analyzed by flow cytometry. Results Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from invasive and pre-invasive pancreatic tumors had an immune-suppressive, M2-like phenotype, compared with control mice. Pancreata from mice exposed to radiation had fewer CD8+ T cells than controls and greater numbers of CD4+ T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. An antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Conclusions Radiation exposure causes macrophages in PDAs

Dried Plum Protects From Radiation-Induced Bone Loss by Attenuating Pro-Osteoclastic and Oxidative Stress Responses

NASA Technical Reports Server (NTRS)

Globus, Ruth

2015-01-01

Future space explorations beyond the earths magnetosphere will increase human exposure to space radiation and associated risks to skeletal health. We hypothesize that oxidative stress resulting from radiation exposure plays a major role in progressive bone loss and dysfunction in associated tissue. In animal studies, increased free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. Our long-term goals are to define the mechanisms and risk of bone loss in the spaceflight environment and to facilitate the development of effective countermeasures. We had previously reported that exposure to low or high-LET radiation correlates with an acute increase in the expression of pro-osteoclastic and oxidative stress genes in bone during the early response to radiation followed by pathological changes in skeletal structure. We then conducted systematic screening for potential countermeasures against bone loss where we tested the ability of various antioxidants to mitigate the radiation-induced increase in expression of these markers. For the screen, 16-week old C57Bl6J mice were treated with a dietary antioxidant cocktail, injectable DHLA or a dried plum-enriched diet (DP). Mice were then exposed to 2Gy 137Cs radiation and one day later, marrow cells were collected and the relevant genes analyzed for expression levels. Among the candidate countermeasures tested, DP was most effective in reducing the expression of genes associated with bone loss. Furthermore, analysis of skeletal structure by microcomputed tomography (microCT) revealed that DP also prevents the radiation-induced deterioration in skeletal microarchitecture as indicated by parameters such as percent bone volume (BVTV), trabecular spacing and trabecular number. We also found that DP has similar protective effects on skeletal structure in a follow-up study using 1 Gy of

Analyzing the dose-dependence of the Saccharomyces cerevisiae global transcriptional response to methyl methanesulfonate and ionizing radiation.

PubMed

Benton, Michael G; Somasundaram, Swetha; Glasner, Jeremy D; Palecek, Sean P

2006-12-01

One of the most crucial tasks for a cell to ensure its long term survival is preserving the integrity of its genetic heritage via maintenance of DNA structure and sequence. While the DNA damage response in the yeast Saccharomyces cerevisiae, a model eukaryotic organism, has been extensively studied, much remains to be elucidated about how the organism senses and responds to different types and doses of DNA damage. We have measured the global transcriptional response of S. cerevisiae to multiple doses of two representative DNA damaging agents, methyl methanesulfonate (MMS) and gamma radiation. Hierarchical clustering of genes with a statistically significant change in transcription illustrated the differences in the cellular responses to MMS and gamma radiation. Overall, MMS produced a larger transcriptional response than gamma radiation, and many of the genes modulated in response to MMS are involved in protein and translational regulation. Several clusters of coregulated genes whose responses varied with DNA damaging agent dose were identified. Perhaps the most interesting cluster contained four genes exhibiting biphasic induction in response to MMS dose. All of the genes (DUN1, RNR2, RNR4, and HUG1) are involved in the Mec1p kinase pathway known to respond to MMS, presumably due to stalled DNA replication forks. The biphasic responses of these genes suggest that the pathway is induced at lower levels as MMS dose increases. The genes in this cluster with a threefold or greater transcriptional response to gamma radiation all showed an increased induction with increasing gamma radiation dosage. Analyzing genome-wide transcriptional changes to multiple doses of external stresses enabled the identification of cellular responses that are modulated by magnitude of the stress, providing insights into how a cell deals with genotoxicity.

Influence of inhomogeneous surface heat capacity on the estimation of radiative response coefficients in a two-zone energy balance model

NASA Astrophysics Data System (ADS)

Park, Jungmin; Choi, Yong-Sang

2018-04-01

Observationally constrained values of the global radiative response coefficient are pivotal to assess the reliability of modeled climate feedbacks. A widely used approach is to measure transient global radiative imbalance related to surface temperature changes. However, in this approach, a potential error in the estimate of radiative response coefficients may arise from surface inhomogeneity in the climate system. We examined this issue theoretically using a simple two-zone energy balance model. Here, we dealt with the potential error by subtracting the prescribed radiative response coefficient from those calculated within the two-zone framework. Each zone was characterized by the different magnitude of the radiative response coefficient and the surface heat capacity, and the dynamical heat transport in the atmosphere between the zones was parameterized as a linear function of the temperature difference between the zones. Then, the model system was forced by randomly generated monthly varying forcing mimicking time-varying forcing like an observation. The repeated simulations showed that inhomogeneous surface heat capacity causes considerable miscalculation (down to -1.4 W m-2 K-1 equivalent to 31.3% of the prescribed value) in the global radiative response coefficient. Also, the dynamical heat transport reduced this miscalculation driven by inhomogeneity of surface heat capacity. Therefore, the estimation of radiative response coefficients using the surface temperature-radiation relation is appropriate for homogeneous surface areas least affected by the exterior.

Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

NASA Astrophysics Data System (ADS)

Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai

2016-06-01

Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

Differential Gene Expression in Primary Human Skin Keratinocytes and Fibroblasts in Response to Ionizing Radiation

PubMed Central

Warters, Raymond L.; Packard, Ann T.; Kramer, Gwen F.; Gaffney, David K.; Moos, Philip J.

2009-01-01

Although skin is usually exposed during human exposures to ionizing radiation, there have been no thorough examinations of the transcriptional response of skin fibroblasts and keratinocytes to radiation. The transcriptional response of quiescent primary fibroblasts and keratinocytes exposed to from 10 cGy to 5 Gy and collected 4 h after treatment was examined. RNA was isolated and examined by microarray analysis for changes in the levels of gene expression. Exposure to ionizing radiation altered the expression of 279 genes across both cell types. Changes in RNA expression could be arranged into three main categories: (1) changes in keratinocytes but not in fibroblasts, (2) changes in fibroblasts but not in keratinocytes, and (3) changes in both. All of these changes were primarily of p53 target genes. Similar radiation-induced changes were induced in immortalized fibroblasts or keratinocytes. In separate experiments, protein was collected and analyzed by Western blotting for expression of proteins observed in microarray experiments to be overexpressed at the mRNA level. Both Q-PCR and Western blot analysis experiments validated these transcription changes. Our results are consistent with changes in the expression of p53 target genes as indicating the magnitude of cell responses to ionizing radiation. PMID:19580510

Perception of solar UVB radiation by phytophagous insects: Behavioral responses and ecosystem implications

PubMed Central

Mazza, Carlos A.; Zavala, Jorge; Scopel, Ana L.; Ballaré, Carlos L.

1999-01-01

Most of our present knowledge about the impacts of solar UVB radiation on terrestrial ecosystems comes from studies with plants. Recently, the effects of UVB on the growth and survival of consumer species have begun to receive attention, but very little is known about UVB impacts on animal behavior. Here we report that manipulations of the flux of solar UVB received by field-grown soybean crops had large and consistent effects on the density of the thrips (Caliothrips phaseoli, Thysanoptera: Thripidae) populations that invaded the canopies, as well as on the amount of leaf damage caused by the insects. Solar UVB strongly reduced thrips herbivory. Thrips not only preferred leaves from plants that were not exposed to solar UVB over leaves from UVB-exposed plants in laboratory and field choice experiments, but they also appeared to directly sense and avoid exposure to solar UVB. Additional choice experiments showed that soybean leaf consumption by the late-season soybean worm Anticarsia gemmatalis (Lepidoptera: Noctuidae) was much less intense in leaves with even slight symptoms of an early thrips attack than in undamaged leaves. These experiments suggest that phytophagous insects can present direct and indirect behavioral responses to solar UVB. The indirect responses are mediated by changes in the plant host that are induced by UVB and, possibly, by other insects whose behavior is affected by UVB. PMID:9927679

Early and long term anamnestic response to HBV booster dose among fully vaccinated Egyptian children during infancy.

PubMed

Salama, Iman I; Sami, Samia M; Said, Zeinab N; Salama, Somaia I; Rabah, Thanaa M; Abdel-Latif, Ghada A; Elmosalami, Dalia M; Saleh, Rehan M; Abdel Mohsin, Aida M; Metwally, Ammal M; Hassanin, Amal I; Emam, Hanaa M; Hemida, Samia A; Elserougy, Safaa M; Shaaban, Fatma A; Fouad, Walaa A; Mohsen, Amira; El-Sayed, Manal H

2018-04-05

To evaluate early and long term anamnestic response to a booster dose of HBV vaccine among non-seroprotected children. A national community based project was carried out on 3600 children aged 9 months to 16 years, fully vaccinated during infancy. They were recruited from 6 governorates representing Egypt. It revealed that 1535 children (42.8%) had non sero-protective anti-HBs (<10 IU/L) and were HBsAg or anti-HBc negative. A challenging dose of 10 μg of mono-valent Euvax HBV vaccine was given to 1121/1535 children. Quantitative assessment of anti-HBs was performed to detect early (2-4 weeks) and long term (one year) anamnestic responses. Early anamnestic response developed among 967/1070 children (90.3%).Children having detectable anti-HBs (1-9 IU/L) significantly developed early anamnestic response (90%) compared to 85% with undetectable anti-HBs (<1 IU/L), P < 0.001. Multiple logistic analysis revealed that undetectable anti-HBs, living in rural residence and children aged 15-16 years were the most significant predicting risk factors for the absence of early anamnestic response (<10 IU/L), with AOR 2.7, 2.7 & 4.7 respectively. After one year, long term anamnestic response was absent among 15% of children who previously showed early response. Poor early anamnestic response and undetectable pre-booster anti-HBs were the significant predicting risk factors for absent long term anamnestic response, with AOR 18.7 & 2.7 respectively. Immunological memory for HBV vaccine outlasts the presence of anti- HBs and HBV vaccination program provides effective long term protection even in children showing waning or undetectable concentrations of anti-HBs. This signifies no need for a booster dose especially to healthy children. Copyright © 2018 Elsevier Ltd. All rights reserved.

Diffuse optical measurements of head and neck tumor hemodynamics for early prediction of radiation therapy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Dong, Lixin; Kudrimoti, Mahesh; Irwin, Daniel; Chen, Li; Shang, Yu; Li, Xingzhe; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

2016-03-01

Radiation therapy is a principal modality for head and neck cancers and its efficacy depends on tumor hemodynamics. Our laboratory developed a hybrid diffuse optical instrument allowing for simultaneous measurements of tumor blood flow and oxygenation. In this study, the clinically involved cervical lymph node was monitored by the hybrid instrument once a week over the treatment period of seven weeks. Based on treatment outcomes within one year, patients were classified into a complete response group (CR) and an incomplete response group (IR) with remote metastasis and/or local recurrence. A linear mixed models was used to compare tumor hemodynamic responses to the treatment between the two groups. Interestingly, we found that human papilloma virus (HPV-16) status largely affected tumor hemodynamic responses. For HPV-16 negative tumors, significant differences in blood flow index (BFI, p = 0.007) and reduced scattering coefficient (μs', p = 0.0005) were observed between the two groups; IR tumors exhibited higher μs' values and a continuous increase in BFI over the treatment period. For HPV-16 positive tumors, oxygenated hemoglobin concentration ([HbO2]) and blood oxygen saturation (StO2) were significant different (p = 0.003 and 0.01, respectively); IR group showed lower [HbO2] and StO2. Our results imply HPV-16 negative tumors with higher density of vasculature (μs') and higher blood flow show poor responses to radiotherapy and HPV-16 positive tumors with lower tissue oxygenation level (lower StO2 and [HbO2]) exhibit poor treatment outcomes. Our diffuse optical measurements show the great potential for early prediction of radiotherapy in head and neck cancers.

Dependence of Early and Late Chromosomal Aberrations on Radiation Quality and Cell Types

NASA Technical Reports Server (NTRS)

Lu, Tao; Zhang, Ye; Krieger, Stephanie; Yeshitla, Samrawit; Goss, Rosalin; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Rohde, Larry; Wu, Honglu

2017-01-01

Exposure to radiation induces different types of DNA damage, increases mutation and chromosome aberration rates, and increases cellular transformation in vitro and in vivo. The susceptibility of cells to radiation depends on genetic background and growth condition of cells, as well as types of radiation. Mammalian cells of different tissue types and with different genetic background are known to have different survival rate and different mutation rate after cytogenetic insults. Genomic instability, induced by various genetic, metabolic, and environmental factors including radiation, is the driving force of tumorigenesis. Accurate measurements of the relative biological effectiveness (RBE) is important for estimating radiation-related risks. To further understand genomic instability induced by charged particles and their RBE, we exposed human lymphocytes ex vivo, human fibroblast AG1522, human mammary epithelial cells (CH184B5F5/M10), and bone marrow cells isolated from CBA/CaH(CBA) and C57BL/6 (C57) mice to high energy protons and Fe ions. Normal human fibroblasts AG1522 have apparently normal DNA damage response and repair mechanisms, while mammary epithelial cells (M10) are deficient in the repair of DNA DSBs. Mouse strain CBA is radio-sensitive while C57 is radio-resistant. Metaphase chromosomes at different cell divisions after radiation exposure were collected and chromosome aberrations were analyzed as RBE for different cell lines exposed to different radiations at various time points up to one month post irradiation.

Pretreatment Growth Rate Predicts Radiation Response in Vestibular Schwannomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Niu, Nina N.; Harvard Medical School, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Niemierko, Andrzej

Purpose: Vestibular schwannomas (VS) are often followed without initial therapeutic intervention because many tumors do not grow and radiation therapy is associated with potential adverse effects. In an effort to determine whether maximizing initial surveillance predicts for later treatment response, the predictive value of preirradiation growth rate of VS on response to radiation therapy was assessed. Methods and Materials: Sixty-four patients with 65 VS were treated with single-fraction stereotactic radiation surgery or fractionated stereotactic radiation therapy. Pre- and postirradiation linear expansion rates were estimated using volumetric measurements on sequential magnetic resonance images (MRIs). In addition, postirradiation tumor volume change wasmore » classified as demonstrating shrinkage (ratio of volume on last follow-up MRI to MRI immediately preceding irradiation <80%), stability (ratio 80%-120%), or expansion (ratio >120%). The median pre- and postirradiation follow-up was 20.0 and 27.5 months, respectively. Seven tumors from neurofibromatosis type 2 (NF2) patients were excluded from statistical analyses. Results: In the 58 non-NF2 patients, there was a trend of correlation between pre- and postirradiation volume change rates (slope on linear regression, 0.29; P=.06). Tumors demonstrating postirradiation expansion had a median preirradiation growth rate of 89%/year, and those without postirradiation expansion had a median preirradiation growth rate of 41%/year (P=.02). As the preirradiation growth rate increased, the probability of postirradiation expansion also increased. Overall, 24.1% of tumors were stable, 53.4% experienced shrinkage, and 22.5% experienced expansion. Predictors of no postirradiation tumor expansion included no prior surgery (P=.01) and slower tumor growth rate (P=.02). The control of tumors in NF2 patients was only 43%. Conclusions: Radiation therapy is an effective treatment for VS, but tumors that grow quickly

Radiation dose response of N channel MOSFET submitted to filtered X-ray photon beam

NASA Astrophysics Data System (ADS)

Gonçalves Filho, Luiz C.; Monte, David S.; Barros, Fabio R.; Santos, Luiz A. P.

2018-01-01

MOSFET can operate as a radiation detector mainly in high-energy photon beams, which are normally used in cancer treatments. In general, such an electronic device can work as a dosimeter from threshold voltage shift measurements. The purpose of this article is to show a new way for measuring the dose-response of MOSFETs when they are under X-ray beams generated from 100kV potential range, which is normally used in diagnostic radiology. Basically, the method consists of measuring the MOSFET drain current as a function of the radiation dose. For this the type of device, it has to be biased with a high value resistor aiming to see a substantial change in the drain current after it has been irradiated with an amount of radiation dose. Two types of N channel device were used in the experiment: a signal transistor and a power transistor. The delivered dose to the device was varied and the electrical curves were plotted. Also, a sensitivity analysis of the power MOSFET response was made, by varying the tube potential of about 20%. The results show that both types of devices have responses very similar, the shift in the electrical curve is proportional to the radiation dose. Unlike the power MOSFET, the signal transistor does not provide a linear function between the dose rate and its drain current. We also have observed that the variation in the tube potential of the X-ray equipment produces a very similar dose-response.

The Reasons behind Early Adolescents' Responses to Peer Victimization

ERIC Educational Resources Information Center

Bellmore, Amy; Chen, Wei-Ting; Rischall, Emily

2013-01-01

Victims of school-based peer harassment face a range of risks including psycho-social, physical, and academic harm. The aim of the present study was to examine the behavioral coping responses used by early adolescents when they face peer victimization. To meet this aim, 216 sixth grade students (55% girls) from two urban middle schools and 254…

A Framework for Providing Culturally Responsive Early Intervention Services

ERIC Educational Resources Information Center

Bradshaw, Wendy

2013-01-01

The purpose of this article is to provide a framework that offers a way for early intervention (EI) service providers to better meet the needs of the culturally diverse children and families they serve. This framework was created to organize existing research and literature on cultural responsiveness in a way that fit the unique context of EI. The…

Mechanisms underlying cellular responses of cells from haemopoietic tissue to low dose/low LET radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Munira A Kadhim

2010-03-05

To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e., less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these “non-targeted” responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry andmore » risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate radiation-induced genomic instability and bystander responses in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/H and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition on two non-targeted radiation responses in these models; the bystander effect and genomic instability, which we believe are closely related. We will specifically focus on the effects of low doses of low LET radiation, down to doses approaching a single electron traversal. Using conventional X-ray and γ-ray sources, novel dish separation and targeted irradiation approaches, we will be able to assess the role of genetic variation under various bystander conditions at doses down to a few electron tracks. Irradiations will be carried out using facilities in routine operation for bystander targeted studies. Mechanistic studies of instability and the bystander response in different cell lineages will focus initially on the role of cytokines which have been shown to be involved in bystander signaling and the initiation of instability. These studies

Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Veen, Sonja J. van der; Faber, Hette; Ghobadi, Ghazaleh

2016-01-01

Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed themore » dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and

Liquid jet response to internal modulated ultrasonic radiation pressure and stimulated drop production.

PubMed

Lonzaga, Joel B; Osterhoudt, Curtis F; Thiessen, David B; Marston, Philip L

2007-06-01

Experimental evidence shows that a liquid jet in air is an acoustic waveguide having a cutoff frequency inversely proportional to the jet diameter. Ultrasound applied to the jet supply liquid can propagate within the jet when the acoustic frequency is near to or above the cutoff frequency. Modulated radiation pressure is used to stimulate large amplitude deformations and the breakup of the jet into drops. The jet response to the modulated internal ultrasonic radiation pressure was monitored along the jet using (a) an optical extinction method and (b) images captured by a video camera. The jet profile oscillates at the frequency of the radiation pressure modulation and where the response is small, the amplitude was found to increase in proportion to the square of the acoustic pressure amplitude as previously demonstrated for oscillating drops [P.L. Marston and R.E. Apfel, J. Acoust. Soc. Am. 67, 27-37 (1980)]. Small amplitude deformations initially grow approximately exponentially with axial distance along the jet. Though aspects of the perturbation growth can be approximated from Rayleigh's analysis of the capillary instability, some detailed features of the observed jet response to modulated ultrasound are unexplained neglecting the effects of gravity.

Arsenic and Immune Response to Infection During Pregnancy and Early Life

PubMed Central

Attreed, Sarah E.; Navas-Acien, Ana

2017-01-01

Purpose of Review Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity—including the specific mechanisms in humans—is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. Recent Findings The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Summary Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines. PMID:28488132

Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals.

PubMed

Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

2017-06-07

Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals

PubMed Central

Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

2017-01-01

Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process. PMID:28590456

Redox Protein Expression Predicts Radiotherapeutic Response in Early-Stage Invasive Breast Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woolston, Caroline M.; Al-Attar, Ahmad; Storr, Sarah J.

2011-04-01

Purpose: Early-stage invasive breast cancer patients have commonly undergone breast-conserving surgery and radiotherapy. In a large majority of these patients, the treatment is effective; however, a proportion will develop local recurrence. Deregulated redox systems provide cancer cells protection from increased oxidative stress, such as that induced by ionizing radiation. Therefore, the expression of redox proteins was examined in tumor specimens from this defined cohort to determine whether such expression could predict response. Methods and Materials: The nuclear and cytoplasmic expression of nine redox proteins (glutathione, glutathione reductase, glutaredoxin, glutathione peroxidase 1, 3, and 4, and glutathione S-transferase-{theta}, -{pi}, and -{alpha})more » was assessed using conventional immunohistochemistry on a tissue microarray of 224 tumors. Results: A high cytoplasmic expression of glutathione S-transferase-{theta} significantly correlated with a greater risk of local recurrence (p = .008) and, when combined with a low nuclear expression (p = .009), became an independent predictive factor (p = .002) for local recurrence. High cytoplasmic expression of glutathione S-transferase-{theta} also correlated with a worse overall survival (p = .009). Low nuclear and cytoplasmic expression of glutathione peroxidase 3 (p = .002) correlated with a greater risk of local recurrence and was an independent predictive factor (p = .005). These proteins did not correlate with tumor grade, suggesting their function might be specific to the regulation of oxidative stress rather than alterations of tumor phenotype. Only nuclear (p = .005) and cytoplasmic (p = .001) expression of glutathione peroxidase 4 correlated with the tumor grade. Conclusions: Our results support the use of redox protein expression, namely glutathione S-transferase-{theta} and glutathione peroxidase 3, to predict the response to radiotherapy in early-stage breast cancer patients. If incorporated

Response of transformed and normal mouse cell lines to anti-melanin compounds, hyperthermia, and radiation.

PubMed

Raaphorst, G P; Azzam, E I

1992-02-01

Five cell lines (one parental, two transformed melanin producing, and two transformed non-melanin producing) were evaluated for the responses to 2- and 4-hydroxyanisole (2HA, 4HA) alone or combined with hyperthermia or radiation. All cells exhibited a non-specific toxic response to the two compounds and the effect was exposure time and concentration dependent and was greater for 4HA compared to 2HA. In addition, the two melanin-producing cell lines were more sensitive, demonstrating specific toxicity to such cell lines. The treatment with either 2HA or 4HA combined with heat and radiation resulted mostly in additive or antagonistic effects, except for one combination of 2HA plus radiation in the melanin-producing R25 cells. Thus, while these compounds may be useful in therapy for pigmented melanomas, combined treatment with radiation is not recommended.

Organic Matter Responses to Radiation under Lunar Conditions

PubMed Central

Matthewman, Richard; Crawford, Ian A.; Jones, Adrian P.; Joy, Katherine H.

2016-01-01

Abstract Large bodies, such as the Moon, that have remained relatively unaltered for long periods of time have the potential to preserve a record of organic chemical processes from early in the history of the Solar System. A record of volatiles and impactors may be preserved in buried lunar regolith layers that have been capped by protective lava flows. Of particular interest is the possible preservation of prebiotic organic materials delivered by ejected fragments of other bodies, including those originating from the surface of early Earth. Lava flow layers would shield the underlying regolith and any carbon-bearing materials within them from most of the effects of space weathering, but the encapsulated organic materials would still be subject to irradiation before they were buried by regolith formation and capped with lava. We have performed a study to simulate the effects of solar radiation on a variety of organic materials mixed with lunar and meteorite analog substrates. A fluence of ∼3 × 1013 protons cm−2 at 4–13 MeV, intended to be representative of solar energetic particles, has little detectable effect on low-molecular-weight (≤C30) hydrocarbon structures that can be used to indicate biological activity (biomarkers) or the high-molecular-weight hydrocarbon polymer poly(styrene-co-divinylbenzene), and has little apparent effect on a selection of amino acids (≤C9). Inevitably, more lengthy durations of exposure to solar energetic particles may have more deleterious effects, and rapid burial and encapsulation will always be more favorable to organic preservation. Our data indicate that biomarker compounds that may be used to infer biological activity on their parent planet can be relatively resistant to the effects of radiation and may have a high preservation potential in paleoregolith layers on the Moon. Key Words: Radiation—Moon—Regolith—Amino acids—Biomarkers. Astrobiology 16, 900–912. PMID:27870583

Exploring early public responses to geoengineering.

PubMed

Pidgeon, Nick; Corner, Adam; Parkhill, Karen; Spence, Alexa; Butler, Catherine; Poortinga, Wouter

2012-09-13

Proposals for geoengineering the Earth's climate are prime examples of emerging or 'upstream' technologies, because many aspects of their effectiveness, cost and risks are yet to be researched, and in many cases are highly uncertain. This paper contributes to the emerging debate about the social acceptability of geoengineering technologies by presenting preliminary evidence on public responses to geoengineering from two of the very first UK studies of public perceptions and responses. The discussion draws upon two datasets: qualitative data (from an interview study conducted in 42 households in 2009), and quantitative data (from a subsequent nationwide survey (n=1822) of British public opinion). Unsurprisingly, baseline awareness of geoengineering was extremely low in both cases. The data from the survey indicate that, when briefly explained to people, carbon dioxide removal approaches were preferred to solar radiation management, while significant positive correlations were also found between concern about climate change and support for different geoengineering approaches. We discuss some of the wider considerations that are likely to shape public perceptions of geoengineering as it enters the media and public sphere, and conclude that, aside from technical considerations, public perceptions are likely to prove a key element influencing the debate over questions of the acceptability of geoengineering proposals.

Comparison of survival between radiation therapy and trans-oral laser microsurgery for early glottic cancer patients; a retrospective cohort study.

PubMed

De Santis, R J; Poon, I; Lee, J; Karam, I; Enepekides, D J; Higgins, K M

2016-08-02

The literature reports various treatment methodologies, such as trans-oral laser microsurgery, radiation therapy, total/partial laryngectomies, and concurrent radiation chemotherapy for patients with early larynx cancer. However, at the forefront of early glottis treatment is trans-oral laser microsurgery and radiation therapy, likely due to better functional and survival outcomes. Here we conduct the largest Canadian head-to-head comparison of consecutive patients treated with either radiation therapy or trans-oral laser microsurgery. Additionally, we compare these two treatments and their 5-year survival rates post treatment to add to the existing literature. Charts of patients who were diagnosed with early glottic cancer between 2006 and 2013 were reviewed. Seventy-five patients were identified, and split into 2 groups based on their primary treatment, trans-oral laser microsurgery and radiation therapy. Kaplan-Meier survival curves, life-tables, and the log-rank statistic were reported to determine if there was a difference between the two treatment groups and their disease-specific survival, disease-free survival, and total laryngectomy-free survival. Additionally, each different survival analysis was stratified by potential confounding variables, to help conclude which treatment is more efficacious in this population. The 5-year disease-specific survival rate is 93.3 % σ = 0.063 and 90.8 % σ = 0.056 for patients treated with trans-oral laser microsurgery and radiation therapy, respectively (χ (2) < 0.001, p = 0.983). The disease free survival rate is 60.0 % (σ =0.121) for patients treated with trans-oral laser microsurgery, and 67.2 % (σ = 0.074) for those who received RT (χ (2) = 0.19, p = 0.663). Additionally, the total laryngectomy-free survival rate is 84.1 % (σ = 0.1) and 79.1 % (σ = 0.072) for patients' early glottic cancer treated by trans-oral laser microsurgery and radiation therapy, respectively (�

Consequences of an Early PSA Response to Enzalutamide Treatment for Japanese Patients with Metastatic Castration-resistant Prostate Cancer.

PubMed

Kato, Haruo; Furuya, Yosuke; Miyazawa, Yoshiyuki; Miyao, Takeshi; Syuto, Takahiro; Nomura, Masashi; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Ito, Kazuto; Suzuki, Kazuhiro

2016-11-01

Recent studies have shown that an early prostate-specific antigen (PSA) response to androgen receptor (AR)-targeting agents in metastatic castration-resistant prostate cancer (mCRPC) is associated with a better prognosis. We analyzed early PSA response to enzalutamide and oncological outcomes to study their prognostic significance in the Japanese population. Fifty-one patients with mCRPC (26 of pre-docetaxel and 25 of post-docetaxel status) were treated with enzalutamide. The PSA progression-free survival (PFS), radiographic PFS (rPFS) and overall survival (OS) were assessed. The association of rPFS and OS in patients with an early PSA response at 4 weeks after commencement of enzalutamide was studied. Early PSA responses were significantly associated with a longer rPFS (median of 47.9 vs. 20.1 weeks, p<0.001, in patients exhibiting a 50% PSA response; median of 40.9 vs. 20.1 weeks, p=0.016, in patients exhibiting a 30% PSA response). OS was also significantly associated with an early PSA response (p=0.002 for patients exhibiting a 50% PSA response, p=0.003 for patients exhibiting a 30% PSA response). Multivariate analysis showed that the predictors of a 50% PSA response were an interval to mCRPC and a docetaxel treatment history, while the predictor of a 30% PSA response was a docetaxel treatment history. Furthermore, a 50% PSA response was independently prognostic of rPFS. An early PSA response to enzalutamide was significantly associated with a longer rPFS and OS. This information will aid in the management of patients treated with enzalutamide. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Response of Two Plant Species to Two Ultraviolet-B Radiation Regimes

NASA Technical Reports Server (NTRS)

Levy, Daniel L.; Skiles, J. W.; Peterson, David (Technical Monitor)

1996-01-01

The depleted stratospheric ozone layer has been directly linked to increased levels of ultraviolet radiation at the earth's surface. It is important to understand what effect this will have on plants. We tested the hypothesis that in response to increased UV-B radiation (280-320 man), soybean (Glycine max Merrill) and alfalfa (Mercado Saliva L.) would produce higher concentrations of flavonoids than plants screened from UV-B. Soybean and alfalfa plants were grown successively in a growth chamber that provided UV-B radiation intensities 45% above summer field levels. A wooden frame was used to suspend mylar-D film over one group of plants and mono-acetate film over another group. Mylar is opaque in the 280-316 nm range, and acetate absorbs most radiation from 280-290 nm and then reduces intensities in the 290-320 nm range by roughly 15%. Leaf chlorophyll concentration was determined with a Minolta SPAD-502 chlorophyll meter; the BRAD meter was calibrated with N,N- extractions. Flavonoids were extracted with an acidified methanol/water solution. Soybean grown under the acetate treatment showed 26% smaller internodal lengths and higher concentrations of flavonoids compared to plants grown under mylar. Significant results for alfalfa included 22% greater leaf flavonoid concentration under acetate, 14% greater leaf chlorophyll concentration under mylar, and 32% greater above-ground biomass under mylar. We found that increased UV-B radiation leads to increased production of UV-B absorbing compounds (i.e. flavonoids) in soybean and alfalfa leaves. This suggests that a protective mechanism in these plants is triggered by UV-B. In response, flavonoids are produced that absorb UV-B, and consequently decrease potentially damaging effects to the plants. In addition, we hypothesize that this flavonoid protection mechanism saturates at certain UV-B intensities.

Enhancing early child care quality and learning for toddlers at risk: the responsive early childhood program.

PubMed

Landry, Susan H; Zucker, Tricia A; Taylor, Heather B; Swank, Paul R; Williams, Jeffrey M; Assel, Michael; Crawford, April; Huang, Weihua; Clancy-Menchetti, Jeanine; Lonigan, Christopher J; Phillips, Beth M; Eisenberg, Nancy; Spinrad, Tracy L; de Villiers, Jill; de Villiers, Peter; Barnes, Marcia; Starkey, Prentice; Klein, Alice

2014-02-01

Despite reports of positive effects of high-quality child care, few experimental studies have examined the process of improving low-quality center-based care for toddler-age children. In this article, we report intervention effects on child care teachers' behaviors and children's social, emotional, behavioral, early literacy, language, and math outcomes as well as the teacher-child relationship. The intervention targeted the use of a set of responsive teacher practices, derived from attachment and sociocultural theories, and a comprehensive curriculum. Sixty-five childcare classrooms serving low-income 2- and 3-year-old children were randomized into 3 conditions: business-as-usual control, Responsive Early Childhood Curriculum (RECC), and RECC plus explicit social-emotional classroom activities (RECC+). Classroom observations showed greater gains for RECC and RECC+ teachers' responsive practices including helping children manage their behavior, establishing a predictable schedule, and use of cognitively stimulating activities (e.g., shared book reading) compared with controls; however, teacher behaviors did not differ for focal areas such as sensitivity and positive discipline supports. Child assessments demonstrated that children in the interventions outperformed controls in areas of social and emotional development, although children's performance in control and intervention groups was similar for cognitive skills (language, literacy, and math). Results support the positive impact of responsive teachers and environments providing appropriate support for toddlers' social and emotional development. Possible explanations for the absence of systematic differences in children's cognitive skills are considered, including implications for practice and future research targeting low-income toddlers.

Characterization of a smartphone camera's response to ultraviolet A radiation.

PubMed

Igoe, Damien; Parisi, Alfio; Carter, Brad

2013-01-01

As part of a wider study into the use of smartphones as solar ultraviolet radiation monitors, this article characterizes the ultraviolet A (UVA; 320-400 nm) response of a consumer complementary metal oxide semiconductor (CMOS)-based smartphone image sensor in a controlled laboratory environment. The CMOS image sensor in the camera possesses inherent sensitivity to UVA, and despite the attenuation due to the lens and neutral density and wavelength-specific bandpass filters, the measured relative UVA irradiances relative to the incident irradiances range from 0.0065% at 380 nm to 0.0051% at 340 nm. In addition, the sensor demonstrates a predictable response to low-intensity discrete UVA stimuli that can be modelled using the ratio of recorded digital values to the incident UVA irradiance for a given automatic exposure time, and resulting in measurement errors that are typically less than 5%. Our results support the idea that smartphones can be used for scientific monitoring of UVA radiation. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

Pretreatment of low dose radiation reduces radiation-induced apoptosis in mouse lymphoma (EL4) cells.

PubMed

Kim, J H; Hyun, S J; Yoon, M Y; Ji, Y H; Cho, C K; Yoo, S Y

1997-06-01

Induction of an adaptive response to ionizing radiation in mouse lymphoma (EL4) cells was studied by using cell survival fraction and apoptotic nucleosomal DNA fragmentation as biological end points. Cells in early log phase were pre-exposed to low dose of gamma-rays (0.01 Gy) 4 or 20 hrs prior to high dose gamma-ray (4, 8 and 12 Gy for cell survival fraction analysis; 8 Gy for DNA fragmentation analysis) irradiation. Then cell survival fractions and the extent of DNA fragmentation were measured. Significant adaptive response, increase in cell survival fraction and decrease in the extent of DNA fragmentation were induced when low and high dose gamma-ray irradiation time interval was 4 hr. Addition of protein or RNA synthesis inhibitor, cycloheximide or 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRFB), respectively during adaptation period, the period from low dose gamma-ray irradiation to high dose gamma-ray irradiation, was able to inhibit the induction of adaptive response, which is the reduction of the extent DNA fragmentation in irradiated EL4 cells. These data suggest that the induction of adaptive response to ionizing radiation in EL4 cells required both protein and RNA synthesis.

Capturing early signs of deterioration: the dutch-early-nurse-worry-indicator-score and its value in the Rapid Response System.

PubMed

Douw, Gooske; Huisman-de Waal, Getty; van Zanten, Arthur R H; van der Hoeven, Johannes G; Schoonhoven, Lisette

2017-09-01

To determine the predictive value of individual and combined dutch-early-nurse-worry-indicator-score indicators at various Early Warning Score levels, differentiating between Early Warning Scores reaching the trigger threshold to call a rapid response team and Early Warning Score levels not reaching this point. Dutch-early-nurse-worry-indicator-score comprises nine indicators underlying nurses' 'worry' about a patient's condition. All indicators independently show significant association with unplanned intensive care/high dependency unit admission or unexpected mortality. Prediction of this outcome improved by adding the dutch-early-nurse-worry-indicator-score indicators to an Early Warning Score based on vital signs. An observational cohort study was conducted on three surgical wards in a tertiary university-affiliated teaching hospital. Included were surgical, native-speaking, adult patients. Nurses scored presence of 'worry' and/or dutch-early-nurse-worry-indicator-score indicators every shift or when worried. Vital signs were measured according to the prevailing protocol. Unplanned intensive care/high dependency unit admission or unexpected mortality was the composite endpoint. Percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators were calculated at various Early Warning Score levels in control and event groups. Entering all dutch-early-nurse-worry-indicator-score indicators in a multiple logistic regression analysis, we calculated a weighted score and calculated sensitivity, specificity, positive predicted value and negative predicted value for each possible total score. In 3522 patients, 102 (2·9%) had an unplanned intensive care/high dependency unit admissions (n = 97) or unexpected mortality (n = 5). Patients with such events and only slightly changed vital signs had significantly higher percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators expressed than patients in the control group. Increasing number

Response to Therapy Following Retreatment of Serofast Early Syphilis Patients With Benzathine Penicillin

PubMed Central

Seña, Arlene C.; Wolff, Mark; Behets, Frieda; Van Damme, Kathleen; Martin, David H.; Leone, Peter; McNeil, Linda; Hook, Edward W.

2013-01-01

Persistent nontreponemal titers after treatment are common among patients with early syphilis. We retreated 82 human immunodeficiency virus–negative early syphilis participants who were serofast at 6 months using benzathine penicillin. Only 27% exhibited serological response after retreatment and after an additional 6 months of follow-up. PMID:23118269

Tying the spectral ends of the M9.0 Tohoku-Oki earthquake sequence: High-frequency radiators and early quasi-static afterslip

NASA Astrophysics Data System (ADS)

Inbal, A.; Ampuero, J. P.; Avouac, J.; Lengliné, O.; Helmberger, D. V.

2012-12-01

The March 11, 2011 M9.0 Tohoku-Oki earthquake was recorded by dense seismological and geodetical networks deployed in Japan, as well as by a vast number of seismic stations worldwide. These observations allow us to study the properties of the subduction interface with unprecedented accuracy and resolution. Here we examine the spectral tails of the co- and post-seismic stages using local geodetic and seismological recordings. First, we study the details of high-frequency (HF) energy radiation during the rupture by using strong-motion recordings. Second, we jointly invert 1Hz GPS, ocean-bottom GPS and aftershock data for the spatio-temporal distribution of early afterslip. In order to constrain the spatial distribution of HF radiators we model waveform envelopes recorded by Kik-net borehole accelerometers located in northeastern Japan. We compute theoretical envelopes for waves traveling in a heterogeneous scattering medium, and invert for the location and amplitude of energy radiators for frequencies ranging from 1 to 16 Hz. Because the inversion is extremely sensitive to the response of individual sites, we adopt an empirical approach and iteratively separate the source and site terms from the stacked spectra of numerous events recorded by the network. The output response functions for each site are used to stabilize the inversion. Preliminary results are consistent with far-field observations and suggest that the HF energy emitted during the M9.0 event originated at the down-dip limit of the rupture zone. We apply waveform cross-correlation to identify repeating events within the aftershock sequence, and locate them by match-filtering their waveforms with known templates. Many of these events occur on seismic asperities loaded by the surrounding creep. We jointly invert the slip histories on these fault patches and the available GPS data for the spatio-temporal distribution of afterslip during the first few hours following the mainshock. We use the Principal

Simulated Space Radiation: Murine Skeletal Responses During Recovery and with Mechanical Stimulation

NASA Technical Reports Server (NTRS)

Shirazi-Fard, Yasaman; Zaragoza, Josergio; Schreurs, Ann-Sofie; Truong, Tiffany; Tahimic, Candice; Alwood, Joshua S.; Castillo, Alesha B.; Globus, R. K.

2016-01-01

Simulated space radiation at doses similar to those of solar particle events or a round-trip sojourn to Mars (1-2Gy) may cause skeletal tissue degradation and deplete stem/progenitor cell pools throughout the body. We hypothesized that simulated space radiation (SSR) causes late, time-dependent deficits in bone structure and bone cell function reflected by changes in gene expression in response to anabolic stimuli. We used a unique sequential dual ion exposure (proton and iron) for SSR to investigate time-dependence of responses in gene expression, cell function, and microarchitecture with respect to radiation and an anabolic stimulus of axial loading (AL). Male 16-wk C57BL6/J mice (n=120 total) were exposed to 0Gy (Sham, n=10), 56Fe (2Gy, positive control dose, n=10), or sequential ions for SSR (1Gy 1H/56Fe/1H, n=10) by total body irradiation (IR), and the tissues were harvested 2 or 6 mo. later. Further, to assess the response to anabolic stimuli, we subjected additional Sham-AL (n=15) and SSR-AL (n=15) groups to rest-inserted tibial axial loading (AL) starting at 1 and 5 months post-IR (-9N, 60 cycles/day, 3 days/wk, 4 wks). Exposure to 56Fe caused a significant reduction in cancellous bone volume fraction (BV/TV) compared to Sham (-34%) and SSR (-20%) in the proximal tibia metaphysis at 2-months post-IR; however BV/TV for SSR group was not different than Sham. Both 56Fe and SSR caused significant reduction in trabecular number (Tb.N) compared to Sham (-33% and -16%, respectively). Further, Tb.N for 56Fe (2Gy) was significantly lower than SSR (-21%). Ex vivo culture of marrow cells to assess growth and differentiation of osteoblast lineage cells 6 months post-IR showed that both 56Fe and SSR exposures significantly impaired colony formation compared to Sham (-66% and -54%, respectively), as well as nodule mineralization (-90% and -51%, respectively). Two-way analysis of variance showed that both mechanical loading and radiation reduced BV/TV, mechanical loading

Simulated Space Radiation: Murine Skeletal Responses During Recovery and with Mechanical Stimulation

NASA Technical Reports Server (NTRS)

Shirazi-Fard, Yasaman; Zaragoza, Josergio; Schreurs, Ann-Sofie; Truong, Tiffany; Tahimic, Candice; Alwood, Joshua S.; Globus, R. K.

2016-01-01

Simulated space radiation at doses similar to those of solar particle events or a round-trip sojourn to Mars (1-2Gy) may cause skeletal tissue degradation and deplete stem/progenitor cell pools throughout the body. We hypothesized that simulated space radiation (SSR) causes late, time-dependent deficits in bone structure and bone cell function reflected by changes in gene expression in response to anabolic stimuli. We used a unique sequential dual ion exposure (proton and iron) for SSR to investigate time-dependence of responses in gene expression, cell function, and microarchitecture with respect to radiation and an anabolic stimulus of axial loading (AL). Male 16-wk C57BL6/J mice (n=120 total) were exposed to 0Gy (Sham, n=10), 56Fe (2Gy, positive control dose, n=10), or sequential ions for SSR (1Gy 1H/56Fe/1H, n=10) by total body irradiation (IR), and the tissues were harvested 2 or 6 mo. later. Further, to assess the response to anabolic stimuli, we subjected additional Sham-AL (n=15) and SSR-AL (n=15) groups to rest-inserted tibial axial loading (AL) starting at 1 and 5 months post-IR (-9N, 60 cycles/day, 3 days/wk, 4 wks). Exposure to 56Fe caused a significant reduction in cancellous bone volume fraction (BV/TV) compared to Sham (-34%) and SSR (-20%) in the proximal tibia metaphysis at 2-months post-IR; however BV/TV for SSR group was not different than Sham. Both 56Fe and SSR caused significant reduction in trabecular number (Tb.N) compared to Sham (-33% and -16%, respectively). Further, Tb.N for 56Fe (2Gy) was significantly lower than SSR (-21%). Ex vivo culture of marrow cells to assess growth and differentiation of osteoblast lineage cells 6 months post-IR showed that both 56Fe and SSR exposures significantly impaired colony formation compared to Sham (-66% and -54%, respectively), as well as nodule mineralization (-90% and -51%, respectively). Two-way analysis of variance showed that both mechanical loading and radiation reduced BV/TV, mechanical loading

[Radiation-induced bystander effect: the important part of ionizing radiation response. Potential clinical implications].

PubMed

Wideł, Maria; Przybyszewski, Waldemar; Rzeszowska-Wolny, Joanna

2009-08-18

It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the "bystander effect" or "radiation-induced bystander effect" (RIBE). This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy), but also after conventional irradiation (X-rays, gamma rays) at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not definitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effect may have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation field and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The bystander effect may be a

GROWTH RESPONSE OF SYMBODINIUM SPP. TO COMBINED TEMPERATURE AND UV RADIATION

EPA Science Inventory

Rogers, J.E. and D. Marcovich. In press. Growth Response of a Coral Symbiont, Symbiodinium sp., to Combined Temperature and UV Radiation Exposure (Abstract). To be presented at the ASLO 2004 Summer Meeting: The Changing Landscapes of Oceans and Freshwater, 13-18 June 2004, Savann...

Radiation Hardness Assurance (RHA) for Space Systems

NASA Technical Reports Server (NTRS)

Poivey, Christian; Buchner, Stephen

2007-01-01

This presentation discusses radiation hardness assurance (RHA) for space systems, providing both the programmatic aspects of RHA and the RHA procedure. RHA consists of all activities undertaken to ensure that the electronics and materials of a space system perform to their design specifications after exposure to the space radiation environment. RHA also pertains to environment definition, part selection, part testing, spacecraft layout, radiation tolerant design, and mission/system/subsystems requirements. RHA procedure consists of establishing mission requirements, defining and evaluating the radiation hazard, selecting and categorizing the appropriate parts, and evaluating circuit response to hazard. The RHA approach is based on risk management and is confined only to parts, it includes spacecraft layout, system/subsystem/circuit design, and system requirements and system operations. RHA should be taken into account in the early phases of a program including the proposal and feasibility analysis phases.

Bridging Plant and Human Radiation Response and DNA Repair through an In Silico Approach

PubMed Central

Nikitaki, Zacharenia; Pavlopoulou, Athanasia; Holá, Marcela; Donà, Mattia; Michalopoulos, Ioannis; Balestrazzi, Alma; Angelis, Karel J.; Georgakilas, Alexandros G.

2017-01-01

The mechanisms of response to radiation exposure are conserved in plants and animals. The DNA damage response (DDR) pathways are the predominant molecular pathways activated upon exposure to radiation, both in plants and animals. The conserved features of DDR in plants and animals might facilitate interdisciplinary studies that cross traditional boundaries between animal and plant biology in order to expand the collection of biomarkers currently used for radiation exposure monitoring (REM) in environmental and biomedical settings. Genes implicated in trans-kingdom conserved DDR networks often triggered by ionizing radiation (IR) and UV light are deposited into biological databases. In this study, we have applied an innovative approach utilizing data pertinent to plant and human genes from publicly available databases towards the design of a ‘plant radiation biodosimeter’, that is, a plant and DDR gene-based platform that could serve as a REM reliable biomarker for assessing environmental radiation exposure and associated risk. From our analysis, in addition to REM biomarkers, a significant number of genes, both in human and Arabidopsis thaliana, not yet characterized as DDR, are suggested as possible DNA repair players. Last but not least, we provide an example on the applicability of an Arabidopsis thaliana—based plant system monitoring the role of cancer-related DNA repair genes BRCA1, BARD1 and PARP1 in processing DNA lesions. PMID:28587301

Bridging Plant and Human Radiation Response and DNA Repair through an In Silico Approach.

PubMed

Nikitaki, Zacharenia; Pavlopoulou, Athanasia; Holá, Marcela; Donà, Mattia; Michalopoulos, Ioannis; Balestrazzi, Alma; Angelis, Karel J; Georgakilas, Alexandros G

2017-06-06

The mechanisms of response to radiation exposure are conserved in plants and animals. The DNA damage response (DDR) pathways are the predominant molecular pathways activated upon exposure to radiation, both in plants and animals. The conserved features of DDR in plants and animals might facilitate interdisciplinary studies that cross traditional boundaries between animal and plant biology in order to expand the collection of biomarkers currently used for radiation exposure monitoring (REM) in environmental and biomedical settings. Genes implicated in trans-kingdom conserved DDR networks often triggered by ionizing radiation (IR) and UV light are deposited into biological databases. In this study, we have applied an innovative approach utilizing data pertinent to plant and human genes from publicly available databases towards the design of a 'plant radiation biodosimeter', that is, a plant and DDR gene-based platform that could serve as a REM reliable biomarker for assessing environmental radiation exposure and associated risk. From our analysis, in addition to REM biomarkers, a significant number of genes, both in human and Arabidopsis thaliana, not yet characterized as DDR, are suggested as possible DNA repair players. Last but not least, we provide an example on the applicability of an Arabidopsis thaliana- based plant system monitoring the role of cancer-related DNA repair genes BRCA1 , BARD1 and PARP1 in processing DNA lesions.

Environmental exposure to low-doses of ionizing radiation. Effects on early nephrotoxicity in mice.

PubMed

Bellés, Montserrat; Gonzalo, Sergio; Serra, Noemí; Esplugas, Roser; Arenas, Meritxell; Domingo, José Luis; Linares, Victoria

2017-07-01

Nuclear accidents of tremendous magnitude, such as those of Chernobyl (1986) and Fukushima (2011), mean that individuals living in the contaminated areas are potentially exposed to ionizing radiation (IR). However, the dose-response relationship for effects of low doses of radiation is not still established. The present study was aimed at investigating in mice the early effects of low-dose internal radiation exposure on the kidney. Adult male (C57BL/6J) mice were divided into three groups. Two groups received a single subcutaneous (s.c.) doses of cesium ( 137 Cs) with activities of 4000 and 8000Bq/kg bw. A third group (control group) received a single s.c. injection of 0.9% saline. To evaluate acute and subacute effects, mice (one-half of each group) were euthanized at 72h and 10 days post-exposure to 137 Cs, respectively. Urine samples were collected for biochemical analysis, including the measurement of F2-isoprostane (F2-IsoP) and kidney injury molecule-1 (KIM-1) levels. Moreover, the concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA damage, were measured in renal tissue. Urinary excretion of total protein significantly increased at 72h in mice exposed to Cs4000. Uric acid and lactate dehydrogenase (LDH) decreased significantly at both times post-exposure in animals exposed to Cs8000. After 72h and 10d of exposure to Cs4000, a significant increase in the γ-glutamil transferase (GGT) and N-acetyl-β-D-glucosaminidase (NAG) activities was observed. In turn, F2-IsoP levels increased -mainly in the Cs4000 group- at 72h post-exposure. Following irradiation ( 137 Cs), the highest level of KIM-1 was corresponded to the Cs4000 group at 72h. Likewise, the main DNA damage was detected in mice exposed to Cs4000, mainly at 10d after irradiation. The alterations observed in several biomarkers suggest an immediate renal damage following exposure to low doses of IR (given as 137 Cs). Further investigations are required to clarify the

Early Peritoneal Immune Response during Echinococcus granulosus Establishment Displays a Biphasic Behavior

PubMed Central

Mourglia-Ettlin, Gustavo; Marqués, Juan Martín; Chabalgoity, José Alejandro; Dematteis, Sylvia

2011-01-01

Background Cystic echinococcosis is a worldwide distributed helminth zoonosis caused by the larval stage of Echinococcus granulosus. Human secondary cystic echinococcosis is caused by dissemination of protoscoleces after accidental rupture of fertile cysts and is due to protoscoleces ability to develop into new metacestodes. In the experimental model of secondary cystic echinococcosis mice react against protoscoleces producing inefficient immune responses, allowing parasites to develop into cysts. Although the chronic phase of infection has been analyzed in depth, early immune responses at the site of infection establishment, e.g., peritoneal cavity, have not been well studied. Because during early stages of infection parasites are thought to be more susceptible to immune attack, this work focused on the study of cellular and molecular events triggered early in the peritoneal cavity of infected mice. Principal Findings Data obtained showed disparate behaviors among subpopulations within the peritoneal lymphoid compartment. Regarding B cells, there is an active molecular process of plasma cell differentiation accompanied by significant local production of specific IgM and IgG2b antibodies. In addition, peritoneal NK cells showed a rapid increase with a significant percentage of activated cells. Peritoneal T cells showed a substantial increase, with predominance in CD4+ T lymphocytes. There was also a local increase in Treg cells. Finally, cytokine response showed local biphasic kinetics: an early predominant induction of Th1-type cytokines (IFN-γ, IL-2 and IL-15), followed by a shift toward a Th2-type profile (IL-4, IL-5, IL-6, IL-10 and IL-13). Conclusions Results reported here open new ways to investigate the involvement of immune effectors players in E. granulosus establishment, and also in the sequential promotion of Th1- toward Th2-type responses in experimental secondary cystic echinococcosis. These data would be relevant for designing rational therapies

Early life adversity influences stress response association with smoking relapse.

PubMed

al'Absi, Mustafa; Lemieux, Andrine; Westra, Ruth; Allen, Sharon

2017-11-01

We examined the hypothesis that stress-related blunting of cortisol in smokers is particularly pronounced in those with a history of severe life adversity. The two aims of this study were first to examine hormonal, craving, and withdrawal symptoms during ad libitum smoking and after the first 24 h of abstinence in smokers who experienced high or low levels of adversity. Second, we sought to examine the relationship between adversity and hypothalamic-pituitary-adrenal (HPA) hormones to predict relapse during the first month of a smoking cessation attempt. Hormonal and self-report measures were collected from 103 smokers (49 women) during ad libitum smoking and after the first 24 h of abstinence. HPA hormones were measured during baseline rest and in response to acute stress in both conditions. All smokers were interested in smoking cessation, and we prospectively used stress response measures to predict relapse during the first 4 weeks of the smoking cessation attempt. The results showed that high adversity was associated with higher distress and smoking withdrawal symptoms. High level of early life adversity was associated with elevated HPA activity, which was found in both salivary and plasma cortisol. Enhanced adrenocorticotropic hormone (ACTH) stress response was evident in high-adversity but not in low-adversity relapsers. This study demonstrated that early life adversity is associated with stress-related HPA responses. The study also demonstrated that, among smokers who experienced a high level of life adversity, heightened ACTH and cortisol responses were linked with increased risk for smoking relapse.

Radiation Therapy Induces Macrophages to Suppress T-Cell Responses Against Pancreatic Tumors in Mice.

PubMed

Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Giao Ly, Nancy Ngoc; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

2016-06-01

The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcomes compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of preinvasive foci. We investigated the effects of radiation therapy in p48(Cre);LSL-Kras(G12D) (KC) and p48(Cre);LSLKras(G12D);LSL-Trp53(R172H) (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony-stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2 to 12 Gy and analyzed by flow cytometry. Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from radiation treated invasive and preinvasive pancreatic tumors had an immune-suppressive, M2-like phenotype compared with control mice. Pancreata from mice exposed to radiation had fewer CD8(+) T cells than controls, and greater numbers of CD4(+) T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. A neutralizing antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Radiation treatment causes macrophages

Early host response in the mammary gland after experimental Streptococcus uberis challenge in heifers.

PubMed

de Greeff, Astrid; Zadoks, Ruth; Ruuls, Lisette; Toussaint, Mathilda; Nguyen, Thi Kim Anh; Downing, Alison; Rebel, Johanna; Stockhofe-Zurwieden, Norbert; Smith, Hilde

2013-06-01

Streptococcus uberis is a highly prevalent causative agent of bovine mastitis, which leads to large economic losses in the dairy industry. The aim of this study was to examine the host response during acute inflammation after experimental challenge with capsulated Strep. uberis. Gene expression in response to Strep. uberis was compared between infected and control quarters in 3 animals. All quarters (n=16) were sampled at 16 different locations. Microarray data showed that 239 genes were differentially expressed between infected and control quarters. No differences in gene expression were observed between the different locations. Microarray data were confirmed for several genes using quantitative PCR analysis. Genes differentially expressed due to early Strep. uberis mastitis represented several stages of the process of infection: (1) pathogen recognition; (2) chemoattraction of neutrophils; (3) tissue repair mechanisms; and (4) bactericidal activity. Three different pathogen recognition genes were induced: ficolins, lipopolysaccharide binding protein, and toll-like receptor 2. Calgranulins were found to be the most strongly upregulated genes during early inflammation. By histology and immunohistochemistry, we demonstrated that changes in gene expression in response to Strep. uberis were induced both in infiltrating somatic milk cells and in mammary epithelial cells, demonstrating that the latter cell type plays a role in milk production as well as immune responsiveness. Given the rapid development of inflammation or mastitis after infection, early diagnosis of (Strep. uberis) mastitis is required for prevention of disease and spread of the pathogen. Insight into host responses could help to design immunomodulatory therapies to dampen inflammation after (early) diagnosis of Strep. uberis mastitis. Future research should focus on development of these early diagnostics and immunomodulatory components for mastitis treatment. Copyright © 2013 American Dairy Science

Hyberbaric oxygen as sole treatment for severe radiation - induced haemorrhagic cystitis

PubMed Central

Dellis, Athanasios; Papatsoris, Athanasios; Kalentzos, Vasileios; Deliveliotis, Charalambos; Skolarikos, Andreas

2017-01-01

ABSTRACT Purpose To examine the safety and efficacy of hyperbaric oxygen as the primary and sole treatment for severe radiation-induced haemorrhagic cystitis. Materials and methods Hyperbaric oxygen was prospectively applied as primary treatment in 38 patients with severe radiation cystitis. Our primary endpoint was the incidence of complete and partial response to treatment, while the secondary endpoints included the duration of response, the correlation of treatment success-rate to the interval between the onset of haematuria and initiation of therapy, blood transfusion need and total radiation dose, the number of sessions to success, the avoidance of surgery and the overall survival. Results All patients completed therapy without complications with a mean follow-up of 29.33 months. Median number of sessions needed was 33. Complete and partial response rate was 86.8% and 13.2%, respectively. All 33 patients with complete response received therapy within 6 months of the haematuria onset. One patient needed cystectomy, while 33 patients were alive at the end of follow-up. Conclusions Our study suggests the early primary use of hyperbaric oxygen for radiation-induced severe cystitis as an effective and safe treatment option. PMID:28338304

Human response to high-background radiation environments on Earth and in space

NASA Astrophysics Data System (ADS)

Durante, M.; Manti, L.

The main long-term goal of the space exploration program is the colonization of the planets of the Solar System The high cosmic radiation equivalent dose rate represents a major problem for a stable and safe colonization of the planets The dose rate on Mars ranges between 60 and 150 mSv year depending on the Solar cycle and altitude and can reach values as high as 360 mSv year on the Moon The average dose rate on the Earth is about 3 mSv year reduced to about 1 mSv year excluding the internal exposure to Rn daughters However some areas of the Earth have anomalously high levels of background radiation Values 200-400 times higher than the world average are found in regions where monazite sand deposits are abundant Population in Tibet experience a high cosmic radiation background Epidemiological studies did not detect any adverse health effects in the populations living in those high-background radiation areas on Earth Chromosomal aberrations in the peripheral blood lymphocytes from the population living in the high-background radiation areas have been measured in several studies because the chromosomal damage represents an early biomarker of cancer risk Similar cytogenetic studies have been recently performed in cohort of astronauts involved in single or repeated space flights over many years A comparison of the cytogenetic findings in populations exposed at high dose rate on Earth or in space will be described

Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation

PubMed Central

Kadekaro, Ana Luisa; Leachman, Sancy; Kavanagh, Renny J.; Swope, Viki; Cassidy, Pamela; Supp, Dorothy; Sartor, Maureen; Schwemberger, Sandy; Babcock, George; Wakamatsu, Kazumasa; Ito, Shosuke; Koshoffer, Amy; Boissy, Raymond E.; Manga, Prashiela; Sturm, Richard A.; Abdel-Malek, Zalfa A.

2010-01-01

The melanocortin 1 receptor gene is a main determinant of human pigmentation, and a melanoma susceptibility gene, because its variants that are strongly associated with red hair color increase melanoma risk. To test experimentally the association between melanocortin 1 receptor genotype and melanoma susceptibility, we compared the responses of primary human melanocyte cultures naturally expressing different melanocortin 1 receptor variants to α-melanocortin and ultraviolet radiation. We found that expression of 2 red hair variants abolished the response to α-melanocortin and its photoprotective effects, evidenced by lack of functional coupling of the receptor, and absence of reduction in ultraviolet radiation-induced hydrogen peroxide generation or enhancement of repair of DNA photoproducts, respectively. These variants had different heterozygous effects on receptor function. Microarray data confirmed the observed differences in responses of melanocytes with functional vs. nonfunctional receptor to α-melanocortin and ultraviolet radiation, and identified DNA repair and antioxidant genes that are modulated by α-melanocortin. Our findings highlight the molecular mechanisms by which the melanocortin 1 receptor genotype controls genomic stability of and the mutagenic effect of ultraviolet radiation on human melanocytes.—Kadekaro, A. L., Leachman, S., Kavanagh, R. J., Swope, V., Cassidy, P., Supp, D., Sartor, M., Schwemberger, S., Babcock, G., Wakamatsu, K., Ito, S., Koshoffer, A., Boissy, R. E., Manga, P., Sturm, R. A., Abdel-Malek, Z. A. Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation. PMID:20519635

Spectral Kernel Approach to Study Radiative Response of Climate Variables and Interannual Variability of Reflected Solar Spectrum

NASA Technical Reports Server (NTRS)

Jin, Zhonghai; Wielicki, Bruce A.; Loukachine, Constantin; Charlock, Thomas P.; Young, David; Noeel, Stefan

2011-01-01

The radiative kernel approach provides a simple way to separate the radiative response to different climate parameters and to decompose the feedback into radiative and climate response components. Using CERES/MODIS/Geostationary data, we calculated and analyzed the solar spectral reflectance kernels for various climate parameters on zonal, regional, and global spatial scales. The kernel linearity is tested. Errors in the kernel due to nonlinearity can vary strongly depending on climate parameter, wavelength, surface, and solar elevation; they are large in some absorption bands for some parameters but are negligible in most conditions. The spectral kernels are used to calculate the radiative responses to different climate parameter changes in different latitudes. The results show that the radiative response in high latitudes is sensitive to the coverage of snow and sea ice. The radiative response in low latitudes is contributed mainly by cloud property changes, especially cloud fraction and optical depth. The large cloud height effect is confined to absorption bands, while the cloud particle size effect is found mainly in the near infrared. The kernel approach, which is based on calculations using CERES retrievals, is then tested by direct comparison with spectral measurements from Scanning Imaging Absorption Spectrometer for Atmospheric Cartography (SCIAMACHY) (a different instrument on a different spacecraft). The monthly mean interannual variability of spectral reflectance based on the kernel technique is consistent with satellite observations over the ocean, but not over land, where both model and data have large uncertainty. RMS errors in kernel ]derived monthly global mean reflectance over the ocean compared to observations are about 0.001, and the sampling error is likely a major component.

Microfluidics as a new tool in radiation biology

PubMed Central

Lacombe, Jerome; Phillips, Shanna Leslie; Zenhausern, Frederic

2016-01-01

Ionizing radiations interact with molecules at the cellular and molecular levels leading to several biochemical modifications that may be responsible for biological effects on tissue or whole organisms. The study of these changes is difficult because of the complexity of the biological response(s) to radiations and the lack of reliable models able to mimic the whole molecular phenomenon and different communications between the various cell networks, from the cell activation to the macroscopic effect at the tissue or organismal level. Microfluidics, the science and technology of systems that can handle small amounts of fluids in confined and controlled environment, has been an emerging field for several years. Some microfluidic devices, even at early stages of development, may already help radiobiological research by proposing new approaches to study cellular, tissue and total-body behavior upon irradiation. These devices may also be used in clinical biodosimetry since microfluidic technology is frequently developed for integrating complex bioassay chemistries into automated user-friendly, reproducible and sensitive analyses. In this review, we discuss the use, numerous advantages, and possible future of microfluidic technology in the field of radiobiology. We will also examine the disadvantages and required improvements for microfluidics to be fully practical in radiation research and to become an enabling tool for radiobiologists and radiation oncologists. PMID:26704304

Parkin regulates translesion DNA synthesis in response to UV radiation

PubMed Central

Huang, Min; Liu, Hongmei; Wang, Fengli; Gong, Juanjuan; Wang, Jiuqiang; Li, Xiaoling; Chen, Qian; Shen, Hongyan; Zhu, Shu; Wang, Yun; Liu, Yang; Guo, Caixia; Tang, Tie-Shan

2017-01-01

Deficiency of Parkin is a major cause of early-onset Parkinson's disease (PD). Notably, PD patients also exhibit a significantly higher risk in melanoma and other skin tumors, while the mechanism remains largely unknown. In this study, we show that depletion of Parkin causes compromised cell viability and genome stability after ultraviolet (UV) radiation. We demonstrate that Parkin promotes efficient Rad18-dependent proliferating cell nuclear antigen (PCNA) monoubiquitination by facilitating the formation of Replication protein A (RPA)-coated ssDNA upon UV radiation. Furthermore, Parkin is found to physically interact with NBS1 (Nijmegen breakage syndrome 1), and to be required for optimal recruitment of NBS1 and DNA polymerase eta (Polη) to UV-induced damage sites. Consequently, depletion of Parkin leads to increased UV-induced mutagenesis. These findings unveil an important role of Parkin in protecting genome stability through positively regulating translesion DNA synthesis (TLS) upon UV damage, providing a novel mechanistic link between Parkin deficiency and predisposition to skin cancers in PD patients. PMID:28430587

The promise of dynamic contrast-enhanced imaging in radiation therapy.

PubMed

Cao, Yue

2011-04-01

Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and computed tomography (CT) scanning are emerging as valuable tools to quantitatively map the spatial distribution of vascular parameters, such as perfusion, vascular permeability, blood volume, and mean transit time in tumors and normal organs. DCE MRI/CT have shown prognostic and predictive value for response of certain cancers to chemotherapy and radiation therapy. DCE MRI/CT offer the promise of early assessment of tumor response to radiation therapy, opening a window for adaptively optimizing radiation therapy based upon functional alterations that occur earlier than morphologic changes. DCE MRI/CT has also shown the potential of mapping dose responses in normal organs and tissue for evaluation of individual sensitivity to radiation, providing additional opportunities to minimize risks of radiation injury. The evidence for potentially applying DCE MRI and CT for selection and delineation of radiation boost targets is growing. The clinical use of DCE MRI and CT scanning as a biomarker or even a surrogate endpoint for radiation therapy assessment of tumor and normal organs must consider technical validation issues, including standardization, reproducibility, accuracy and robustness, and clinical validation of the sensitivity and specificity for each specific problem of interest. Although holding great promise, to date, DCE MRI and CT scanning have not been qualified as a surrogate endpoint for radiation therapy assessment or for treatment modification in any prospective phase III clinical trial for any tumor site. Copyright © 2011 Elsevier Inc. All rights reserved.

Atypical radiation response of SCID cells

NASA Astrophysics Data System (ADS)

Chawapun, Nisa

Murine SCID (severe combined immune deficiency) cells are well known for their defect in DNA double-strand break repair and in variable(diversity)joining [V(D)J] recombination due to a mutation in a catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). As a consequence, scid cells are hypersensitive to ionizing radiation. The present study showed that asynchronous populations of scid cells were about two-fold more sensitive than Balb/c with respect to cell killing and the defect in scid cells was corrected by complementation with human chromosome 8. Analysis of the survival of synchronized populations as a function of the cell cycle revealed that while scid cells were hypersensitive in all cell cycle phases compared to wild-type cells, this hypersensitivity is even more pronounced in G1 phase. The hypersensitivity reduced as the cells progressed into S phase suggested that homologous recombination repair plays a role. The results imply that there are at least two pathways for the repair of DSB DNA, consistent with a model previously proposed by others. The scid cells were also more sensitive to UVC light (254 nm) killing as compared to wild type cells by clonogenic survival. Using a host cell reactivation (HCR) assay to study the nucleotide excision repair (NER) which is the major repair pathway for UV-photoproducts, the results showed that NER in scid cells was not as efficient as CB- 17. This suggests that DNA-PK is involved in NER as well as non-homologous end-joining (NHEJ) DSB repair which is responsible for ionizing radiation sensitivity in scid cells. Repair in scid cells was not totally absent as shown by low dose rate sparing of cell killing after exposure to 137Cs γ-rays at dose rate of 0.6 cGy/h, 1.36 cGy/h, 6 cGy/h as compared to high dose rate at 171 cGy/min, although this phenomenon could be explained partly by proliferation. However, for radiation induced transformation, no significant dose rate effect was seen. A plot of transformation

The Impact of Early Substance Use Disorder Treatment Response on Treatment Outcomes Among Pregnant Women With Primary Opioid Use.

PubMed

Tuten, Michelle; Fitzsimons, Heather; Hochheimer, Martin; Jones, Hendree E; Chisolm, Margaret S

2018-03-13

This study examined the impact of early patient response on treatment utilization and substance use among pregnant participants enrolled in substance use disorder (SUD) treatment. Treatment responders (TRs) and treatment nonresponders (TNRs) were compared on pretreatment and treatment measures. Regression models predicted treatment utilization and substance use. TR participants attended more treatment and had lower rates of substance use relative to TNR participants. Regression models for treatment utilization and substance use were significant. Maternal estimated gestational age (EGA) and baseline cocaine use were negatively associated with treatment attendance. Medication-assisted treatment, early treatment response, and baseline SUD treatment were positively associated with treatment attendance. Maternal EGA was negatively associated with counseling attendance; early treatment response was positively associated with counseling attendance. Predictors of any substance use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline cocaine use. The single predictor of any substance use at 2 months was early treatment nonresponse. Predictors of opioid use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline SUD treatment. Predictors of opioid use at 2 months were early treatment nonresponse, and baseline cocaine and marijuana use. Predictors of cocaine use at 1 month were early treatment nonresponse, baseline cocaine use, and baseline SUD treatment. Predictors of cocaine use at 2 months were early treatment nonresponse and baseline cocaine use. Early treatment response predicts more favorable maternal treatment utilization and substance use outcomes. Treatment providers should implement interventions to maximize patient early response to treatment.

The effect of hypofractionated radiation and magnetic nanoparticle hyperthermia on tumor immunogenicity and overall treatment response

NASA Astrophysics Data System (ADS)

Hoopes, P. Jack; Wagner, Robert J.; Song, Ailin; Osterberg, Bjorn; Gladstone, David J.; Bursey, Alicea A.; Fiering, Steven N.; Giustini, Andrew J.

2017-02-01

It is now known that many tumors develop molecular signals (immune checkpoint modulators) that inhibit an effective tumor immune response. New information also suggest that even well-known cancer treatment modalities such as radiation and hyperthermia generate potentially beneficial immune responses that have been blocked or mitigated by such immune checkpoints, or similar molecules. The cancer therapy challenge is to; a) identify these treatment-based immune signals (proteins, antigens, etc.); b) the treatment doses or regimens that produce them; and c) the mechanisms that block or have the potential to promote them. The goal of this preliminary study, using the B6 mouse - B16 tumor model, clinically relevant radiation doses and fractionation schemes (including those used clinically in hypofractionated radiation therapy), magnetic nanoparticle hyperthermia (mNPH) and sophisticated protein, immune and tumor growth analysis techniques and modulators, is to determine the effect of specific radiation or hyperthermia alone and combined on overall treatment efficacy and immunologic response mechanisms. Preliminary analysis suggests that radiation dose (10 Gy vs. 2 Gy) significantly alters the mechanism of cell death (apoptosis vs. mitosis vs. necrosis) and the resulting immunogenicity. Our hypothesis and data suggest this difference is protein/antigen and immune recognition-based. Similarly, our evidence suggest that radiation doses larger than the conventional 2 Gy dose and specific hyperthermia doses and techniques (including mNP hyperthermia treatment) can be immunologically different, and potentially superior to, the radiation and heat therapy regimens that are typically used in research and clinical practice.

A Comparison of Responsive Interventions on Kindergarteners' Early Reading Achievement

ERIC Educational Resources Information Center

Little, Mary E.; Rawlinson, D'Ann; Simmons, Deborah C.; Kim, Minjung; Kwok, Oi-man; Hagan-Burke, Shanna; Simmons, Leslie E.; Fogarty, Melissa; Oslund, Eric; Coyne, Michael D.

2012-01-01

This study compared the effects of Tier 2 reading interventions that operated in response-to-intervention contexts. Kindergarten children (N = 90) who were identified as at risk for reading difficulties were stratified by school and randomly assigned to receive (a) Early Reading Intervention (ERI; Pearson/Scott Foresman, 2004) modified in response…

Diffusion MRI in early cancer therapeutic response assessment

PubMed Central

Galbán, C. J.; Hoff, B. A.; Chenevert, T. L.; Ross, B. D.

2016-01-01

Imaging biomarkers for the predictive assessment of treatment response in patients with cancer earlier than standard tumor volumetric metrics would provide new opportunities to individualize therapy. Diffusion-weighted MRI (DW-MRI), highly sensitive to microenvironmental alterations at the cellular level, has been evaluated extensively as a technique for the generation of quantitative and early imaging biomarkers of therapeutic response and clinical outcome. First demonstrated in a rodent tumor model, subsequent studies have shown that DW-MRI can be applied to many different solid tumors for the detection of changes in cellularity as measured indirectly by an increase in the apparent diffusion coefficient (ADC) of water molecules within the lesion. The introduction of quantitative DW-MRI into the treatment management of patients with cancer may aid physicians to individualize therapy, thereby minimizing unnecessary systemic toxicity associated with ineffective therapies, saving valuable time, reducing patient care costs and ultimately improving clinical outcome. This review covers the theoretical basis behind the application of DW-MRI to monitor therapeutic response in cancer, the analytical techniques used and the results obtained from various clinical studies that have demonstrated the efficacy of DW-MRI for the prediction of cancer treatment response. PMID:26773848

Radiation and temperature effects on the time-dependent response of T300/934 graphite/epoxy

NASA Technical Reports Server (NTRS)

Yancey, Robert N.; Pindera, Marek-Jerzy

1988-01-01

A time-dependent characterization study was performed on T300/934 graphite/epoxy in a simulated space environment. Creep tests on irradiated and nonirradiated graphite/epoxy and bulk resin specimens were carried out at temperatures of 72 and 250 F. Irradiated specimens were exposed to dosages of penetrating electron radiation equal to 30 years exposure at GEO-synchronous orbit. Radiation was shown to have little effect on the creep response of both the composite and bulk resin specimens at 72 F while radiation had a significant effect at 250 F. A healing process was shown to be present in the irradiated specimens where broken bonds in the epoxy due to radiation recombined over time to form cross-links in the 934 resin structure. An analytical micromechanical model was also developed to predict the viscoelastic response of fiber reinforced composite materials. The model was shown to correlate well with experimental results for linearly viscoelastic materials with relatively small creep strains.

Singular F(R) cosmology unifying early- and late-time acceleration with matter and radiation domination era

NASA Astrophysics Data System (ADS)

Odintsov, S. D.; Oikonomou, V. K.

2016-06-01

We present some cosmological models which unify the late- and early-time acceleration eras with the radiation and the matter domination era, and we realize the cosmological models by using the theoretical framework of F(R) gravity. Particularly, the first model unifies the late- and early-time acceleration with the matter domination era, and the second model unifies all the evolution eras of our Universe. The two models are described in the same way at early and late times, and only the intermediate stages of the evolution have some differences. Each cosmological model contains two Type IV singularities which are chosen to occur one at the end of the inflationary era and one at the end of the matter domination era. The cosmological models at early times are approximately identical to the R 2 inflation model, so these describe a slow-roll inflationary era which ends when the slow-roll parameters become of order one. The inflationary era is followed by the radiation era and after that the matter domination era follows, which lasts until the second Type IV singularity, and then the late-time acceleration era follows. The models have two appealing features: firstly they produce a nearly scale invariant power spectrum of primordial curvature perturbations and a scalar-to-tensor ratio which are compatible with the most recent observational data and secondly, it seems that the deceleration-acceleration transition is crucially affected by the presence of the second Type IV singularity which occurs at the end of the matter domination era. As we demonstrate, the Hubble horizon at early times shrinks, as expected for an initially accelerating Universe, then during the matter domination era, it expands and finally after the Type IV singularity, the Hubble horizon starts to shrink again, during the late-time acceleration era. Intriguingly enough, the deceleration-acceleration transition, occurs after the second Type IV singularity. In addition, we investigate which F(R) gravity

Early prediction of blonanserin response in Japanese patients with schizophrenia.

PubMed

Kishi, Taro; Matsuda, Yuki; Fujita, Kiyoshi; Iwata, Nakao

2014-01-01

Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8. Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia), and 28 (75.7%) completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS) total score (P<0.0001) and in positive (P<0.0001), negative (P<0.0001), and general subscale scores (P<0.0001). In terms of percentage improvement of PANSS total scores from baseline to week 8, 64.9% of patients showed a ≥20% reduction in the PANSS total score and 48.6% showed a ≥30% reduction. However, 8.1% of patients experienced at least one adverse event. Using the 20% reduction in the PANSS total score at week 4 as a definition of an early response, the negative predictive values for later responses (ie, reductions of ≥30 and ≥40 in the PANSS total scores) were 88.9% and 94.1%, respectively. The specificities were 80.0% and 51.6%, respectively. Our results suggest that the blonanserin response at week 4 could predict the later response at week 8.

Early prediction of blonanserin response in Japanese patients with schizophrenia

PubMed Central

Kishi, Taro; Matsuda, Yuki; Fujita, Kiyoshi; Iwata, Nakao

2014-01-01

Background Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. Methods An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8. Results Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia), and 28 (75.7%) completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS) total score (P<0.0001) and in positive (P<0.0001), negative (P<0.0001), and general subscale scores (P<0.0001). In terms of percentage improvement of PANSS total scores from baseline to week 8, 64.9% of patients showed a ≥20% reduction in the PANSS total score and 48.6% showed a ≥30% reduction. However, 8.1% of patients experienced at least one adverse event. Using the 20% reduction in the PANSS total score at week 4 as a definition of an early response, the negative predictive values for later responses (ie, reductions of ≥30 and ≥40 in the PANSS total scores) were 88.9% and 94.1%, respectively. The specificities were 80.0% and 51.6%, respectively. Conclusion Our results suggest that the blonanserin response at week 4 could predict the later response at week 8. PMID:25285009

The Use of Radiation Response (RR) in Selecting the Method of Treatment of Carcinoma Cervicis Uteri

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chesterman, John N.

1963-03-01

Attempts were made to determine the choice treatment of cervical squamous carcinoma (surgery, radiation, or surgery with radiation) in Stages I and II. A study of 50 patients showed good results from surgery in patients with poor radiation response (RR) and that the RR, estimated by a precise and uniform technique, will identify those patients who will not respond well to complete radiation therapy. Moreover, it will do this after a first radium application of moderate dosage, at a time when it is still possible to interrupt this therapy. A radiation dose of at least 1000 r at the cervixmore » will be followed by the maximum RR, in a good response, between the 8th and 14th (especially 10th to 12th) days. A poor RR will reach its maximum earlier than a good one, on about the 10th day after radium implantation. When deciding the definition of good RR, it was found that the radiation changes present in a count of 100 cells were seen in more than 70 cells. There is evidence that age, menopause, and hormonal status influence the radiation reaction. If poor RR is more frequently found with high estrogenic activity, young patients treated by radiation should be expected to have a worse survival rate than old. The survival rate is about 1/3) in the young patient as against 1/2 in the postmenopausal. A good sensitization response (SR) was, in most cases, followed by good RR after radiation. Of 39 patients with good SR, 34 had good RR after one application of radium. However, this correlation was absent when the SR was poor. Of 41 patients with poor SR, 18 remained poor after radiation and 23 developed good RR. Finally, this SR should not be taken alone as a guide to treatment, but all patients should be given the first radium application and the RR assessed.« less

Human radiation studies: Remembering the early years. Oral history of biochemist John Randolph Totter, Ph.D., January 23, 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-09-01

This document is a transcript of an interview of Dr. John Randolph Tottler by representatives of the US DOE Office of Human Radiation Experiments. Dr. Tottler was selected for this interview because of his career with the Atomic Energy Commission Division of Biology and Medicine (DBM), particularly as its director from 1967 to 1972. After a short biographical sketch Dr. Tottler discusses his remembrances on a wide range topics including nucleic acid and leukemia research at Oak Ridge, AEC biochemistry training in South America, DBM`s research focus on radiation effects, early leadership of DBM, relations with the US Public Healthmore » Service, controversies on low-level radiation, iodine from fallout, on John Gofman, and Project Plowshare, funding for AEC Research Programs and for international research, testicular irradiation of prisoners in Washington State and Oregon, Plutonium injections, ethics of government radiation research, and opinions of public misperceptions about radiation and cancer.« less

Radiative and Dynamical Feedbacks Limit the Climate Response to Extremely Large Volcanic Eruptions

NASA Astrophysics Data System (ADS)

Wade, D. C.; Vidal, C. M.; Keeble, J. M.; Griffiths, P. T.; Archibald, A. T.

2017-12-01

Explosive volcanic eruptions are a major cause of chemical and climatic perturbations to the atmosphere, injecting chemically and radiatively active species such as sulfur dioxide (SO2) into the stratosphere. The rate determining step for sulfate aerosol production is SO2 + OH +M → HSO3 +M. This means that chemical feedbacks on the hydroxyl radical, OH, can modulate the production rate of sulfate aerosol and hence the climate effects of large volcanic eruptions. Radiative feedbacks due to aerosols, ozone and sulfur dioxide and subsequent dynamical changes also affect the evolution of the aerosol cloud. Here we assess the role of radiative and chemical feedbacks on sulfate aerosol production using UM-UKCA, a chemistry-climate model coupled to GLOMAP, a prognostic modal aerosol model. A 200 Tg (10x Pinatubo) emission scenario is investigated. Accounting for radiative feedbacks, the SO2 lifetime is 55 days compared to 26 days in the baseline 20 Tg (1x Pinatubo) simulation. By contrast, if all radiative feedbacks are neglected the lifetime is 73 days. Including radiative feedbacks reduces the SO2 lifetime: heating of the lower stratosphere by aerosol increases upwelling and increases transport of water vapour across the tropopause, increasing OH concentrations. The maximum effective radius of the aerosol particles increases from 1.09 µm to 1.34 µm as the production of aerosol is quicker. Larger and fewer aerosol particles are produced which are less effective at scattering shortwave radiation and will more quickly sediment from the stratosphere. As a result, the resulting climate cooling by the eruption will be less strong when accounting for these radiative feedbacks. We illustrate the consequences of these effects for the 1257 Samalas eruption, the largest common era volcanic eruption, using UM-UKCA in a coupled atmosphere-ocean configuration. As a potentially halogen rich eruption, we investigate the differing ozone response to halogen-rich and halogen

Intensity Modulated Radiation Therapy for Early-Stage Primary Gastric Diffuse Large B-Cell Lymphoma: Dosimetric Analysis, Clinical Outcome, and Quality of Life

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xin; Fang, Hui; Tian, Yuan

Purpose: To evaluate the dosimetric superiority, efficacy, toxicity, and quality of life (QOL) data of intensity modulated radiation therapy (IMRT) in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL). Methods and Materials: Forty-six consecutive patients with early-stage PG-DLBCL underwent IMRT after chemotherapy. The majority of patients (61.5%) were subclassified as the non-germinal center B cell–like subtype. Dosimetric parameters of the planning target volume (PTV) and organs at risk were assessed. Survival rates were depicted with the Kaplan-Meier method and compared with the log-rank test. Quality of life was evaluated using the QLQ-C30-STO22 questionnaires at the last follow-up contact. Results: Themore » median PTV mean dose was 41.6 Gy. Only 0.73% of the PTV received <95% of the prescribed dose, indicating excellent target coverage. The median kidney V20 and liver V30 were 14.1% and 16.1%, respectively. The 5-year overall survival (OS), progression-free survival, and locoregional control rates for all patients were 80.4%, 75.0%, and 93.2%, respectively. Stage, lactate dehydrogenase level, and immunophenotype were significant prognostic factors for OS, and only stage was a significant factor for locoregional control. Consolidation IMRT in patients with complete response after chemotherapy resulted in significantly better OS and progression-free survival than salvage IMRT in patients with non-complete response. Two of 8 patients who had chronic liver disease experienced grade 4 or grade 5 acute hepatic failure after 4 to 5 cycles of rituximab-based chemotherapy and IMRT (40 Gy). No other serious acute or late toxicity was observed. The long-term global and functional QOL scales were excellent, with negligible symptom scales. Conclusions: Intensity modulated radiation therapy yielded excellent target coverage and critical tissue sparing and achieved favorable outcomes with acceptable toxicity and good long-term QOL in early

The early response during the interaction of fungal phytopathogen and host plant.

PubMed

Shen, Yilin; Liu, Na; Li, Chuang; Wang, Xin; Xu, Xiaomeng; Chen, Wan; Xing, Guozhen; Zheng, Wenming

2017-05-01

Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum , rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding. © 2017 The Authors.

The early response during the interaction of fungal phytopathogen and host plant

PubMed Central

Shen, Yilin; Liu, Na; Li, Chuang; Wang, Xin; Xu, Xiaomeng; Chen, Wan; Xing, Guozhen

2017-01-01

Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum, rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding. PMID:28469008

Comparison of the X-radiation, drug and ultraviolet-radiation responses of clones isolated from a human colorectal tumor cell line.

PubMed

Qutob, Sami S; Multani, Asha S; Pathak, S; Feng, Y; Kendal, Wayne S; Ng, Cheng E

2004-03-01

We isolated several clones with a wide range of responses to X radiation from an unirradiated human colorectal (HCT 116) tumor cell line. The responses of one of these clones (HCT116-Clone10) and nine other clones to either fractionated or acute (i.e. single, nonfractionated doses) X irradiation in vitro was similar to that of the parental cell line. By contrast, after the same types of treatment, another clone (HCT116-Clone2) manifested a significantly increased survival whereas a third clone (HCT116-CloneK) manifested a significantly decreased survival relative to the parental cell line. This suggested that they were, respectively, a radioresistant and a radiosensitive clone. All three clones (clones 2, 10, K) retained their tumorigenic phenotype and formed tumors in nude mice. G-banding studies demonstrated that they were of human origin and were derived from the same parental cell line. The metaphases of HCT116-Clone2 demonstrated features commonly associated with genomic instability (i.e. mitotic catastrophe including chromosome and chromatid breaks, dicentrics and additional nonclonal markers). Data obtained by quantitative fluorescence in situ hybridization (Q- FISH) analysis failed to demonstrate any apparent correlation between the radiosensitivity and the relative telomere content of these three clones. Interestingly, HCT116-CloneK was the most resistant to several chemotherapeutic drugs (topotecan, camptothecin, etoposide and cisplatin) with diverse mechanisms of action. Also, there were no significant differences in the survivals of the three clones after treatment with UV radiation. Because of the lack of overlap among the relative sensitivities of these clones to X radiation, chemotherapeutic drugs and UV radiation, these clones may be useful models for evaluating the genetic basis of the response of human tumor cells to these treatment agents both in vitro and in vivo.

Identification of conserved pathways of DNA-damage response and radiation protection by genome-wide RNAi.

PubMed

van Haaften, Gijs; Romeijn, Ron; Pothof, Joris; Koole, Wouter; Mullenders, Leon H F; Pastink, Albert; Plasterk, Ronald H A; Tijsterman, Marcel

2006-07-11

Ionizing radiation is extremely harmful for human cells, and DNA double-strand breaks (DSBs) are considered to be the main cytotoxic lesions induced. Improper processing of DSBs contributes to tumorigenesis, and mutations in DSB response genes underlie several inherited disorders characterized by cancer predisposition. Here, we performed a comprehensive screen for genes that protect animal cells against ionizing radiation. A total of 45 C. elegans genes were identified in a genome-wide RNA interference screen for increased sensitivity to ionizing radiation in germ cells. These genes include orthologs of well-known human cancer predisposition genes as well as novel genes, including human disease genes not previously linked to defective DNA-damage responses. Knockdown of eleven genes also impaired radiation-induced cell-cycle arrest, and seven genes were essential for apoptosis upon exposure to irradiation. The gene set was further clustered on the basis of increased sensitivity to DNA-damaging cancer drugs cisplatin and camptothecin. Almost all genes are conserved across animal phylogeny, and their relevance for humans was directly demonstrated by showing that their knockdown in human cells results in radiation sensitivity, indicating that this set of genes is important for future cancer profiling and drug development.

Response of different regional online coupled models to aerosol-radiation interactions

NASA Astrophysics Data System (ADS)

Forkel, Renate; Balzarini, Alessandra; Brunner, Dominik; Baró, Rocio; Curci, Gabriele; Hirtl, Marcus; Honzak, Luka; Jiménez-Guerrero, Pedro; Jorba, Oriol; Pérez, Juan L.; Pirovano, Guido; San José, Roberto; Schröder, Wolfram; Tuccella, Paolo; Werhahn, Johannes; Wolke, Ralf; Žabkar, Rahela

2016-04-01

The importance of aerosol-meteorology interactions and their representation in online coupled regional atmospheric chemistry-meteorology models was investigated in COST Action ES1004 (EuMetChem, http://eumetchem.info/). Case study results from different models (COSMO-Muscat, COSMO-ART, and different configurations of WRF-Chem), which were applied for Europe as a coordinated exercise for the year 2010, are analyzed with respect to inter-model variability and the response of the different models to direct and indirect aerosol-radiation interactions. The main focus was on two episodes - the Russian heat wave and wildfires episode in July/August 2010 and a period in October 2010 with enhanced cloud cover and rain and including an of Saharan dust transport to Europe. Looking at physical plausibility the decrease in downward solar radiation and daytime temperature due to the direct aerosol effect is robust for all model configurations. The same holds for the pronounced decrease in cloud water content and increase in solar radiation for cloudy conditions and very low aerosol concentrations that was found for WRF-Chem when aerosol cloud interactions were considered. However, when the differences were tested for statistical significance no significant differences in mean solar radiation and mean temperature between the baseline case and the simulations including the direct and indirect effect from simulated aerosol concentrations were found over Europe for the October episode. Also for the fire episode differences between mean temperature and radiation from the simulations with and without the direct aerosol effect were not significant for the major part of the modelling domain. Only for the region with high fire emissions in Russia, the differences in mean solar radiation and temperature due to the direct effect were found to be significant during the second half of the fire episode - however only for a significance level of 0.1. The few observational data indicate that

Modeling Space Radiation with Radiomimetic Agent Bleomycin

NASA Technical Reports Server (NTRS)

Lu, Tao

2017-01-01

Space radiation consists of proton and helium from solar particle events (SPE) and high energy heavy ions from galactic cosmic ray (GCR). This mixture of radiation with particles at different energy levels has different effects on biological systems. Currently, majority studies of radiation effects on human were based on single-source radiation due to the limitation of available method to model effects of space radiation on living organisms. While NASA Space Radiation Laboratory is working on advanced switches to make it possible to have a mixed field radiation with particles of different energies, the radiation source will be limited. Development of an easily available experimental model for studying effects of mixed field radiation could greatly speed up our progress in our understanding the molecular mechanisms of damage and responses from exposure to space radiation, and facilitate the discovery of protection and countermeasures against space radiation, which is critical for the mission to Mars. Bleomycin, a radiomimetic agent, has been widely used to study radiation induced DNA damage and cellular responses. Previously, bleomycin was often compared to low low Linear Energy Transfer (LET) gamma radiation without defined characteristics. Our recent work demonstrated that bleomycin could induce complex clustered DNA damage in human fibroblasts that is similar to DNA damage induced by high LET radiation. These type of DNA damage is difficult to repair and can be visualized by gamma-H2Ax staining weeks after the initial insult. The survival ratio between early and late plating of human fibroblasts after bleomycin treatment is between low LET and high LET radiation. Our results suggest that bleomycin induces DNA damage and other cellular stresses resembling those resulted from mixed field radiation with both low and high LET particles. We hypothesize that bleomycin could be used to mimic space radiation in biological systems. Potential advantages and limitations of

Ionizing Radiation-Induced Responses in Human Cells with Differing TP53 Status

PubMed Central

Mirzayans, Razmik; Andrais, Bonnie; Scott, April; Wang, Ying W.; Murray, David

2013-01-01

Ionizing radiation triggers diverse responses in human cells encompassing apoptosis, necrosis, stress-induced premature senescence (SIPS), autophagy, and endopolyploidy (e.g., multinucleation). Most of these responses result in loss of colony-forming ability in the clonogenic survival assay. However, not all modes of so-called clonogenic cell “death” are necessarily advantageous for therapeutic outcome in cancer radiotherapy. For example, the crosstalk between SIPS and autophagy is considered to influence the capacity of the tumor cells to maintain a prolonged state of growth inhibition that unfortunately can be succeeded by tumor regrowth and disease recurrence. Likewise, endopolyploid giant cells are able to segregate into near diploid descendants that continue mitotic activities. Herein we review the current knowledge on the roles that the p53 and p21WAF1 tumor suppressors play in determining the fate of human fibroblasts (normal and Li-Fraumeni syndrome) and solid tumor-derived cells after exposure to ionizing radiation. In addition, we discuss the important role of WIP1, a p53-regulated oncogene, in the temporal regulation of the DNA damage response and its contribution to p53 dynamics post-irradiation. This article highlights the complexity of the DNA damage response and provides an impetus for rethinking the nature of cancer cell resistance to therapeutic agents. PMID:24232458

The Global Statistical Response of the Outer Radiation Belt During Geomagnetic Storms

NASA Astrophysics Data System (ADS)

Murphy, K. R.; Watt, C. E. J.; Mann, I. R.; Jonathan Rae, I.; Sibeck, D. G.; Boyd, A. J.; Forsyth, C. F.; Turner, D. L.; Claudepierre, S. G.; Baker, D. N.; Spence, H. E.; Reeves, G. D.; Blake, J. B.; Fennell, J.

2018-05-01

Using the total radiation belt electron content calculated from Van Allen Probe phase space density, the time-dependent and global response of the outer radiation belt during storms is statistically studied. Using phase space density reduces the impacts of adiabatic changes in the main phase, allowing a separation of adiabatic and nonadiabatic effects and revealing a clear modality and repeatable sequence of events in storm time radiation belt electron dynamics. This sequence exhibits an important first adiabatic invariant (μ)-dependent behavior in the seed (150 MeV/G), relativistic (1,000 MeV/G), and ultrarelativistic (4,000 MeV/G) populations. The outer radiation belt statistically shows an initial phase dominated by loss followed by a second phase of rapid acceleration, while the seed population shows little loss and immediate enhancement. The time sequence of the transition to the acceleration is also strongly μ dependent and occurs at low μ first, appearing to be repeatable from storm to storm.

Perceived early-life maternal care and the cortisol response to repeated psychosocial stress.

PubMed

Engert, Veronika; Efanov, Simona I; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C

2010-11-01

In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic-pituitary-adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group.

Effectiveness of Community-Based Early Intervention Based on Pivotal Response Treatment

ERIC Educational Resources Information Center

Smith, Isabel M.; Flanagan, Helen E.; Garon, Nancy; Bryson, Susan E.

2015-01-01

Preschoolers (n = 118) with autism spectrum disorder (ASD) participated in this prospective effectiveness study of an early intervention program. Treatment entailed parent training and therapist-implemented components, incorporating Pivotal Response Treatment and Positive Behaviour Support. Standardized ability and behavioural measures were…

Effects of a fire response trait on diversification in replicated radiations.

PubMed

Litsios, Glenn; Wüest, Rafael O; Kostikova, Anna; Forest, Félix; Lexer, Christian; Linder, H Peter; Pearman, Peter B; Zimmermann, Niklaus E; Salamin, Nicolas

2014-02-01

Fire has been proposed as a factor explaining the exceptional plant species richness found in Mediterranean regions. A fire response trait that allows plants to cope with frequent fire by either reseeding or resprouting could differentially affect rates of species diversification. However, little is known about the generality of the effects of differing fire response on species evolution. We study this question in the Restionaceae, a family that radiated in Southern Africa and Australia. These radiations occurred independently and represent evolutionary replicates. We apply Bayesian approaches to estimate trait-specific diversification rates and patterns of climatic niche evolution. We also compare the climatic heterogeneity of South Africa and Australia. Reseeders diversify faster than resprouters in South Africa, but not in Australia. We show that climatic preferences evolve more rapidly in reseeder lineages than in resprouters and that the optima of these climatic preferences differ between the two strategies. We find that South Africa is more climatically heterogeneous than Australia, independent of the spatial scale we consider. We propose that rapid shifts between states of the fire response trait promote speciation by separating species ecologically, but this only happens when the landscape is sufficiently heterogeneous. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

In vivo space radiation-induced non-targeted responses: late effects on molecular signaling in mitochondria.

PubMed

Jain, Mohit R; Li, Min; Chen, Wei; Liu, Tong; de Toledo, Sonia M; Pandey, Badri N; Li, Hong; Rabin, Bernard M; Azzam, Edouard I

2011-06-01

The lack of clear knowledge about space radiation-induced biological effects has been singled out as the most important factor limiting the prediction of radiation risk associated with human space exploration. The expression of space radiation-induced non-targeted effects is thought to impact our understanding of the health risks associated with exposure to low fluences of particulate radiation encountered by astronauts during prolonged space travel. Following a brief review of radiation-induced bystander effects and the growing literature for the involvement of oxidative metabolism in their expression, we show novel data on the induction of in vivo non-targeted effects following exposure to 1100 MeV/nucleon titanium ions. Analyses of proteins by two-dimensional gel electrophoresis in non-targeted liver of cranially-irradiated Sprague Dawley rats revealed that the levels of key proteins involved in mitochondrial fatty acid metabolism are decreased. In contrast, those of proteins involved in various cellular defense mechanisms, including antioxidation, were increased. These data contribute to our understanding of the mechanisms underlying the biological responses to space radiation, and support the involvement of mitochondrial processes in the expression of radiation induced non-targeted effects. Significantly, they reveal the cross-talk between propagated stressful effects and induced adaptive responses. Together, with the accumulating data in the field, our results may help reduce the uncertainty in the assessment of the health risks to astronauts. They further demonstrate that 'network analyses' is an effective tool towards characterizing the signaling pathways that mediate the long-term biological effects of space radiation.

Improvement and Analysis of the Radiation Response of RADFET Dosimeters

DTIC Science & Technology

1992-06-15

TLD ), silicon p-i-n diode responses and silicon calorimetry (AWE Dosimetry Service). Intensive preparations were made by REM and the experiments were...SUB-GROUP dose: RADFET : tactical dosimetry silicon : metal-oxide- 0705 emiconductor (MOS) field effect transistor (FET) : silicon Idioxide space...1.1 Principle of a dosimetry system, based on the RADFET (radiation-sensitive field-effect transistor) (a) microscopic cross-section of chip (b) chip

The bradykinin B2 receptor in the early immune response against Listeria infection.

PubMed

Kaman, Wendy E; Wolterink, Arthur F W M; Bader, Michael; Boele, Linda C L; van der Kleij, Desiree

2009-02-01

The endogenous danger signal bradykinin was recently found implicated in the development of immunity against parasites via dendritic cells. We here report an essential role of the B(2) (B(2)R) bradykinin receptor in the early immune response against Listeria infection. Mice deficient in B(2)R (B(2)R(-/-) mice) were shown to suffer from increased hepatic bacterial burden and concomitant dramatic weight loss during infection with Listeria monocytogenes. Levels of cytokines known to play a pivotal role in the early phase immune response against L. monocytogenes, IL-12p70 and IFN-gamma, were reduced in B(2)R(-/-) mice. To extend these findings to the human system, we show that bradykinin potentiates the production of IL-12p70 in human monocyte-derived dendritic cells. Thus, we show that bradykinin and the B(2)R play a role in early innate immune functions during bacterial infection.

UV light-induced survival response in a highly radiation-resistant isolate of the Moraxella-acinetobacter group

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keller, L.C.; Thompson, T.L.; Maxcy, R.B.

1982-02-01

A highly radiation-resistant member of the Moraxella-Acinetobacter group, isolate 4, obtained from meat, was studied to determine the effect of preexposure to UV radiation on subsequent UV light resistance. Cultures that were preexposed to UV light and incubated for a short time in plate count broth exhibited increased survival of a UV light challenge dose. This response was inhibited in the presence of chloramphenicol. Frequencies of mutation to streptomycin, trimethoprim, and sulfanilamide resistance remained the same after the induction of this survival response and were not altered by treatment with mutagens, with the exception of mutation to streptomycin resistance aftermore » ..gamma..-irradiation or nitrosoguanidine or methyl methane sulfonate treatment. The results indicated that isolate 4 has a UV light-inducible UV light resistance mechanism which is not associated with increased mutagenesis. The characteristics of the radiation resistance response in this organism are similar to those of certain other common food contaminants. Therefore, considered as part of the total microflora of meat, isolate 4 and the other radiation-resistant Moraxella-Acinetobacter isolates should not pose unique problems in a proposed radappertizaton process.« less

[Inflammasome and its role in immunological and inflammatory response at early stage of burns].

PubMed

Zhang, Fang; Li, Jiahui; Xia, Zhaofan

2014-06-01

Inflammasomes are large multi-protein complexes that serve as a platform for caspase-1 activation, and this process induces subsequent maturation and secretion of the proinflammatory cytokines IL-1β and IL-18, as well as pyroptosis. As an important component of the innate immune system, early activation of inflammasomes in a variety of immune cell subsets can mediate inflammatory response and immunological conditions after burn injury. Here, we review the current knowledge of inflammasomes and its role in immunological and inflammatory response at the early stage of burn injury.

Initial Human Response to Nuclear Radiation

DTIC Science & Technology

1982-04-01

radiation from a linear accelerator . Victim A , age 31, received a dose of 100 rads; victim B, age 29... The radiation has always been in the million-electron- volt range, usually from a cobalt 60 source but sometimes using linear accelerators prouucing up...more recent medical experience, Appendix B presents comments by a radiation oncologist on the

Gene Expression Profiling in Response to Ultraviolet Radiation in Maize Genotypes with Varying Flavonoid Content1[w

PubMed Central

Casati, Paula; Walbot, Virginia

2003-01-01

Microarray hybridization was used to assess acclimation responses to four UV regimes by near isogenic maize (Zea mays) lines varying in flavonoid content. We found that 355 of the 2,500 cDNAs tested were regulated by UV radiation in at least one genotype. Among these, 232 transcripts are assigned putative functions, whereas 123 encode unknown proteins. UV-B increased expression of stress response and ribosomal protein genes, whereas photosynthesis-associated genes were down-regulated; lines lacking UV-absorbing pigments had more dramatic responses than did lines with these pigments, confirming the shielding role of these compounds. Sunlight filtered to remove UV-B or UV-B plus UV-A resulted in significant expression changes in many genes not previously associated with UV responses. Some pathways regulated by UV radiation are shared with defense, salt, and oxidative stresses; however, UV-B radiation can activate additional pathways not shared with other stresses. PMID:12913132

The tonic response to the infant knee jerk as an early sign of cerebral palsy.

PubMed

Hamer, Elisa G; La Bastide-Van Gemert, Sacha; Boxum, Anke G; Dijkstra, Linze J; Hielkema, Tjitske; Jeroen Vermeulen, R; Hadders-Algra, Mijna

2018-04-01

Early identification of infants at risk of cerebral palsy (CP) is desirable in order to provide early intervention. We previously demonstrated differences in knee jerk responses between 3-month-old high risk and typically developing infants. To improve early identification by investigating whether the presence of tonic responses (continuous muscle activity occurring after the typical phasic response), clonus or contralateral responses to the knee jerk during infancy is associated with CP. Longitudinal EMG-study. We included 34 high-risk infants (median gestational age 31.9 weeks) who participated in the LEARN2MOVE 0-2 years trial. Video-recorded knee jerk EMG-assessments were performed during infancy (1-4 times). Developmental outcome was assessed at 21 months corrected age (CA). Binomial generalized estimating equations models with repeated measurements were fitted using predictor variables. Infants who later were diagnosed with CP (n = 18) showed more often than infants who were not diagnosed with CP i) tonic responses - from 4 months CA onwards, ii) clonus - from 13 months CA onwards, and iii) contralateral responses - from 15 months CA onwards. The main limitation is the relatively small sample size. The assessment of tonic responses to the knee jerk using EMG may be a valuable add-on tool to appraise a high risk of CP. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of UV-B screening compounds in response to variation in ambient levels of UV-B radiation

NASA Astrophysics Data System (ADS)

Sullivan, Joe H.; Xu, Chenping; Gao, Wei; Slusser, James R.

2005-08-01

The induction of UV-B screening compounds in response to exposure to UV-B radiation is a commonly reported response and is generally considered to be an adaptive response of plants for protection from UVinduced damage. However, a number of questions remain to be answered including the importance of qualitative and localization differences among species in providing protection, indirect consequences of changes in leaf secondary chemistry on ecological processes and the dose response of metabolite accumulation. In this study we utilized UV monitoring data provided on site by the USDA UV-B Monitoring and Research Program to monitor the changes in UV-screening compounds in soybeans under a range of UV-B levels due to natural variation in ambient UV-B radiation. Soybean cultivars Essex, Clark and Clark-magenta, an isoline of Clark that produces minimal levels of flavonols, were grown beneath shelters covered either with polyester to block most UV-B radiation or teflon which is nearly transparent in the UV range and harvested at regular intervals for pigment and protein analysis. Daily levels of weighted UV-B varied from <1 to >7 kJ m-2. Increases in UV-screening compounds showed a positive dose response to UV-B radiation in all cultivars with Essex showing the steepest dose response. UV-A also induced screening compounds in all species The hydroxycinnimates of the magenta isoline showed a steep dose response to UV-A and a rather constant (non dose specific) but small additional increment in response to UV-B. The Clark isoline, which produced primarily the flavonol quercetin, showed a dose response to UV-B intermediate between that of Clark-magenta and Essex. All three cultivars show similar tolerance to UV-B in field conditions indicating that UV-induced pigment production is adequate to protect them from excessive UV-B damage.

Proteomic identification of early salicylate- and flg22-responsive redox-sensitive proteins in Arabidopsis

PubMed Central

Liu, Pei; Zhang, Huoming; Yu, Boying; Xiong, Liming; Xia, Yiji

2015-01-01

Accumulation of reactive oxygen species (ROS) is one of the early defense responses against pathogen infection in plants. The mechanism about the initial and direct regulation of the defense signaling pathway by ROS remains elusive. Perturbation of cellular redox homeostasis by ROS is believed to alter functions of redox-sensitive proteins through their oxidative modifications. Here we report an OxiTRAQ-based proteomic study in identifying proteins whose cysteines underwent oxidative modifications in Arabidopsis cells during the early response to salicylate or flg22, two defense pathway elicitors that are known to disturb cellular redox homeostasis. Among the salicylate- and/or flg22-responsive redox-sensitive proteins are those involved in transcriptional regulation, chromatin remodeling, RNA processing, post-translational modifications, and nucleocytoplasmic shuttling. The identification of the salicylate-/flg22-responsive redox-sensitive proteins provides a foundation from which further study can be conducted toward understanding biological significance of their oxidative modifications during the plant defense response. PMID:25720653

Accelerated Partial Breast Irradiation Using Only Intraoperative Electron Radiation Therapy in Early Stage Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maluta, Sergio; Dall'Oglio, Stefano, E-mail: stefano.dalloglio@ospedaleuniverona.it; Marciai, Nadia

2012-10-01

Background: We report the results of a single-institution, phase II trial of accelerated partial breast irradiation (APBI) using a single dose of intraoperative electron radiation therapy (IOERT) in patients with low-risk early stage breast cancer. Methods and Materials: A cohort of 226 patients with low-risk, early stage breast cancer were treated with local excision and axillary management (sentinel node biopsy with or without axillary node dissection). After the surgeon temporarily reapproximated the excision cavity, a dose of 21 Gy using IOERT was delivered to the tumor bed, with a margin of 2 cm laterally. Results: With a mean follow-up ofmore » 46 months (range, 28-63 months), only 1 case of local recurrence was reported. The observed toxicity was considered acceptable. Conclusions: APBI using a single dose of IOERT can be delivered safely in women with early, low-risk breast cancer in carefully selected patients. A longer follow-up is needed to ascertain its efficacy compared to that of the current standard treatment of whole-breast irradiation.« less

Vulnerability and behavioral response to ultraviolet radiation in the components of a foliar mite prey-predator system.

PubMed

Tachi, Fuyuki; Osakabe, Masahiro

2012-12-01

Ambient ultraviolet-B (UVB) radiation impacts plant-dwelling arthropods including herbivorous and predatory mites. However, the effects of UVB on prey-predator systems, such as that between the herbivorous spider mite and predatory phytoseiid mite, are poorly understood. A comparative study was conducted to determine the vulnerability and behavioral responses of these mites to ultraviolet (UV) radiation. First, we analyzed dose-response (cumulative irradiance-mortality) curves for the eggs of phytoseiid mites (Neoseiulus californicus, Neoseiulus womersleyi, and Phytoseiulus persimilis) and the spider mite (Tetranychus urticae) to UVB radiation from a UV lamp. This indicated that the phytoseiid mites were more vulnerable than the spider mite, although P. persimilis was slightly more tolerant than the other two phytoseiid mites. Second, we compared the avoidance behavior of adult female N. californicus and two spider mite species (T. urticae, a lower leaf surface user; Panonychus citri, an upper leaf surface user) in response to solar UV and visible light. N. californicus actively avoided both types of radiation, whereas P. citri showed only minimal avoidance behavior. T. urticae actively avoided UV as well as N. californicus but exhibited a slow response to visible light as well as P. citri. Such variation in vulnerability and avoidance behavior accounts for differences in the species adaptations to solar UVB radiation. This may be the primary factor determining habitat use among these mites on host plant leaves, subsequently affecting accessibility by predators and also intraguild competition.

Vulnerability and behavioral response to ultraviolet radiation in the components of a foliar mite prey-predator system

NASA Astrophysics Data System (ADS)

Tachi, Fuyuki; Osakabe, Masahiro

2012-12-01

Ambient ultraviolet-B (UVB) radiation impacts plant-dwelling arthropods including herbivorous and predatory mites. However, the effects of UVB on prey-predator systems, such as that between the herbivorous spider mite and predatory phytoseiid mite, are poorly understood. A comparative study was conducted to determine the vulnerability and behavioral responses of these mites to ultraviolet (UV) radiation. First, we analyzed dose-response (cumulative irradiance-mortality) curves for the eggs of phytoseiid mites ( Neoseiulus californicus, Neoseiulus womersleyi, and Phytoseiulus persimilis) and the spider mite ( Tetranychus urticae) to UVB radiation from a UV lamp. This indicated that the phytoseiid mites were more vulnerable than the spider mite, although P. persimilis was slightly more tolerant than the other two phytoseiid mites. Second, we compared the avoidance behavior of adult female N. californicus and two spider mite species ( T. urticae, a lower leaf surface user; Panonychus citri, an upper leaf surface user) in response to solar UV and visible light. N. californicus actively avoided both types of radiation, whereas P. citri showed only minimal avoidance behavior. T. urticae actively avoided UV as well as N. californicus but exhibited a slow response to visible light as well as P. citri. Such variation in vulnerability and avoidance behavior accounts for differences in the species adaptations to solar UVB radiation. This may be the primary factor determining habitat use among these mites on host plant leaves, subsequently affecting accessibility by predators and also intraguild competition.

Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daila S. Gridley, PhD

2012-03-30

FINAL TECHNICAL REPORT Supported by the Low Dose Radiation Research Program, Office of Science U.S. Department of Energy Grant No. DE-FG02-07ER64345 Project ID: 0012965 Award Register#: ER64345 Project Manager: Noelle F. Metting, Sc.D. Phone: 301-903-8309 Division SC-23.2 noelle.metting@science.doe.gov Submitted March 2012 To: https://www.osti.gov/elink/241.3.jsp Title: Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation PI: Daila S. Gridley, Ph.D. Human low dose radiation data have been derived primarily from studies of space and airline flight personnel, nuclear plant workers and others exposed occupationally, as well as victims in the vicinity of atomic bomb explosions. The findingsmore » remain inconclusive due to population inconsistencies and complex interactions among total dose, dose rate, radiation quality and age at exposure. Thus, safe limits for low dose occupational irradiation are currently based on data obtained with doses far exceeding the levels expected for the general population and health risks have been largely extrapolated using the linear-nonthreshold dose-response model. The overall working hypothesis of the present study is that priming with low dose, low-linear energy transfer (LET) radiation can ameliorate the response to acute high-dose radiation exposure. We also propose that the efficacy of low-dose induced protection will be dependent upon the form and regimen of the high-dose exposure: photons versus protons versus simulated solar particle event protons (sSPE). The emphasis has been on gene expression and function of CD4+ T helper (Th) lymphocytes harvested from spleens of whole-body irradiated C57BL/6 mice, a strain that provides the genetic background for many genetically engineered strains. Evaluations of the responses of other selected cells, tissues such as skin, and organs such as lung, liver and brain were also initiated (partially funded by other sources). The long-term goal is to provide

Risk of Fatal Cerebrovascular Accidents after External Beam Radiation Therapy for Early Stage Glottic Larynx Cancer

PubMed Central

Swisher-McClure, Samuel; Mitra, Nandita; Lin, Alexander; Ahn, Peter; Wan, Fei; O’Malley, Bert; Weinstein, Gregory S.; Bekelman, Justin E.

2013-01-01

Background This study compared the risk of fatal cerebrovascular accidents (CVA) in patients with early stage glottic larynx cancer receiving surgery or external beam radiation therapy (EBRT). Methods and Materials Using a competing risks survival analysis, we compared the risk of death due to CVA among patients with early stage glottic larynx cancer receiving surgery or EBRT in the SEER database. Results The cumulative incidence of fatal CVA at 15 years was higher in patients receiving EBRT (2.8 %; 95% CI 2.3%–3.4%) compared to surgery (1.5 %; 95% CI 0.8 %–2.3%, p= 0.024). In multivariable competing risks regression models, EBRT remained associated with an increased risk of fatal CVA compared to surgery (adjusted HR 1.75; 95% CI 1.04–2.96, p= 0.037). Conclusion Treatment of early stage glottic larynx cancer with EBRT was associated with a small increase in the risk of late fatal CVA events relative to surgery. PMID:23595858

Parallel Study of HEND, RAD, and DAN Instrument Response to Martian Radiation and Surface Conditions

NASA Technical Reports Server (NTRS)

Martiniez Sierra, Luz Maria; Jun, Insoo; Litvak, Maxim; Sanin, Anton; Mitrofanov, Igor; Zeitlin, Cary

2015-01-01

Nuclear detection methods are being used to understand the radiation environment at Mars. JPL (Jet Propulsion Laboratory) assets on Mars include: Orbiter -2001 Mars Odyssey [High Energy Neutron Detector (HEND)]; Mars Science Laboratory Rover -Curiosity [(Radiation Assessment Detector (RAD); Dynamic Albedo Neutron (DAN))]. Spacecraft have instruments able to detect ionizing and non-ionizing radiation. Instrument response on orbit and on the surface of Mars to space weather and local conditions [is discussed] - Data available at NASA-PDS (Planetary Data System).

Radiative-photochemical response of the mesosphere to dynamical forcing

NASA Technical Reports Server (NTRS)

Frederick, J. E.

1981-01-01

Combination of the chemical continuity equation for odd oxygen with the second law of thermodynamics yields analytic solutions which describe the coupled behavior of temperature and ozone perturbations in response to an externally specified forcing. The results appear in a form which allows easy physical interpretation of the coupling between radiative and photochemical processes. When the forcing is chosen to mimic a planetary scale wave, the theory shows that photochemical acceleration of radiative damping reduces the amplitude of the temperature perturbation by an amount which increases with the wave period. Although ozone fluctuations are anti-correlated with those in temperature, minima in ozone do not coincide exactly in longitude with temperature maxima. The percentage variation in ozone increases upward and is always larger than that in temperature at the same pressure. This demonstrates that variations in ozone on constant pressure surfaces may serve as a sensitive indicator of wave activity in the mesosphere.

Ultra Low-Dose Radiation: Stress Responses and Impacts Using Rice as a Grass Model

PubMed Central

Rakwal, Randeep; Agrawal, Ganesh Kumar; Shibato, Junko; Imanaka, Tetsuji; Fukutani, Satoshi; Tamogami, Shigeru; Endo, Satoru; Sahoo, Sarata Kumar; Masuo, Yoshinori; Kimura, Shinzo

2009-01-01

We report molecular changes in leaves of rice plants (Oryza sativa L. - reference crop plant and grass model) exposed to ultra low-dose ionizing radiation, first using contaminated soil from the exclusion zone around Chernobyl reactor site. Results revealed induction of stress-related marker genes (Northern blot) and secondary metabolites (LC-MS/MS) in irradiated leaf segments over appropriate control. Second, employing the same in vitro model system, we replicated results of the first experiment using in-house fabricated sources of ultra low-dose gamma (γ) rays and selected marker genes by RT-PCR. Results suggest the usefulness of the rice model in studying ultra low-dose radiation response/s. PMID:19399245

Vascular-mediated signalling involved in early phosphate stress response in plants.

PubMed

Zhang, Zhaoliang; Zheng, Yi; Ham, Byung-Kook; Chen, Jieyu; Yoshida, Akiko; Kochian, Leon V; Fei, Zhangjun; Lucas, William J

2016-04-04

Depletion of finite global rock phosphate (Pi) reserves will impose major limitations on future agricultural productivity and food security. Hence, modern breeding programmes seek to develop Pi-efficient crops with sustainable yields under reduced Pi fertilizer inputs. In this regard, although the long-term responses of plants to Pi stress are well documented, the early signalling events have yet to be elucidated. Here, we show plant tissue-specific responses to early Pi stress at the transcription level and a predominant role of the plant vascular system in this process. Specifically, imposition of Pi stress induces rapid and major changes in the mRNA population in the phloem translocation stream, and grafting studies have revealed that many hundreds of phloem-mobile mRNAs are delivered to specific sink tissues. We propose that the shoot vascular system acts as the site of root-derived Pi stress perception, and the phloem serves to deliver a cascade of signals to various sinks, presumably to coordinate whole-plant Pi homeostasis.

Early Cognitive Outcomes Following Proton Radiation in Pediatric Patients With Brain and Central Nervous System Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pulsifer, Margaret B., E-mail: mpulsifer@mgh.harvard.edu; Sethi, Roshan V.; Kuhlthau, Karen A.

Purpose: To report, from a longitudinal study, cognitive outcome in pediatric patients treated with proton radiation therapy (PRT) for central nervous system (CNS) tumors. Methods and Materials: Sixty patients receiving PRT for medulloblastoma (38.3%), gliomas (18.3%), craniopharyngioma (15.0%), ependymoma (11.7%), and other CNS tumors (16.7%) were administered age-appropriate measures of cognitive abilities at or near PRT initiation (baseline) and afterward (follow-up). Patients were aged ≥6 years at baseline to ensure consistency in neurocognitive measures. Results: Mean age was 12.3 years at baseline; mean follow-up interval was 2.5 years. Treatment included prior surgical resection (76.7%) and chemotherapy (61.7%). Proton radiation therapy included craniospinal irradiationmore » (46.7%) and partial brain radiation (53.3%). At baseline, mean Wechsler Full Scale IQ was 104.6; means of all 4 Index scores were also in the average range. At follow-up, no significant change was observed in mean Wechsler Full Scale IQ, Verbal Comprehension, Perceptual Reasoning/Organization, or Working Memory. However, Processing Speed scores declined significantly (mean 5.2 points), with a significantly greater decline for subjects aged <12 years at baseline and those with the highest baseline scores. Cognitive outcome was not significantly related to gender, extent of radiation, radiation dose, tumor location, histology, socioeconomic status, chemotherapy, or history of surgical resection. Conclusions: Early cognitive outcomes after PRT for pediatric CNS tumors are encouraging, compared with published outcomes from photon radiation therapy.« less

Microfluidics as a new tool in radiation biology.

PubMed

Lacombe, Jerome; Phillips, Shanna Leslie; Zenhausern, Frederic

2016-02-28

Ionizing radiations interact with molecules at the cellular and molecular levels leading to several biochemical modifications that may be responsible for biological effects on tissue or whole organisms. The study of these changes is difficult because of the complexity of the biological response(s) to radiations and the lack of reliable models able to mimic the whole molecular phenomenon and different communications between the various cell networks, from the cell activation to the macroscopic effect at the tissue or organismal level. Microfluidics, the science and technology of systems that can handle small amounts of fluids in confined and controlled environment, has been an emerging field for several years. Some microfluidic devices, even at early stages of development, may already help radiobiological research by proposing new approaches to study cellular, tissue and total-body behavior upon irradiation. These devices may also be used in clinical biodosimetry since microfluidic technology is frequently developed for integrating complex bioassay chemistries into automated user-friendly, reproducible and sensitive analyses. In this review, we discuss the use, numerous advantages, and possible future of microfluidic technology in the field of radiobiology. We will also examine the disadvantages and required improvements for microfluidics to be fully practical in radiation research and to become an enabling tool for radiobiologists and radiation oncologists. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Extracorporeal Shock Wave Therapy Suppresses the Early Proinflammatory Immune Response to a Severe Cutaneous Burn Injury

DTIC Science & Technology

2009-02-01

Burn wound model Mice were anaesthetised using isoflurane inha- lation. After shaving the dorsum, the exposed skin was washed gently with room...Extracorporeal shock wave therapy suppresses the early proinflammatory immune response to a severe cutaneous burn injury* Thomas A Davis, Alexander...S, Peoples GE, Tadaki D, Elster EA. Extracorporeal shock wave therapy suppresses the early proinflammatory immune response to a severe cutaneous burn

Perceived early-life maternal care and the cortisol response to repeated psychosocial stress

PubMed Central

Engert, Veronika; Efanov, Simona I.; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C.

2010-01-01

Background In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic–pituitary–adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. Methods In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Results Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Limitations Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. Conclusion We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group. PMID:20964960

Human response to high-background radiation environments on Earth and in space

NASA Astrophysics Data System (ADS)

Durante, M.; Manti, L.

2008-09-01

The main long-term objective of the space exploration program is the colonization of the planets of the Solar System. The high cosmic radiation equivalent dose rate represents an inescapable problem for the safe establishment of permanent human settlements on these planets. The unshielded equivalent dose rate on Mars ranges between 100 and 200 mSv/year, depending on the Solar cycle and altitude, and can reach values as high as 360 mSv/year on the Moon. The average annual effective dose on Earth is about 3 mSv, nearly 85% of which comes from natural background radiation, reduced to less than 1 mSv if man-made sources and the internal exposure to Rn daughters are excluded. However, some areas on Earth display anomalously high levels of background radiation, as is the case with thorium-rich monazite bearing sand deposits where values 200 400 times higher than the world average can be found. About 2% of the world’s population live above 3 km and receive a disproportionate 10% of the annual effective collective dose due to cosmic radiation, with a net contribution to effective dose by the neutron component which is 3 4 fold that at sea level. Thus far, epidemiological studies have failed to show any adverse health effects in the populations living in these terrestrial high-background radiation areas (HBRA), which provide an unique opportunity to study the health implications of an environment that, as closely as possibly achievable on Earth, resembles the chronic exposure of future space colonists to higher-than-normal levels of ionizing radiation. Chromosomal aberrations in the peripheral blood lymphocytes from the HBRA residents have been measured in several studies because chromosomal damage represents an early biomarker of cancer risk. Similar cytogenetic studies have been recently performed in a cohort of astronauts involved in single or repeated space flights over many years. The cytogenetic findings in populations exposed to high dose-rate background radiation

Longitudinal changes in gray matter regions after cranial radiation and comparative analysis with whole body radiation: a DTI study.

PubMed

Watve, Apurva; Gupta, Mamta; Khushu, Subash; Rana, Poonam

2018-06-01

Radiation-induced white matter changes are well known and vastly studied. However, radiation-induced gray matter alterations are still a research question. In the present study, these changes were assessed in a longitudinal manner using Diffusion Tensor Imaging (DTI) and further compared for cranial and whole body radiation exposure. Male mice (C57BL/6) were irradiated with cranial or whole body radiation followed by DTI study at 7T animal MRI system during predose, subacute and early delayed phases of radiation sickness. Fractional anisotropy (FA) and mean diffusivity (MD) values were obtained from brain's gray matter regions. Decreased FA with increased MD was observed prominently in animals exposed to cranial radiation showing most changes at 8 months post irradiation. However, whole body radiation induced FA changes were mostly observed at 1 month post irradiation as compared to controls. The differential response after whole body and cranial irradiation observed in the study depicts that radiation exposure of 5 Gy could induce permanent alterations in gray matter regions prominently as observed in Caudoputamen region at all the time points. Thus, our study has bolstered the role of DTI to probe microstructural changes in gray matter regions of brain after radiation exposure.

Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective.

PubMed

Harder, Jeffrey M; Braine, Catherine E; Williams, Pete A; Zhu, Xianjun; MacNicoll, Katharine H; Sousa, Gregory L; Buchanan, Rebecca A; Smith, Richard S; Libby, Richard T; Howell, Gareth R; John, Simon W M

2017-05-09

Various immune response pathways are altered during early, predegenerative stages of glaucoma; however, whether the early immune responses occur secondarily to or independently of neuronal dysfunction is unclear. To investigate this relationship, we used the Wld s allele, which protects from axon dysfunction. We demonstrate that DBA/2J .Wld s mice develop high intraocular pressure (IOP) but are protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes that otherwise occur early in DBA/2J glaucoma. Despite this, immune pathways are still altered in DBA/2J .Wld s mice. This suggests that immune changes are not secondary to RGC dysfunction or altered neuroglial interactions, but may be directly induced by the increased strain imposed by high IOP. One early immune response following IOP elevation is up-regulation of complement C3 in astrocytes of DBA/2J and DBA/2J. Wld s mice. Unexpectedly, because the disruption of other complement components, such as C1Q, is protective in glaucoma, C3 deficiency significantly increased the number of DBA/2J eyes with nerve damage and RGC loss at an early time point after IOP elevation. Transcriptional profiling of C3-deficient cultured astrocytes implicated EGFR signaling as a hub in C3-dependent responses. Treatment with AG1478, an EGFR inhibitor, also significantly increased the number of DBA/2J eyes with glaucoma at the same early time point. These findings suggest that C3 protects from early glaucomatous damage, a process that may involve EGFR signaling and other immune responses in the optic nerve head. Therefore, therapies that target specific components of the complement cascade, rather than global inhibition, may be more applicable for treating human glaucoma.

Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective

PubMed Central

Harder, Jeffrey M.; Braine, Catherine E.; Williams, Pete A.; Zhu, Xianjun; MacNicoll, Katharine H.; Sousa, Gregory L.; Buchanan, Rebecca A.; Smith, Richard S.; Howell, Gareth R.; John, Simon W. M.

2017-01-01

Various immune response pathways are altered during early, predegenerative stages of glaucoma; however, whether the early immune responses occur secondarily to or independently of neuronal dysfunction is unclear. To investigate this relationship, we used the Wlds allele, which protects from axon dysfunction. We demonstrate that DBA/2J.Wlds mice develop high intraocular pressure (IOP) but are protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes that otherwise occur early in DBA/2J glaucoma. Despite this, immune pathways are still altered in DBA/2J.Wlds mice. This suggests that immune changes are not secondary to RGC dysfunction or altered neuroglial interactions, but may be directly induced by the increased strain imposed by high IOP. One early immune response following IOP elevation is up-regulation of complement C3 in astrocytes of DBA/2J and DBA/2J.Wlds mice. Unexpectedly, because the disruption of other complement components, such as C1Q, is protective in glaucoma, C3 deficiency significantly increased the number of DBA/2J eyes with nerve damage and RGC loss at an early time point after IOP elevation. Transcriptional profiling of C3-deficient cultured astrocytes implicated EGFR signaling as a hub in C3-dependent responses. Treatment with AG1478, an EGFR inhibitor, also significantly increased the number of DBA/2J eyes with glaucoma at the same early time point. These findings suggest that C3 protects from early glaucomatous damage, a process that may involve EGFR signaling and other immune responses in the optic nerve head. Therefore, therapies that target specific components of the complement cascade, rather than global inhibition, may be more applicable for treating human glaucoma. PMID:28446616

Regulation of the Low Dose Radiation Paracrine-Specific Anchorage-Independent Growth Response by Annexin A2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weber, Thomas J.; Opresko, Lee K.; Waisman, David M.

2009-07-13

ABSTRACT-Here we identify release of annexin A2 into the culture medium in response to low dose X-ray radiation exposure and establish functional linkages to an established paracrine factor-mediated anchorage-independent growth response. Using a standard bicameral coculture model, we observe that annexin A2 levels associated with non-irradiated neighboring cells seeded in the lower chamber (annexin A2 silenced [shRNA] JB6 cells) are increased upon coculture with irradiated (10-50 cGy) JB6 cells seeded in the upper chamber, relative to coculture with sham exposed JB6 cells seeded in the upper chamber, suggesting that annexin A2 released into the medium is capable of communicating inmore » a paracrine fashion. Using a previously established coculture model, we observed that the paracrine factor-mediated anchorage-independent growth response to low dose X-ray radiation is markedly reduced when irradiated annexin A2 silenced (shRNA) JB6 cells are used, relative to coculture with irradiated annexin A2 competent vector control counterparts. These observations suggest that annexin A2 is functionally linked to the radiation paracrine factor-specific anchorage-independent growth response in JB6 cells.« less

The stress response: A radiation study section workshop

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The following manuscript represents the proceedings of a 1-day symposium held in Santa Fe, NM, on February 22, 1995 in conjunction with a regular meeting of the Radiation Study Section of the Division of Research Grants (DRG), National Institutes of Health (NIH). The purpose of the symposium was to educate Study Section members on various aspects of the heat-shock, or stress, response in mammalian systems and to inform them of the most recent developments in this area. The symposium was organized by Paul Strudler, the Scientific Review Administrator for the Radiation Study Section, and was co-chaired, and this report edited,more » by Eugene Gerner (University of Arizona, Tucson) and Peter Corry (Beaumont Hospital, Royal Oak, MI). The invited speakers, their affiliations and their general topics were Stuart Calderwood (Dana Farber Cancer Institute, Boston, tolerance and signal transduction), Michael Freeman (Vanderbilt University, Nashville, oxidative stress), Andrei Laszlo (Washington University, St. Louis, chaperones), Gloria Li (Memorial Sloan Kettering, New York, hsp-70), John Subjeck (Roswell Park Cancer Institute, Buffalo, hsp-110) and Lee Weber (University of Nevada, Reno, hsp-27). 97 refs.« less

American Society for Radiation Oncology (ASTRO) Survey of Radiation Biology Educators in U.S. and Canadian Radiation Oncology Residency Programs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenstein, Barry S., E-mail: barry.rosenstein@mssm.ed; Department of Radiation Oncology, New York University School of Medicine, New York, NY; Held, Kathryn D.

2009-11-01

Purpose: To obtain, in a survey-based study, detailed information on the faculty currently responsible for teaching radiation biology courses to radiation oncology residents in the United States and Canada. Methods and Materials: In March-December 2007 a survey questionnaire was sent to faculty having primary responsibility for teaching radiation biology to residents in 93 radiation oncology residency programs in the United States and Canada. Results: The responses to this survey document the aging of the faculty who have primary responsibility for teaching radiation biology to radiation oncology residents. The survey found a dramatic decline with time in the percentage of educatorsmore » whose graduate training was in radiation biology. A significant number of the educators responsible for teaching radiation biology were not fully acquainted with the radiation sciences, either through training or practical application. In addition, many were unfamiliar with some of the organizations setting policies and requirements for resident education. Freely available tools, such as the American Society for Radiation Oncology (ASTRO) Radiation and Cancer Biology Practice Examination and Study Guides, were widely used by residents and educators. Consolidation of resident courses or use of a national radiation biology review course was viewed as unlikely by most programs. Conclusions: A high priority should be given to the development of comprehensive teaching tools to assist those individuals who have responsibility for teaching radiation biology courses but who do not have an extensive background in critical areas of radiobiology related to radiation oncology. These findings also suggest a need for new graduate programs in radiobiology.« less

Early warning systems and rapid response to the deteriorating patient in hospital: A realist evaluation.

PubMed

McGaughey, Jennifer; O'Halloran, Peter; Porter, Sam; Trinder, John; Blackwood, Bronagh

2017-12-01

To test the Rapid Response Systems programme theory against actual practice components of the Rapid Response Systems implemented to identify those contexts and mechanisms which have an impact on the successful achievement of desired outcomes in practice. Rapid Response Systems allow deteriorating patients to be recognized using Early Warning Systems, referred early via escalation protocols and managed at the bedside by competent staff. Realist evaluation. The research design was an embedded multiple case study approach of four wards in two hospitals in Northern Ireland which followed the principles of Realist Evaluation. We used various mixed methods including individual and focus group interviews, observation of nursing practice between June-November 2010 and document analysis of Early Warning Systems audit data between May-October 2010 and hospital acute care training records over 4.5 years from 2003-2008. Data were analysed using NiVivo8 and SPPS. A cross-case analysis highlighted similar patterns of factors which enabled or constrained successful recognition, referral and response to deteriorating patients in practice. Key enabling factors were the use of clinical judgement by experienced nurses and the empowerment of nurses as a result of organizational change associated with implementation of Early Warning System protocols. Key constraining factors were low staffing and inappropriate skill mix levels, rigid implementation of protocols and culturally embedded suboptimal communication processes. Successful implementation of Rapid Response Systems was dependent on adopting organizational and cultural changes that facilitated staff empowerment, flexible implementation of protocols and ongoing experiential learning. © 2017 John Wiley & Sons Ltd.

Quantitative Proteomic Profiling of Early and Late Responses to Salicylic Acid in Cucumber Leaves

PubMed Central

Li, Liang; Shang, Qing-Mao

2016-01-01

Salicylic acid (SA) is an important phytohormone that plays vital regulatory roles in plant growth, development, and stress responses. However, studies on the molecular mechanism of SA, especially during the early SA responses, are lagging behind. In this study, we initiated a comprehensive isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to explore the early and late SA-responsive proteins in leaves of cucumber (Cucumis sativus L.) seedlings. Upon SA application through the roots, endogenous SA accumulated in cucumber leaves. By assaying the changes in marker gene expression and photosynthetic rate, we collected samples at 12 h and 72 h post treatment (hpt) to profile the early and late SA responsiveness, respectively. The iTRAQ assay followed by tandem mass spectrometry revealed 135 differentially expressed proteins (DEPs) at 12 hpt and 301 DEPs at 72 hpt. The functional categories for these SA-responsive proteins included in a variety of biochemical processes, including photosynthesis, redox homeostasis, carbohydrate and energy metabolism, lipid metabolism, transport, protein folding and modification, proteolysis, cell wall organization, and the secondary phenylpropanoid pathway. Conclusively, based on the abundant changes of these DEPs, together with their putative functions, we proposed a possible SA-responsive protein network. It appears that SA could elicit reactive oxygen species (ROS) production via enhancing the photosynthetic electron transferring, and then confer some growth-promoting and stress-priming effects on cells during the late phase, including enhanced photosynthesis and ROS scavenging, altered carbon metabolic flux for the biosynthesis of amino acids and nucleotides, and cell wall reorganization. Overall, the present iTRAQ assay provides higher proteome coverage and deepened our understanding of the molecular basis of SA-responses. PMID:27551830

Identifying Urinary and Serum Exosome Biomarkers for Radiation Exposure Using a Data Dependent Acquisition and SWATH-MS Combined Workflow.

PubMed

Kulkarni, Shilpa; Koller, Antonius; Mani, Kartik M; Wen, Ruofeng; Alfieri, Alan; Saha, Subhrajit; Wang, Jian; Patel, Purvi; Bandeira, Nuno; Guha, Chandan; Chen, Emily I

2016-11-01

Early and accurate assessment of radiation injury by radiation-responsive biomarkers is critical for triage and early intervention. Biofluids such as urine and serum are convenient for such analysis. Recent research has also suggested that exosomes are a reliable source of biomarkers in disease progression. In the present study, we analyzed total urine proteome and exosomes isolated from urine or serum for potential biomarkers of acute and persistent radiation injury in mice exposed to lethal whole body irradiation (WBI). For feasibility studies, the mice were irradiated at 10.4 Gy WBI, and urine and serum samples were collected 24 and 72 hours after irradiation. Exosomes were isolated and analyzed using liquid chromatography mass spectrometry/mass spectrometry-based workflow for radiation exposure signatures. A data dependent acquisition and SWATH-MS combined workflow approach was used to identify significantly exosome biomarkers indicative of acute or persistent radiation-induced responses. For the validation studies, mice were exposed to 3, 6, 8, or 10 Gy WBI, and samples were analyzed for comparison. A comparison between total urine proteomics and urine exosome proteomics demonstrated that exosome proteomic analysis was superior in identifying radiation signatures. Feasibility studies identified 23 biomarkers from urine and 24 biomarkers from serum exosomes after WBI. Urinary exosome signatures identified different physiological parameters than the ones obtained in serum exosomes. Exosome signatures from urine indicated injury to the liver, gastrointestinal, and genitourinary tracts. In contrast, serum showed vascular injuries and acute inflammation in response to radiation. Selected urinary exosomal biomarkers also showed changes at lower radiation doses in validation studies. Exosome proteomics revealed radiation- and time-dependent protein signatures after WBI. A total of 47 differentially secreted proteins were identified in urinary and serum exosomes

Identifying Urinary and Serum Exosome Biomarkers for Radiation Exposure Using a Data Dependent Acquisition and SWATH-MS Combined Workflow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kulkarni, Shilpa; Koller, Antonius; Proteomics Shared Resource, Herbert Irving Comprehensive Cancer Center, New York, New York

Purpose: Early and accurate assessment of radiation injury by radiation-responsive biomarkers is critical for triage and early intervention. Biofluids such as urine and serum are convenient for such analysis. Recent research has also suggested that exosomes are a reliable source of biomarkers in disease progression. In the present study, we analyzed total urine proteome and exosomes isolated from urine or serum for potential biomarkers of acute and persistent radiation injury in mice exposed to lethal whole body irradiation (WBI). Methods and Materials: For feasibility studies, the mice were irradiated at 10.4 Gy WBI, and urine and serum samples were collected 24more » and 72 hours after irradiation. Exosomes were isolated and analyzed using liquid chromatography mass spectrometry/mass spectrometry-based workflow for radiation exposure signatures. A data dependent acquisition and SWATH-MS combined workflow approach was used to identify significantly exosome biomarkers indicative of acute or persistent radiation-induced responses. For the validation studies, mice were exposed to 3, 6, 8, or 10 Gy WBI, and samples were analyzed for comparison. Results: A comparison between total urine proteomics and urine exosome proteomics demonstrated that exosome proteomic analysis was superior in identifying radiation signatures. Feasibility studies identified 23 biomarkers from urine and 24 biomarkers from serum exosomes after WBI. Urinary exosome signatures identified different physiological parameters than the ones obtained in serum exosomes. Exosome signatures from urine indicated injury to the liver, gastrointestinal, and genitourinary tracts. In contrast, serum showed vascular injuries and acute inflammation in response to radiation. Selected urinary exosomal biomarkers also showed changes at lower radiation doses in validation studies. Conclusions: Exosome proteomics revealed radiation- and time-dependent protein signatures after WBI. A total of 47 differentially

Augmentation of sensory-evoked hemodynamic response in an early Alzheimer's disease mouse model.

PubMed

Kim, Jinho; Jeong, Yong

2013-01-01

Based on enlarged blood oxygen level-dependent (BOLD) responses in cognitively normal subjects at risk for Alzheimer's disease (AD), compensatory neuronal hyperactivation has been proposed as an early marker for diagnosis of AD. The BOLD response results from neurovascular coupling, i.e., hemodynamic response induced by neuronal activity. However, there has been no evidence of task-induced increases in hemodynamic response in animal models of AD. Here, we observed an augmented hemodynamic response pattern in a transgenic AβPP(SWE)/PS1ΔE9 mouse model of AD using three in vivo imaging methods: intrinsic optical signal imaging, multi-photon laser scanning microscopy, and laser Doppler flowmetry. Sensory stimulation resulted in augmented and prolonged hemodynamic responses in transgenic mice evidenced by changes in total, oxygenated, and deoxygenated hemoglobin concentration. This difference between transgenic and wild-type mice was significant at 7 months of age when amyloid plaques and cerebral amyloid angiopathy had developed but not at younger or older ages. Correspondingly, sensory stimulation-induced pial arteriole diameter was also augmented and prolonged in transgenic mice at 7 months of age. Cerebral blood flow response in transgenic mice was augmented but not prolonged. These results are consistent with the existence of BOLD signal hyperactivation in non-demented AD-risk human subjects, supporting its potential use as an early diagnostic marker of AD.

Modeling Hematopoiesis and Responses to Radiation Countermeasures in a Bone Marrow-on-a-Chip.

PubMed

Torisawa, Yu-Suke; Mammoto, Tadanori; Jiang, Elisabeth; Jiang, Amanda; Mammoto, Akiko; Watters, Alexander L; Bahinski, Anthony; Ingber, Donald E

2016-05-01

Studies on hematopoiesis currently rely on animal models because in vitro culture methods do not accurately recapitulate complex bone marrow physiology. We recently described a bone marrow-on-a-chip microfluidic device that enables the culture of living hematopoietic bone marrow and mimics radiation toxicity in vitro. In the present study, we used this microdevice to demonstrate continuous blood cell production in vitro and model bone marrow responses to potential radiation countermeasure drugs. The device maintained mouse hematopoietic stem and progenitor cells in normal proportions for at least 2 weeks in culture. Increases in the number of leukocytes and red blood cells into the microfluidic circulation also could be detected over time, and addition of erythropoietin induced a significant increase in erythrocyte production. Exposure of the bone marrow chip to gamma radiation resulted in reduction of leukocyte production, and treatment of the chips with two potential therapeutics, granulocyte-colony stimulating factor or bactericidal/permeability-increasing protein (BPI), induced significant increases in the number of hematopoietic stem cells and myeloid cells in the fluidic outflow. In contrast, BPI was not found to have any effect when analyzed using static marrow cultures, even though it has been previously shown to accelerate recovery from radiation-induced toxicity in vivo. These findings demonstrate the potential value of the bone marrow-on-a-chip for modeling blood cell production, monitoring responses to hematopoiesis-modulating drugs, and testing radiation countermeasures in vitro.

Air pollution and climate response to aerosol direct radiative ...

EPA Pesticide Factsheets

Decadal hemispheric Weather Research and Forecast-Community Multiscale Air Quality simulations from 1990 to 2010 were conducted to examine the meteorology and air quality responses to the aerosol direct radiative effects. The model's performance for the simulation of hourly surface temperature, relative humidity, wind speed, and direction was evaluated through comparison with observations from NOAA's National Climatic Data Center Integrated Surface Data. The inclusion of aerosol direct radiative effects improves the model's ability to reproduce the trend in daytime temperature range which over the past two decades was increasing in eastern China but decreasing in eastern U.S. and Europe. Trends and spatial and diurnal variations of the surface-level gaseous and particle concentrations to the aerosol direct effect were analyzed. The inclusion of aerosol direct radiative effects was found to increase the surface-level concentrations of SO2, NO2, O3, SO42−, NO3−, and particulate matter 2.5 in eastern China, eastern U.S., and Europe by 1.5–2.1%, 1–1.5%, 0.1–0.3%, 1.6–2.3%, 3.5–10.0%, and 2.2–3.2%, respectively, on average over the entire 21 year period. However, greater impacts are noted during polluted days with increases of 7.6–10.6%, 6.2–6.7%, 2.0–3.0%, 7.8–9.5%, 11.1–18.6%, and 7.2–10.1%, respectively. Due to the aerosol direct radiative effects, stabilizing of the atmosphere associated with reduced planetary boundary layer height a

Population Response Profiles in Early Visual Cortex Are Biased in Favor of More Valuable Stimuli

PubMed Central

Saproo, Sameer

2010-01-01

Voluntary and stimulus-driven shifts of attention can modulate the representation of behaviorally relevant stimuli in early areas of visual cortex. In turn, attended items are processed faster and more accurately, facilitating the selection of appropriate behavioral responses. Information processing is also strongly influenced by past experience and recent studies indicate that the learned value of a stimulus can influence relatively late stages of decision making such as the process of selecting a motor response. However, the learned value of a stimulus can also influence the magnitude of cortical responses in early sensory areas such as V1 and S1. These early effects of stimulus value are presumed to improve the quality of sensory representations; however, the nature of these modulations is not clear. They could reflect nonspecific changes in response amplitude associated with changes in general arousal or they could reflect a bias in population responses so that high-value features are represented more robustly. To examine this issue, subjects performed a two-alternative forced choice paradigm with a variable-interval payoff schedule to dynamically manipulate the relative value of two stimuli defined by their orientation (one was rotated clockwise from vertical, the other counterclockwise). Activation levels in visual cortex were monitored using functional MRI and feature-selective voxel tuning functions while subjects performed the behavioral task. The results suggest that value not only modulates the relative amplitude of responses in early areas of human visual cortex, but also sharpens the response profile across the populations of feature-selective neurons that encode the critical stimulus feature (orientation). Moreover, changes in space- or feature-based attention cannot easily explain the results because representations of both the selected and the unselected stimuli underwent a similar feature-selective modulation. This sharpening in the population

The temporal response of recombination events to gamma radiation of meiotic cells in Sordaria brevicollis.

PubMed

Lewis, L A

1982-01-01

The temporal frequencies of different stages of prophase I were determined cytologically in Sordaria brevicollis (Olive and Fantini) as the basis for ascertaining the degree of synchrony in meiosis in this ascomycete. Croziers, karyogamy-zygotene and pachytene asci were shown to be in significant majorities at three distinct periods of the meiotic cycle. The response of recombination frequency to ionizing radiation was examined for the entire meiotic cycle. Three radiosensitive periods were determined. This response, which correlated temporally with each of the three peaks in ascal frequency, is interpreted as showing that the meiotic cycle of this organism is divided into periods of recombination commitment (radiation reduced frequencies) during the pre-meiotic S phase and recombination consummation (radiation induced frequencies) during zygotene and pachytene. The results are discussed in the context of the time at which recombination is consummated in eukaryotes such as yeast and Drosophila.

Early versus later response to treatment in patients with community-acquired pneumonia: analysis of the REACH study.

PubMed

Blasi, Francesco; Ostermann, Helmut; Racketa, Jill; Medina, Jesús; McBride, Kyle; Garau, Javier

2014-01-22

Key goals in the treatment of CAP include early response to treatment and achievement of clinical stability. The US FDA recommends early response endpoints (72 hours after initiation of treatment) in clinical trials for the treatment of community-acquired bacterial pneumonia. REACH (REtrospective Study to Assess the Clinical Management of Patients With Moderate-to-Severe Complicated Skin and Soft Tissue Infections [cSSTI] or CAP in the Hospital Setting) was a retrospective observational study, providing current data on the clinical management and resource burden of CAP in real-life settings in European hospitals. This analysis reviews the characteristics and outcomes of patients showing early positive response to treatment (time to clinical stability [TCS] ≤4 days, as assessed by Halm's criteria) compared with patients with later positive response (TCS >4 days). Patients were adults, hospitalized with CAP (2010-2011) and requiring in-hospital treatment with intravenous antibiotics. Of the 2039 patients included in REACH, 585 (28.7%) had TCS assessed by Halm's criteria: 332 (56.8%) showed early response (median 3.0 days), and 253 (43.2%) showed later response to treatment (median 7.0 days). Use of Halm's criteria varied across participating countries, ranging from 0% (Belgium) to 49.1% (UK). Patient characteristics and relevant medical history were similar between the two groups. There were no notable differences in initial antibiotic therapy between groups, except that more early responders had been treated with amoxicillin-clavulanate and amoxicillin monotherapy (22.6%; 7.5%, respectively) than later responders (5.9%; 1.2%, respectively). Initial treatment modification and re-infection or recurrences were less frequent in early responders compared with later responders (14.2% and 3.3% vs. 34.8% and 5.9%, respectively). Early responders had a shorter duration of hospitalization (mean 9.4 ± SD 7.0; median 8.0 days vs. mean 15.6 ± SD 10.5; median 12

Opposite Roles for p38MAPK-Driven Responses and Reactive Oxygen Species in the Persistence and Resolution of Radiation-Induced Genomic Instability

PubMed Central

Werner, Erica; Wang, Huichen; Doetsch, Paul W.

2014-01-01

We report the functional and temporal relationship between cellular phenotypes such as oxidative stress, p38MAPK-dependent responses and genomic instability persisting in the progeny of cells exposed to sparsely ionizing low-Linear Energy Transfer (LET) radiation such as X-rays or high-charge and high-energy (HZE) particle high-LET radiation such as 56Fe ions. We found that exposure to low and high-LET radiation increased reactive oxygen species (ROS) levels as a threshold-like response induced independently of radiation quality and dose. This response was sustained for two weeks, which is the period of time when genomic instability is evidenced by increased micronucleus formation frequency and DNA damage associated foci. Indicators for another persisting response sharing phenotypes with stress-induced senescence, including beta galactosidase induction, increased nuclear size, p38MAPK activation and IL-8 production, were induced in the absence of cell proliferation arrest during the first, but not the second week following exposure to high-LET radiation. This response was driven by a p38MAPK-dependent mechanism and was affected by radiation quality and dose. This stress response and elevation of ROS affected genomic instability by distinct pathways. Through interference with p38MAPK activity, we show that radiation-induced stress phenotypes promote genomic instability. In contrast, exposure to physiologically relevant doses of hydrogen peroxide or increasing endogenous ROS levels with a catalase inhibitor reduced the level of genomic instability. Our results implicate persistently elevated ROS following exposure to radiation as a factor contributing to genome stabilization. PMID:25271419