Punishment insensitivity and impaired reinforcement learning in preschoolers.

PubMed

Briggs-Gowan, Margaret J; Nichols, Sara R; Voss, Joel; Zobel, Elvira; Carter, Alice S; McCarthy, Kimberly J; Pine, Daniel S; Blair, James; Wakschlag, Lauren S

2014-01-01

Youth and adults with psychopathic traits display disrupted reinforcement learning. Advances in measurement now enable examination of this association in preschoolers. The current study examines relations between reinforcement learning in preschoolers and parent ratings of reduced responsiveness to socialization, conceptualized as a developmental vulnerability to psychopathic traits. One hundred and fifty-seven preschoolers (mean age 4.7 ± 0.8 years) participated in a substudy that was embedded within a larger project. Children completed the 'Stars-in-Jars' task, which involved learning to select rewarded jars and avoid punished jars. Maternal report of responsiveness to socialization was assessed with the Punishment Insensitivity and Low Concern for Others scales of the Multidimensional Assessment of Preschool Disruptive Behavior (MAP-DB). Punishment Insensitivity, but not Low Concern for Others, was significantly associated with reinforcement learning in multivariate models that accounted for age and sex. Specifically, higher Punishment Insensitivity was associated with significantly lower overall performance and more errors on punished trials ('passive avoidance'). Impairments in reinforcement learning manifest in preschoolers who are high in maternal ratings of Punishment Insensitivity. If replicated, these findings may help to pinpoint the neurodevelopmental antecedents of psychopathic tendencies and suggest novel intervention targets beginning in early childhood. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

A record-based case-control study of natural background radiation and the incidence of childhood leukaemia and other cancers in Great Britain during 1980–2006

PubMed Central

Kendall, Gerald M.; Little, Mark P.; Wakeford, Richard; Bunch, Kathryn J.; Miles, Jon C.H.; Vincent, Timothy J.; Meara, Jill R.; Murphy, Michael F.G.

2014-01-01

We conducted a large record-based case-control study testing associations between childhood cancer and natural background radiation. Cases (27 447) born and diagnosed in Great Britain during 1980–2006 and matched cancer-free controls (36 793) were from the National Registry of Childhood Tumours. Radiation exposures were estimated for mother’s residence at the child’s birth from national databases, using the County District mean for gamma-rays, and a predictive map based on domestic measurements grouped by geological boundaries for radon. There was 12% excess relative risk (95% CI 3, 22; 2-sided p=0.01) of childhood leukaemia per millisievert of cumulative red-bone-marrow dose from gamma-radiation; the analogous association for radon was not significant, excess relative risk 3% (95% CI −4, 11; p=0.35). Associations for other childhood cancers were not significant for either exposure. Excess risk was insensitive to adjustment for measures of socio-economic status. The statistically significant leukaemia risk reported in this reasonably-powered study (power ~50%) is consistent with high dose-rate predictions. Substantial bias is unlikely, and we cannot identify mechanisms by which confounding might plausibly account for the association, which we regard as likely to be causal. The study supports the extrapolation of high dose-rate risk models to protracted exposures at natural background exposure levels. PMID:22766784

Relationship between cocaine-induced subjective effects and dopamine transporter occupancy

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

Volkow, N.D.; Fischman, M.; Wang, G.J.

The ability of cocaine to occupy the dopamine transporter has been linked to its reinforcing properties. However, such a relationship has not been demonstrated in humans. Methods: Positron Emission Tomography and [C-11]cocaine were used to estimate dopamine transporter occupancies after different doses of cocaine in 18 active cocaine abusers. The ratio of the distribution volume of [C-11]cocaine in striatum to that in cerebellum, which corresponds to Bmax/Kd +1 and is insensitive to changes in cerebral blood flow, was our measure of dopamine transporter availability. In parallel subjective effects were measured to assess the relationship between dopamine transporter occupancy and cocainesmore » behavioral effects. Intravenous cocaine produced a significant dose,-dependent blockade of dopamine transporters: 73 % for 0.6 mg/kg; 601/6 for 0.3 mg/kg; 48 % for 0.1 mg/kg iv and 40 % for 0.05 mg/kg. In addition, dopamine transporter occupancies were significantly correlated with cocaine plasma concentration (r = 0.55 p < 0.001). Cocaine also produced dose-dependent increases in self-reported ratings of {open_quotes}high{close_quotes} which were significantly correlated with the levels of dopamine transporter blockade. Discussion: These results provide the first documentation in humans that dopamine transporter occupancy is associated with cocaine induced subjective effects. They also suggest that dopamine transporter occupancies equal to or greater than 60% are required to produce significant effects on ratings of {open_quotes}high{close_quotes}.« less

Instructional Influence on Human Performance: Insensitivity to Contingencies. Interim Report September 1, 1979 through August 31, 1980.

ERIC Educational Resources Information Center

Shimoff, Eliot H.; Matthews, Byron A.

Five experiments were conducted to determine whether properties inherent in some training procedures may subtly influence the adaptability of skilled performance of complex tasks. The first two experiments assessed the insensitivity of low-rate performances. Examined in the third experiment was the issue of whether instructions that focus…

A new method for determining dose rate distribution from radioimmuno-therapy using radiochromic media

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

Mayer, R.; Dillehay, L.E.; Shao, Y.

The purpose of this study is to describe and evaluate a new, simple, inexpensive method for directly measuring the radiation dose and its spatial distribution generated from explanted tissues of animals previously injected with radiolabeled immunoconjugates or other agents. This technique uses the newly developed radiochromic dye medium (Gafchromic[trademark]) which responds reproducibly for therapeutic dose exposures, has high spatial resolution, does not require film processing, and is relatively insensitive to ambient light. The authors have evaluated the dose distribution from LS174T tumors and selected normal tissues in nude mice previously injected with [sup 90]Y labeled anti-carcinoembryonic antigen antibodies. Individual tissuesmore » from sacrificed animals are halved and the flat section of the tissue is placed onto the dosimetry media and then frozen. The dosimetry medium is exposed to beta and Bremsstrahlung radiation originating from the frozen tissues. The relative darkening of the dosimetry medium depends on the dose deposited in the film. The dosimetry medium is scanned with a commercial flatbed scanner and the image intensity is digitally stored and quantitatively analyzed. Isodose curves are generated and compared to the actual tissue outline. The absorbed dose distribution due to [sup 90]Y exposure show only slight gradients in the interior of the tissue, with a markedly decreasing dose near the edges of the tissue. In addition, the isodose curves follow the tissue outline except in regions having radii of curvature smaller than the range of the beta-particle (R90 = 5 mm). These results suggest that the shape of the tumor, and its curvature, are important in determining the minimum dose delivered to the tumor by radiation from [sup 90]Y monoclonal antibodies, and hence in evaluating the tumor response to the radiation. 28 refs., 8 figs.« less

National culture moderates the influence of mental effort on subjective and cardiovascular measures.

PubMed

Widyanti, Ari; de Waard, Dick; Johnson, Addie; Mulder, Ben

2013-01-01

Subjective measures of mental effort have been shown to be relatively insensitive in Indonesian participants. An open question is whether this insensitivity reflects how mental effort is experienced or how it is reported. We compared the performance, subjective workload ratings, heart rate and heart-rate variability (HRV) of 31 Dutch and 30 Indonesian participants under single- and dual-task conditions. Indonesians performed faster but less accurately and used a narrower range of subjective workload ratings than did the Dutch. Dutch participants showed a decrease in HRV both in the mid-frequency (MF) and high-frequency bands and an increase in heart rate during task performance compared with the resting period. Indonesians showed this pattern in the MF band only. The decrease of HRV in the MF band in both groups suggests that the relative insensitivity of subjective mental effort scales among Indonesians has to do with how workload is reported rather than with how it is experienced. The sensitivity of the subjective measures of mental workload has been shown to depend on culture. Here, we show that heart-rate variability reacts similarly to workload in Eastern as in Western participants. This suggests that culture influences more how invested mental effort is reported than how it is experienced psychophysiologically.

Polarization-insensitive techniques for optical signal processing

NASA Astrophysics Data System (ADS)

Salem, Reza

2006-12-01

This thesis investigates polarization-insensitive methods for optical signal processing. Two signal processing techniques are studied: clock recovery based on two-photon absorption in silicon and demultiplexing based on cross-phase modulation in highly nonlinear fiber. The clock recovery system is tested at an 80 Gb/s data rate for both back-to-back and transmission experiments. The demultiplexer is tested at a 160 Gb/s data rate in a back-to-back experiment. We experimentally demonstrate methods for eliminating polarization dependence in both systems. Our experimental results are confirmed by theoretical and numerical analysis.

Use of tracheal auscultation for the assessment of bronchial responsiveness in asthmatic children.

PubMed Central

Sprikkelman, A. B.; Grol, M. H.; Lourens, M. S.; Gerritsen, J.; Heymans, H. S.; van Aalderen, W. M.

1996-01-01

BACKGROUND: It can be difficult to assess bronchial responsiveness in children because of their inability to perform spirometric tests reliably. In bronchial challenges lung sounds could be used to detect the required 20% fall in the forced expiratory volume in one second (FEV1). A study was undertaken to determine whether a change in lung sounds corresponded with a 20% fall in FEV1 after methacholine challenge, and whether the occurrence of wheeze was the most important change. METHODS: Fifteen children with asthma (eight boys) of mean age 10.8 years (range 8-15) were studied. All had normal chest auscultation before the methacholine challenge test. Lung sounds were recorded over the trachea for one minute and stored on tape. They were analysed directly and also scored blindly from the tape recording by a second investigator. Wheeze, cough, increase in respiratory rate, and prolonged expiration were assessed. RESULTS: The total cumulative methacholine dose causing a fall in FEV1 of 20% or more (PD20) was detected in 12 children by a change in lung sounds - in four by wheeze and in eight by cough, increased respiratory rate, and/or prolonged expiration. In two subjects altered lung sounds were detectable one dose step before PD20 was reached. In three cases in whom no fall in FEV1 occurred, no change in lung sounds could be detected at the highest methacholine dose. CONCLUSION: Changes in lung sounds correspond well with a 20% fall in FEV1 after methacholine challenge. Wheeze is an insensitive indicator for assessing bronchial responsiveness. Cough, increase in respiratory rate, and prolonged expiration occurs more frequently. PMID:8779140

Heart-Rate and Breath-Rate Monitor

NASA Technical Reports Server (NTRS)

Cooper, T. G.

1983-01-01

Circuit requiring only four integrated circuits (IC's) measures both heart rate and breath rate. Phase-locked loops lock on heart-rate and respiration-rate input signals. Each loop IC contains two phase comparators. Positive-edge-triggered circuit used in making monitors insensitive to dutycycle variations.

Effects of Low-Dose Aspirin and Fish Oil on Platelet Function and NF-kappaB in Adults with Diabetes Mellitus

PubMed Central

Block, Robert C; Abdolahi, Amir; Smith, Brian; Meednu, N; Thevenet-Morrison, Kelly; Cai, Xueya; Cui, Huadong; Mousa, Shaker; Brenna, J. Thomas; Georas, S

2013-01-01

SUMMARY Introduction Many diabetics are insensitive to aspirin’s platelet anti-aggregation effects. The possible modulating effects of coadministration of aspirin and fish oil in subjects with diabetes are poorly characterized. Participants and Methods Thirty adults with type 2 diabetes mellitus were treated with aspirin 81 mg/d for 7 days, then with fish oil 4g/day for 28 days, then the combination of fish oil and aspirin for another 7 days. Results Aspirin alone and in combination with fish oil reduced platelet aggregation in most participants. Five of 7 participants classified as aspirin insensitive 1 week after daily aspirin ingestion were sensitive after the combination. Although some platelet aggregation measures correlated positively after aspirin and fish oil ingestion alone and (in combination) in all individuals, correlation was only observed in those who were aspirin insensitive after ingestion of the combination. Conclusions Co-adminstration of aspirin and fish oil may reduce platelet aggregation more than aspirin alone in adults with diabetes mellitus. PMID:23664596

Hershberger Assays for Di-2-ethylhexyl Phthalate and Its Substitute Candidates

PubMed Central

Kim, Hee-Su; Cheon, Yong-Pil; Lee, Sung-Ho

2018-01-01

ABSTRACT In the present study, we employed Hershberger assay to determine possible androgenic or antiandrogenic activities of three di-2-ethylhexyl phthalate (DEHP) substitute candidates. The assay was carried out using immature castrated Sprague–Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were DEHP, 2-ethylhexyl oleate (IOO), 2-ethylhexyl stearate (IOS) and triethyl 2-acetylcitrate (ATEC). The rats were necropsied, and then the weights of five androgen-dependent tissues [ventral prostate, seminal vesicle, coagulating glands, levator ani-bulbocavernosus (LABC) muscle, paired Cowper’s glands, and glans penis] and four androgen-insensitive tissues (kidney, adrenal glands, spleen and liver) were measured. All test materials including DEHP did not exhibit any androgenic activity in the assay. On the contrary, antiandrogen-like activities were found in all test groups, and the order of the intensity was ATEC < DEHP < ISO < IOO in the five androgen-sensitive tissues. There was no statistical difference between low dose treatment and high dose treatment of all replacement candidate groups. In DEHP groups, high dose treatment exhibited significant weight gains in LABC and Glan Penis. There was no statistical difference in androgen-insensitive tissue measurements. Since the effects of ATEC treatment on the accessory sex organs were much less or not present at all when compared to those of DEHP, ATEC could be a strong candidate to replace DEHP. IOO treatment brought most severe weight reduction in all of androgen-sensitive tissues, so this material should be excluded for further screening of DEHP substitute selection. PMID:29707681

Dose reduction in LDR brachytherapy by implanted prostate gold fiducial markers.

PubMed

Landry, Guillaume; Reniers, Brigitte; Lutgens, Ludy; Murrer, Lars; Afsharpour, Hossein; de Haas-Kock, Danielle; Visser, Peter; van Gils, Francis; Verhaegen, Frank

2012-03-01

The dosimetric impact of gold fiducial markers (FM) implanted prior to external beam radiotherapy of prostate cancer on low dose rate (LDR) brachytherapy seed implants performed in the context of combined therapy was investigated. A virtual water phantom was designed containing a single FM. Single and multi source scenarios were investigated by performing Monte Carlo dose calculations, along with the influence of varying orientation and distance of the FM with respect to the sources. Three prostate cancer patients treated with LDR brachytherapy for a recurrence following external beam radiotherapy with implanted FM were studied as surrogate cases to combined therapy. FM and brachytherapy seeds were identified on post implant CT scans and Monte Carlo dose calculations were performed with and without FM. The dosimetric impact of the FM was evaluated by quantifying the amplitude of dose shadows and the volume of cold spots. D(90) was reported based on the post implant CT prostate contour. Large shadows are observed in the single source-FM scenarios. As expected from geometric considerations, the shadows are dependent on source-FM distance and orientation. Large dose reductions are observed at the distal side of FM, while at the proximal side a dose enhancement is observed. In multisource scenarios, the importance of shadows appears mitigated, although FM at the periphery of the seed distribution caused underdosage (

Impact of a program to diminish gender insensitivity and sexual harassment at a medical school.

PubMed

Jacobs, C D; Bergen, M R; Korn, D

2000-05-01

To measure the effect of an intervention to reduce gender insensitivity and sexual harassment at one medical school. Stanford University School of Medicine undertook a multifaceted program to educate faculty and students regarding gender issues and to diminish sexual harassment. The authors developed a survey instrument to assess the faculty's perceptions regarding environment (five scales) and incidences of sexual harassment. Faculty were surveyed twice during the interventions (1994 and 1995). Between the two years, the authors measured significant improvements in mean ratings for positive climate (p = .004) and cohesion (p = .006) and decreases in the faculty's perceptions of sexual harassment (p = 0006), gender insensitivity (p = .001), and gender discrimination (p = .004). The faculty also reported fewer observations of harassing behavior during the study period. An intervention program to diminish gender insensitivity and sexual harassment can measurably improve a medical school's environment.

Characterisation of the epithermal neutron irradiation facility at the Portuguese research reactor using MCNP.

PubMed

Beasley, D G; Fernandes, A C; Santos, J P; Ramos, A R; Marques, J G; King, A

2015-05-01

The radiation field at the epithermal beamline and irradiation chamber installed at the Portuguese Research Reactor (RPI) at the Campus Tecnológico e Nuclear of Instituto Superior Técnico was characterised in the context of Prompt Gamma Neutron Activation Analysis (PGNAA) applications. Radiographic films, activation foils and thermoluminescence dosimeters were used to measure the neutron fluence and photon dose rates in the irradiation chamber. A fixed-source MCNPX model of the beamline and chamber was developed and compared to measurements in the first step towards planning a new irradiation chamber. The high photon background from the reactor results in the saturation of the detector and the current facility configuration yields an intrinsic insensitivity to various elements of interest for PGNAA. These will be addressed in future developments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Radiation-hard erbium optical fiber and fiber amplifier for both low- and high-dose space missions.

PubMed

Girard, S; Laurent, A; Pinsard, E; Robin, T; Cadier, B; Boutillier, M; Marcandella, C; Boukenter, A; Ouerdane, Y

2014-05-01

We present a new structure for erbium-doped optical fibers [hole-assisted carbon-coated, (HACC)] that, combined with an appropriate choice of codopants in the core, strongly enhances their radiation tolerance. We built an erbium-doped fiber amplifier based on this HACC fiber and characterize its degradation under γ-ray doses up to 315 krad (SiO2) in the ON mode. The 31 dB amplifier is practically radiation insensitive, with a gain change of merely -2.2×10(-3) dB/krad. These performances authorize the use of HACC doped fibers and amplifiers for various applications in environments associated with today's missions (of doses up to 50 krad) and even for future space missions associated with higher dose constraints.

Performance optimization of the Varian aS500 EPID system.

PubMed

Berger, Lucie; François, Pascal; Gaboriaud, Geneviève; Rosenwald, Jean-Claude

2006-01-01

Today, electronic portal imaging devices (EPIDs) are widely used as a replacement to portal films for patient position verification, but the image quality is not always optimal. The general aim of this study was to optimize the acquisition parameters of an amorphous silicon EPID commercially available for clinical use in radiation therapy with the view to avoid saturation of the system. Special attention was paid to selection of the parameter corresponding to the number of rows acquired between accelerator pulses (NRP) for various beam energies and dose rates. The image acquisition system (IAS2) has been studied, and portal image acquisition was found to be strongly dependent on the accelerator pulse frequency. This frequency is set for each "energy - dose rate" combination of the linear accelerator. For all combinations, the image acquisition parameters were systematically changed to determine their influence on the performances of the Varian aS500 EPID system. New parameters such as the maximum number of rows (MNR) and the number of pulses per frame (NPF) were introduced to explain portal image acquisition theory. Theoretical and experimental values of MNR and NPF were compared, and they were in good agreement. Other results showed that NRP had a major influence on detector saturation and dose per image. A rule of thumb was established to determine the optimum NRP value to be used. This practical application was illustrated by a clinical example in which the saturation of the aSi EPID was avoided by NRP optimization. Moreover, an additional study showed that image quality was relatively insensitive to this parameter.

Relative contributions of mercury bioavailability and microbial growth rate on net methylmercury production by anaerobic mixed cultures

DOE PAGES

Kucharzyk, Katarzyna H.; Deshusses, Marc A.; Porter, Kaitlyn A.; ...

2015-01-01

Net production of methylmercury correlated with sulfate reduction rates in cultures exposed to dissolved Hg, but was insensitive to sulfate reduction rates for cultures exposed to nanoparticulate HgS.

The Role of Sociodemographic Risk and Maternal Behavior in the Prediction of Infant Attachment Disorganization

PubMed Central

Gedaly, Lindsey R.; Leerkes, Esther M.

2017-01-01

Predictors of infant attachment disorganization were examined among 203 primiparous mothers (52% European American, 48% African American) and their infants (104 female). The Strange Situation Procedure was administered at 1 year. Global maternal insensitivity and overtly negative maternal behavior were observed during distress-eliciting tasks when infants were 6 months and 1 year old. Mothers reported on their demographics to yield a measure of sociodemographic risk (i.e., age, education, income-to-needs). Overtly negative maternal behavior was positively associated with the infant attachment disorganization rating scale score, but did not predict being classified as disorganized. Global maternal insensitivity was associated with higher attachment disorganization, both the rating and the classification, when sociodemographic risk was high but not when sociodemographic risk was low. The pattern of results did not vary by maternal race. The results provide some support for the view that negative maternal behavior and the combination of sociodemographic risk and global maternal insensitivity play a role in the development of infant attachment disorganization. PMID:27477050

The role of sociodemographic risk and maternal behavior in the prediction of infant attachment disorganization.

PubMed

Gedaly, Lindsey R; Leerkes, Esther M

2016-12-01

Predictors of infant attachment disorganization were examined among 203 primiparous mothers (52% European American, 48% African American) and their infants (104 female). The Strange Situation Procedure was administered at one year. Global maternal insensitivity and overtly negative maternal behavior were observed during distress-eliciting tasks when infants were six months and one year old. Mothers reported on their demographics to yield a measure of sociodemographic risk (i.e., age, education, income-to-needs). Overtly negative maternal behavior was positively associated with the infant attachment disorganization rating scale score, but did not predict being classified as disorganized. Global maternal insensitivity was associated with higher attachment disorganization, both the rating and the classification, when sociodemographic risk was high but not when sociodemographic risk was low. The pattern of results did not vary by maternal race. The results provide some support for the view that negative maternal behavior and the combination of sociodemographic risk and global maternal insensitivity play a role in the development of infant attachment disorganization.

Laser-evoked potentials mediated by mechano-insensitive nociceptors in human skin.

PubMed

Dusch, M; van der Ham, J; Weinkauf, B; Benrath, J; Rukwied, R; Ringkamp, M; Schmelz, M; Treede, R-D; Baumgärtner, U

2016-05-01

Laser-evoked potentials (LEP) were assessed after peripheral nerve block of the lateral femoral cutaneous nerve (LFCN) in healthy volunteers from partially anesthetized skin areas to differentially stimulate mechano-insensitive nociceptors. An ultrasound-guided nerve block of the LFCN was performed in 12 healthy male subjects with Ropivacain 1%. After 30 min, the nerve block induced significantly larger anesthetic areas to mechanical stimuli than to electrical stimuli revealing an area of differential sensitivity. LEPs, reaction times and pain ratings were recorded in response to the laser stimuli of (1) completely anesthetic skin, (2) mechano-insensitive, but electrically excitable skin ('differential sensitivity'), (3) normal skin. LEP latencies in the area of differential sensitivity were increased compared to unaffected skin (228 ± 8.5 ms, vs. 181 ± 3.6 ms, p < 0.01) and LEP amplitudes were reduced (14.8 ± 1.2 μV vs. 24.6 ± 1.7 μV, p < 0.01). Correspondingly, psychophysically assessed response latencies in the differentially anesthetic skin were increased (649 ms vs. 427 ms, p < 0.01) and pain ratings reduced (1.5/10 vs. 5/10 NRS, p < 0.01). The increase in LEP latency suggests that mechano-insensitive heat-sensitive Aδ nociceptors (MIA, type II) have a slower conduction velocity or higher utilization time than mechano-sensitive type II Aδ nociceptors. Moreover, widely branched, slowly conducting and mechano-insensitive branches of Aδ nociceptors can explain our finding. LEPs in the differentially anesthetized skin provide specific information about a mechanically insensitive but heat-sensitive subpopulation of Aδ nociceptors. These findings support the concept that A-fibre nociceptors exhibit a similar degree of modality specificity as C-fibre nociceptors. © 2015 European Pain Federation - EFIC®

Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity.

PubMed

Chernausek, Steven D; Backeljauw, Philippe F; Frane, James; Kuntze, Joyce; Underwood, Louis E

2007-03-01

Children with severe IGF-I deficiency due to congenital or acquired defects in GH action have short stature that cannot be remedied by GH treatment. The objective of the study was to examine the long-term efficacy and safety of recombinant human IGF-I (rhIGF-I) therapy for short children with severe IGF-I deficiency. Seventy-six children with IGF-I deficiency due to GH insensitivity were treated with rhIGF-I for up to 12 yr under a predominantly open-label design. The study was conducted at general clinical research centers and with collaborating endocrinologists. Entry criteria included: age older than 2 yr, sd scores for height and circulating IGF-I concentration less than -2 for age and sex, and evidence of resistance to GH. rhIGF-I was administered sc in doses between 60 and 120 microg/kg twice daily. Height velocity, skeletal maturation, and adverse events were measured. Height velocity increased from 2.8 cm/yr on average at baseline to 8.0 cm/yr during the first year of treatment (P < 0.0001) and was dependent on the dose administered. Height velocities were lower during subsequent years but remained above baseline for up to 8 yr. The most common adverse event was hypoglycemia, which was observed both before and during therapy. It was reported by 49% of treated subjects. The next most common adverse events were injection site lipohypertrophy (32%) and tonsillar/adenoidal hypertrophy (22%). Treatment with rhIGF-I stimulates linear growth in children with severe IGF-I deficiency due to GH insensitivity. Adverse events are common but are rarely of sufficient severity to interrupt or modify treatment.

Cost-effectiveness of the Adjuvanted Herpes Zoster Subunit Vaccine in Older Adults.

PubMed

Le, Phuc; Rothberg, Michael B

2018-02-01

The live attenuated herpes zoster vaccine (ZVL) is recommended for immunocompetent adults 60 years or older, but the efficacy wanes with age and over time. A new adjuvanted herpes zoster subunit vaccine (HZ/su) has higher efficacy but might be more expensive. The choice of vaccines depends on their relative values. To assess the cost-effectiveness of HZ/su. Markov decision model with transition probabilities based on the US medical literature. Participants were immunocompetent adults 60 years or older. Data were derived from participant groups ranging in number from less than 100 to more than 30 000 depending on the variable assessed. The study dates were July 1 to 31, 2017. No vaccination, ZVL (single dose), and HZ/su (2-dose series) vaccine administered at different ages. Total costs and quality-adjusted life-years (QALYs) were estimated. Based on randomized clinical trial data, at a price of $280 per series ($140 per dose), HZ/su was more effective and less expensive than ZVL at all ages. The incremental cost-effectiveness ratios compared with no vaccination ranged from $20 038 to $30 084 per QALY, depending on vaccination age. The finding was insensitive to variations in most model inputs other than the vaccine price and certain combinations of low adherence rate with a second dose and low efficacy of a single dose of HZ/su. At the current ZVL price ($213 per dose), HZ/su had lower overall costs than ZVL up to a price of $350 per 2-dose series. In probabilistic sensitivity analysis, HZ/su had 73% probability of being cost-effective for 60-year-olds at $50 000 per QALY. Under conservative assumptions, at a price of $280 per series ($140 per dose), HZ/su would cost less than ZVL and has a high probability of offering good value.

Effects of exogenous growth hormone administration on dexamethasone-induced growth impairment in adolescent male rats

PubMed Central

Kim, Myung-Gyou; Oh, Jeong-Seok; Kim, Hye Kyung; Leem, Kang-Hyun

2017-01-01

Growth impairment (GI) is one of the adverse effects of dexamethasone (DXM), and growth hormone (GH) has been used clinically to improve GI. The present study aimed to evaluate the manner in which DXM disturbs the growth rate of longitudinal bones, and the recovery effects of GH on DXM-induced GI in the longitudinal bones of adolescent male rats. In the first experiment, DXM (0, 0.5, 1, 2 and 5 mg/kg) was administered subcutaneously to identify a potential dose-dependent activity and calculate the median effective dose (ED50) of DXM-induced GI. The ED50 was identified to be 1.15 mg/kg. In the second experiment, GH (0, 2.5, 5 and 10 mg/kg) with 1.15 mg/kg DXM was injected subcutaneously to assess the recovery effects of GH on DXM-induced GI. The growth rates of the longitudinal bones, total height of the growth plate, local mRNA expressions of insulin-like growth factor 1 (IGF-1), GH receptor (GHR) and IGF-1 receptor (IGF-1R), and local protein expression of IGF-1 were measured to evaluate the recovery effects of GH on DXM-induced GI. The local expressions of IGF-1, GHR and IGF-1R mRNA, and IGF-1 protein were measured using quantitative polymerase chain reaction following laser microdissection and antigen-specific immunohistochemistry, respectively. GH administration partially recovered DXM-induced GI in the longitudinal bones and growth plate. GH significantly increased the levels of IGF-1, GHR and IGF-1R mRNA in the proliferative zone of the control group (P<0.05), whereas it failed to increase them in the proliferative zone of the DXM-treated group. Furthermore, GH increased the levels of IGF-1, GHR and IGF-1R mRNA in the hypertrophic zone of both the vehicle and DXM-treated groups (P<0.05). Immunohistochemical analysis of IGF-1 protein expression revealed a similar pattern to that of IGF-1 mRNA. These results suggest that increased GH insensitivity in the proliferative zone of the growth plate, induced by DXM, leads to GI in longitudinal bones. Thus, combined administration of GH with GH insensitivity-alleviating medications may be more effective in the treatment of DXM-induced GI. PMID:29042933

Multiplexed memory-insensitive quantum repeaters.

PubMed

Collins, O A; Jenkins, S D; Kuzmich, A; Kennedy, T A B

2007-02-09

Long-distance quantum communication via distant pairs of entangled quantum bits (qubits) is the first step towards secure message transmission and distributed quantum computing. To date, the most promising proposals require quantum repeaters to mitigate the exponential decrease in communication rate due to optical fiber losses. However, these are exquisitely sensitive to the lifetimes of their memory elements. We propose a multiplexing of quantum nodes that should enable the construction of quantum networks that are largely insensitive to the coherence times of the quantum memory elements.

Development of constitutive models for cyclic plasticity and creep behavior of super alloys at high temperature

NASA Technical Reports Server (NTRS)

Haisler, W. E.

1983-01-01

An uncoupled constitutive model for predicting the transient response of thermal and rate dependent, inelastic material behavior was developed. The uncoupled model assumes that there is a temperature below which the total strain consists essentially of elastic and rate insensitive inelastic strains only. Above this temperature, the rate dependent inelastic strain (creep) dominates. The rate insensitive inelastic strain component is modelled in an incremental form with a yield function, blow rule and hardening law. Revisions to the hardening rule permit the model to predict temperature-dependent kinematic-isotropic hardening behavior, cyclic saturation, asymmetric stress-strain response upon stress reversal, and variable Bauschinger effect. The rate dependent inelastic strain component is modelled using a rate equation in terms of back stress, drag stress and exponent n as functions of temperature and strain. A sequence of hysteresis loops and relaxation tests are utilized to define the rate dependent inelastic strain rate. Evaluation of the model has been performed by comparison with experiments involving various thermal and mechanical load histories on 5086 aluminum alloy, 304 stainless steel and Hastelloy X.

Force generation and temperature-jump and length-jump tension transients in muscle fibers.

PubMed Central

Davis, J S; Rodgers, M E

1995-01-01

Muscle tension rises with increasing temperature. The kinetics that govern the tension rise of maximally Ca(2+)-activated, skinned rabbit psoas fibers over a temperature range of 0-30 degrees C was characterized in laser temperature-jump experiments. The kinetic response is simple and can be readily interpreted in terms of a basic three-step mechanism of contraction, which includes a temperature-sensitive rapid preequilibrium(a) linked to a temperature-insensitive rate-limiting step and followed by a temperature-sensitive tension-generating step. These data and mechanism are compared and contrasted with the more complex length-jump Huxley-Simmons phases in which all states that generate tension or bear tension are perturbed. The rate of the Huxley-Simmons phase 4 is temperature sensitive at low temperatures but plateaus at high temperatures, indicating a change in rate-limiting step from a temperature-sensitive (phase 4a) to a temperature-insensitive reaction (phase 4b); the latter appears to correlate with the slow, temperature-insensitive temperature-jump relaxation. Phase 3 is absent in the temperature-jump, which excludes it from tension generation. We confirm that de novo tension generation occurs as an order-disorder transition during phase 2slow and the equivalent, temperature-sensitive temperature-jump relaxation. PMID:7612845

Method for preparing dosimeter for measuring skin dose

DOEpatents

Jones, Donald E.; Parker, DeRay; Boren, Paul R.

1982-01-01

A personnel dosimeter includes a plurality of compartments containing thermoluminescent dosimeter phosphors for registering radiation dose absorbed in the wearer's sensitive skin layer and for registering more deeply penetrating radiation. Two of the phosphor compartments communicate with thin windows of different thicknesses to obtain a ratio of shallowly penetrating radiation, e.g. beta. A third phosphor is disposed within a compartment communicating with a window of substantially greater thickness than the windows of the first two compartments for estimating the more deeply penetrating radiation dose. By selecting certain phosphors that are insensitive to neutrons and by loading the holder material with neutron-absorbing elements, energetic neutron dose can be estimated separately from other radiation dose. This invention also involves a method of injection molding of dosimeter holders with thin windows of consistent thickness at the corresponding compartments of different holders. This is achieved through use of a die insert having the thin window of precision thickness in place prior to the injection molding step.

Dosimeter for measuring skin dose and more deeply penetrating radiation

DOEpatents

Jones, Donald E.; Parker, DeRay; Boren, Paul R.

1981-01-01

A personnel dosimeter includes a plurality of compartments containing thermoluminescent dosimeter phosphors for registering radiation dose absorbed in the wearer's sensitive skin layer and for registering more deeply penetrating radiation. Two of the phosphor compartments communicate with thin windows of different thicknesses to obtain a ratio of shallowly penetrating radiation, e.g. beta. A third phosphor is disposed within a compartment communicating with a window of substantially greater thickness than the windows of the first two compartments for estimating the more deeply penetrating radiation dose. By selecting certain phosphors that are insensitive to neutrons and by loading the holder material with netruon-absorbing elements, energetic neutron dose can be estimated separately from other radiation dose. This invention also involves a method of injection molding of dosimeter holders with thin windows of consistent thickness at the corresponding compartments of different holders. This is achieved through use of a die insert having the thin window of precision thickness in place prior to the injection molding step.

Aldosterone increases cardiac vagal tone via G protein-coupled oestrogen receptor activation

PubMed Central

Brailoiu, G Cristina; Benamar, Khalid; Arterburn, Jeffrey B; Gao, Erhe; Rabinowitz, Joseph E; Koch, Walter J; Brailoiu, Eugen

2013-01-01

In addition to acting on mineralocorticoid receptors, aldosterone has been recently shown to activate the G protein-coupled oestrogen receptor (GPER) in vascular cells. In light of the newly identified role for GPER in vagal cardiac control, we examined whether or not aldosterone activates GPER in rat nucleus ambiguus. Aldosterone produced a dose-dependent increase in cytosolic Ca2+ concentration in retrogradely labelled cardiac vagal neurons of nucleus ambiguus; the response was abolished by pretreatment with the GPER antagonist G-36, but was not affected by the mineralocorticoid receptor antagonists, spironolactone and eplerenone. In Ca2+-free saline, the response to aldosterone was insensitive to blockade of the Ca2+ release from lysosomes, while it was reduced by blocking the Ca2+ release via ryanodine receptors and abolished by blocking the IP3 receptors. Aldosterone induced Ca2+ influx via P/Q-type Ca2+ channels, but not via L-type and N-type Ca2+ channels. Aldosterone induced depolarization of cardiac vagal neurons of nucleus ambiguus that was sensitive to antagonism of GPER but not of mineralocorticoid receptor. in vivo studies, using telemetric measurement of heart rate, indicate that microinjection of aldosterone into the nucleus ambiguus produced a dose-dependent bradycardia in conscious, freely moving rats. Aldosterone-induced bradycardia was blocked by the GPER antagonist, but not by the mineralocorticoid receptor antagonists. In summary, we report for the first time that aldosterone decreases heart rate by activating GPER in cardiac vagal neurons of nucleus ambiguus. PMID:23878371

Context sensitive regulation of pain and emotion: Development and initial validation of a scale for context insensitive avoidance.

PubMed

Flink, Ida K; Klein-Strandberg, Ester; Linton, Steven J

2017-10-01

Context insensitivity has been put forward as a potential mechanism explaining the high co-occurrence of pain and emotional distress. In the pain literature, the concept has only been introduced at a theoretical level and an assessment tool for exploring its impact is lacking. In an interpersonal setting, a core aspect of context sensitivity and insensitivity concerns when to disclose and when to avoid expressing pain and related distress. Both context insensitive disclosure and context insensitive avoidance may hamper interpersonal support and fuel the problem. This exploratory study describes an attempt to develop a self-report instrument to assess tendencies to disclose vs. avoid expressions of pain and related distress, as well as self-perceived adjustment of disclosure vs. avoidance to the context. A pool of items was systematically developed to assess different aspects of context insensitivity, including disclosure vs. avoidance of expression. 105 participants with persistent pain were recruited at pain rehabilitation clinics (80% of the sample) and in a university setting (20% of the sample). The participants responded to the pool of items as well as to a number of validated self-report instruments covering pain, pain-related disability, pain catastrophizing, emotion regulation tendencies, self-compassion and pain acceptance. The analyses explored the factorial structure of the initial instrument, as well as the criterion and construct validity. The analyses confirmed a stable underlying structure of the initial scale, with four distinct factors explaining 64.4% of the total variance. However, the criterion and construct validity could only be confirmed for one of the factors, which contained items reflecting context insensitive avoidance of expression. Consequently, only this factor, demonstrating very good internal consistency, was kept in the final version of the instrument which was named context insensitive avoidance (CIA). We found support for the final version of our instrument, capturing one prominent aspect of context insensitivity. Avoidance of expression was related to higher ratings of pain, disability, catastrophizing and suppression as well as to lower levels of self-compassion. We encourage further studies to explore the impact of context insensitive avoidance for regulating pain and associated negative emotions. Yet, more research is needed that goes beyond self-report and includes other aspects of context. It is urgent to develop systematic ways for assessing context insensitivity, as it will enhance our understanding of regulatory strategies as potential transdiagnostic mechanisms in pain and emotion. This tool for assessing contextually insensitive avoidance of expression could potentially be used both clinically and in future research to advance our understanding of comorbid problems with pain and emotional distress. Further research is needed to develop methods for assessing other aspects of context insensitivity to fully understand its impact in patients suffering from pain. Copyright © 2017 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Phototoxicity of three PAHs to Chironomus tentans in the presence and absence of a metabolic inhibitor

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

Monson, P.D.; Sheedy, B.R.; Cox, J.S.

1995-12-31

Chironomus tentans has been observed to be insensitive to photoinduced toxicity of polycyclic aromatic hydrocarbons (PAHs) relative to other benthic test species. The midge is generally accepted to have the ability to metabolize organic compounds (e.g. pesticides) via the cytochrome P450 monooxygenase system, which may explain in part the organisms insensitivity. The objective of this study was to characterize the enhanced effects, if any, of a metabolic inhibitor of P450, piperonyl butoxide (PBO) on the phototoxicity and tissue concentrations of three PAHs (fluoranthene, anthracene and pyrene) using C. tentans. Results indicated that phototoxicity (time to mortality) to the midge exposedmore » to PAH + PBO followed the order fluoranthene > pyrene {much_gt} anthracene. These differences in phototoxicity were not as marked in exposures without PBO. However, based on a lethal tissue dose (LD50), anthracene was the most toxic of the three. Tissue concentrations corresponded with toxicity results in that higher concentrations of PAH accumulated in exposures containing PBO. Though presence of PBO increased tissue concentrations and phototoxicity of the PAHs to the midge, the differences were slight and suggest that metabolism of PAHs by the cytochrome P450 pathway is not solely responsible for the midges relative insensitivity to this class of compounds.« less

Arginine vasopressin antagonizes the effects of prostaglandin E2 on the spontaneous activity of warm-sensitive and temperature-insensitive neurons in the medial preoptic area in rats.

PubMed

Xu, Jian-Hui; Hou, Xiao-Yu; Tang, Yu; Luo, Rong; Zhang, Jie; Liu, Chang; Yang, Yong-Lu

2018-01-01

Arginine vasopressin (AVP) plays an important role in thermoregulation and antipyresis. We have demonstrated that AVP could change the spontaneous activity of thermosensitive and temperature insensitive neurons in the preoptic area. However, whether AVP influences the effects of prostaglandin E 2 (PGE 2 ) on the spontaneous activity of neurons in the medial preoptic area (MPO) remains unclear. Our experiment showed that PGE 2 decreased the spontaneous activity of warm-sensitive neurons, and increased that of low-slope temperature-insensitive neurons in the MPO. AVP attenuated the inhibitory effect of PGE 2 on warm-sensitive neurons, and reversed the excitatory effect of PGE 2 on low-slope temperature-insensitive neurons, demonstrating that AVP antagonized the effects of PGE 2 on the spontaneous activity of these neurons. The effect of AVP was suppressed by an AVP V 1a receptor antagonist, suggesting that V 1a receptor mediated the action of AVP. We also demonstrated that AVP attenuated the PGE 2 -induced decrease in the prepotential's rate of rise in warm-sensitive neurons and the PGE 2 -induced increase in that in low-slope temperature-insensitive neurons through the V 1a receptor. Together, these data indicated that AVP antagonized the PGE 2 -induced change in the spontaneous activity of warm-sensitive and low-slope temperature-insensitive neurons in the MPO partly by reducing the PGE 2 -induced change in the prepotential of these neurons in a V 1a receptor-dependent manner. Copyright © 2017 Elsevier B.V. All rights reserved.

Experimental investigation of polarization insensitivity and cascadability with semiconductor optical amplifier-based differential phase-shift keyed wavelength converter

NASA Astrophysics Data System (ADS)

Mao, Yaya; Wu, Chongqing; Liu, Bo; Ullah, Rahat; Tian, Feng

2017-12-01

We experimentally investigate the polarization insensitivity and cascadability of an all-optical wavelength converter for differential phase-shift keyed (DPSK) signals for the first time. The proposed wavelength converter is composed of a one-bit delay interferometer demodulation stage followed by a single semiconductor optical amplifier. The impact of input DPSK signal polarization fluctuation on receiver sensitivity for the converted signal is carried out. It is found that this scheme is almost insensitive to the state of polarization of the input DPSK signal. Furthermore, the cascadability of the converter is demonstrated in a two-path recirculating loop. Error-free transmission is achieved with 20 stage cascaded wavelength conversions over 2800 km, where the power penalty is <3.4 dB at bit error rate of 10-9.

Tradeoff studies in multiobjective insensitive design of airplane control systems

NASA Technical Reports Server (NTRS)

Schy, A. A.; Giesy, D. P.

1983-01-01

A computer aided design method for multiobjective parameter-insensitive design of airplane control systems is described. Methods are presented for trading off nominal values of design objectives against sensitivities of the design objectives to parameter uncertainties, together with guidelines for designer utilization of the methods. The methods are illustrated by application to the design of a lateral stability augmentation system for two supersonic flight conditions of the Shuttle Orbiter. Objective functions are conventional handling quality measures and peak magnitudes of control deflections and rates. The uncertain parameters are assumed Gaussian, and numerical approximations of the stochastic behavior of the objectives are described. Results of applying the tradeoff methods to this example show that stochastic-insensitive designs are distinctly different from deterministic multiobjective designs. The main penalty for achieving significant decrease in sensitivity is decreased speed of response for the nominal system.

Design of pseudo-symmetric high bit rate, bend insensitive optical fiber applicable for high speed FTTH

NASA Astrophysics Data System (ADS)

Makouei, Somayeh; Koozekanani, Z. D.

2014-12-01

In this paper, with sophisticated modification on modal-field distribution and introducing new design procedure, the single-mode fiber with ultra-low bending-loss and pseudo-symmetric high bit-rate of uplink and downlink, appropriate for fiber-to-the-home (FTTH) operation is presented. The bending-loss reduction and dispersion management are done by the means of Genetic Algorithm. The remarkable feature of this methodology is designing a bend-insensitive fiber without reduction of core radius and MFD. Simulation results show bending loss of 1.27×10-2 dB/turn at 1.55 μm for 5 mm curvature radius. The MFD and Aeff are 9.03 μm and 59.11 μm2. Moreover, the upstream and downstream bit-rates are approximately 2.38 Gbit/s-km and 3.05 Gbit/s-km.

Molecular Origins of Internal Friction Effects on Protein Folding Rates

PubMed Central

Sirur, Anshul

2014-01-01

Recent experiments on protein folding dynamics have revealed strong evidence for internal friction effects. That is, observed relaxation times are not simply proportional to the solvent viscosity as might be expected if the solvent were the only source of friction. However, a molecular interpretation of this remarkable phenomenon is currently lacking. Here, we use all-atom simulations of peptide and protein folding in explicit solvent, to probe the origin of the unusual viscosity dependence. We find that an important contribution to this effect, explaining the viscosity dependence of helix formation and the folding of a helix-containing protein, is the insensitivity of torsion angle isomerization to solvent friction. The influence of this landscape roughness can, in turn, be quantitatively explained by a rate theory including memory friction. This insensitivity of local barrier crossing to solvent friction is expected to contribute to the viscosity dependence of folding rates in larger proteins. PMID:24986114

Molecular origins of internal friction effects on protein-folding rates.

PubMed

de Sancho, David; Sirur, Anshul; Best, Robert B

2014-07-02

Recent experiments on protein-folding dynamics have revealed strong evidence for internal friction effects. That is, observed relaxation times are not simply proportional to the solvent viscosity as might be expected if the solvent were the only source of friction. However, a molecular interpretation of this remarkable phenomenon is currently lacking. Here, we use all-atom simulations of peptide and protein folding in explicit solvent, to probe the origin of the unusual viscosity dependence. We find that an important contribution to this effect, explaining the viscosity dependence of helix formation and the folding of a helix-containing protein, is the insensitivity of torsion angle isomerization to solvent friction. The influence of this landscape roughness can, in turn, be quantitatively explained by a rate theory including memory friction. This insensitivity of local barrier crossing to solvent friction is expected to contribute to the viscosity dependence of folding rates in larger proteins.

Polarization insensitive all-fiber mode-lockers functioned by carbon nanotubes deposited onto tapered fibers

NASA Astrophysics Data System (ADS)

Song, Yong-Won; Morimune, Keiyo; Set, Sze Y.; Yamashita, Shinji

2007-01-01

The authors demonstrate a nonblocked all-fiber mode locker operated by the interaction of carbon nanotubes with the evanescent field of propagating light in a tapered fiber. Symmetric cross section of the device with the randomly oriented nanotubes guarantees the polarization insensitive operation of the pulse formation. In order to minimize the scattering, the carbon nanotubes are deposited within a designed area around the tapered waist. The demonstrated passively pulsed laser has the repetition rate of 7.3MHz and the pulse width of 829fs.

Polarization-insensitive ultralow-power second-harmonic generation frequency-resolved optical gating.

PubMed

Miao, Houxun; Weiner, Andrew M; Langrock, Carsten; Roussev, Rostislav V; Fejer, Martin M

2007-04-01

We demonstrate polarization-insensitive ultralow-power second-harmonic generation frequency-resolved optical gating (FROG) measurements with a fiber-pigtailed, aperiodically poled lithium niobate waveguide. By scrambling the polarization much faster than the measurement integration time, we eliminate the impairment that frequency-independent random polarization fluctuations induce in FROG measurements. As a result we are able to retrieve intensity and phase profiles of few hundred femtosecond optical pulses with 50 MHz repetition rates at 5.2 nW coupled average power without control of the input polarization.

Dose conversion coefficients for neutron exposure to the lens of the human eye.

PubMed

Manger, R P; Bellamy, M B; Eckerman, K F

2012-03-01

Dose conversion coefficients for the lens of the human eye have been calculated for neutron exposure at energies from 1 × 10(-9) to 20 MeV and several standard orientations: anterior-to-posterior, rotational and right lateral. MCNPX version 2.6.0, a Monte Carlo-based particle transport package, was used to determine the energy deposited in the lens of the eye. The human eyeball model was updated by partitioning the lens into sensitive and insensitive volumes as the anterior portion (sensitive volume) of the lens being more radiosensitive and prone to cataract formation. The updated eye model was used with the adult UF-ORNL mathematical phantom in the MCNPX transport calculations.

Rare behavior of growth processes via umbrella sampling of trajectories

NASA Astrophysics Data System (ADS)

Klymko, Katherine; Geissler, Phillip L.; Garrahan, Juan P.; Whitelam, Stephen

2018-03-01

We compute probability distributions of trajectory observables for reversible and irreversible growth processes. These results reveal a correspondence between reversible and irreversible processes, at particular points in parameter space, in terms of their typical and atypical trajectories. Thus key features of growth processes can be insensitive to the precise form of the rate constants used to generate them, recalling the insensitivity to microscopic details of certain equilibrium behavior. We obtained these results using a sampling method, inspired by the "s -ensemble" large-deviation formalism, that amounts to umbrella sampling in trajectory space. The method is a simple variant of existing approaches, and applies to ensembles of trajectories controlled by the total number of events. It can be used to determine large-deviation rate functions for trajectory observables in or out of equilibrium.

Iberiotoxin-sensitive and -insensitive BK currents in Purkinje neuron somata

PubMed Central

Benton, Mark D.; Lewis, Amanda H.; Bant, Jason S.

2013-01-01

Purkinje cells have specialized intrinsic ionic conductances that generate high-frequency action potentials. Disruptions of their Ca or Ca-activated K (KCa) currents correlate with altered firing patterns in vitro and impaired motor behavior in vivo. To examine the properties of somatic KCa currents, we recorded voltage-clamped KCa currents in Purkinje cell bodies isolated from postnatal day 17–21 mouse cerebellum. Currents were evoked by endogenous Ca influx with approximately physiological Ca buffering. Purkinje somata expressed voltage-activated, Cd-sensitive KCa currents with iberiotoxin (IBTX)-sensitive (>100 nS) and IBTX-insensitive (>75 nS) components. IBTX-sensitive currents activated and partially inactivated within milliseconds. Rapid, incomplete macroscopic inactivation was also evident during 50- or 100-Hz trains of 1-ms depolarizations. In contrast, IBTX-insensitive currents activated more slowly and did not inactivate. These currents were insensitive to the small- and intermediate-conductance KCa channel blockers apamin, scyllatoxin, UCL1684, bicuculline methiodide, and TRAM-34, but were largely blocked by 1 mM tetraethylammonium. The underlying channels had single-channel conductances of ∼150 pS, suggesting that the currents are carried by IBTX-resistant (β4-containing) large-conductance KCa (BK) channels. IBTX-insensitive currents were nevertheless increased by small-conductance KCa channel agonists EBIO, chlorzoxazone, and CyPPA. During trains of brief depolarizations, IBTX-insensitive currents flowed during interstep intervals, and the accumulation of interstep outward current was enhanced by EBIO. In current clamp, EBIO slowed spiking, especially during depolarizing current injections. The two components of BK current in Purkinje somata likely contribute differently to spike repolarization and firing rate. Moreover, augmentation of BK current may partially underlie the action of EBIO and chlorzoxazone to alleviate disrupted Purkinje cell firing associated with genetic ataxias. PMID:23446695

Dynamics of leaf and spikelet primordia initiation in wheat as affected by Ppd-1a alleles under field conditions.

PubMed

Ochagavía, Helga; Prieto, Paula; Savin, Roxana; Griffiths, Simon; Slafer, GustavoA

2018-04-27

Wheat adaptation is affected by Ppd genes, but the role of these alleles in the rates of leaf and spikelet initiation has not been properly analysed. Twelve near isogenic lines (NILs) combining Ppd-1a alleles from different donors introgressed in A, B, and/or D genomes were tested under field conditions during two growing seasons together with the wild type, Paragon. Leaf initiation rate was unaffected by Ppd-1a alleles so the final leaf number (FLN) was reduced in parallel with reductions in the duration of the vegetative phase. Spikelet primordia initiation was accelerated and consequently the effect on spikelets per spike was less than proportional to the effect on the duration of spikelet initiation. The magnitude of these effects on spikelet plastochron depended on the doses of Ppd-1 homoeoalleles and the specific insensitivity alleles carried. Double ridge was consistently later than floral initiation, but the difference between them was not affected by Ppd-1a alleles. These findings have potential for selecting the best combinations from the Ppd-1 homoeoallelic series for manipulating adaptation taking into consideration particular effects on spikelet number.

Dynamics of leaf and spikelet primordia initiation in wheat as affected by Ppd-1a alleles under field conditions

PubMed Central

Ochagavía, Helga; Prieto, Paula; Griffiths, Simon

2018-01-01

Abstract Wheat adaptation is affected by Ppd genes, but the role of these alleles in the rates of leaf and spikelet initiation has not been properly analysed. Twelve near isogenic lines (NILs) combining Ppd-1a alleles from different donors introgressed in A, B, and/or D genomes were tested under field conditions during two growing seasons together with the wild type, Paragon. Leaf initiation rate was unaffected by Ppd-1a alleles so the final leaf number (FLN) was reduced in parallel with reductions in the duration of the vegetative phase. Spikelet primordia initiation was accelerated and consequently the effect on spikelets per spike was less than proportional to the effect on the duration of spikelet initiation. The magnitude of these effects on spikelet plastochron depended on the doses of Ppd-1 homoeoalleles and the specific insensitivity alleles carried. Double ridge was consistently later than floral initiation, but the difference between them was not affected by Ppd-1a alleles. These findings have potential for selecting the best combinations from the Ppd-1 homoeoallelic series for manipulating adaptation taking into consideration particular effects on spikelet number. PMID:29562296

Urine colorimetry to detect Low rifampin exposure during tuberculosis therapy: a proof-of-concept study.

PubMed

Zentner, Isaac; Schlecht, Hans P; Khensouvann, Lorna; Tamuhla, Neo; Kutzler, Michele; Ivaturi, Vijay; Pasipanodya, Jotam G; Gumbo, Tawanda; Peloquin, Charles A; Bisson, Gregory P; Vinnard, Christopher

2016-06-01

The cost and complexity of current approaches to therapeutic drug monitoring during tuberculosis (TB) therapy limits widespread use in areas of greatest need. We sought to determine whether urine colorimetry could have a novel application as a form of therapeutic drug monitoring during anti-TB therapy. Among healthy volunteers, we evaluated 3 dose sizes of rifampin (150 mg, 300 mg, and 600 mg), performed intensive pharmacokinetic sampling, and collected a timed urine void at 4 h post-dosing. The absorbance peak at 475 nm was measured after rifamycin extraction. The optimal cutoff was evaluated in a study of 39 HIV/TB patients undergoing TB treatment in Botswana. In the derivation study, a urine colorimetric assay value of 4.0 × 10(-2) Abs, using a timed void 4 h after dosing, demonstrated a sensitivity of 92 % and specificity of 60 % to detect a peak rifampin concentration (Cmax) under 8 mg/L, with an area under the ROC curve of 0.92. In the validation study, this cutoff was specific (100 %) but insensitive (28 %). We observed similar test characteristics for a target Cmax target of 6.6 mg/L, and a target area under the drug concentration-versus-time curve (AUC0-8) target of 24.1 mg•hour/L. The urine colorimetric assay was specific but insensitive to detect low rifampin serum concentrations among HIV/TB patients. In future work we will attempt to optimize sampling times and assay performance, with the goal of delivering a method that can translate into a point-of-care assessment of rifampin exposure during anti-TB therapy.

Ethanol induces impulsive-like responding in a delay-of-reward operant choice procedure: impulsivity predicts autoshaping.

PubMed

Tomie, A; Aguado, A S; Pohorecky, L A; Benjamin, D

1998-10-01

Autoshaping conditioned responses (CRs) are reflexive and targeted motor responses expressed as a result of experience with reward. To evaluate the hypothesis that autoshaping may be a form of impulsive responding, within-subjects correlations between performance on autoshaping and impulsivity tasks were assessed in 15 Long-Evans hooded rats. Autoshaping procedures [insertion of retractable lever conditioned stimulus (CS) followed by the response-independent delivery of food (US)] were followed by testing for impulsive-like responding in a two-choice lever-press operant delay-of-reward procedure (immediate small food reward versus delayed large food reward). Delay-of-reward functions revealed two distinct subject populations. Subjects in the Sensitive group (n=7) were more impulsive-like, increasing immediate reward choices at longer delays for large reward, while those in the Insensitive group (n=8) responded predominantly on only one lever. During the prior autoshaping phase, the Sensitive group had performed more autoshaping CRs, and correlations revealed that impulsive subjects acquired the autoshaping CR in fewer trials. In the Sensitive group, acute injections of ethanol (0, 0.25, 0.50, 1.00, 1.50 g/kg) given immediately before delay-of-reward sessions yielded an inverted U-shaped dose-response curve with increased impulsivity induced by the 0.25, 0.50, and 1.00 g/kg doses of ethanol, while choice strategy of the Insensitive group was not influenced by ethanol dose. Ethanol induced impulsive-like responding only in rats that were flexible in their response strategy (Sensitive group), and this group also performed more autoshaping CRs. Data support the hypothesis that autoshaping and impulsivity are linked.

Matching Electron Beams Without Secondary Collimation for Treatment of Extensive Recurrent Chest-Wall Carcinoma

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

Feygelman, Vladimir; Department of Physics, University of Manitoba, Winnipeg, MB; Mandelzweig, Yuri

2015-01-15

Matching electron beams without secondary collimators (applicators) were used for treatment of extensive, recurrent chest-wall carcinoma. Due to the wide penumbra of such beams, the homogeneity of the dose distribution at and around the junction point is clinically acceptable and relatively insensitive to positional errors. Specifically, dose around the junction point is homogeneous to within ±4% as calculated from beam profiles, while the positional error of 1 cm leaves this number essentially unchanged. The experimental isodose distribution in an anthropomorphic phantom supports this conclusion. Two electron beams with wide penumbra were used to cover the desired treatment area with satisfactorymore » dose homogeneity. The technique is relatively simple yet clinically useful and can be considered a viable alternative for treatment of extensive chest-wall disease. The steps are suggested to make this technique more universal.« less

Effect of N. sativa oil on impaired glucose tolerance and insulin insensitivity induced by high-fat-diet and turpentine-induced trauma.

PubMed

Alsaif, Mohammed A

2008-04-15

The aim of this study was to investigate the effect of N. sativa oil on impaired glucose tolerance and insulin insensitivity induced by high-fat diet and trauma. Three dietary groups were used in this study; Rat-Chow (RC), N. sativa oil diet (Combination 4% N. sativa oil and 16% butter oil) (NSOD) and 20% Butter Oil Diet (BOD). Each group was subdivided in two groups; control and trauma. Diets were supplemented for five consecutive weeks body weight increase per week was calculated. At end of the dietary treatments, single dose (2 mL kg(-1) body weight) of turpentine was injected in the dorso-lumber region. Intravenous glucose tolerance test (i.v. GTT) was performed, insulinogenic index and insulin sensitivity was measured. The results showed butter oil diet significantly increased the body weights and visceral fats compared other two groups, respectively. Fasting glucose levels did not change in trauma induced rats while insulin levels increased significantly and it found highest in butter oil diet fed animals. Impaired glucose tolerance was found sever in BOD fed traumatized rats. N. sativa oil diet protected impaired glucose tolerance and insulin insensitivity induced either via saturated fatty acids or injury. In conclusion, N. sativa oil may be used in post surgery diabetic patients to prevent the long going adverse effects from surgical trauma.

Dose conversion coefficients for neutron exposure to the lens of the human eye

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

Manger, Ryan P; Bellamy, Michael B; Eckerman, Keith F

Dose conversion coefficients for the lens of the human eye have been calculated for neutron exposure at energies from 1 x 10{sup -9} to 20 MeV and several standard orientations: anterior-to-posterior, rotational and right lateral. MCNPX version 2.6.0, a Monte Carlo-based particle transport package, was used to determine the energy deposited in the lens of the eye. The human eyeball model was updated by partitioning the lens into sensitive and insensitive volumes as the anterior portion (sensitive volume) of the lens being more radiosensitive and prone to cataract formation. The updated eye model was used with the adult UF-ORNL mathematicalmore » phantom in the MCNPX transport calculations.« less

Measurement of Absorbed Dose from Radionuclide Solutions Mixed Intimately with the Fbx Dosimeter.

NASA Astrophysics Data System (ADS)

Benedetto, Anthony Richard

Chemical dosimeters are used widely for accurate measurement of large radiation doses due to external beam irradiation from radioisotope sources and from particle accelerators. Their use for measurement of absorbed doses from radioactive solutions mixed in the dosimeter solution was reported as early as 1952, but the large activities needed to produce suitable absorbance values in the relatively insensitive dosimeters of that time discouraged further work. This manuscript reports the results of an investigation into the suitability of the ferrous sulfate-benzoic acid -xylenol orange (FBX) dosimeter for measurement of small absorbed doses caused by radionuclide solutions dissolved in the dosimeter solution. The FBX dosimeter exhibited a linear dose response as a function of activity for two common radiopharmaceuticals, technetium-99m sodium pertechnetate and iodine-131 sodium iodide. Conditions under which the FBX dosimeter may be used with radionuclide solutions were studied and were found to be amenable to routine use by laboratories possessing relatively unsophisticated instrumentation. It appears likely that any radionuclide could be studied using this dosimeter. Finally, potential applications and future research work are suggested, including measurement of absorbed dose from radiopharmaceuticals using realistic human-like phantoms to assess the risk from clinical nuclear medicine studies.

Bioaccumulation kinetics of the conventional energetics TNT and RDX relative to insensitive munitions constituents DNAN and NTO in Rana pipiens tadpoles.

PubMed

Lotufo, Guilherme R; Biedenbach, James M; Sims, Jerre G; Chappell, Pornsawan; Stanley, Jacob K; Gust, Kurt A

2015-04-01

The manufacturing of explosives and their loading, assembling, and packing into munitions for use in testing on training sites or battlefields has resulted in contamination of terrestrial and aquatic sites that may pose risk to populations of sensitive species. The bioaccumulative potential of the conventional explosives 2,4,6-trinitrotoluene (TNT) and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and of the insensitive munitions (i.e., less shock sensitive) compound 2,4-dinitroanisole (DNAN) were assessed using the Northern leopard frog, Rana pipiens. Trinitrotoluene entering the organism was readily biotransformed to aminodinitrotoluenes, whereas no transformation products were measured for RDX or DNAN. Uptake clearance rates were relatively slow and similar among compounds (1.32-2.19 L kg(-1) h(-1) ). Upon transfer to uncontaminated water, elimination rate was very fast, resulting in the prediction of fast time to approach steady state (5 h or less) and short elimination half-lives (1.2 h or less). A preliminary bioconcentration factor of 0.25 L kg(-1) was determined for the insensitive munitions compound 3-nitro-1,2,4-trizole-5-one (NTO) indicating negligible bioaccumulative potential. Because of the rapid elimination rate for explosives, tadpoles inhabiting contaminated areas are expected to experience harmful effects only if under constant exposure conditions given that body burdens can rapidly depurate preventing tissue concentrations from persisting at levels that may cause detrimental biological effects. © 2014 SETAC.

Sensitivity analysis of radionuclides atmospheric dispersion following the Fukushima accident

NASA Astrophysics Data System (ADS)

Girard, Sylvain; Korsakissok, Irène; Mallet, Vivien

2014-05-01

Atmospheric dispersion models are used in response to accidental releases with two purposes: - minimising the population exposure during the accident; - complementing field measurements for the assessment of short and long term environmental and sanitary impacts. The predictions of these models are subject to considerable uncertainties of various origins. Notably, input data, such as meteorological fields or estimations of emitted quantities as function of time, are highly uncertain. The case studied here is the atmospheric release of radionuclides following the Fukushima Daiichi disaster. The model used in this study is Polyphemus/Polair3D, from which derives IRSN's operational long distance atmospheric dispersion model ldX. A sensitivity analysis was conducted in order to estimate the relative importance of a set of identified uncertainty sources. The complexity of this task was increased by four characteristics shared by most environmental models: - high dimensional inputs; - correlated inputs or inputs with complex structures; - high dimensional output; - multiplicity of purposes that require sophisticated and non-systematic post-processing of the output. The sensitivities of a set of outputs were estimated with the Morris screening method. The input ranking was highly dependent on the considered output. Yet, a few variables, such as horizontal diffusion coefficient or clouds thickness, were found to have a weak influence on most of them and could be discarded from further studies. The sensitivity analysis procedure was also applied to indicators of the model performance computed on a set of gamma dose rates observations. This original approach is of particular interest since observations could be used later to calibrate the input variables probability distributions. Indeed, only the variables that are influential on performance scores are likely to allow for calibration. An indicator based on emission peaks time matching was elaborated in order to complement classical statistical scores which were dominated by deposit dose rates and almost insensitive to lower atmosphere dose rates. The substantial sensitivity of these performance indicators is auspicious for future calibration attempts and indicates that the simple perturbations used here may be sufficient to represent an essential part of the overall uncertainty.

Physical basis for altered stem elongation rates in internode length mutants of Pisum

NASA Technical Reports Server (NTRS)

Behringer, F. J.; Cosgrove, D. J.; Reid, J. B.; Davies, P. J.

1990-01-01

Biophysical parameters related to gibberellin (GA)-dependent stem elongation were examined in dark-grown stem-length genotypes of Pisum sativum L. The rate of internode expansion in these genotypes is altered due to recessive mutations which affect either the endogenous levels of, or response to, GA. The GA deficient dwarf L181 (ls), two GA insensitive semierectoides dwarfs NGB5865 and NGB5862 (lka and lkb, respectively) and the slender' line L197 (la crys), which is tall regardless of GA content, were compared to the wild-type tall cultivar, Torsdag. Osmotic pressure, estimated by vapor pressure osmometry, and turgor pressure, measured directly with a pressure probe, did not correlate with the differences in growth rate among the genotypes. Mechanical wall properties of frozen-thawed tissue were measured using a constant force assay. GA deficiency resulted in increased wall stiffness judged both on the basis of plastic compliance and plastic extensibility normalized for equal stem circumference. Plastic compliance was not reduced in the GA insensitive dwarfs, though lka reduced circumference-normalized plasticity. In contrast, in vivo wall relaxation, determined by the pressure-block technique, differed among genotypes in a manner which did correlate with extension rates. The wall yield threshold was 1 bar or less in the tall lines, but ranged from 3 to 6 bars in the dwarf genotypes. The results with the ls mutant indicate that GA enhances stem elongation by both decreasing the wall yield threshold and increasing the wall yield coefficient. In the GA-insensitive mutants, lka and lkb, the wall yield threshold is substantially elevated. Plants possessing lka may also possess a reduced wall yield coefficient.

Demonstration of 20Gb/s polarization-insensitive wavelength switching system for high-speed free-space optical network

NASA Astrophysics Data System (ADS)

Qian, Feng-chen; Ye, Ya-lin; Wen, Yu; Duan, Tao; Feng, Huan

2015-10-01

A 20Gb/s polarization-insensitive all-optical wavelength switching system for high-speed free-space optical communication (FSO) network is experimentally demonstrated All-optical wavelength conversion (AOWC) is implemented using four-wave mixing (FWM) by highly-nonlinear fiber (HNLF). In the experimental setup, a simple actively mode-locked fiber ring laser (AML-FRL) with repetition frequency from 1 to 15 GHz is used to generate eight 2.5Gb/s tributary signals, which are multiplexed into one 20Gb/s optical data stream. At the receiver, the 20 Gb/s OTDM data stream is demultiplexed down to 2.5 Gb/s via a polarization-insensitive FWM scheme. The whole space communication distance is over 10 meters in building hallway. The experimental results show that this system can stably run over 24 hours at 10-9 BER level, thus the proposed architecture can work at higher rate with wavelength-division multiplexing (WDM) and high order modulation schemes.

CT dose equilibration and energy absorption in polyethylene cylinders with diameters from 6 to 55 cm

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

Li, Xinhua; Zhang, Da; Liu, Bob, E-mail: bliu7@mgh.harvard.edu

2015-06-15

Purpose: ICRU Report No. 87 Committee and AAPM Task Group 200 designed a three-sectional polyethylene phantom of 30 cm in diameter and 60 cm in length for evaluating the midpoint dose D{sub L}(0) and its rise-to-the-equilibrium curve H(L) = D{sub L}(0)/D{sub eq} from computed tomography (CT) scanning, where D{sub eq} is the equilibrium dose. To aid the use of the phantom in radiation dose assessment and to gain an understanding of dose equilibration and energy absorption in polyethylene, the authors evaluated the short (20 cm) to long (60 cm) phantom dose ratio with a polyethylene diameter of 30 cm, assessedmore » H(L) in polyethylene cylinders of 6–55 cm in diameters, and examined energy absorption in these cylinders. Methods: A GEANT4-based Monte Carlo program was used to simulate the single axial scans of polyethylene cylinders (diameters 6–55 cm and length 90 cm, as well as diameter 30 cm and lengths 20 and 60 cm) on a clinical CT scanner (Somatom Definition dual source CT, Siemens Healthcare). Axial dose distributions were computed on the phantom central and peripheral axes. An average dose over the central 23 or 100 mm region was evaluated for modeling dose measurement using a 0.6 cm{sup 3} thimble chamber or a 10 cm long pencil ion chamber, respectively. The short (20 cm) to long (90 cm) phantom dose ratios were calculated for the 30 cm diameter polyethylene phantoms scanned at four tube voltages (80–140 kV) and a range of beam apertures (1–25 cm). H(L) was evaluated using the dose integrals computed with the 90 cm long phantoms. The resultant H(L) data were subsequently used to compute the fraction of the total energy absorbed inside or outside the scan range (E{sub in}/E or E{sub out}/E) on the phantom central and peripheral axes, where E = LD{sub eq} was the total energy absorbed along the z axis. Results: The midpoint dose in the 60 cm long polyethylene phantom was equal to that in the 90 cm long polyethylene phantom. The short-to-long phantom dose ratios changed with beam aperture and phantom axis but were insensitive to tube voltage. H(L) was insensitive to tube voltage and CT scanner model. As phantom diameter increased from 6 to 55 cm, E{sub in}/E generally decreased but asymptotically approached constant levels on the peripheral axes of large phantoms. The curve of E{sub in}/E versus scan length was almost identical to that of H(L). Similarly, E{sub out}/E increased with scan length and asymptotically approached the equilibrium for large scan lengths. E{sub out}/D{sub eq} was much less than the equilibrium length L{sub eq} where H(L) = 0.98, even with scan lengths much larger than L{sub eq}. Conclusions: The polyethylene phantom designed by ICRU Report No. 87 Committee and AAPM Task Group 200 is adequately long for assessing the midpoint dose and its equilibration in CT scanning. The short-to-long phantom dose ratios and the H(L) data provided in this paper allow easy evaluations of the midpoint dose, longitudinal dose distribution, and energy absorption in polyethylene phantoms. The results of dose equilibration and energy absorption presented herein may be insightful for the clinical CT scans with various subject sizes and scan lengths.« less

Toward acquiring comprehensive radiosurgery field commissioning data using the PRESAGE®/ optical-CT 3D dosimetry system

NASA Astrophysics Data System (ADS)

Clift, Corey; Thomas, Andrew; Adamovics, John; Chang, Zheng; Das, Indra; Oldham, Mark

2010-03-01

Achieving accurate small field dosimetry is challenging. This study investigates the utility of a radiochromic plastic PRESAGE® read with optical-CT for the acquisition of radiosurgery field commissioning data from a Novalis Tx system with a high-definition multileaf collimator (HDMLC). Total scatter factors (Sc, p), beam profiles, and penumbrae were measured for five different radiosurgery fields (5, 10, 20, 30 and 40 mm) using a commercially available optical-CT scanner (OCTOPUS, MGS Research). The percent depth dose (PDD), beam profile and penumbra of the 10 mm field were also measured using a higher resolution in-house prototype CCD-based scanner. Gafchromic EBT® film was used for independent verification. Measurements of Sc, p made with PRESAGE® and film agreed with mini-ion chamber commissioning data to within 4% for every field (range 0.2-3.6% for PRESAGE®, and 1.6-3.6% for EBT). PDD, beam profile and penumbra measurements made with the two PRESAGE®/optical-CT systems and film showed good agreement with the high-resolution diode commissioning measurements with a competitive resolution (0.5 mm pixels). The in-house prototype optical-CT scanner allowed much finer resolution compared with previous applications of PRESAGE®. The advantages of the PRESAGE® system for small field dosimetry include 3D measurements, negligible volume averaging, directional insensitivity, an absence of beam perturbations, energy and dose rate independence.

Toward acquiring comprehensive radiosurgery field commissioning data using the PRESAGE®/optical-CT 3D dosimetry system

PubMed Central

Clift, Corey; Thomas, Andrew; Adamovics, John; Chang, Zheng; Das, Indra; Oldham, Mark

2010-01-01

Achieving accurate small field dosimetry is challenging. This study investigates the utility of a radiochromic plastic PRESAGE® read with optical-CT for the acquisition of radiosurgery field commissioning data from a Novalis Tx system with a high-definition multileaf collimator (HDMLC). Total scatter factors (Sc, p), beam profiles, and penumbrae were measured for five different radiosurgery fields (5, 10, 20, 30 and 40 mm) using a commercially available optical-CT scanner (OCTOPUS, MGS Research). The percent depth dose (PDD), beam profile and penumbra of the 10 mm field were also measured using a higher resolution in-house prototype CCD-based scanner. Gafchromic EBT® film was used for independent verification. Measurements of Sc, p made with PRESAGE® and film agreed with mini-ion chamber commissioning data to within 4% for every field (range 0.2–3.6% for PRESAGE®, and 1.6–3.6% for EBT). PDD, beam profile and penumbra measurements made with the two PRESAGE®/optical-CT systems and film showed good agreement with the high-resolution diode commissioning measurements with a competitive resolution (0.5 mm pixels). The in-house prototype optical-CT scanner allowed much finer resolution compared with previous applications of PRESAGE®. The advantages of the PRESAGE® system for small field dosimetry include 3D measurements, negligible volume averaging, directional insensitivity, an absence of beam perturbations, energy and dose rate independence. PMID:20134082

RNASeq-derived transcriptome comparisons reveal neuromodulatory deficiency in the CO2 insensitive brown Norway rat

PubMed Central

Puissant, Madeleine M; Echert, Ashley E; Yang, Chun; Mouradian, Gary C; Novotny, Tyler; Liu, Pengyuan; Liang, Mingyu; Hodges, Matthew R

2015-01-01

Raphé-derived serotonin (5-HT) and thyrotropin-releasing hormone (TRH) play important roles in fundamental, homeostatic control systems such as breathing and specifically the ventilatory CO2 chemoreflex. Brown Norway (BN) rats exhibit an inherent and severe ventilatory insensitivity to hypercapnia but also exhibit relatively normal ventilation at rest and during other conditions, similar to multiple genetic models of 5-HT system dysfunction in mice. Herein, we tested the hypothesis that the ventilatory insensitivity to hypercapnia in BN rats is due to altered raphé gene expression and the consequent deficiencies in raphé-derived neuromodulators such as TRH. Medullary raphé transcriptome comparisons revealed lower expression of multiple 5-HT neuron-specific genes in BN compared to control Dahl salt-sensitive rats, predictive of reduced central nervous system monoamines by bioinformatics analyses and confirmed by high-performance liquid chromatography measurements. In particular, raphé Trh mRNA and peptide levels were significantly reduced in BN rats, and injections of the stable TRH analogue Taltirelin (TAL) stimulated breathing dose-dependently, with greater effects in BN versus control Sprague–Dawley rats. Importantly, TAL also effectively normalized the ventilatory CO2 chemoreflex in BN rats, but TAL did not affect CO2 sensitivity in control Sprague–Dawley rats. These data establish a molecular basis of the neuromodulatory deficiency in BN rats, and further suggest an important functional role for TRH signalling in the mammalian CO2 chemoreflex. PMID:25630262

Oral toxicity of 3-nitro-1,2,4-triazol-5-one in rats.

PubMed

Crouse, Lee C B; Lent, Emily May; Leach, Glenn J

2015-01-01

3-Nitro-1,2,4-triazol-5-one (NTO), an insensitive explosive, was evaluated to assess potential environmental and human health effects. A 14-day oral toxicity study in Sprague-Dawley rats was conducted with NTO in polyethylene glycol -200 by gavage at doses of 0, 250, 500, 1000, 1500, or 2000 mg/kg-d. Body mass and food consumption decreased in males (2000 mg/kg-d), and testes mass was reduced at doses of 500 mg/kg-d and greater. Based on the findings in the 14-day study, a 90-day study was conducted at doses of 0, 30, 100, 315, or 1000 mg/kg-d NTO. There was no effect on food consumption, body mass, or neurobehavioral parameters. Males in the 315 and 1000 mg/kg-d groups had reduced testes mass with associated tubular degeneration and atrophy. The testicular effects were the most sensitive adverse effect and were used to derive a benchmark dose (BMD) of 70 mg/kg-d with a 10% effect level (BMDL10) of 40 mg/kg-d. © The Author(s) 2015.

Inhibition of the HDAC/Suv39/G9a pathway restores the expression of DNA damage-dependent major histocompatibility complex class I-related chain A and B in cancer cells.

PubMed

Nakajima, Nakako Izumi; Niimi, Atsuko; Isono, Mayu; Oike, Takahiro; Sato, Hiro; Nakano, Takashi; Shibata, Atsushi

2017-08-01

Immunotherapy is expected to be promising as a next generation cancer therapy. Immunoreceptors are often activated constitutively in cancer cells, however, such levels of ligand expression are not effectively recognized by the native immune system due to tumor microenvironmental adaptation. Studies have demonstrated that natural-killer group 2, member D (NKG2D), a major activating immunoreceptor, responds to DNA damage. The upregulation of major histocompatibility complex class I-related chain A and B (MICA/B) (members of NKG2D ligands) expression after DNA damage is associated with NK cell-mediated killing of cancer cells. However, the regulation of DNA damage-induced MICA/B expression has not been fully elucidated in the context of the types of cancer cell lines. In the present study, we found that MICA/B expression varied between cancer cell lines after DNA damage. Screening in terms of chromatin remodeling identified that inhibitors related to chromatin relaxation via post-translational modification on histone H3K9, i.e. HDAC, Suv39 or G9a inhibition, restored DNA damage-dependent MICA/B expression in insensitive cells. In addition, we revealed that the restored MICA/B expression was dependent on ATR as well as E2F1, a transcription factor. We further revealed that low‑dose treatment of an HDAC inhibitor was sufficient to restore MICA/B expression in insensitive cells. Finally, we demonstrated that HDAC inhibition restored DNA damage‑dependent cytotoxic NK activity against insensitive cells. Thus, the present study revealed that DNA damage‑dependent MICA/B expression in insensitive cancer cells can be restored by chromatin relaxation via the HDAC/Suv39/G9a pathway. Collectively, manipulation of chromatin status by therapeutic cancer drugs may potentiate the antitumor effect by enhancing immune activation following radiotherapy and DNA damage-associated chemotherapy.

A tertiary care experience with paclitaxel and cetuximab as palliative chemotherapy in platinum sensitive and nonsensitive in head and neck cancers

PubMed Central

Noronha, Vanita; Patil, Vijay M.; Joshi, Amit; Bhattacharjee, Atanu; Paul, Davinder; Dhumal, Sachin; Juvekar, Shashikant; Arya, Supreeta; Prabhash, Kumar

2017-01-01

Background: The combination of paclitaxel and cetuximab (PaCe) has led to an encouraging response rate in Phase 2 setting with limited toxicity. The aim of our study was to assess the efficacy of this regimen in our setting in platinum sensitive and nonsensitive patients. Methods: This was a retrospective analysis of head and neck cancer patients treated with weekly PaCe as palliative chemotherapy between May 2010 and August 2014. The standard schedule of cetuximab along with 80 mg/m2 of weekly paclitaxel was administered till either disease progression or withdrawal of patient's consent. The toxicity and response were noted in accordance with CTCAE version 4.02 and RECIST version 1.1 criteria, respectively. The response rates between platinum sensitive and nonsensitive patients were compared by Chi-square test. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan–Meier survival method and log-rank test was used for comparison. Cox proportional hazard model was used for identification of factors affecting PFS and OS. Results: One Hundred patients with a median age of 52 years (interquartile range: 46–56 years) were included. Forty-five patients (45%) were platinum insensitive, whereas 55 patients (55%) were platinum sensitive. In platinum insensitive patients and sensitive patients, the response rates were 38.5% and 22.2%, respectively (P = 0.104), whereas the symptomatic benefit in pain was seen in 89.5% and 71.7%, respectively (P = 0.044). The median PFS in platinum insensitive and sensitive patients were 150 and 152 days, respectively (P = 0.932), whereas the median OS was 256 days (95% confidence interval [95% CI]: 168.2–343.8 days) and 314 days (95% CI: 227.6–400.4 days), respectively (P = 0.23). Nineteen patients (19%) had grades 3–4 adverse events during chemotherapy. Conclusion: Weekly paclitaxel combined with cetuximab has promising efficacy and good tolerability in the palliative setting in advanced head and neck cancer in both platinum sensitive and insensitive patients. PMID:28413788

The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate

PubMed Central

Gergely, P; Nuesslein-Hildesheim, B; Guerini, D; Brinkmann, V; Traebert, M; Bruns, C; Pan, S; Gray, NS; Hinterding, K; Cooke, NG; Groenewegen, A; Vitaliti, A; Sing, T; Luttringer, O; Yang, J; Gardin, A; Wang, N; Crumb, WJ; Saltzman, M; Rosenberg, M; Wallström, E

2012-01-01

BACKGROUND AND PURPOSE BAF312 is a next-generation sphingosine 1-phosphate (S1P) receptor modulator, selective for S1P1 and S1P5 receptors. S1P1 receptors are essential for lymphocyte egress from lymph nodes and a drug target in immune-mediated diseases. Here, we have characterized the immunomodulatory potential of BAF312 and the S1P receptor-mediated effects on heart rate using preclinical and human data. EXPERIMENTAL APPROACH BAF312 was tested in a rat experimental autoimmune encephalomyelitis (EAE) model. Electrophysiological recordings of G-protein-coupled inwardly rectifying potassium (GIRK) channels were carried out in human atrial myocytes. A Phase I multiple-dose trial studied the pharmacokinetics, pharmacodynamics and safety of BAF312 in 48 healthy subjects. KEY RESULTS BAF312 effectively suppressed EAE in rats by internalizing S1P1 receptors, rendering them insensitive to the egress signal from lymph nodes. In healthy volunteers, BAF312 caused preferential decreases in CD4+ T cells, Tnaïve, Tcentral memory and B cells within 4–6 h. Cell counts returned to normal ranges within a week after stopping treatment, in line with the elimination half-life of BAF312. Despite sparing S1P3 receptors (associated with bradycardia in mice), BAF312 induced rapid, transient (day 1 only) bradycardia in humans. BAF312-mediated activation of GIRK channels in human atrial myocytes can fully explain the bradycardia. CONCLUSION AND IMPLICATIONS This study illustrates species-specific differences in S1P receptor specificity for first-dose cardiac effects. Based on its profound but rapidly reversible inhibition of lymphocyte trafficking, BAF312 may have potential as a treatment for immune-mediated diseases. PMID:22646698

QMRA for Drinking Water: 2. The Effect of Pathogen Clustering in Single-Hit Dose-Response Models.

PubMed

Nilsen, Vegard; Wyller, John

2016-01-01

Spatial and/or temporal clustering of pathogens will invalidate the commonly used assumption of Poisson-distributed pathogen counts (doses) in quantitative microbial risk assessment. In this work, the theoretically predicted effect of spatial clustering in conventional "single-hit" dose-response models is investigated by employing the stuttering Poisson distribution, a very general family of count distributions that naturally models pathogen clustering and contains the Poisson and negative binomial distributions as special cases. The analysis is facilitated by formulating the dose-response models in terms of probability generating functions. It is shown formally that the theoretical single-hit risk obtained with a stuttering Poisson distribution is lower than that obtained with a Poisson distribution, assuming identical mean doses. A similar result holds for mixed Poisson distributions. Numerical examples indicate that the theoretical single-hit risk is fairly insensitive to moderate clustering, though the effect tends to be more pronounced for low mean doses. Furthermore, using Jensen's inequality, an upper bound on risk is derived that tends to better approximate the exact theoretical single-hit risk for highly overdispersed dose distributions. The bound holds with any dose distribution (characterized by its mean and zero inflation index) and any conditional dose-response model that is concave in the dose variable. Its application is exemplified with published data from Norovirus feeding trials, for which some of the administered doses were prepared from an inoculum of aggregated viruses. The potential implications of clustering for dose-response assessment as well as practical risk characterization are discussed. © 2016 Society for Risk Analysis.

Nonadherence in the era of severe asthma biologics and thermoplasty

PubMed Central

Lee, Joy; Tay, Tunn Ren; Radhakrishna, Naghmeh; Hore-Lacy, Fiona; Mackay, Anna; Hoy, Ryan; Dabscheck, Eli; O'Hehir, Robyn; Hew, Mark

2018-01-01

Nonadherence to inhaled preventers impairs asthma control. Electronic monitoring devices (EMDs) can objectively measure adherence. Their use has not been reported in difficult asthma patients potentially suitable for novel therapies, i.e. biologics and bronchial thermoplasty. Consecutive patients with difficult asthma were assessed for eligibility for novel therapies. Medication adherence, defined as taking >75% of prescribed doses, was assessed by EMD and compared with standardised clinician assessment over an 8-week period. Among 69 difficult asthma patients, adherence could not be analysed in 13, due to device incompatibility or malfunction. Nonadherence was confirmed in 20 out of 45 (44.4%) patients. Clinical assessment of nonadherence was insensitive (physician 15%, nurse 28%). Serum eosinophils were higher in nonadherent patients. Including 11 patients with possible nonadherence (device refused or not returned) increased the nonadherence rate to 31 out of 56 (55%) patients. Severe asthma criteria were fulfilled by 59 out of 69 patients. 47 were eligible for novel therapies, with confirmed nonadherence in 16 out of 32 (50%) patients with EMD data; including seven patients with possible nonadherence increased the nonadherence rate to 23 out of 39 (59%). At least half the patients eligible for novel therapies were nonadherent to preventers. Nonadherence was often undetectable by clinical assessments. Preventer adherence must be confirmed objectively before employing novel severe asthma therapies. PMID:29519922

Hypoxanthine enters human vascular endothelial cells (ECV 304) via the nitrobenzylthioinosine-insensitive equilibrative nucleoside transporter.

PubMed Central

Osses, N; Pearson, J D; Yudilevich, D L; Jarvis, S M

1996-01-01

The transport properties of the nucleobase hypoxanthine were examined in the human umbilical vein endothelial cell line ECV 304. Initial rates of hypoxanthine influx were independent of extracellular cations: replacement of Na+ with Li+, Rb+, N-methyl-D-glucamine or choline had no significant effect on hypoxanthine uptake by ECV 304 cells. Kinetic analysis demonstrated the presence of a single saturable system for the transport of hypoxanthine in ECV 304 cells with an apparent K(m) of 320 +/- 10 microM and a Vmax of 5.6 +/- 0.9 pmol/10(6) cells per s. Hypoxanthine uptake was inhibited by the nucleosides adenosine, uridine and thymidine (apparent Ki 41 +/- 6, 240 +/- 27 and 59 +/- 8 microM respectively) and the nucleoside transport inhibitors nitrobenzylthioinosine (NBMPR), dilazep and dipyridamole (apparent Ki 2.5 +/- 0.3, 11 +/- 3 and 0.16 +/- 0.006 microM respectively), whereas the nucleobases adenine, guanine and thymine had little effect (50% inhibition at > 1 mM). ECV 304 cells were also shown to transport adenosine via both the NBMPR-sensitive and -insensitive nucleoside carriers. Hypoxanthine specifically inhibited adenosine transport via the NBMPR-insensitive system in a competitive manner (apparent Ki 290 +/- 14 microM). These results indicate that hypoxanthine entry into ECV 304 endothelial cells is mediated by the NBMPR-insensitive nucleoside carrier present in these cells. PMID:8760371

Insensitive fuze train for high explosives

DOEpatents

Cutting, Jack L.; Lee, Ronald S.; Von Holle, William G.

1994-01-01

A generic insensitive fuze train to initiate insensitive high explosives, such as PBXW-124. The insensitive fuze train uses a slapper foil to initiate sub-gram quantities of an explosive, such as HNS-IV or PETN. This small amount of explosive drives a larger metal slapper onto a booster charge of an insensitive explosive, such as UF-TATB. The booster charge initiates a larger charge of an explosive, such as LX-17, which in turn, initiates the insensitive high explosive, such as PBXW-124.

Insensitive fuze train for high explosives

DOEpatents

Cutting, J.L.; Lee, R.S.; Von Holle, W.G.

1994-01-04

A generic insensitive fuze train to initiate insensitive high explosives, such as PBXW-124 is described. The insensitive fuze train uses a slapper foil to initiate sub-gram quantities of an explosive, such as HNS-IV or PETN. This small amount of explosive drives a larger metal slapper onto a booster charge of an insensitive explosive, such as UF-TATB. The booster charge initiates a larger charge of an explosive, such as LX-17, which in turn, initiates the insensitive high explosive, such as PBXW-124. 3 figures.

A rate insensitive linear viscoelastic model for soft tissues

PubMed Central

Zhang, Wei; Chen, Henry Y.; Kassab, Ghassan S.

2012-01-01

It is well known that many biological soft tissues behave as viscoelastic materials with hysteresis curves being nearly independent of strain rate when loading frequency is varied over a large range. In this work, the rate insensitive feature of biological materials is taken into account by a generalized Maxwell model. To minimize the number of model parameters, it is assumed that the characteristic frequencies of Maxwell elements form a geometric series. As a result, the model is characterized by five material constants: μ0, τ, m, ρ and β, where μ0 is the relaxed elastic modulus, τ the characteristic relaxation time, m the number of Maxwell elements, ρ the gap between characteristic frequencies, and β = μ1/μ0 with μ1 being the elastic modulus of the Maxwell body that has relaxation time τ. The physical basis of the model is motivated by the microstructural architecture of typical soft tissues. The novel model shows excellent fit of relaxation data on the canine aorta and captures the salient features of vascular viscoelasticity with significantly fewer model parameters. PMID:17512585

Does the Hall Effect Solve the Flux Pileup Saturation Problem?

NASA Technical Reports Server (NTRS)

Dorelli, John C.

2010-01-01

It is well known that magnetic flux pileup can significantly speed up the rate of magnetic reconnection in high Lundquist number resistive MHD,allowing reconnection to proceed at a rate which is insensitive to the plasma resistivity over a wide range of Lundquist number. Hence, pileup is a possible solution to the Sweet-Parker time scale problem. Unfortunately, pileup tends to saturate above a critical value of the Lundquist number, S_c, where the value ofS_c depends on initial and boundary conditions, with Sweet-Parker scaling returning above S_c. It has been argued (see Dorelli and Bim [2003] and Dorelli [2003]) that the Hall effect can allow flux pileup to saturate (when the scale of the current sheet approaches ion inertial scale, di) before the reconnection rate begins to stall. However, the resulting saturated reconnection rate, while insensitive to the plasma resistivity, was found to depend strongly on the di. In this presentation, we revisit the problem of magnetic island coalescence (which is a well known example of flux pileup reconnection), addressing the dependence of the maximum coalescence rate on the ratio of di in the "large island" limit in which the following inequality is always satisfied: l_eta di lambda, where I_eta is the resistive diffusion length and lambda is the island wavelength.

The quantitative and functional relation between insulin-like growth factor-I (IGF) and IGF-binding proteins during human osteoarthritis.

PubMed

Morales, Teresa I

2008-04-01

A previous hypothesis stated that during osteoarthritis (OA) increased insulin-like growth factor (IGF) binding proteins (IGFBPs) sequester IGFs and limit their access to the cell. The objective of this article was to test this by: (1) quantifying IGF and IGFBP-3 as well as their ratios in human OA cartilages, and (2) measuring the metabolic responses of diseased cartilage to IGF-I and its IGFBP-insensitive analogs. Knee or hip OA cartilages were staged for OA by histology. Cartilage slices were either extracted for assays of IGF proteins, or maintained intact as organ cultures. Proteoglycan (PG) metabolism +/- IGFs was measured by use of the (35)S-sulfate precursor. IGFBP-3 (ng/mg protein) was weakly correlated with OA score by regression analysis (R(2) = 0.122; p = 0.040; n = 35). IGF-I (ng/mg protein) was constant across all OA groups (ANOVA; p = .428, n = 18) and the IGF-I/IGFBP-3 ratios were > 1 in most samples. All OA cartilages responded to hrIGF-I by increasing PG synthesis [average 2.29-fold +/- 0.55 (+/-SD) at saturation, n = 12] irrespective of OA score. The des (1-3) IGF-I analog (which lacks the three N-terminal amino acids) had similar maximal effects (average 2.23-fold stimulation +/- 0.71, n = 10), but it was more effective in two out of three samples at suboptimal doses. The effect of hrIGF-I, des (1-3) IGF-I, or the B-chain analog on degradation was minimal. In summary, catabolism was insensitive to IGF-I, and this was probably not due to IGFBPs. By contrast, IGF-I exerted a robust stimulation of anabolism at sufficiently high doses, even though IGFBPs could tone down the ligand effect at low doses. (c) 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Local Network Wideband Interconnection Alternatives.

DTIC Science & Technology

1984-01-01

signal. 3.2.2 Limitations Although satellites offer the advantages of insensitivity to distance, point-to-multipoint communication capability and...Russell, the CATV franchisee for the town of Bedford, has not yit set rates for leasing channels on their network. If this network were interconnected

Punishment Insensitivity and Impaired Reinforcement Learning in Preschoolers

ERIC Educational Resources Information Center

Briggs-Gowan, Margaret J.; Nichols, Sara R.; Voss, Joel; Zobel, Elvira; Carter, Alice S.; McCarthy, Kimberly J.; Pine, Daniel S.; Blair, James; Wakschlag, Lauren S.

2014-01-01

Background: Youth and adults with psychopathic traits display disrupted reinforcement learning. Advances in measurement now enable examination of this association in preschoolers. The current study examines relations between reinforcement learning in preschoolers and parent ratings of reduced responsiveness to socialization, conceptualized as a…

Human peripheral blood mononuclear cell in vitro system to test the efficacy of food bioactive compounds: Effects of polyunsaturated fatty acids and their relation with BMI.

PubMed

Cifre, Margalida; Díaz-Rúa, Rubén; Varela-Calviño, Rubén; Reynés, Bàrbara; Pericás-Beltrán, Jordi; Palou, Andreu; Oliver, Paula

2017-04-01

To analyse the usefulness of isolated human peripheral blood mononuclear cells (PBMC) to rapidly/easily reflect n-3 long-chain polyunsaturated fatty acid (LCPUFA) effects on lipid metabolism/inflammation gene profile, and evaluate if these effects are body mass index (BMI) dependent. PBMC from normoweight (NW) and overweight/obese (OW/OB) subjects were incubated with physiological doses of docosahexaenoic (DHA), eicosapentaenoic acid (EPA), or their combination. PBMC reflected increased beta-oxidation-like capacity (CPT1A expression) in OW/OB but only after DHA treatment. However, insensitivity to n-3 LCPUFA was evident in OW/OB for lipogenic genes: both PUFA diminished FASN and SREBP1C expression in NW, but no effect was observed for DHA in PBMC from high-BMI subjects. This insensitivity was also evident for inflammation gene profile: all treatments inhibited key inflammatory genes in NW; nevertheless, no effect was observed in OW/OB after DHA treatment, and EPA effect was impaired. SLC27A2, IL6 and TNFα PBMC expression analysis resulted especially interesting to determine obesity-related n-3 LCPUFA insensitivity. A PBMC-based human in vitro system reflects n-3 LCPUFA effects on lipid metabolism/inflammation which is impaired in OW/OB. These results confirm the utility of PBMC ex vivo systems for bioactive-compound screening to promote functional food development and to establish appropriate dietary strategies for obese population. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improved format for radiocardiographic data

NASA Technical Reports Server (NTRS)

Dimeff, J.; Sevelius, G.

1973-01-01

Technique involves introduction of radioactive sample into antecubital vein. Scintillation crystal mounted in collimating housing views portion of right and left hearts. As radioactive sample passes through heart, counting rate is measured by crystal and recorded on strip chart. Data is insensitive to geometric effects and other parameters.

Outdoor dissolution of detonation residues of three insensitive munitions (IM) formulations.

PubMed

Taylor, Susan; Dontsova, Katerina; Walsh, Marianne E; Walsh, Michael R

2015-09-01

We seek to understand the environmental fate of three new insensitive munitions, explosive formulations developed to reduce the incidence of unintended detonations. To this end, we measured the size distribution of residues from low order detonations of IMX 101, IMX 104, and PAX 21-filled munitions and are studying how these three formulations weather and dissolve outdoors. The largest pieces collected from the detonations were centimeter-sized and we studied 12 of these in the outdoors test. We found that the particles break easily and that the dissolution of 2,4-dinitroanisole (DNAN) is quasi-linear as a function of water volume. DNAN is the matrix and the least soluble major constituent of the three formulations. We used DNAN's linear dissolution rate to estimate the life span of the pieces. Particles ranging in mass from 0.3 to 3.5 g will completely dissolve in 3-21 years given 100 cm y(-1) precipitation rates. Published by Elsevier Ltd.

Estimating Rain Rates from Tipping-Bucket Rain Gauge Measurements

NASA Technical Reports Server (NTRS)

Wang, Jianxin; Fisher, Brad L.; Wolff, David B.

2007-01-01

This paper describes the cubic spline based operational system for the generation of the TRMM one-minute rain rate product 2A-56 from Tipping Bucket (TB) gauge measurements. Methodological issues associated with applying the cubic spline to the TB gauge rain rate estimation are closely examined. A simulated TB gauge from a Joss-Waldvogel (JW) disdrometer is employed to evaluate effects of time scales and rain event definitions on errors of the rain rate estimation. The comparison between rain rates measured from the JW disdrometer and those estimated from the simulated TB gauge shows good overall agreement; however, the TB gauge suffers sampling problems, resulting in errors in the rain rate estimation. These errors are very sensitive to the time scale of rain rates. One-minute rain rates suffer substantial errors, especially at low rain rates. When one minute rain rates are averaged to 4-7 minute or longer time scales, the errors dramatically reduce. The rain event duration is very sensitive to the event definition but the event rain total is rather insensitive, provided that the events with less than 1 millimeter rain totals are excluded. Estimated lower rain rates are sensitive to the event definition whereas the higher rates are not. The median relative absolute errors are about 22% and 32% for 1-minute TB rain rates higher and lower than 3 mm per hour, respectively. These errors decrease to 5% and 14% when TB rain rates are used at 7-minute scale. The radar reflectivity-rainrate (Ze-R) distributions drawn from large amount of 7-minute TB rain rates and radar reflectivity data are mostly insensitive to the event definition.

Inhibitory effect of a Microcystis sp (cyanobacteria) toxin on development of preimplantation mouse embryos.

PubMed

Sepulveda, M S; Rojas, M; Zambrano, F

1992-07-01

1. A soluble toxin, purified from the algae bloom of an eutrophic lake dominated by Microcystis, is a very effective inhibitor of early embryo development in a dose-response relationship. 2. Two- and 8-cell mouse embryos under the influence of Microcystis toxin do not reach the developmental stages of morula and blastocyst, respectively. 3. Actin cortex is disorganized without change in the microtubules structure. 4. Results are discussed in terms of the possible mechanisms by which the toxin arrests development considering, specifically, effects on the cytoskeleton and/or on voltage-insensitive transmembrane Ca2+ channels.

CAR T Cell Immunotherapy Promising in Refractory Leukemia | Center for Cancer Research

Cancer.gov

B-cell acute lymphoblastic leukemia (B-ALL) is a common childhood malignancy that also affects young adults. Although current treatments have significant toxicities, children with chemotherapy susceptible subtypes have high survival rates. However, less than 10 percent of children and young adults with newly-diagnosed or recurrent B-ALL that is insensitive to therapy survive, and this rate has not budged in the last 20 years.

Poor environmental tracking can make extinction risk insensitive to the colour of environmental noise

PubMed Central

van de Pol, Martijn; Vindenes, Yngvild; Sæther, Bernt-Erik; Engen, Steinar; Ens, Bruno J.; Oosterbeek, Kees; Tinbergen, Joost M.

2011-01-01

The relative importance of environmental colour for extinction risk compared with other aspects of environmental noise (mean and interannual variability) is poorly understood. Such knowledge is currently relevant, as climate change can cause the mean, variability and temporal autocorrelation of environmental variables to change. Here, we predict that the extinction risk of a shorebird population increases with the colour of a key environmental variable: winter temperature. However, the effect is weak compared with the impact of changes in the mean and interannual variability of temperature. Extinction risk was largely insensitive to noise colour, because demographic rates are poor in tracking the colour of the environment. We show that three mechanisms—which probably act in many species—can cause poor environmental tracking: (i) demographic rates that depend nonlinearly on environmental variables filter the noise colour, (ii) demographic rates typically depend on several environmental signals that do not change colour synchronously, and (iii) demographic stochasticity whitens the colour of demographic rates at low population size. We argue that the common practice of assuming perfect environmental tracking may result in overemphasizing the importance of noise colour for extinction risk. Consequently, ignoring environmental autocorrelation in population viability analysis could be less problematic than generally thought. PMID:21561978

Cost-effectiveness decision analysis of intramuscular ceftriaxone versus oral cefixime in adolescents with gonococcal cervicitis.

PubMed

Friedland, L R; Kulick, R M; Biro, F M; Patterson, A

1996-03-01

We compared the cost-effectiveness of two single-dose treatment strategies for adolescents with uncomplicated Neisseria gonorrhoeae cervicitis. We used a cost-effectiveness decision- analysis model to compare the two methods: the standard, ceftriaxone 125 mg given by IM injection; and an alternative, cefixime 400 mg given orally. The effect of the costs associated with the risk of accidental needlestick during IM administration was also evaluated. Key baseline assumptions (with ranges, when tested) were from the literature or costs to our hospital. These included ceftriaxone, $8.60 per dose; cefixime, $4.67 per dose; ceftriaxone efficacy, 98% (range, 94.9% to 100%); cefixime efficacy, 97% (94.1% to 100%); and a 15% probability of pelvic inflammatory disease (PID) related to failed treatment. We included costs for PID necessitating hospitalization, disseminated gonococcal infection, infertility, and ectopic pregnancy. Assumptions related to accidental needlestick included the rate of needlesticks with the disposable syringe, 6.9 per 100,000 injections (range, 0 to 69); cost of accidental needlestick to hospital; risk of HIV seroconversion after needlestick exposure to HIV-infected blood, .36% (range, 0% to .86%); rate of HIV infection in 15- to 19-year-olds attending sexually transmitted diseases clinics, .4% (range, 0 to 5); and lifetime treatment costs for a person with HIV. At baseline values the model favored ceftriaxone ($45 per patient) or cefixime ($59 per patient). However, over the range of efficacy of both drugs, two-way sensitivity analysis revealed no consistent cost advantage for either drug. The model was also insensitive to the economic effects associated with the risk of accidental needlestick during IM injection. over the range of efficacy by the 95% confidence intervals of both drugs, our analysis demonstrated no clear cost advantage for either. The economic effects of accidental needlestick do not change this conclusion. Compared with the IM alternative, oral cefixime is painless to the patient and simpler for the practitioner to administer. Oral cefixime also eliminates the psychologic effects associated with needlesticks in health care workers. For these reasons, we favor the use of oral cefixime for uncomplicated gonococcal cervicitis in adolescents.

Demonstration of polarization-insensitive spatial light modulation using a single polarization-sensitive spatial light modulator.

PubMed

Liu, Jun; Wang, Jian

2015-07-06

We present a simple configuration incorporating a single polarization-sensitive phase-only liquid crystal spatial light modulator (LC-SLM) to facilitate polarization-insensitive spatial light modulation. The polarization-insensitive configuration is formed by a polarization beam splitter (PBS), a polarization-sensitive phase-only LC-SLM, a half-wave plate (HWP), and a mirror in a loop structure. We experimentally demonstrate polarization-insensitive spatial light modulations for incident linearly polarized beams with different polarization states and polarization-multiplexed beams. Polarization-insensitive spatial light modulations generating orbital angular momentum (OAM) beams are demonstrated in the experiment. The designed polarization-insensitive configuration may find promising applications in spatial light modulations accommodating diverse incident polarizations.

Accelerated evaporation of water on graphene oxide.

PubMed

Wan, Rongzheng; Shi, Guosheng

2017-03-29

Using molecular dynamics simulations, we show that the evaporation of nanoscale volumes of water on patterned graphene oxide is faster than that on homogeneous graphene oxide. The evaporation rate of water is insensitive to variation in the oxidation degree of the oxidized regions, so long as the water film is only distributed on the oxidized regions. The evaporation rate drops when the water film spreads onto the unoxidized regions. Further analysis showed that varying the oxidation degree observably changed the interaction between the outmost water molecules and the solid surface, but the total interaction for the outmost water molecules only changed a very limited amount due to the correspondingly regulated water-water interaction when the water film is only distributed on the oxidized regions. When the oxidation degree is too low and some unoxidized regions are also covered by the water film, the thickness of the water film decreases, which extends the lifetime of the hydrogen bonds for the outmost water molecules and lowers the evaporation rate of the water. The insensitivity of water evaporation to the oxidation degree indicates that we only need to control the scale of the unoxidized and oxidized regions for graphene oxide to regulate the evaporation of nanoscale volumes of water.

Development of near zero-order release dosage forms using three-dimensional printing (3-DP) technology.

PubMed

Wang, Chen-Chao; Tejwani Motwani, Monica R; Roach, Willie J; Kay, Jennifer L; Yoo, Jaedeok; Surprenant, Henry L; Monkhouse, Donald C; Pryor, Timothy J

2006-03-01

Three near zero-order controlled-release pseudoephedrine hydrochloride (PEH) formulations demonstrating proportional release rates were developed using 3-Dimensional Printing (3-DP) technology. Mixtures of Kollidon SR and hydroxypropylmethyl cellulose (HPMC) were used as drug carriers. The release rates were adjusted by varying the Kollidon SR-HPMC ratio while keeping fabrication parameters constant. The dosage forms were composed of an immediate release core and a release rate regulating shell, fabricated with an aqueous PEH and an ethanolic triethyl citrate (TEC) binder, respectively. The dosage form design called for the drug to be released via diffusional pathways formed by HPMC in the shell matrix. The release rate was shown to increase correspondingly with the fraction of HPMC contained in the polymer blend. The designed formulations resulted in dosage forms that were insensitive to changes in pH of the dissolution medium, paddle stirring rate, and the presence/absence of a sinker. The near zero-order release properties were unchanged regardless of the dissolution test being performed on either single cubes or on a group of eight cubes encased within a gelatin capsule shell. The chemical and dissolution properties of the three formulations remained unchanged following 1 month's exposure to 25 degrees C/60% RH or 40 degrees C/75% RH environment under open container condition. The in vivo performance of the three formulations was evaluated using a single-dose, randomized, open-label, four-way crossover clinical study composed of 10 fasted healthy volunteers. The pharmacokinetic parameters were analyzed using a noncompartmental model. Qualitative rank order linear correlations between in vivo absorption profiles and in vitro dissolution parameters (with slope and intercept close to unity and origin, respectively) were obtained for all three formulations, indicating good support for a Level A in vivo/in vitro correlation.

Tyrosine - Effects on catecholamine release

NASA Technical Reports Server (NTRS)

Acworth, Ian N.; During, Matthew J.; Wurtman, Richard J.

1988-01-01

Tyrosine administration elevates striatal levels of dopamine metabolites in animals given treatments that accelerate nigrostriatal firing, but not in untreated rats. We examined the possibility that the amino acid might actually enhance dopamine release in untreated animals, but that the technique of measuring striatal dopamine metabolism was too insensitive to demonstrate such an effect. Dopamine release was assessed directly, using brain microdialysis of striatal extracellular fluid. Tyrosine administration (50-200 mg/kg IP) did indeed cause a dose related increase in extracellular fluid dopamine levels with minor elevations in levels of DOPAC and HVA, its major metabolites, which were not dose-related. The rise in dopamine was short-lived, suggesting that receptor-mediated feedback mechanisms responded to the increased dopamine release by diminishing neuronal firing or sensitivity to tyrosine. These observations indicate that measurement of changes in striatal DOPAC and HVA, if negative, need not rule out increases in nigrostriatal dopamine release.

Expatriate Executive Failure: An Overview of the Underlying Causes.

ERIC Educational Resources Information Center

Rankis, Olaf E.; Beebe, Steven A.

The high attrition rate among North American expatriate executives has become a significant problem for firms doing business in foreign countries. A review of the literature reveals a number of factors contributing to attrition, including culture shock, family problems, managerial style and practice differences, insensitivity to host cultures, and…

Selective labelling of diazepam-insensitive GABAA receptors in vivo using [3H]Ro 15-4513.

PubMed

Pym, Luanda J; Cook, Susan M; Rosahl, Thomas; McKernan, Ruth M; Atack, John R

2005-11-01

Classical benzodiazepines (BZs), such as diazepam, bind to GABAA receptors containing alpha1, alpha2, alpha3 or alpha5 subunits that are therefore described as diazepam-sensitive (DS) receptors. However, the corresponding binding site of GABAA receptors containing either an alpha4 or alpha6 subunit do not bind the classical BZs and are therefore diazepam-insensitive (DIS) receptors; a difference attributable to a single amino acid (histidine in alpha1, alpha2, alpha3 and alpha5 subunits and arginine in alpha4 and alpha6). Unlike classical BZs, the imidazobenzodiazepines Ro 15-4513 and bretazenil bind to both DS and DIS populations of GABAA receptors. In the present study, an in vivo assay was developed using lorazepam to fully occupy DS receptors such that [3H]Ro 15-4513 was then only able to bind to DIS receptors. When dosed i.v., [3H]Ro 15-4513 rapidly entered and was cleared from the brain, with approximately 70% of brain radioactivity being membrane-bound. Essentially all membrane binding to DS+DIS receptors could be displaced by unlabelled Ro 15-4513 or bretazenil, with respective ID50 values of 0.35 and 1.2 mg kg(-1). A dose of 30 mg kg(-1) lorazepam was used to block all DS receptors in a [3H]Ro 15-1788 in vivo binding assay. When predosed in a [3H]Ro 15-4513 binding assay, lorazepam blocked [3H]Ro 15-4513 binding to DS receptors, with the remaining binding to DIS receptors accounting for 5 and 23% of the total (DS plus DIS) receptors in the forebrain and cerebellum, respectively. The in vivo binding of [3H]Ro 15-4513 to DIS receptors in the presence of lorazepam was confirmed using alpha1H101R knock-in mice, in which alpha1-containing GABAA receptors are rendered diazepam insensitive by mutation of the histidine that confers diazepam sensitivity to arginine. In these mice, and in the presence of lorazepam, there was an increase of in vivo [3H]Ro 15-4513 binding in the forebrain and cerebellum from 4 and 15% to 36 and 59% of the total (i.e. DS plus DIS) [3H]Ro 15-4513 binding observed in the absence of lorazepam.

Response of the RIF-1 tumor in vitro and in C3H/Km mice to x-radiation (cell survival, regrowth delay, and tumor control), chemotherapeutic agents, and activated macrophages

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

Brown, J.M.; Twentyman, P.R.; Zamvil, S.S.

1980-03-01

The radiation response of logarithmic growth phase and fed plateau phase RIF-1 cells in vitro was found to be characterized by D/sub 0/ values of 110 and 133 rads and extrapolation numbs of 36 and 28, respectively. The response of the tumor in vivo to X-irradiation in nonanesthetized mice showed a dependence on the tumor implantation site. In the leg muscle, the response indicated that most cells were at an intermediate level of oxygenation, whereas in the subcutaneous tissue of the flank, the response of the tumor indicated that it had a small fraction of hypoxic cells of maximum radioresistance.more » Misonidazole radiosensitized the leg-implanted tumor as measured both by cell survival and regrowth delay. The tumor was relatively insensitive to a single dose of 1,3-bis(2-chloroethyl)-1-nitrosourea, sensitive to a single dose of cis-platinum, and highly sensitive to a single dose of cyclophosphamide.« less

Molecular weight distribution of organic matter by ozonation and biofiltration.

PubMed

Lin, Yen-Hui

2012-01-01

Molecular weight (MW) distribution of organic matter by ozonation and biofiltration was evaluated using gel chromatography. The MW distribution of organic matter by Sephadex G-25 was observed from groups 2 (MW = 1,029-7,031 g/mol) and 3 (MW = 303-1,029 g/mol) shifted to groups 2, 3 and 4 (MW < 303 g/mol) under ozone doses of 0.1 and 0.4 mg O₃/mg total organic carbon (TOC). The shift in MW increases as ozone dosage increases. Biofiltration effectively degraded the organic molecule of group 2; however, the biofiltration only slightly degraded the organic molecule of group 4. Increased ozone dose destroyed functional groups C═C in phenolic and C-O in alcoholic compounds and increased UV-insensitive biodegradable organic carbon for subsequent biofiltration. Biofiltration effectively degraded organic compounds of alcohols and alkenes at an ozone dose of 0.1 mg O₃/mg TOC. Experimental approaches in this study can be applied to evaluate and diagnose the function of a full-scale process combining ozonation and biofiltration in drinking water treatment plants.

Computational Study of 3-D Hot-Spot Initiation in Shocked Insensitive High-Explosive

NASA Astrophysics Data System (ADS)

Najjar, F. M.; Howard, W. M.; Fried, L. E.

2011-06-01

High explosive shock sensitivity is controlled by a combination of mechanical response, thermal properties, and chemical properties. The interplay of these physical phenomena in realistic condensed energetic materials is currently lacking. A multiscale computational framework is developed investigating hot spot (void) ignition in a single crystal of an insensitive HE, TATB. Atomistic MD simulations are performed to provide the key chemical reactions and these reaction rates are used in 3-D multiphysics simulations. The multiphysics code, ALE3D, is linked to the chemistry software, Cheetah, and a three-way coupled approach is pursued including hydrodynamics, thermal and chemical analyses. A single spherical air bubble is embedded in the insensitive HE and its collapse due to shock initiation is evolved numerically in time; while the ignition processes due chemical reactions are studied. Our current predictions showcase several interesting features regarding hot spot dynamics including the formation of a ``secondary'' jet. Results obtained with hydro-thermo-chemical processes leading to ignition growth will be discussed for various pore sizes and different shock pressures. LLNL-ABS-471438. This work performed under the auspices of the U.S. Department of Energy by LLNL under Contract DE-AC52-07NA27344.

Demonstration of polarization-insensitive spatial light modulation using a single polarization-sensitive spatial light modulator

PubMed Central

Liu, Jun; Wang, Jian

2015-01-01

We present a simple configuration incorporating a single polarization-sensitive phase-only liquid crystal spatial light modulator (LC-SLM) to facilitate polarization-insensitive spatial light modulation. The polarization-insensitive configuration is formed by a polarization beam splitter (PBS), a polarization-sensitive phase-only LC-SLM, a half-wave plate (HWP), and a mirror in a loop structure. We experimentally demonstrate polarization-insensitive spatial light modulations for incident linearly polarized beams with different polarization states and polarization-multiplexed beams. Polarization-insensitive spatial light modulations generating orbital angular momentum (OAM) beams are demonstrated in the experiment. The designed polarization-insensitive configuration may find promising applications in spatial light modulations accommodating diverse incident polarizations. PMID:26146032

Strain Insensitive Optical Phase Locked Loop

NASA Technical Reports Server (NTRS)

Egalon, Claudio Oliviera (Inventor); Rogowski, Robert S. (Inventor)

1996-01-01

An apparatus is provided to allow for quasi distributed sensing of strain within a test object. Strain insensitive fiber is used to deliver a light signal to a strain sensitive fiber in an optical phase locked loop sensor configuration. The use of strain insensitive delivery fiber allows for non-integrated measurements of strain without the use of expensive electronics such as those employed in ODTR techniques. The novelty of the present invention lies in the use of strain insensitive multimode fiber. The inventors had previously developed a similar sensor with strain insensitive fiber, however it was restricted to the use of single or few mode fibers. The use of an optical phase locked loop arrangement allows for the use of multimode strain insensitive fiber.

Comparison of TID Effects in Space-Like Variable Dose Rates and Constant Dose Rates

NASA Technical Reports Server (NTRS)

Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Evans, Robin W.; Jun, Insoo

2008-01-01

The degradation of the LM193 dual voltage comparator has been studied at different TID dose rate profiles, including several different constant dose rates and a variable dose rate that simulates the behavior of a solar flare. A comparison of results following constant dose rate vs. variable dose rates is made to explore how well the constant dose rates used for typical part testing predict the performance during a simulated space-like mission. Testing at a constant dose rate equal to the lowest dose rate seen during the simulated flare provides an extremely conservative estimate of the overall amount of degradation. A constant dose rate equal to the average dose rate is also more conservative than the variable rate. It appears that, for this part, weighting the dose rates by the amount of total dose received at each rate (rather than the amount of time at each dose rate) results in an average rate that produces an amount of degradation that is a reasonable approximation to that received by the variable rate.

Life-Cycle-Cost Analysis of the Microwave Landing System Ground and Airborne Systems

DTIC Science & Technology

1981-10-01

constant 1980 dollars, with a production rate variability. Table S-3 presents the life-cycle costs by MLS configuration and total system implementation... PRODUCTION RATE VARIABILITY OVER A THREE-YEAR PFODUCTXION RUN (MILLIONS OF CONSTANT 1980 DOLLARS) Pruduction (Juantitl•e and Costs system Typ 75...Implementation strategies * Production schedules for MLS equipment The LCC was determined to be relatively insensitive to changes in MTBF. This was expected

SU-F-T-20: Novel Catheter Lumen Recognition Algorithm for Rapid Digitization

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

Dise, J; McDonald, D; Ashenafi, M

Purpose: Manual catheter recognition remains a time-consuming aspect of high-dose-rate brachytherapy (HDR) treatment planning. In this work, a novel catheter lumen recognition algorithm was created for accurate and rapid digitization. Methods: MatLab v8.5 was used to create the catheter recognition algorithm. Initially, the algorithm searches the patient CT dataset using an intensity based k-means filter designed to locate catheters. Once the catheters have been located, seed points are manually selected to initialize digitization of each catheter. From each seed point, the algorithm searches locally in order to automatically digitize the remaining catheter. This digitization is accomplished by finding pixels withmore » similar image curvature and divergence parameters compared to the seed pixel. Newly digitized pixels are treated as new seed positions, and hessian image analysis is used to direct the algorithm toward neighboring catheter pixels, and to make the algorithm insensitive to adjacent catheters that are unresolvable on CT, air pockets, and high Z artifacts. The algorithm was tested using 11 HDR treatment plans, including the Syed template, tandem and ovoid applicator, and multi-catheter lung brachytherapy. Digitization error was calculated by comparing manually determined catheter positions to those determined by the algorithm. Results: he digitization error was 0.23 mm ± 0.14 mm axially and 0.62 mm ± 0.13 mm longitudinally at the tip. The time of digitization, following initial seed placement was less than 1 second per catheter. The maximum total time required to digitize all tested applicators was 4 minutes (Syed template with 15 needles). Conclusion: This algorithm successfully digitizes HDR catheters for a variety of applicators with or without CT markers. The minimal axial error demonstrates the accuracy of the algorithm, and its insensitivity to image artifacts and challenging catheter positioning. Future work to automatically place initial seed positions would improve the algorithm speed.« less

Topical dihydrotestosterone to treat micropenis secondary to partial androgen insensitivity syndrome (PAIS) before, during, and after puberty - a case series.

PubMed

Becker, David; Wain, Lisa M; Chong, Yih Harng; Gosai, Sonal J; Henderson, Nina K; Milburn, Jacqui; Stott, Victoria; Wheeler, Benjamin J

2016-02-01

X-linked partial androgen insensitivity syndrome (PAIS) causes under-virilization at all stages of development. In two thirds of males, this results in micropenis. Dihydrotestosterone (DHT) is a potent androgen that is critical for male genital development, which when applied topically, has been shown to increase penile length with micropenis of varying etiologies. We present the first case series using topical DHT gel to treat micropenis in 46,XY males with PAIS, before, during, and after puberty. Three related 46,XY males with confirmed p.L712F androgen receptor mutations exhibited varying degrees of micropenis post-surgical correction. They were of pre-pubertal, peri-pubertal and adult ages, respectively. Following baseline clinical and laboratory assessments all completed a 4-month course of daily DHT gel 2.5% (androstanolone) topically to penis (0.3 mg/kg body weight), with monitoring for adverse effects. Primary outcome was change in stretched penile length (SPL) following treatment. Mixed results were obtained following topical DHT therapy. In the pre- and peri- pubertal patients, SPL changed from 2.5 cm to 3.5 cm (+40%), and 3.5 cm to 5.7 cm (+63%), respectively. In the adult patient with 1 year of prior high-dose weekly testosterone therapy, no additional change in SPL was seen. No adverse effects of topical DHT were reported or observed throughout the 4 months of treatment. Topical DHT treatment appears to be a safe and well-tolerated method of virilising micropenis both prior to and during puberty in children with PAIS. Questions remain about long-term outcomes into adulthood, and efficacy in adults with prior lengthy exposure to high-dose testosterone.

Ethanol-induced conditioned taste aversion in male sprague-dawley rats: impact of age and stress.

PubMed

Anderson, Rachel I; Varlinskaya, Elena I; Spear, Linda P

2010-12-01

Age-specific characteristics may contribute to the elevation in ethanol intake commonly reported among adolescents compared to adults. This study was designed to examine age-related differences in sensitivity to ethanol's aversive properties using a conditioned taste aversion (CTA) procedure with sucrose serving as the conditioned stimulus (CS). Given that ontogenetic differences in responsiveness to stressors have been previously reported, the role of stressor exposure on the development of CTA was also assessed. Experiment 1 examined the influence of 5 days of prior restraint stress exposure on the expression of CTA in a 2-bottle test following 1 pairing of a sucrose solution with ethanol. In Experiment 2, the effects of 7 days of social isolation on the development of CTA were observed using a 1-bottle test following multiple sucrose-ethanol pairings. This study revealed age-related differences in the development of ethanol-induced CTA. In Experiment 1, adolescents required a higher dose of ethanol than adults to demonstrate an aversion. In Experiment 2, adolescents required not only a higher ethanol dose but also more pairings of ethanol with the sucrose CS. No effects of prior stressor exposure were observed in either experiment. Together, these experiments demonstrate an adolescent-specific insensitivity to the aversive properties of ethanol that elicit CTA, a pattern not influenced by repeated restraint stress or housing in social isolation. This age-related insensitivity to the dysphoric effects of ethanol is consistent with other work from our laboratory, adding further to the evidence that adolescent rats are less susceptible to negative consequences of ethanol that may serve as cues to curb consumption. Copyright © 2010 by the Research Society on Alcoholism.

Molecular identification and functional expression of mu 3, a novel alternatively spliced variant of the human mu opiate receptor gene.

PubMed

Cadet, Patrick; Mantione, Kirk J; Stefano, George B

2003-05-15

Studies from our laboratory have revealed a novel mu opiate receptor, mu 3, which is expressed in both vascular tissues and leukocytes. The mu 3 receptor is selective for opiate alkaloids and is insensitive to opioid peptides. We now identify the mu 3 receptor at the molecular level using a 441-bp conserved region of the mu 1 receptor. Sequence analysis of the isolated cDNA suggests that it is a novel, alternatively spliced variant of the mu opiate receptor gene. To determine whether protein expressed from this cDNA exhibits the biochemical characteristics expected of the mu 3 receptor, the cDNA clone was expressed in a heterologous system. At the functional level, COS-1 cells transfected with the mu 3 receptor cDNA exhibited dose-dependent release of NO following treatment with morphine, but not opioid peptides (i.e., Met-enkephalin). Naloxone was able to block the effect of morphine on COS-1 transfected cells. Nontransfected COS-1 cells did not produce NO in the presence of morphine or the opioid peptides at similar concentrations. Receptor binding analysis with [(3)H]dihydromorphine further supports the opiate alkaloid selectivity and opioid peptide insensitivity of this receptor. These data suggest that this new mu opiate receptor cDNA encodes the mu 3 opiate receptor, since it exhibits biochemical characteristics known to be unique to this receptor (opiate alkaloid selective and opioid peptide insensitive). Furthermore, using Northern blot, RT-PCR, and sequence analysis, we have demonstrated the expression of this new mu variant in human vascular tissue, mononuclear cells, polymorphonuclear cells, and human neuroblastoma cells.

Point mutations in acetylcholinesterase 1 associated with chlorpyrifos resistance in the brown planthopper, Nilaparvata lugens Stål.

PubMed

Zhang, Y; Yang, B; Li, J; Liu, M; Liu, Z

2017-08-01

Insecticide resistance frequently results from target-site insensitivity, such as point mutations in acetylcholinesterases (AChEs) for resistance to organophosphates and carbamates. From a field-originated population of Nilaparvata lugens, a major rice pest, a resistant population (R9) was obtained by nine-generation continuous selection with chlorpyrifos. From the same field population, a relatively susceptible population (S9) was also constructed through rearing without any insecticides. Compared to the susceptible strain, Sus [medium lethal dose (LC 50 ) = 0.012 mg/l], R9 had a resistance ratio (RR) of 253.08-fold, whereas the RR of S9 was only 2.25-fold. Piperonyl butoxide and triphenyl phosphate synergized chlorpyrifos in R9 less than three-fold, indicating other important mechanisms for high resistance. The target-site insensitivity was supported by the key property differences of crude AChEs between R9 and S9. Compared to S9, three mutations (G119S, F331C and I332L) were detected in NlAChE1 from individuals of the R9 and field populations, but no mutation was detected in NlAChE2. G119S and F331C could decreased insecticide sensitivities in recombinant NlAChE1, whereas I332L took effect through increasing the influence of F331C on target insensitivity. F331C might be deleterious because of its influence on the catalytic efficiency of NlAChE1, whereas I332L would decrease these adverse effects and maintain the normal functions of AChEs. © 2017 The Royal Entomological Society.

Supertaster, super reactive: oral sensitivity for bitter taste modulates emotional approach and avoidance behavior in the affective startle paradigm.

PubMed

Herbert, Cornelia; Platte, Petra; Wiemer, Julian; Macht, Michael; Blumenthal, Terry D

2014-08-01

People differ in both their sensitivity for bitter taste and their tendency to respond to emotional stimuli with approach or avoidance. The present study investigated the relationship between these sensitivities in an affective picture paradigm with startle responding. Emotion-induced changes in arousal and attention (pupil modulation), priming of approach and avoidance behavior (startle reflex modulation), and subjective evaluations (ratings) were examined. Sensitivity for bitter taste was assessed with the 6-n-propylthiouracil (PROP)-sensitivity test, which discriminated individuals who were highly sensitive to PROP compared to NaCl (PROP-tasters) and those who were less sensitive or insensitive to the bitter taste of PROP. Neither pupil responses nor picture ratings differed between the two taster groups. The startle eye blink response, however, significantly differentiated PROP-tasters from PROP-insensitive subjects. Facilitated response priming to emotional stimuli emerged in PROP-tasters but not in PROP-insensitive subjects at shorter startle lead intervals (200-300ms between picture onset and startle stimulus onset). At longer lead intervals (3-4.5s between picture onset and startle stimulus onset) affective startle modulation did not differ between the two taster groups. This implies that in PROP-sensitive individuals action tendencies of approach or avoidance are primed immediately after emotional stimulus exposure. These results suggest a link between PROP taste perception and biologically relevant patterns of emotional responding. Direct perception-action links have been proposed to underlie motivational priming effects of the startle reflex, and the present results extend these to the sensory dimension of taste. Copyright © 2014 Elsevier Inc. All rights reserved.

Three-dimensional cluster formation and structure in heterogeneous dose distribution of intensity modulated radiation therapy.

PubMed

Chao, Ming; Wei, Jie; Narayanasamy, Ganesh; Yuan, Yading; Lo, Yeh-Chi; Peñagarícano, José A

2018-05-01

To investigate three-dimensional cluster structure and its correlation to clinical endpoint in heterogeneous dose distributions from intensity modulated radiation therapy. Twenty-five clinical plans from twenty-one head and neck (HN) patients were used for a phenomenological study of the cluster structure formed from the dose distributions of organs at risks (OARs) close to the planning target volumes (PTVs). Initially, OAR clusters were searched to examine the pattern consistence among ten HN patients and five clinically similar plans from another HN patient. Second, clusters of the esophagus from another ten HN patients were scrutinized to correlate their sizes to radiobiological parameters. Finally, an extensive Monte Carlo (MC) procedure was implemented to gain deeper insights into the behavioral properties of the cluster formation. Clinical studies showed that OAR clusters had drastic differences despite similar PTV coverage among different patients, and the radiobiological parameters failed to positively correlate with the cluster sizes. MC study demonstrated the inverse relationship between the cluster size and the cluster connectivity, and the nonlinear changes in cluster size with dose thresholds. In addition, the clusters were insensitive to the shape of OARs. The results demonstrated that the cluster size could serve as an insightful index of normal tissue damage. The clinical outcome of the same dose-volume might be potentially different. Copyright © 2018 Elsevier B.V. All rights reserved.

The influence of Monte Carlo source parameters on detector design and dose perturbation in small field dosimetry

NASA Astrophysics Data System (ADS)

Charles, P. H.; Crowe, S. B.; Kairn, T.; Knight, R.; Hill, B.; Kenny, J.; Langton, C. M.; Trapp, J. V.

2014-03-01

To obtain accurate Monte Carlo simulations of small radiation fields, it is important model the initial source parameters (electron energy and spot size) accurately. However recent studies have shown that small field dosimetry correction factors are insensitive to these parameters. The aim of this work is to extend this concept to test if these parameters affect dose perturbations in general, which is important for detector design and calculating perturbation correction factors. The EGSnrc C++ user code cavity was used for all simulations. Varying amounts of air between 0 and 2 mm were deliberately introduced upstream to a diode and the dose perturbation caused by the air was quantified. These simulations were then repeated using a range of initial electron energies (5.5 to 7.0 MeV) and electron spot sizes (0.7 to 2.2 FWHM). The resultant dose perturbations were large. For example 2 mm of air caused a dose reduction of up to 31% when simulated with a 6 mm field size. However these values did not vary by more than 2 % when simulated across the full range of source parameters tested. If a detector is modified by the introduction of air, one can be confident that the response of the detector will be the same across all similar linear accelerators and the Monte Carlo modelling of each machine is not required.

Comparison of risk of radiogenic second cancer following photon and proton craniospinal irradiation for a pediatric medulloblastoma patient

NASA Astrophysics Data System (ADS)

Zhang, Rui; Howell, Rebecca M.; Giebeler, Annelise; Taddei, Phillip J.; Mahajan, Anita; Newhauser, Wayne D.

2013-02-01

Pediatric patients who received radiation therapy are at risk of developing side effects such as radiogenic second cancer. We compared proton and photon therapies in terms of the predicted risk of second cancers for a 4 year old medulloblastoma patient receiving craniospinal irradiation (CSI). Two CSI treatment plans with 23.4 Gy or Gy (RBE) prescribed dose were computed: a three-field 6 MV photon therapy plan and a four-field proton therapy plan. The primary doses for both plans were determined using a commercial treatment planning system. Stray radiation doses for proton therapy were determined from Monte Carlo simulations, and stray radiation doses for photon therapy were determined from measured data. Dose-risk models based on the Biological Effects of Ionization Radiation VII report were used to estimate the risk of second cancer in eight tissues/organs. Baseline predictions of the relative risk for each organ were always less for proton CSI than for photon CSI at all attained ages. The total lifetime attributable risk of the incidence of second cancer considered after proton CSI was much lower than that after photon CSI, and the ratio of lifetime risk was 0.18. Uncertainty analysis revealed that the qualitative findings of this study were insensitive to any plausible changes of dose-risk models and mean radiation weighting factor for neutrons. Proton therapy confers lower predicted risk of second cancer than photon therapy for the pediatric medulloblastoma patient.

The creatine kinase response to eccentric exercise with atorvastatin 10 mg or 80 mg.

PubMed

Kearns, Amy K; Bilbie, Cherie L; Clarkson, Priscilla M; White, C Michael; Sewright, Kim A; O'Fallon, Kevin S; Gadarla, Mamatha; Thompson, Paul D

2008-09-01

Hydroxy-methyl-glutaryl co-enzyme A (HMG-CoA) reductase inhibitors or statins are well tolerated by most patients, but can produce a variety of skeletal muscle problems including myalgia, creatine kinase (CK) elevations and clinically important rhabdomyolysis. We have previously demonstrated that the CK response to downhill walking is greater in statin compared to placebo treated subjects. This study examined the CK response to downhill walking in subjects treated with low and high dose of atorvastatin. 79 subjects with LDL cholesterol>100mg/dL were randomly assigned to atorvastatin 10mg (N=42) or 80 mg (N=37) for 5 weeks. Subjects performed a downhill walking exercise during the fifth week of treatment. Leg muscle soreness, plasma CK and CK-MB levels were measured daily for 4 days following the exercise. CK, CK-MB and muscle soreness increased above pre-exercise levels in all subjects after the exercise. There were no differences in the CK, CK-MB or soreness response between the high and low dose treatment groups at any time point. The downhill walking model of muscle injury does not distinguish between high and low dose atorvastatin therapy either because this test is insensitive to differences among statin doses or because there is no difference in muscle injury between these two drug doses with this statin. Clinicians should be aware, however, that exercise can increase CK levels with even low dose statin therapy.

Effects of ranitidine (antacid), food, and formulation on the pharmacokinetics of fostamatinib: results from five phase I clinical studies.

PubMed

Flanagan, Talia; Martin, Paul; Gillen, Michael; Mathews, David; Lisbon, Eleanor; Kruusmägi, Martin

2017-02-01

Fostamatinib is an orally dosed phosphate prodrug that is cleaved by intestinal alkaline phosphatase to the active metabolite R406. Clinical studies were performed to assess the effect of food and ranitidine on exposure, to support in vitro-in vivo relationships (IVIVR) understanding and formulation transitions and to investigate absolute oral bioavailability. A series of in vitro dissolution and clinical pharmacokinetic studies were performed to support the design and introduction of a new formulation, understand the impact of changes in in vitro dissolution on in vivo performance for two fostamatinib formulations, to characterize the effects of food and ranitidine on exposure, and determine the absolute oral bioavailability. The in vivo performance of fostamatinib was generally insensitive to changes in in vitro dissolution performance, although marked slowing of the dissolution rate did impact exposures. Food and ranitidine had minor effects on R406 exposure that were not considered clinically relevant. The absolute oral bioavailability of fostamatinib was 54.6 %. The absolute oral bioavailability of fostamatinib was ~55 %. Food and ranitidine had minor effects on R406 exposure. An in vitro dissolution versus clinical performance relationship was determined that supported formulation transitions.

SU-E-T-556: Monte Carlo Generated Dose Distributions for Orbital Irradiation Using a Single Anterior-Posterior Electron Beam and a Hanging Lens Shield

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

Duwel, D; Lamba, M; Elson, H

Purpose: Various cancers of the eye are successfully treated with radiotherapy utilizing one anterior-posterior (A/P) beam that encompasses the entire content of the orbit. In such cases, a hanging lens shield can be used to spare dose to the radiosensitive lens of the eye to prevent cataracts. Methods: This research focused on Monte Carlo characterization of dose distributions resulting from a single A-P field to the orbit with a hanging shield in place. Monte Carlo codes were developed which calculated dose distributions for various electron radiation energies, hanging lens shield radii, shield heights above the eye, and beam spoiler configurations.more » Film dosimetry was used to benchmark the coding to ensure it was calculating relative dose accurately. Results: The Monte Carlo dose calculations indicated that lateral and depth dose profiles are insensitive to changes in shield height and electron beam energy. Dose deposition was sensitive to shield radius and beam spoiler composition and height above the eye. Conclusion: The use of a single A/P electron beam to treat cancers of the eye while maintaining adequate lens sparing is feasible. Shield radius should be customized to have the same radius as the patient’s lens. A beam spoiler should be used if it is desired to substantially dose the eye tissues lying posterior to the lens in the shadow of the lens shield. The compromise between lens sparing and dose to diseased tissues surrounding the lens can be modulated by varying the beam spoiler thickness, spoiler material composition, and spoiler height above the eye. The sparing ratio is a metric that can be used to evaluate the compromise between lens sparing and dose to surrounding tissues. The higher the ratio, the more dose received by the tissues immediately posterior to the lens relative to the dose received by the lens.« less

Biosynthesis of Ethylene from Methionine in Aminoethoxyvinylglycine-Resistant Avocado Tissue

PubMed Central

Baker, James E.; Anderson, James D.; Adams, Douglas O.; Apelbaum, Akiva; Lieberman, Morris

1982-01-01

This study was conducted to determine if aminoethoxyvinylglycine (AVG) insensitivity in avocado (Persea americana Mill., Lula, Haas, and Bacon) tissue was due to an alternate pathway of ethylene biosynthesis from methionine. AVG, at 0.1 millimolar, had little or no inhibitory effect on either total ethylene production or [14C] ethylene production from [14C]methionine in avocado tissue at various stages of ripening. However, aminoxyacetic acid (AOA), which inhibits 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (the AVG-sensitive enzyme of ethylene biosynthesis), inhibited ethylene production in avocado tissue. Total ethylene production was stimulated, and [14C]ethylene production from [14C]methionine was lowered by treating avocado tissue with 1 millimolar ACC. An inhibitor of methionine adenosyltransferase (EC 2.5.1.6), l-2-amino-4-hexynoic acid (AHA), at 1.5 millimolar, effectively inhibited [14C]ethylene production from [14C]methionine in avocado tissue but had no effect on total ethylene production during a 2-hour incubation. Rates of [14C]AVG uptake by avocado and apple (Malus domestica Borkh., Golden Delicious) tissues were similar, and [14C]AVG was the only radioactive compound in alcohol-soluble fractions of the tissues. Hence, AVG-insensitivity in avocado tissue does not appear to be due to lack of uptake or to metabolism of AVG by avocado tissue. ACC synthase activity in extracts of avocado tissue was strongly inhibited (about 60%) by 10 micromolar AVG. Insensitivity of ethylene production in avocado tissue to AVG may be due to inaccessibility of ACC synthase to AVG. AVG-resistance in the avocado system is, therefore, different from that of early climacteric apple tissue, in which AVG-insensitivity of total ethylene production appears to be due to a high level of endogenous ACC relative to its rate of conversion to ethylene. However, the sensitivity of the avocado system to AOA and AHA, dilution of labeled ethylene production by ACC, and stimulation of total ethylene production by ACC provide evidence for the methionine → SAM → ACC → ethylene pathway in avocado and do not suggest the operation of an alternate pathway. PMID:16662192

The Rate of Charge Tunneling through Self-Assembled Monolayers is Insensitive to Many Functional Group Substitutions**

PubMed Central

Yoon, Hyo Jae; Shapiro, Nathan D.; Park, Kyeng Min; Thuo, Martin M.; Soh, Siowling

2012-01-01

This paper characterizes the rates of charge transport by tunneling across a series of molecules—arrayed in self-assembled monolayers—containing a common head group and body (HS(CH2)4CONH(CH2)2-) and structurally varied tail groups (-R). These molecules are assembled in junctions of the structure AgTS/SAM//Ga2O3/EGaIn. Over a range of common aliphatic, aromatic, and heteroaromatic organic tail groups, changing the structure of R does not significantly influence the rate of tunneling. PMID:22504880

ViroSpot microneutralization assay for antigenic characterization of human influenza viruses.

PubMed

van Baalen, Carel A; Jeeninga, Rienk E; Penders, Germaine H W M; van Gent, Brenda; van Beek, Ruud; Koopmans, Marion P G; Rimmelzwaan, Guus F

2017-01-03

The hemagglutination inhibition (HI) assay has been used for the antigenic characterization of influenza viruses for decades. However, the majority of recent seasonal influenza A viruses of the H3N2 subtype has lost the capacity to agglutinate erythrocytes of various species. The hemagglutination (HA) activity of other A(H3N2) strains is generally sensitive to the action of the neuraminidase inhibitor oseltamivir, which indicates that the neuraminidase and not the hemagglutinin is responsible for the HA activity. These findings complicate the antigenic characterization and selection of A(H3N2) vaccine strains, calling for alternative antigenic characterization assays. Here we describe the development and use of the ViroSpot microneutralization (MN) assay as a reliable and robust alternative for the HI assay. Serum neutralization of influenza A(H3N2) reference virus strains and epidemic isolates was determined by automated readout of immunostained cell monolayers, in a format designed to minimize the influence of infectious virus doses on serum neutralization titers. Neutralization of infection was largely independent from rates of viral replication and cell-to-cell transmission, facilitating the comparison of different virus isolates. Other advantages of the ViroSpot MN assay include its relative insensitivity to variation in test dose of infectious virus, automated capture and analyses of residual infection patterns, and compatibility with standardized large scale analyses. Using this assay, a number of epidemic influenza A(H3N2) strains that failed to agglutinate erythrocytes, were readily characterized antigenically. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Lubricant based determination of design space for continuously manufactured high dose paracetamol tablets.

PubMed

Taipale-Kovalainen, Krista; Karttunen, Anssi-Pekka; Ketolainen, Jarkko; Korhonen, Ossi

2018-03-30

The objective of this study was to devise robust and stable continuous manufacturing process settings, by exploring the design space after an investigation of the lubrication-based parameters influencing the continuous direct compression tableting of high dose paracetamol tablets. Experimental design was used to generate a structured study plan which involved 19 runs. The formulation variables studied were the type of lubricant (magnesium stearate or stearic acid) and its concentration (0.5, 1.0 and 1.5%). Process variables were total production feed rate (5, 10.5 and 16kg/h), mixer speed rpm (500, 850 and 1200rpm), and mixer inlet port for lubricant (A or B). The continuous direct compression tableting line consisted of loss-in-weight feeders, a continuous mixer and a tablet press. The Quality Target Product Profile (QTPP) was defined for the final product, as the flowability of powder blends (2.5s), tablet strength (147N), dissolution in 2.5min (90%) and ejection force (425N). A design space was identified which fulfilled all the requirements of QTPP. The type and concentration of lubricant exerted the greatest influence on the design space. For example, stearic acid increased the tablet strength. Interestingly, the studied process parameters had only a very minor effect on the quality of the final product and the design space. It is concluded that the continuous direct compression tableting process itself is insensitive and can cope with changes in lubrication, whereas formulation parameters exert a major influence on the end product quality. Copyright © 2017 Elsevier B.V. All rights reserved.

Out-of-field in vivo dosimetry using TLD in SABR for primary kidney cancer involving mixed photon fields.

PubMed

Lonski, P; Keehan, S; Siva, S; Pham, D; Franich, R D; Taylor, M L; Kron, T

2017-05-01

To assess out-of-field dose using three different variants of LiF thermoluminescence dosimeters (TLD) for ten patients who underwent stereotactic ablative body radiotherapy (SABR) for primary renal cell carcinoma (RCC) and compare with treatment planning system (TPS) dose calculations. Thermoluminescent dosimeter (TLD) measurements were conducted at 20, 30, 40 and 50cm from isocentre on ten patients undergoing SABR for primary RCC. Three types of high-sensitivity LiF:Mg,Cu,P TLD material with different 6 Li/ 7 Li isotope ratios were used. Patient plans were calculated using Eclipse Anisotropic Analytical Algorithm (AAA) for clinical evaluation and recalculated using Pencil Beam Convolution (PBC) algorithm for comparison. Both AAA and PBC showed diminished accuracy for photon doses at increasing distance out-of-field. At 50cm, measured photon dose was 0.3cGy normalised to a 10Gy prescription on average with only small variation across all patients. This is likely due to the leakage component of the out-of-field dose. The 6 Li-enriched TLD materials showed increased signal attributable to additional neutron contribution. LiF:Mg,Cu,P TLD containing 6 Li is sensitive enough to measure out-of-field dose 50cm from isocentre however will over-estimate the photon component of out-of-field dose in high energy treatments due to the presence of thermal neutrons. 7 Li enriched materials which are insensitive to neutrons are therefore required for accurate photon dosimetry. Neutron signal has been shown here to increase with MUs and is higher for patients treated using certain non coplanar beam arrangements. Further work is required to convert this additional neutron signal to dose. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Dose-rate effects on the radiation-induced oxidation of electric cable used in nuclear power plants

NASA Astrophysics Data System (ADS)

Reynolds, A. B.; Bell, R. M.; Bryson, N. M. N.; Doyle, T. E.; Hall, M. B.; Mason, L. R.; Quintric, L.; Terwilliger, P. L.

1995-01-01

Dose-rate effects were measured for typical ethylene propylene rubber (EPR) and crosslinked polyethylene (XLPE) electric cable used in nuclear power plants. The radiation source was the 60Co Irradiation Facility at the University of Virginia. Dose rates were varied from 5 Gy/h to 2500 Gy/h. It was found that there is little or no dose-rate effect at low doses for four of the five EPR cable products tested from 2500 Gy/h down to dose rates of 5 Gy/h but perhaps a small dose-rate effect at high doses for dose rates above 340 Gy/h. A small dose-rate exists for the fifth EPR above 340 Gy/h at all doses. A dose-rate effect exists above 40 Gy/h for two of the three XLPE cable products tested, but there is no dose-rate for these XLPE's between 40 Gy/h and 5 Gy/h. These results indicate that the dose-rate effects observed are due to oxygen diffusion effects during heterogeneous aging and suggest that there is no dose-rate effect for either EPR or XLPE during homogeneous aging.

Typical doses and dose rates in studies pertinent to radiation risk inference at low doses and low dose rates

PubMed Central

Rühm, Werner; Azizova, Tamara; Bouffler, Simon; Cullings, Harry M; Grosche, Bernd; Little, Mark P; Shore, Roy S; Walsh, Linda; Woloschak, Gayle E

2018-01-01

Abstract In order to quantify radiation risks at exposure scenarios relevant for radiation protection, often extrapolation of data obtained at high doses and high dose rates down to low doses and low dose rates is needed. Task Group TG91 on ‘Radiation Risk Inference at Low-dose and Low-dose Rate Exposure for Radiological Protection Purposes’ of the International Commission on Radiological Protection is currently reviewing the relevant cellular, animal and human studies that could be used for that purpose. This paper provides an overview of dose rates and doses typically used or present in those studies, and compares them with doses and dose rates typical of those received by the A-bomb survivors in Japan. PMID:29432579

Punishment insensitivity in early childhood: A developmental, dimensional approach

PubMed Central

Nichols, Sara R.; Briggs-Gowan, Margaret; Estabrook, Ryne; Burns, James; Kestler, Jacqueline; Berman, Grace; Henry, David; Wakschlag, Lauren

2014-01-01

Impairment in learning from punishment ("punishment insensitivity") is an established feature of severe antisocial behavior in adults and youth but it has not been well studied as a developmental phenomenon. In early childhood, differentiating a normal:abnormal spectrum of punishment insensitivity is key for distinguishing normative misbehavior from atypical manifestations. This study employed a novel measure, the Multidimensional Assessment Profile of Disruptive Behavior (MAPDB), to examine the distribution, dimensionality, and external validity of punishment insensitivity in a large, demographically diverse community sample of preschoolers (three-five years) recruited from pediatric clinics (N=1,855). Caregivers completed surveys from which a seven-item Punishment Insensitivity scale was derived. Findings indicated that Punishment Insensitivity behaviors are relatively common in young children, with at least 50% of preschoolers exhibiting them sometimes. Item response theory analyses revealed a Punishment Insensitivity spectrum. Items varied along a severity continuum: most items needed to occur "Often" in order to be severe and behaviors that were qualitatively atypical or intense were more severe. Although there were item-level differences across sociodemographic groups, these were small. Construct, convergent, and divergent validity were demonstrated via association to low concern for others and noncompliance, motivational regulation, and a disruptive family context. Incremental clinical utility was demonstrated in relation to impairment. Early childhood punishment insensitivity varies along a severity continuum and is atypical when it predominates. Implications for understanding the phenomenology of emergent disruptive behavior are discussed. PMID:25425187

Osteopenia as a feature of the androgen insensitivity syndrome.

PubMed

Soule, S G; Conway, G; Prelevic, G M; Prentice, M; Ginsburg, J; Jacobs, H S

1995-12-01

The syndrome of androgen insensitivity, a paradigm of a hormone resistance syndrome, manifests as failure of masculinization despite normal or high concentrations of serum testosterone. The defect in these 46 XY patients resides in the androgen receptor gene, with consequent defective androgen action and abnormal sexual differentiation. We sought to evaluate whether the adverse sequelae of androgen resistance may extend to skeletal tissue by measuring bone mineral density in six patients with androgen insensitivity. A cross-sectional retrospective study. Bone mineral density was measured by means of a Dexa (Hologic QDR 1000 scanner). The diagnosis of androgen insensitivity was confirmed in each patient by karyotype and assay of sex hormones. The five adult patients with androgen insensitivity had been exposed to both defective androgen action and variable periods of oestrogen deficiency. The latter resulted from the low circulating oestrogen concentrations (for premenopausal females) before gonadectomy and inadequate oestrogen replacement after gonadectomy. All five adults with androgen insensitivity had osteopenia in both the lumbar spine (T-score -1.52 to -3.85) and femoral neck (T-score -1.34 to -4.91). Osteopenia in patients with androgen insensitivity may relate to defective androgen action, oestrogen deficiency or a combination of the two. These observations have implications for the management of patients with androgen insensitivity and may provide insight into the effects of androgens on the female as well as the male skeleton.

Effect of quantifying peptide release on ruminal protein degradation determined using the inhibitor in vitro system

USDA-ARS?s Scientific Manuscript database

The aim of this work was to compare use of an o-phthaldialdehyde (OPA) colorimetric assay (OPA-C), which responds to both free AA and peptides, with an OPA fluorimetric assay (OPA-F), which is insensitive to peptides, to quantify rates of ruminal protein degradation in the inhibitor in vitro system ...

CAR T Cell Immunotherapy Promising in Refractory Leukemia | Center for Cancer Research

Cancer.gov

B-cell acute lymphoblastic leukemia (B-ALL) is a common childhood malignancy that also affects young adults. Although current treatments have significant toxicities, children with chemotherapy susceptible subtypes have high survival rates. However, less than 10 percent of children and young adults with newly-diagnosed or recurrent B-ALL that is insensitive to therapy survive,

Are the Competent the Morally Good? Perspective Taking and Moral Motivation of Children Involved in Bullying

ERIC Educational Resources Information Center

Gasser, Luciano; Keller, Monika

2009-01-01

The present study tested the hypothesis of the cognitively competent but morally insensitive bully. On the basis of teacher and peer ratings, 212 young elementary school children were selected and categorized as bullies, bully-victims, victims, and prosocial children. Children's perspective-taking skills were assessed using theory-of-mind tasks,…

Water temperature and fish growth: otoliths predict growth patterns of a marine fish in a changing climate.

PubMed

Rountrey, Adam N; Coulson, Peter G; Meeuwig, Jessica J; Meekan, Mark

2014-08-01

Ecological modeling shows that even small, gradual changes in body size in a fish population can have large effects on natural mortality, biomass, and catch. However, efforts to model the impact of climate change on fish growth have been hampered by a lack of long-term (multidecadal) data needed to understand the effects of temperature on growth rates in natural environments. We used a combination of dendrochronology techniques and additive mixed-effects modeling to examine the sensitivity of growth in a long-lived (up to 70 years), endemic marine fish, the western blue groper (Achoerodus gouldii), to changes in water temperature. A multi-decadal biochronology (1952-2003) of growth was constructed from the otoliths of 56 fish collected off the southwestern coast of Western Australia, and we tested for correlations between the mean index chronology and a range of potential environmental drivers. The chronology was significantly correlated with sea surface temperature in the region, but common variance among individuals was low. This suggests that this species has been relatively insensitive to past variations in climate. Growth increment and age data were also used in an additive mixed model to predict otolith growth and body size later this century. Although growth was relatively insensitive to changes in temperature, the model results suggested that a fish aged 20 in 2099 would have an otolith about 10% larger and a body size about 5% larger than a fish aged 20 in 1977. Our study shows that species or populations regarded as relatively insensitive to climate change could still undergo significant changes in growth rate and body size that are likely to have important effects on the productivity and yield of fisheries. © 2014 John Wiley & Sons Ltd.

Dose rate mapping of VMAT treatments

NASA Astrophysics Data System (ADS)

Podesta, Mark; Antoniu Popescu, I.; Verhaegen, Frank

2016-06-01

Human tissues exhibit a varying response to radiation dose depending on the dose rate and fractionation scheme used. Dose rate effects have been reported for different radiations, and tissue types. The literature indicates that there is not a significant difference in response for low-LET radiation when using dose rates between 1 Gy min-1 and 12 Gy min-1 but lower dose rates have an observable sparing effect on tissues and a differential effect between tissues. In intensity-modulated radiotherapy such as volumetric modulated arc therapy (VMAT) the dose can be delivered with a wide range of dose rates. In this work we developed a method based on time-resolved Monte Carlo simulations to quantify the dose rate frequency distribution for clinical VMAT treatments for three cancer sites, head and neck, lung, and pelvis within both planning target volumes (PTV) and normal tissues. The results show a wide range of dose rates are used to deliver dose in VMAT and up to 75% of the PTV can have its dose delivered with dose rates  <1 Gy min-1. Pelvic plans on average have a lower mean dose rate within the PTV than lung or head and neck plans but a comparable mean dose rate within the organs at risk. Two VMAT plans that fulfil the same dose objectives and constraints may be delivered with different dose rate distributions, particularly when comparing single arcs to multiple arc plans. It is concluded that for dynamic plans, the dose rate range used varies to a larger degree than previously assumed. The effect of the dose rate range in VMAT on clinical outcome is unknown.

Probability Distribution of Dose and Dose-Rate Effectiveness Factor for use in Estimating Risks of Solid Cancers From Exposure to Low-Let Radiation.

PubMed

Kocher, David C; Apostoaei, A Iulian; Hoffman, F Owen; Trabalka, John R

2018-06-01

This paper presents an analysis to develop a subjective state-of-knowledge probability distribution of a dose and dose-rate effectiveness factor for use in estimating risks of solid cancers from exposure to low linear energy transfer radiation (photons or electrons) whenever linear dose responses from acute and chronic exposure are assumed. A dose and dose-rate effectiveness factor represents an assumption that the risk of a solid cancer per Gy at low acute doses or low dose rates of low linear energy transfer radiation, RL, differs from the risk per Gy at higher acute doses, RH; RL is estimated as RH divided by a dose and dose-rate effectiveness factor, where RH is estimated from analyses of dose responses in Japanese atomic-bomb survivors. A probability distribution to represent uncertainty in a dose and dose-rate effectiveness factor for solid cancers was developed from analyses of epidemiologic data on risks of incidence or mortality from all solid cancers as a group or all cancers excluding leukemias, including (1) analyses of possible nonlinearities in dose responses in atomic-bomb survivors, which give estimates of a low-dose effectiveness factor, and (2) comparisons of risks in radiation workers or members of the public from chronic exposure to low linear energy transfer radiation at low dose rates with risks in atomic-bomb survivors, which give estimates of a dose-rate effectiveness factor. Probability distributions of uncertain low-dose effectiveness factors and dose-rate effectiveness factors for solid cancer incidence and mortality were combined using assumptions about the relative weight that should be assigned to each estimate to represent its relevance to estimation of a dose and dose-rate effectiveness factor. The probability distribution of a dose and dose-rate effectiveness factor for solid cancers developed in this study has a median (50th percentile) and 90% subjective confidence interval of 1.3 (0.47, 3.6). The harmonic mean is 1.1, which implies that the arithmetic mean of an uncertain estimate of the risk of a solid cancer per Gy at low acute doses or low dose rates of low linear energy transfer radiation is only about 10% less than the mean risk per Gy at higher acute doses. Data were also evaluated to define a low acute dose or low dose rate of low linear energy transfer radiation, i.e., a dose or dose rate below which a dose and dose-rate effectiveness factor should be applied in estimating risks of solid cancers.

Temperature-insensitive phase-matched optical harmonic conversion crystal

DOEpatents

Barker, Charles E.; Eimerl, David; Velsko, Stephan P.; Roberts, David

1993-01-01

Temperature-insensitive, phase-matched harmomic frequency conversion of laser light at a preferred wavelength of 1.064 microns can be achieved by use of a crystal of deuterated l-arginine phosphate. The crystal is cut and oriented so that the laser light propagates inside the crystal along one of several required directions, which correspond to a temperature-insensitive, phase-matching locus. The method of measuring and calculating the temperature-insensitive, phase-matching angles can be extended to other fundamental wavelengths and other crystal compositions.

Temperature-insensitive phase-matched optical harmonic conversion crystal

DOEpatents

Barker, C.E.; Eimerl, D.; Velsko, S.P.; Roberts, D.

1993-11-23

Temperature-insensitive, phase-matched harmonic frequency conversion of laser light at a preferred wavelength of 1.064 microns can be achieved by use of a crystal of deuterated l-arginine phosphate. The crystal is cut and oriented so that the laser light propagates inside the crystal along one of several required directions, which correspond to a temperature-insensitive, phase-matching locus. The method of measuring and calculating the temperature-insensitive, phase-matching angles can be extended to other fundamental wavelengths and other crystal compositions. 12 figures.

The impact of the oxygen scavenger on the dose-rate dependence and dose sensitivity of MAGIC type polymer gels

NASA Astrophysics Data System (ADS)

Khan, Muzafar; Heilemann, Gerd; Kuess, Peter; Georg, Dietmar; Berg, Andreas

2018-03-01

Recent developments in radiation therapy aimed at more precise dose delivery along with higher dose gradients (dose painting) and more efficient dose delivery with higher dose rates e.g. flattening filter free (FFF) irradiation. Magnetic-resonance-imaging based polymer gel dosimetry offers 3D information for precise dose delivery techniques. Many of the proposed polymer gels have been reported to exhibit a dose response, measured as relaxation rate ΔR2(D), which is dose rate dependent. A lack of or a reduced dose-rate sensitivity is very important for dosimetric accuracy, especially with regard to the increasing clinical use of FFF irradiation protocols with LINACs at high dose rates. Some commonly used polymer gels are based on Methacrylic-Acid-Gel-Initiated-by-Copper (MAGIC). Here, we report on the dose sensitivity (ΔR2/ΔD) of MAGIC-type gels with different oxygen scavenger concentration for their specific dependence on the applied dose rate in order to improve the dosimetric performance, especially for high dose rates. A preclinical x-ray machine (‘Yxlon’, E  =  200 kV) was used for irradiation to cover a range of dose rates from low \\dot{D} min  =  0.6 Gy min-1 to high \\dot{D} max  =  18 Gy min-1. The dose response was evaluated using R2-imaging of the gel on a human high-field (7T) MR-scanner. The results indicate that all of the investigated dose rates had an impact on the dose response in polymer gel dosimeters, being strongest in the high dose region and less effective for low dose levels. The absolute dose rate dependence \\frac{(Δ R2/Δ D)}{Δ \\dot{D}} of the dose response in MAGIC-type gel is significantly reduced using higher concentrations of oxygen scavenger at the expense of reduced dose sensitivity. For quantitative dose evaluations the relative dose rate dependence of a polymer gel, normalized to its sensitivity is important. Based on this normalized sensitivity the dose rate sensitivity was reduced distinctly using an increased oxygen scavenger concentration with reference to standard MAGIC-type gel formulation at high dose rate levels. The proposed gel composition with high oxygen scavenger concentration exhibits a larger linear active dose response and might be used especially in FFF-radiation applications and preclinical dosimetry at high dose rates. We propose in general to use high dose rates for calibration and evaluation as the change in relative dose sensitivity is reduced at higher dose rates in all of the investigated gel types.

Functional characterization and modified rescue of novel AE1 mutation R730C associated with overhydrated cation leak stomatocytosis.

PubMed

Stewart, Andrew K; Kedar, Prabhakar S; Shmukler, Boris E; Vandorpe, David H; Hsu, Ann; Glader, Bertil; Rivera, Alicia; Brugnara, Carlo; Alper, Seth L

2011-05-01

We report the novel, heterozygous AE1 mutation R730C associated with dominant, overhydrated, cation leak stomatocytosis and well-compensated anemia. Parallel elevations of red blood cell cation leak and ouabain-sensitive Na(+) efflux (pump activity) were apparently unaccompanied by increased erythroid cation channel-like activity, and defined ouabain-insensitive Na(+) efflux pathways of nystatin-treated cells were reduced. Epitope-tagged AE1 R730C at the Xenopus laevis oocyte surface exhibited severely reduced Cl(-) transport insensitive to rescue by glycophorin A (GPA) coexpression or by methanethiosulfonate (MTS) treatment. AE1 mutant R730K preserved Cl(-) transport activity, but R730 substitution with I, E, or H inactivated Cl(-) transport. AE1 R730C expression substantially increased endogenous oocyte Na(+)-K(+)-ATPase-mediated (86)Rb(+) influx, but ouabain-insensitive flux was minimally increased and GPA-insensitive. The reduced AE1 R730C-mediated sulfate influx did not exhibit the wild-type pattern of stimulation by acidic extracellular pH (pH(o)) and, unexpectedly, was partially rescued by exposure to sodium 2-sulfonatoethyl methanethiosulfonate (MTSES) but not to 2-aminoethyl methanethiosulfonate hydrobromide (MTSEA) or 2-(trimethylammonium)ethyl methanethiosulfonate bromide (MTSET). AE1 R730E correspondingly exhibited acid pH(o)-stimulated sulfate uptake at rates exceeding those of wild-type AE1 and AE1 R730K, whereas mutants R730I and R730H were inactive and pH(o) insensitive. MTSES-treated oocytes expressing AE1 R730C and untreated oocytes expressing AE1 R730E also exhibited unprecedented stimulation of Cl(-) influx by acid pH(o). Thus recombinant cation-leak stomatocytosis mutant AE1 R730C exhibits severely reduced anion transport unaccompanied by increased Rb(+) and Li(+) influxes. Selective rescue of acid pH(o)-stimulated sulfate uptake and conferral of acid pH(o)-stimulated Cl(-) influx, by AE1 R730E and MTSES-treated R730C, define residue R730 as critical to selectivity and regulation of anion transport by AE1.

Plasmodium falciparum: attenuation by irradiation

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

Waki, S.; Yonome, I.; Suzuki, M.

The effect of irradiation on the in vitro growth of Plasmodium falciparum was investigated. The cultured malarial parasites at selected stages of development were exposed to gamma rays and the sensitivity of each stage was determined. The stages most sensitive to irradiation were the ring forms and the early trophozoites; late trophozoites were relatively insensitive. The greatest resistance was shown when parasites were irradiated at a time of transition from the late trophozoite and schizont stages to young ring forms. The characteristics of radiosensitive variation in the parasite cycle resembled that of mammalian cells. Growth curves of parasites exposed tomore » doses of irradiation upto 150 gray had the same slope as nonirradiated controls but parasites which were exposed to 200 gray exhibited a growth curve which was less steep than that for parasites in other groups. Less than 10 organisms survived from the 10(6) parasites exposed to this high dose of irradiation; the possibility exists of obtaining radiation-attenuated P. falciparum.« less

High-pressure crystal structures of an insensitive energetic crystal: 1,1-diamino-2,2-dinitroethene

DOE PAGES

Dreger, Zbigniew A.; Stash, Adam I.; Yu, Zhi -Gang; ...

2015-12-03

Understanding the insensitivity/stability of insensitive high explosive crystals requires detailed structural information at high pressures and high temperatures of interest. Synchrotron single crystal x-ray diffraction experiments were used to determine the high-pressure structures of 1,1-diamino-2,2-dinitroethene (FOX-7), a prototypical insensitive high explosive. The phase transition around 4.5 GPa was investigated and the structures were determined at 4.27 GPa (α’-phase) and 5.9 GPa (ε-phase). The α’-phase (monoclinic, P2 1/ n), structurally indistinguishable from the ambient α-phase, transforms to the new ε-phase (triclinic, P1). The most notable features of the ε-phase, compared to the α’-phase, are: formation of planar layers and flattening ofmore » molecules. Density functional theory (DFT-D2) calculations complemented the experimental results. Furthermore, the results presented here are important for understanding the molecular and crystalline attributes governing the high-pressure insensitivity/stability of insensitive high explosive crystals.« less

High-pressure crystal structures of an insensitive energetic crystal: 1,1-diamino-2,2-dinitroethene

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

Dreger, Zbigniew A.; Stash, Adam I.; Yu, Zhi -Gang

Understanding the insensitivity/stability of insensitive high explosive crystals requires detailed structural information at high pressures and high temperatures of interest. Synchrotron single crystal x-ray diffraction experiments were used to determine the high-pressure structures of 1,1-diamino-2,2-dinitroethene (FOX-7), a prototypical insensitive high explosive. The phase transition around 4.5 GPa was investigated and the structures were determined at 4.27 GPa (α’-phase) and 5.9 GPa (ε-phase). The α’-phase (monoclinic, P2 1/ n), structurally indistinguishable from the ambient α-phase, transforms to the new ε-phase (triclinic, P1). The most notable features of the ε-phase, compared to the α’-phase, are: formation of planar layers and flattening ofmore » molecules. Density functional theory (DFT-D2) calculations complemented the experimental results. Furthermore, the results presented here are important for understanding the molecular and crystalline attributes governing the high-pressure insensitivity/stability of insensitive high explosive crystals.« less

Punishment Insensitivity in Early Childhood: A Developmental, Dimensional Approach.

PubMed

Nichols, Sara R; Briggs-Gowan, Margaret J; Estabrook, Ryne; Burns, James L; Kestler, Jacqueline; Berman, Grace; Henry, David B; Wakschlag, Lauren S

2015-08-01

Impairment in learning from punishment ("punishment insensitivity") is an established feature of severe antisocial behavior in adults and youth but it has not been well studied as a developmental phenomenon. In early childhood, differentiating a normal: abnormal spectrum of punishment insensitivity is key for distinguishing normative misbehavior from atypical manifestations. This study employed a novel measure, the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB), to examine the distribution, dimensionality, and external validity of punishment insensitivity in a large, demographically diverse community sample of preschoolers (3-5 years) recruited from pediatric clinics (N = 1,855). Caregivers completed surveys from which a seven-item Punishment Insensitivity scale was derived. Findings indicated that Punishment Insensitivity behaviors are relatively common in young children, with at least 50 % of preschoolers exhibiting them sometimes. Item response theory analyses revealed a Punishment Insensitivity spectrum. Items varied along a severity continuum: most items needed to occur "Often" in order to be severe and behaviors that were qualitatively atypical or intense were more severe. Although there were item-level differences across sociodemographic groups, these were small. Construct, convergent, and divergent validity were demonstrated via association to low concern for others and noncompliance, motivational regulation, and a disruptive family context. Incremental clinical utility was demonstrated in relation to impairment. Early childhood punishment insensitivity varies along a severity continuum and is atypical when it predominates. Implications for understanding the phenomenology of emergent disruptive behavior are discussed.

Log file-based patient dose calculations of double-arc VMAT for head-and-neck radiotherapy.

PubMed

Katsuta, Yoshiyuki; Kadoya, Noriyuki; Fujita, Yukio; Shimizu, Eiji; Majima, Kazuhiro; Matsushita, Haruo; Takeda, Ken; Jingu, Keiichi

2018-04-01

The log file-based method cannot display dosimetric changes due to linac component miscalibration because of the insensitivity of log files to linac component miscalibration. The purpose of this study was to supply dosimetric changes in log file-based patient dose calculations for double-arc volumetric-modulated arc therapy (VMAT) in head-and-neck cases. Fifteen head-and-neck cases participated in this study. For each case, treatment planning system (TPS) doses were produced by double-arc and single-arc VMAT. Miscalibration-simulated log files were generated by inducing a leaf miscalibration of ±0.5 mm into the log files that were acquired during VMAT irradiation. Subsequently, patient doses were estimated using the miscalibration-simulated log files. For double-arc VMAT, regarding planning target volume (PTV), the change from TPS dose to miscalibration-simulated log file dose in D mean was 0.9 Gy and that for tumor control probability was 1.4%. As for organ-at-risks (OARs), the change in D mean was <0.7 Gy and normal tissue complication probability was <1.8%. A comparison between double-arc and single-arc VMAT for PTV showed statistically significant differences in the changes evaluated by D mean and radiobiological metrics (P < 0.01), even though the magnitude of these differences was small. Similarly, for OARs, the magnitude of these changes was found to be small. Using the log file-based method for PTV and OARs, the log file-based method estimate of patient dose using the double-arc VMAT has accuracy comparable to that obtained using the single-arc VMAT. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Depicting changes in tumor biology in response to cetuximab mono- or combination therapy by apoptosis and proliferation imaging using 18F-ICMT-11 and 3'-Deoxy-3'-[18F]Fluorothymidine (18F-FLT) PET.

PubMed

Heinzmann, Kathrin; Nguyen, Quang-De; Honess, Davina Jean; Smith, Donna-Michelle; Stribbling, Stephen; Brickute, Diana; Barnes, Christopher; Griffiths, John Richard; Aboagye, Eric Ofori

2018-05-24

Imaging biomarkers must demonstrate their value in monitoring treatment. Two PET tracers, the caspase-3/7-specific isatin-5-sulfonamide 18 F-ICMT-11 and 3'-Deoxy-3'-[ 18 F]Fluorothymidine ( 18 F-FLT), were employed to detect early treatment-induced changes in tumor biology and whether any changes indicate response to cetuximab, administered as mono- or combination therapy with gemcitabine. Methods: Effects of single or repeated doses of the anti-Epidermal Growth Factor Receptor (EGFR) antibody cetuximab (10mg/kg on day 1 only or day 1 and 2) and/or a single dose of gemcitabine (125mg/kg; day 2) were investigated in mice bearing cetuximab-sensitive H1975 tumors (non-small cell lung cancer) by 18 F-ICMT-11 or 18 F-FLT-PET (day 3). Imaging was also performed in mice bearing cetuximab-insensitive HCT116 tumors (colorectal cancer) after two doses of cetuximab (day 1 and 2). For imaging/histology comparison, tumors were evaluated for proliferation (Ki67; thymidine kinase 1, TK1), cell death (cleaved caspase-3, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL)) and target engagement (EGFR expression) by immunohistochemistry, immunofluorescence and immunoblot, respectively. Tumor and plasma were analysed for thymidine and gemcitabine metabolites by liquid chromatography-mass spectrometry. Results: Retention of both tracers was sensitive to cetuximab in H1975 tumors. 18 F-ICMT-11 uptake and ex vivo cleaved caspase-3 staining notably increased in tumors treated with repeated doses of cetuximab- (75%) and combination-treatment (46%). While one dose of cetuximab was insufficient to induce apoptosis it did affect proliferation. Significant reduction in tumor 18 F-FLT uptake (44 to 50%; P < 0.001) induced by cetuximab mono- and combination-therapy were paralleled with a clear decrease in proliferation (%Ki67 decrease: 72 to 95%; P < 0.0001) and followed by marked tumor growth delay. TK1 expression and tumor thymidine concentrations were profoundly reduced. Neither imaging tracer depicted the gemcitabine-induced tumor changes. However, cleaved caspase-3 and Ki67 staining were not significantly different while TK1 expression and thymidine concentrations increased after gemcitabine-treatment. No cetuximab-induced modulation of the imaging tracers or other response markers was detected in the insensitive model HCT116. Conclusion: 18 F-ICMT-11 and 18 F-FLT are valuable tools to assess cetuximab-sensitivity depicting distinct and time-variant aspects of treatment response. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Effect of slow energy releasing on divergent detonation of Insensitive High Explosives

NASA Astrophysics Data System (ADS)

Hu, Xiaomian; Pan, Hao; Huang, Yong; Wu, Zihui

2014-03-01

There exists a slow energy releasing (SER) process in the slow reaction zone located behind the detonation wave due to the carbon cluster in the detonation products of Insensitive High Explosives (IHEs), and the process will affect the divergent detonation wave's propagation and the driving process of the explosives. To study the potential effect, a new artificial burn model including the SER process based on the programmed burn model is proposed in the paper. Quasi-steady analysis of the new model indicates that the nonlinearity of the detonation speed as a function of front curvature owes to the significant change of the reaction rate and the reaction zone length at the sonic state. What's more, in simulating the detonation of IHE JB-9014, the new model including the slow reaction can predict a slower jump-off velocity, in good agreement with the result of the test.

Multiphysics Simulations of Hot-Spot Initiation in Shocked Insensitive High-Explosive

NASA Astrophysics Data System (ADS)

Najjar, Fady; Howard, W. M.; Fried, L. E.

2010-11-01

Solid plastic-bonded high-explosive materials consist of crystals with micron-sized pores embedded. Under mechanical or thermal insults, these voids increase the ease of shock initiation by generating high-temperature regions during their collapse that might lead to ignition. Understanding the mechanisms of hot-spot initiation has significant research interest due to safety, reliability and development of new insensitive munitions. Multi-dimensional high-resolution meso-scale simulations are performed using the multiphysics software, ALE3D, to understand the hot-spot initiation. The Cheetah code is coupled to ALE3D, creating multi-dimensional sparse tables for the HE properties. The reaction rates were obtained from MD Quantum computations. Our current predictions showcase several interesting features regarding hot spot dynamics including the formation of a "secondary" jet. We will discuss the results obtained with hydro-thermo-chemical processes leading to ignition growth for various pore sizes and different shock pressures.

Large amplitude Fourier transformed ac voltammetry at a rotating disc electrode: a versatile technique for covering Levich and flow rate insensitive regimes in a single experiment.

PubMed

Bano, Kiran; Kennedy, Gareth F; Zhang, Jie; Bond, Alan M

2012-04-14

The theory for large amplitude Fourier transformed ac voltammetry at a rotating disc electrode is described. Resolution of time domain data into dc and ac harmonic components reveals that the mass transport for the dc component is controlled by convective-diffusion, while the background free higher order harmonic components are flow rate insensitive and mainly governed by linear diffusion. Thus, remarkable versatility is available; Levich behaviour of the dc component limiting current provides diffusion coefficient values and access to higher harmonics allows fast electrode kinetics to be probed. Two series of experiments (dc and ac voltammetry) have been required to extract these parameters; here large amplitude ac voltammetry with RDE methodology is used to demonstrate that kinetics and diffusion coefficient information can be extracted from a single experiment. To demonstrate the power of this approach, theoretical and experimental comparisons of data obtained for the reversible [Ru(NH(3))(6)](3+/2+) and quasi-reversible [Fe(CN)(6)](3-/4-) electron transfer processes are presented over a wide range of electrode rotation rates and with different concentrations and electrode materials. Excellent agreement of experimental and simulated data is achieved, which allows parameters such as electron transfer rate, diffusion coefficient, uncompensated resistance and others to be determined using a strategically applied approach that takes into account the different levels of sensitivity of each parameter to the dc or the ac harmonic.

Insensitive detonator apparatus for initiating large failure diameter explosives

DOEpatents

Perry, III, William Leroy

2015-07-28

A munition according to a preferred embodiment can include a detonator system having a detonator that is selectively coupled to a microwave source that functions to selectively prime, activate, initiate, and/or sensitize an insensitive explosive material for detonation. The preferred detonator can include an explosive cavity having a barrier within which an insensitive explosive material is disposed and a waveguide coupled to the explosive cavity. The preferred system can further include a microwave source coupled to the waveguide such that microwaves enter the explosive cavity and impinge on the insensitive explosive material to sensitize the explosive material for detonation. In use the preferred embodiments permit the deployment and use of munitions that are maintained in an insensitive state until the actual time of use, thereby substantially preventing unauthorized or unintended detonation thereof.

Characterisation of neutron-sensitive bubble detectors for application in the measurement of jet aircrew exposure to natural background radiation.

PubMed

Tume, P; Lewis, B J; Bennett, L G; Cousins, T

1998-01-01

A survey of the natural background dose equivalent received by Canadian Forces aircrew was conducted using neutron-sensitive bubble detectors (BDs) as the primary detection tool. Since this study was a new application for these detectors, the BD response to neutron dose equivalent (RD) was extended from thermal to 500 MeV in neutron energy. Based upon the extended RD, it was shown that the manufacturer's calibration can be scaled by 1.5 +/- 0.5 to give a BD sensitivity that takes into account recently recommended fluence-to-neutron dose equivalent conversion functions and the cosmogenic neutron spectrum encountered at jet altitudes. An investigation of the effects of systematic bias caused by the cabin environment (i.e., temperature, pressure and relative humidity) on the in-flight measurements was also conducted. Both simulated and actual aircraft climate tests indicated that the detectors are insensitive to the pressure and relative humidity variations encountered during routine jet aircraft operations. Long term conditioning tests also confirmed that the BD-PND model of detector is sensitive to variations in temperature to within +/- 20%. As part of the testing process, the in-flight measurements also demonstrated that the neutron dose equivalent is distributed uniformly throughout a Boeing 707 jet aircraft, indicating that both pilots and flight attendants are exposed to the same neutron field intensity to within experimental uncertainty.

Dose rate effect of pulsed electron beam on micronucleus frequency in human peripheral blood lymphocytes.

PubMed

Acharya, Santhosh; Sanjeev, Ganesh; Bhat, Nagesh N; Narayana, Yerol

2010-03-01

The micronucleus assay in human peripheral blood lymphocytes is a sensitive indicator of radiation damage and could serve as a biological dosimeter in evaluating suspected overexposure to ionising radiation. Micronucleus (MN) frequency as a measure of chromosomal damage has also extensively been employed to quantify the effects of radiation dose rate on biological systems. Here we studied the effects of 8 MeV pulsed electron beam emitted by Microtron electron accelerator on MN induction at dose rates between 35 Gy min-1 and 352.5 Gy min-1. These dose rates were achieved by varying the pulse repetition rate (PRR). Fricke dosimeter was employed to measure the absorbed dose at different PRR and to ensure uniform dose distribution of the electron beam. To study the dose rate effect, blood samples were irradiated to an absorbed dose of (4.7+/-0.2) Gy at different rates and cytogenetic damage was quantified using the micronucleus assay. The obtained MN frequency showed no dose rate dependence within the studied dose rate range. Our earlier dose effect study using 8 MeV electrons revealed that the response of MN was linear-quadratic. Therefore, in the event of an accident, dose estimation can be made using linear-quadratic dose response parameters, without adding dose rate as a correction factor.

Enhanced Low Dose Rate Sensitivity at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

Chen, Dakai; Pease, Ronald; Forney, James; Carts, Martin; Phan, Anthony; Cox, Stephen; Kruckmeyer, Kriby; Burns, Sam; Albarian, Rafi; Holcombe, Bruce;

The Effects of ELDRS at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

Chen, Dakai; Forney, James; Carts, Martin; Phan, Anthony; Pease, Ronald; Kruckmeyer, Kirby; Cox, Stephen; LaBel, Kenneth; Burns, Samuel; Albarian, Rafi;

RadNuc: A graphical user interface to deliver dose rate patterns encountered in nuclear medicine with a 137Cs irradiator

PubMed Central

Pasternack, Jordan B.; Howell, Roger W.

2012-01-01

The temporal variations in absorbed dose rates to organs and tissues in the body are very large in diagnostic and therapeutic nuclear medicine. The response of biological endpoints of relevance to radiation safety and therapeutic efficacy are generally modulated by dose rate. Therefore, it is important to understand how the complex dose rate patterns encountered in nuclear medicine impact relevant biological responses. Accordingly, a graphical user interface (GUI) was created to control a cesium-137 irradiator to deliver such dose rate patterns. Methods Visual Basic 6.0 was used to create a user-friendly GUI to control the dose rate by varying the thickness of a mercury attenuator. The GUI facilitates the delivery of a number of dose rate patterns including constant, exponential increase or decrease, and multi-component exponential. Extensive visual feedback is provided by the GUI during both the planning and delivery stages. Results The GUI controlled irradiator can achieve a maximum dose rate of 40 cGy/hr and a minimum dose rate of 0.01 cGy/hr. Addition of machined lead blocks can be used to further reduce the minimum dose rate to 0.0001 cGy/hr. Measured dose rate patterns differed from programmed dose rate patterns in total dose by 3.2% to 8.4%. Conclusion The GUI controlled irradiator is able to accurately create dose rate patterns encountered in nuclear medicine and other related fields. This makes it an invaluable tool for studying the effects of chronic constant and variable low dose rates on biological tissues in the contexts of both radiation protection and clinical administration of internal radionuclides. PMID:23265668

RadNuc: a graphical user interface to deliver dose rate patterns encountered in nuclear medicine with a 137Cs irradiator.

PubMed

Pasternack, Jordan B; Howell, Roger W

2013-02-01

The temporal variations in absorbed dose rates to organs and tissues in the body are very large in diagnostic and therapeutic nuclear medicine. The response of biological endpoints of relevance to radiation safety and therapeutic efficacy is generally modulated by dose rate. Therefore, it is important to understand how the complex dose rate patterns encountered in nuclear medicine impact relevant biological responses. Accordingly, a graphical user interface (GUI) was created to control a cesium-137 irradiator to deliver such dose rate patterns. Visual Basic 6.0 was used to create a user-friendly GUI to control the dose rate by varying the thickness of a mercury attenuator. The GUI facilitates the delivery of a number of dose rate patterns including constant, exponential increase or decrease, and multi-component exponential. Extensive visual feedback is provided by the GUI during both the planning and delivery stages. The GUI controlled irradiator can achieve a maximum dose rate of 40 cGy/h and a minimum dose rate of 0.01 cGy/h. Addition of machined lead blocks can be used to further reduce the minimum dose rate to 0.0001 cGy/h. Measured dose rate patterns differed from programmed dose rate patterns in total dose by 3.2% to 8.4%. The GUI controlled irradiator is able to accurately create dose rate patterns encountered in nuclear medicine and other related fields. This makes it an invaluable tool for studying the effects of chronic constant and variable low dose rates on biological tissues in the contexts of both radiation protection and clinical administration of internal radionuclides. Copyright © 2013 Elsevier Inc. All rights reserved.

Repeated functional convergent effects of NaV1.7 on acid insensitivity in hibernating mammals

PubMed Central

Liu, Zhen; Wang, Wei; Zhang, Tong-Zuo; Li, Gong-Hua; He, Kai; Huang, Jing-Fei; Jiang, Xue-Long; Murphy, Robert W.; Shi, Peng

2014-01-01

Hibernating mammals need to be insensitive to acid in order to cope with conditions of high CO2; however, the molecular basis of acid tolerance remains largely unknown. The African naked mole-rat (Heterocephalus glaber) and hibernating mammals share similar environments and physiological features. In the naked mole-rat, acid insensitivity has been shown to be conferred by the functional motif of the sodium ion channel NaV1.7. There is now an opportunity to evaluate acid insensitivity in other taxa. In this study, we tested for functional convergence of NaV1.7 in 71 species of mammals, including 22 species that hibernate. Our analyses revealed a functional convergence of amino acid sequences, which occurred at least six times independently in mammals that hibernate. Evolutionary analyses determined that the convergence results from both parallel and divergent evolution of residues in the functional motif. Our findings not only identify the functional molecules responsible for acid insensitivity in hibernating mammals, but also open new avenues to elucidate the molecular underpinnings of acid insensitivity in mammals. PMID:24352952

Repeated functional convergent effects of NaV1.7 on acid insensitivity in hibernating mammals.

PubMed

Liu, Zhen; Wang, Wei; Zhang, Tong-Zuo; Li, Gong-Hua; He, Kai; Huang, Jing-Fei; Jiang, Xue-Long; Murphy, Robert W; Shi, Peng

2014-02-07

Hibernating mammals need to be insensitive to acid in order to cope with conditions of high CO2; however, the molecular basis of acid tolerance remains largely unknown. The African naked mole-rat (Heterocephalus glaber) and hibernating mammals share similar environments and physiological features. In the naked mole-rat, acid insensitivity has been shown to be conferred by the functional motif of the sodium ion channel NaV1.7. There is now an opportunity to evaluate acid insensitivity in other taxa. In this study, we tested for functional convergence of NaV1.7 in 71 species of mammals, including 22 species that hibernate. Our analyses revealed a functional convergence of amino acid sequences, which occurred at least six times independently in mammals that hibernate. Evolutionary analyses determined that the convergence results from both parallel and divergent evolution of residues in the functional motif. Our findings not only identify the functional molecules responsible for acid insensitivity in hibernating mammals, but also open new avenues to elucidate the molecular underpinnings of acid insensitivity in mammals.

Dose rate in brachytherapy using after-loading machine: pulsed or high-dose rate?

PubMed

Hannoun-Lévi, J-M; Peiffert, D

2014-10-01

Since February 2014, it is no longer possible to use low-dose rate 192 iridium wires due to the end of industrial production of IRF1 and IRF2 sources. The Brachytherapy Group of the French society of radiation oncology (GC-SFRO) has recommended switching from iridium wires to after-loading machines. Two types of after-loading machines are currently available, based on the dose rate used: pulsed-dose rate or high-dose rate. In this article, we propose a comparative analysis between pulsed-dose rate and high-dose rate brachytherapy, based on biological, technological, organizational and financial considerations. Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Munitions having an insensitive detonator system for initiating large failure diameter explosives

DOEpatents

Perry, III, William Leroy

2015-08-04

A munition according to a preferred embodiment can include a detonator system having a detonator that is selectively coupled to a microwave source that functions to selectively prime, activate, initiate, and/or sensitize an insensitive explosive material for detonation. The preferred detonator can include an explosive cavity having a barrier within which an insensitive explosive material is disposed and a waveguide coupled to the explosive cavity. The preferred system can further include a microwave source coupled to the waveguide such that microwaves enter the explosive cavity and impinge on the insensitive explosive material to sensitize the explosive material for detonation. In use the preferred embodiments permit the deployment and use of munitions that are maintained in an insensitive state until the actual time of use, thereby substantially preventing unauthorized or unintended detonation thereof.

Assessing dose rate distributions in VMAT plans

NASA Astrophysics Data System (ADS)

Mackeprang, P.-H.; Volken, W.; Terribilini, D.; Frauchiger, D.; Zaugg, K.; Aebersold, D. M.; Fix, M. K.; Manser, P.

2016-04-01

Dose rate is an essential factor in radiobiology. As modern radiotherapy delivery techniques such as volumetric modulated arc therapy (VMAT) introduce dynamic modulation of the dose rate, it is important to assess the changes in dose rate. Both the rate of monitor units per minute (MU rate) and collimation are varied over the course of a fraction, leading to different dose rates in every voxel of the calculation volume at any point in time during dose delivery. Given the radiotherapy plan and machine specific limitations, a VMAT treatment plan can be split into arc sectors between Digital Imaging and Communications in Medicine control points (CPs) of constant and known MU rate. By calculating dose distributions in each of these arc sectors independently and multiplying them with the MU rate, the dose rate in every single voxel at every time point during the fraction can be calculated. Independently calculated and then summed dose distributions per arc sector were compared to the whole arc dose calculation for validation. Dose measurements and video analysis were performed to validate the calculated datasets. A clinical head and neck, cranial and liver case were analyzed using the tool developed. Measurement validation of synthetic test cases showed linac agreement to precalculated arc sector times within  ±0.4 s and doses  ±0.1 MU (one standard deviation). Two methods for the visualization of dose rate datasets were developed: the first method plots a two-dimensional (2D) histogram of the number of voxels receiving a given dose rate over the course of the arc treatment delivery. In similarity to treatment planning system display of dose, the second method displays the dose rate as color wash on top of the corresponding computed tomography image, allowing the user to scroll through the variation over time. Examining clinical cases showed dose rates spread over a continuous spectrum, with mean dose rates hardly exceeding 100 cGy min-1 for conventional fractionation. A tool to analyze dose rate distributions in VMAT plans with sub-second accuracy was successfully developed and validated. Dose rates encountered in clinical VMAT test cases show a continuous spectrum with a mean less than or near 100 cGy min-1 for conventional fractionation.

Insensitive high-energy energetic structural material of tungsten-polytetrafluoroethylene-aluminum composites

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

Wang, Liu; Liu, Jinxu, E-mail: liujinxu@bit.edu.cn; Zhang, Xinbo

2015-11-15

Energetic structural material is a kind of materials that are inert under normal conditions but could produce exothermic chemical reaction when subjected to impact. This report shows a kind of energetic structural material of tungsten (W)-polytetrafluoroethylene (PTFE)-aluminum (Al) with density of 4.12 g/cm{sup 3}, excellent ductility and dynamic compressive strength of 96 MPa. Moreover, 50W-35PTFE-15Al (wt%) can exhibit a high reaction energy value of more than 2 times of TNT per unit mass and 5 times of TNT per unit volume, respectively, but with excellent insensitivity compared with traditional explosives. Under thermal conditions, the W-PTFE-Al composite can keep stable atmore » 773 K. Under impact loading, when the strain rate up to ∼4820 s{sup −1} coupled with the absorbed energy per unit volume of 120 J/cm{sup 3}, deflagration occurs and combustion lasts for 500 μs. During impact compressive deformation, the PTFE matrix is elongated into nano-fibers, thus significantly increases the reaction activity of W-PTFE-Al composites. The nano-fiber structure is necessary for the reaction of W-PTFE-Al composites. The formation of PTFE nano-fibers must undergo severe plastic deformation, and therefore the W-PTFE-Al composites exhibit excellent insensitivity and safety. Furthermore, the reaction mechanisms of W-PTFE-Al composites in argon and in air are revealed.« less

Effect of temperature on the occurrence of O/sub 2/ and CO/sub 2/ insensitive photosynthesis in field grown plants. [Phaselous vulgaris; capsicum annum; lycopersicon esculentum; scrophularia desertorum; cardaria

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

Sage, R.F.; Sharkey, T.D.

The sensitivity of photosynthesis to O/sub 2/ and CO/sub 2/ was measured in field grown plants of six species (Phaseolus vulgaris, Capsicum annum, Lycopersicon esculentum, Scrophularia desertorum, Cardaria draba and Populus Fremontii) from 5/sup 0/C to 35/sup 0/C. Photosynthesis was insensitive to O/sub 2/ in normal air below a species dependent temperature. CO/sub 2/ insensitivity occurred under the same conditions that resulted in O/sub 2/ insensitivity. A complete loss of O/sub 2/ sensitivity was observed up to 22/sup 0/C (in Lycopersicon) but only up to 6/sup 0/C (in Scrophularia). In Lycopersicon and Populus, O/sub 2/ and CO/sub 2/ insensitivity occurredmore » under conditions regularly encountered during the cooler portions of the day. The authors believe that O/sub 2/ insensitivity is an indicator of feedback limited photosynthesis, and that these results indicate that feedback limitations can play a role in determining plant carbon gain in the field. At higher partial pressures of CO/sub 2/ the temperature at which O/sub 2/ insensitivity occurred was higher, indicating that feedback limitations in the field will become more important as the CO/sub 2/ concentration in the atmosphere increases.« less

Effect of temperature on the occurrence of O/sub 2/ and CO/sub 2/ insensitive photosynthesis in field grown plants. [Phaseolus vulgaris; Capsicum annum; Lycopersicon esculentum, Scrophularia desertorum; Cardaria draba, Populus fremontii

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

Sage, R.F.; Sharkey, T.D.

The sensitivity of photosynthesis to O/sub 2/ and CO/sub 2/ was measured in leaves from field grown plants of six species (Phaseolus vulgaris, Capsicum annuum, Lycopersicon esculentum, Scrophularia desertorum, Cardaria draba, and Populus fremontii) from 5/sup 0/C to 35/sup 0/C using gas-exchange techniques. In all species but Phaseolus, photosynthesis was insensitive to O/sub 2/ in normal air below a species dependent temperature. CO/sub 2/ insensitivity occurred under the same conditions that resulted in O/sub 2/ insensitivity. A complete loss of O/sub 2/ sensitivity occurred up to 22/sup 0/C in Lycopersicon but only up to 6/sup 0/C in Scrophularia. In Lycopersiconmore » and Populus, O/sub 2/ and CO/sub 2/ insensitivity occurred under conditions regularly encountered during the cooler portions of the day. Because O/sub 2/ insensitivity is an indicator of feedback limited photosynthesis, these results indicate that feedback limitations can play a role in determining the diurnal carbon gain in the field. At higher partial pressures of CO/sub 2/ the temperature at which O/sub 2/ insensitivity occurred was higher, indicating that feedback limitations in the field will become more important as the CO/sub 2/ concentration in the atmosphere increases.« less

Environmental Fate of 14C Radiolabeled 2,4-Dinitroanisole in Soil Microcosms.

PubMed

Olivares, Christopher I; Madeira, Camila L; Sierra-Alvarez, Reyes; Kadoya, Warren; Abrell, Leif; Chorover, Jon; Field, Jim A

2017-11-21

2,4-Dinitrosanisole (DNAN) is an insensitive munitions component replacing conventional explosives. While DNAN is known to biotransform in soils to aromatic amines and azo-dimers, it is seldom mineralized by indigenous soil bacteria. Incorporation of DNAN biotransformation products into soil as humus-bound material could serve as a plausible remediation strategy. The present work studied biotransformation of DNAN in soil and sludge microcosms supplemented with uniformly ring-labeled 14 C-DNAN to quantify the distribution of label in soil, aqueous, and gaseous phases. Electron donor amendments, different redox conditions (anaerobic, aerobic, sequential anaerobic-aerobic), and the extracellular oxidoreductase enzyme horseradish peroxidase (HRP) were evaluated to maximize incorporation of DNAN biotransformation products into the nonextractable soil humus fraction, humin. Irreversible humin incorporation of 14 C-DNAN occurred at higher rates in anaerobic conditions, with a moderate increase when pyruvate was added. Additionally, a single dose of HRP resulted in an instantaneous increased incorporation of 14 C-DNAN into the humin fraction. 14 C-DNAN incorporation to the humin fraction was strongly correlated (R 2 = 0.93) by the soil organic carbon (OC) amount present (either intrinsic or amended). Globally, our results suggest that DNAN biotransformation products can be irreversibly bound to humin in soils as a remediation strategy, which can be enhanced by adding soil OC.

Central Effects of Leptin on Glucose Homeostasis are Modified during Pregnancy in the Rat.

PubMed

Ladyman, S R; Grattan, D R

2016-10-01

Despite increased leptin concentrations during pregnancy, fat mass and food intake are increased. The satiety response to central leptin is suppressed, indicating a state of leptin insensitivity in the hypothalamus. Although the regulation of food intake is a major function of leptin, this hormone also influences a wide range of functions within the body. These actions include the regulation of glucose homeostasis, which undergoes major adaptation in the maternal body to generate optimal conditions for foetal development and growth. The present study aimed to investigate the effects of central leptin treatment on glucose homeostasis in pregnant rats to determine whether pregnancy-induced leptin insensitivity is functionally specific, and to further investigate changes in glucose homeostasis during pregnancy. After an overnight fast, nonpregnant and day 14 pregnant rats received an i.c.v. injection of leptin (100 ng or 4 μg) or vehicle then underwent a glucose tolerance test (GTT). Further groups of nonpregnant and day 14 pregnant rats were killed 30 min after leptin (doses ranging from 40 ng-4 μg) or vehicle i.c.v. injections for western blot analysis of phospho-signal transducer and activator of transcription 3 (STAT3) and phospho-Akt in various hypothalamic nuclei. Central leptin injection prior to a GTT lead to lowered basal insulin concentrations and impaired glucose tolerance in nonpregnant female rats, whereas the same doses of leptin had no significant effect on glucose tolerance in day 14 pregnant rats, indicating that, similar to the satiety actions of leptin, the effects of leptin on glucose homeostasis are suppressed during pregnancy. Furthermore, in the arcuate nucleus and ventromedial and dorsomedial nuclei of the hypothalamus, comprising three leptin-sensitive areas, there was no evidence that leptin induced Akt phosphorylation despite significant increases in phospho-STAT3, suggesting that leptin does not act through phospho-Akt in these areas in female rats. © 2016 British Society for Neuroendocrinology.

Ultraviolet-B-induced mechanical hyperalgesia: A role for peripheral sensitisation.

PubMed

Bishop, Thomas; Marchand, Fabien; Young, Antony R; Lewin, Gary R; McMahon, Stephen B

2010-07-01

Ultraviolet (UV) induced cutaneous inflammation is emerging as a model of pain with a novel sensory phenotype. A UVB dose of 1000mJ/cm2 produces a highly significant thermal and mechanical hypersensitivity. Here we examined the properties and mechanisms of such hyperalgesia in rats. Significantly, the mechanical hyperalgesia (with approximately 60% change in withdrawal thresholds) was restricted to the lesion site with no changes in mechanical threshold in adjacent non-irradiated skin (i.e. no secondary hypersensitivity), suggesting a peripheral mechanism. Consistent with this, we found that primary mechanical hypersensitivity showed no significant changes after intrathecal treatment with 10microg of the NMDA-receptor antagonist MK-801. Using an in vitro skin-nerve preparation, in the presence and absence of UVB-inflammation, suprathreshold responses to skin displacement stimuli of 6-768microm of 103 peripheral nociceptors were recorded. At the peak of UVB-induced hyperalgesia we observed that mechanical response properties of Adelta-nociceptors recorded from UVB-inflamed skin (n=19) were significantly diminished, by approximately 50%, compared to those recorded from naïve skin (n=13). The mechanical response properties of heat-sensitive C-nociceptors were unchanged while their heat responses were significantly increased, by approximately 75%, in UVB-inflamed (n=26) compared to naïve skin (n=12). Heat-insensitive C-nociceptors, however, demonstrated significantly enhanced (by approximately 60%) response properties to mechanical stimulation in UVB-inflamed (n=21) compared to naïve skin (n=12). Notably alteration in mechanical responses of Adelta- and heat-insensitive C-nociceptors were particular to stronger stimuli. Spontaneous activity was not induced by this dose of UVB. We conclude that UVB-induced mechanical hyperalgesia may be explained by a net shift in peripheral nociceptor response properties. Copyright 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Incorporating the gas analyzer response time in gas exchange computations.

PubMed

Mitchell, R R

1979-11-01

A simple method for including the gas analyzer response time in the breath-by-breath computation of gas exchange rates is described. The method uses a difference equation form of a model for the gas analyzer in the computation of oxygen uptake and carbon dioxide production and avoids a numerical differentiation required to correct the gas fraction wave forms. The effect of not accounting for analyzer response time is shown to be a 20% underestimation in gas exchange rate. The present method accurately measures gas exchange rate, is relatively insensitive to measurement errors in the analyzer time constant, and does not significantly increase the computation time.

Temperature Insensitive and Radiation Hard Photonics

DTIC Science & Technology

2014-03-19

M. COOK , Lt Col, USAF Deputy Chief, Spacecraft Technology Division Space Vehicles Directorate This report is published in the interest of...Approved for Public Release; distribution is unlimited. ii LIST OF FIGURES Figure 1. OTDM Pulse Multiplexer for Increasing the Output Repetition Rate...QDMLL) for use in extreme environments where ionizing radiation is a substantial threat. Mode-Locked lasers generate a train of optical pulses that have

ELDRS Characterization for a Very High Dose Mission

NASA Technical Reports Server (NTRS)

Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

2010-01-01

Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

Calcium-sensitive and insensitive transient outward current in rabbit ventricular myocytes.

PubMed Central

Hiraoka, M; Kawano, S

1989-01-01

1. A suction pipette whole-cell voltage-clamp technique was used to record membrane currents and potentials of isolated ventricular myocytes from rabbit hearts. 2. Transient outward current (Ito) was activated by voltage steps positive to -20 mV, increasing in amplitude with further depolarization to reach a maximum around +70 mV. The current attained its peak within 10 ms and then it inactivated for 100-200 ms. 3. A large portion of Ito still remained after the calcium current (ICa) was blocked when depolarizing pulses were applied at a frequency of 0.1 Hz or less. Therefore, this current component is referred to as calcium-insensitive Ito or It. 4. It showed voltage- and time-dependent inactivation similar to that observed in Purkinje fibres and other cardiac preparations. 5. The reversal potential of It depended on external K+ concentration, [K+]o, with a slope of 32 mV per 10-fold change in the presence of a normal [Na+]o (143 mM), while the slope was 48 mV per 10-fold change in low [Na+]o (1.0 mM). 6. It was completely inhibited by 2-4 mM-4-aminopyridine. Ito in the presence of ICa was also partially blocked by 4-aminopyridine and the remainder was abolished by 5 mM-caffeine. 7. The calcium-insensitive and caffeine-sensitive Ito differed in their decay rates as well as in their recovery time courses. The former was predominantly available at a slow pulsing rate, while the latter increased its amplitude with high-frequency depolarization. 8. The caffeine-sensitive Ito was inhibited by a blockade of ICa, by replacing Ca2+ with Sr2+, by external application of ryanodine and by internal application of EGTA. This indicates that the current is calcium-sensitive and is dependent on increased myoplasmic Ca2+ through Ca2+ influx via the sarcolemma and Ca2+ release from the sarcoplasmic reticulum. The current is therefore designated as IK, Ca. 9. The physiological functions of IK, Ca and It are indicated by their contribution to ventricular repolarization at fast and slow heart rates, respectively. PMID:2552080

Theoretical study of polarization insensitivity of carrier-induced refractive index change of multiple quantum well.

PubMed

Miao, Qingyuan; Zhou, Qunjie; Cui, Jun; He, Ping-An; Huang, Dexiu

2014-12-29

Characteristics of polarization insensitivity of carrier-induced refractive index change of 1.55 μm tensile-strained multiple quantum well (MQW) are theoretically investigated. A comprehensive MQW model is proposed to effectively extend the application range of previous models. The model considers the temperature variation as well as the nonuniform distribution of injected carrier in MQW. Tensile-strained MQW is expected to achieve polarization insensitivity of carrier-induced refractive index change over a wide wavelength range as temperature varies from 0°C to 40°C, while the magnitude of refractive index change keeps a large value (more than 3 × 10^-3). And that the polarization insensitivity of refractive index change can maintain for a wide range of carrier concentration. Multiple quantum well with different material and structure parameters is anticipated to have the similar polarization insensitivity of refractive index change, which shows the design flexibility.

Dose rate effects in the radiation damage of the plastic scintillators of the CMS hadron endcap calorimeter

DOE PAGES

Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; ...

2016-10-07

We present measurements of the reduction of light output by plastic scintillators irradiated in the CMS detector during the 8 TeV run of the Large Hadron Collider and show that they indicate a strong dose rate effect. The damage for a given dose is larger for lower dose rate exposures. The results agree with previous measurements of dose rate effects, but are stronger due to the very low dose rates probed. Here, we show that the scaling with dose rate is consistent with that expected from diffusion effects.

Novel approaches to the management of noneosinophilic asthma

PubMed Central

Thomson, Neil C.

2016-01-01

Noneosinophilic airway inflammation occurs in approximately 50% of patients with asthma. It is subdivided into neutrophilic or paucigranulocytic inflammation, although the proportion of each subtype is uncertain because of variable cut-off points used to define neutrophilia. This article reviews the evidence for noneosinophilic inflammation being a target for therapy in asthma and assesses clinical trials of licensed drugs, novel small molecules and biologics agents in noneosinophilic inflammation. Current symptoms, rate of exacerbations and decline in lung function are generally less in noneosinophilic asthma than eosinophilic asthma. Noneosinophilic inflammation is associated with corticosteroid insensitivity. Neutrophil activation in the airways and systemic inflammation is reported in neutrophilic asthma. Neutrophilia in asthma may be due to corticosteroids, associated chronic pulmonary infection, altered airway microbiome or delayed neutrophil apoptosis. The cause of poorly controlled noneosinophilic asthma may differ between patients and involve several mechanism including neutrophilic inflammation, T helper 2 (Th2)-low or other subtypes of airway inflammation or corticosteroid insensitivity as well as noninflammatory pathways such as airway hyperreactivity and remodelling. Smoking cessation in asthmatic smokers and removal from exposure to some occupational agents reduces neutrophilic inflammation. Preliminary studies of ‘off-label’ use of licensed drugs suggest that macrolides show efficacy in nonsmokers with noneosinophilic severe asthma and statins, low-dose theophylline and peroxisome proliferator-activated receptor gamma (PPARγ) agonists may benefit asthmatic smokers with noneosinophilic inflammation. Novel small molecules targeting neutrophilic inflammation, such as chemokine (CXC) receptor 2 (CXCR2) antagonists reduce neutrophils, but do not improve clinical outcomes in studies to date. Inhaled phosphodiesterase (PDE)4 inhibitors, dual PDE3 and PDE4 inhibitors, p38MAPK (mitogen-activated protein kinase) inhibitors, tyrosine kinase inhibitors and PI (phosphoinositide) 3kinase inhibitors are under development and these compounds may be of benefit in noneosinophilic inflammation. The results of clinical trials of biological agents targeting mediators associated with noneosinophilic inflammation, such as interleukin (IL)-17 and tumor necrosis factor (TNF)-α are disappointing. Greater understanding of the mechanisms of noneosinophilic inflammation in asthma should lead to improved therapies. PMID:26929306

The role of dose rate in radiation cancer risk: evaluating the effect of dose rate at the molecular, cellular and tissue levels using key events in critical pathways following exposure to low LET radiation

PubMed Central

Brooks, Antone L.; Hoel, David G.; Preston, R. Julian

2016-01-01

Abstract Purpose: This review evaluates the role of dose rate on cell and molecular responses. It focuses on the influence of dose rate on key events in critical pathways in the development of cancer. This approach is similar to that used by the U.S. EPA and others to evaluate risk from chemicals. It provides a mechanistic method to account for the influence of the dose rate from low-LET radiation, especially in the low-dose region on cancer risk assessment. Molecular, cellular, and tissues changes are observed in many key events and change as a function of dose rate. The magnitude and direction of change can be used to help establish an appropriate dose rate effectiveness factor (DREF). Conclusions: Extensive data on key events suggest that exposure to low dose-rates are less effective in producing changes than high dose rates. Most of these data at the molecular and cellular level support a large (2–30) DREF. In addition, some evidence suggests that doses delivered at a low dose rate decrease damage to levels below that observed in the controls. However, there are some data human and mechanistic data that support a dose-rate effectiveness factor of 1. In summary, a review of the available molecular, cellular and tissue data indicates that not only is dose rate an important variable in understanding radiation risk but it also supports the selection of a DREF greater than one as currently recommended by ICRP (2007) and BEIR VII (NRC/NAS 2006). PMID:27266588

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

Allen, I.S.; Gaa, S.T.; Rogers, T.B.

The muscarinic cholinergic agonist, carbachol, and pertussis toxin were used to examine the functional status of the guanine nucleotide-binding protein that inhibits adenylate cyclase (G{sub i}) in cultured neonatal rat heart myocytes. The isoproterenol stimulation of adenylate cyclase activity in myocyte membranes and adenosine 3{prime},5{prime}-cyclic monophosphate (cAMP) accumulation in intact cells (4 days in culture) were insensitive to carbachol. However, in cells cultured for 11 days, carbachol inhibited isoproterenol-stimulated cAMP accumulation by 30%. Angiotensin II (ANG II) was also found to inhibit isoproterenol-stimulated cAMP accumulation in day 11 cells in a dose-dependent manner. Pertussis toxin treatment reversed the inhibitory effectsmore » of both ANG II and carbachol, suggesting a role for G{sub i} in the process. Carbachol binding to membranes from day 4 cells was relatively insensitive to guanine nucleotides when compared with binding to membranes from day 11 or adult cells. Furthermore, pertussis toxin-mediated {sup 32}P incorporation into a 39- to 41-kDa substrate in day 11 membranes was increased 3.2-fold over that measured in day 4 membranes. These findings support the view that, although G{sub i} is expressed, it is nonfunctional in 4-day-old cultured neonatal rat heart myocytes and acquisition of functional G{sub i} is dependent on culture conditions. Furthermore, the ANG II receptor can couple to G{sub i} in heart.« less

Interpersonal touch suppresses visual processing of aversive stimuli

PubMed Central

Kawamichi, Hiroaki; Kitada, Ryo; Yoshihara, Kazufumi; Takahashi, Haruka K.; Sadato, Norihiro

2015-01-01

Social contact is essential for survival in human society. A previous study demonstrated that interpersonal contact alleviates pain-related distress by suppressing the activity of its underlying neural network. One explanation for this is that attention is shifted from the cause of distress to interpersonal contact. To test this hypothesis, we conducted a functional MRI (fMRI) study wherein eight pairs of close female friends rated the aversiveness of aversive and non-aversive visual stimuli under two conditions: joining hands either with a rubber model (rubber-hand condition) or with a close friend (human-hand condition). Subsequently, participants rated the overall comfortableness of each condition. The rating result after fMRI indicated that participants experienced greater comfortableness during the human-hand compared to the rubber-hand condition, whereas aversiveness ratings during fMRI were comparable across conditions. The fMRI results showed that the two conditions commonly produced aversive-related activation in both sides of the visual cortex (including V1, V2, and V5). An interaction between aversiveness and hand type showed rubber-hand-specific activation for (aversive > non-aversive) in other visual areas (including V1, V2, V3, and V4v). The effect of interpersonal contact on the processing of aversive stimuli was negatively correlated with the increment of attentional focus to aversiveness measured by a pain-catastrophizing scale. These results suggest that interpersonal touch suppresses the processing of aversive visual stimuli in the occipital cortex. This effect covaried with aversiveness-insensitivity, such that aversive-insensitive individuals might require a lesser degree of attentional capture to aversive-stimulus processing. As joining hands did not influence the subjective ratings of aversiveness, interpersonal touch may operate by redirecting excessive attention away from aversive characteristics of the stimuli. PMID:25904856

Myxospore Coat Synthesis in Myxococcus xanthus: In Vivo Incorporation of Acetate and Glycine

PubMed Central

Filer, D.; White, D.; Kindler, S. H.; Rosenberg, E.

1977-01-01

Myxospore coat synthesis in Myxococcus xanthus was studied by incorporation of [14C]acetate into intermediates in the biosynthesis of coat polysaccharide and into acid-insoluble material during vegetative growth and after glycerol induction of myxospores. During short labeling periods at 27°C, the radioactivity was shown to be located primarily in N-acetyl groups rather than sugar moieties. Two hours after glycerol induction, the pools of N-acetylglucosamine 6-phosphate and uridine 5′-diphosphate-N-acetylgalactosamine (UDPGalNAc) plus uridine 5′-diphosphate-N-glucosamine increased about twofold and were labeled at twice the rate measured for vegetative cells. The increased rate of synthesis of UDPGalNAc and its precursors could be correlated with increased enzyme activities measured in vitro. Controlled acid hydrolysis revealed that the galactosamine portion of the myxospore coat was N-acetylated. After glycerol induction, the incorporation of acetate into acid-insoluble material increased threefold. This enhanced incorporation was sensitive to neither penicillin nor d-cycloserine. In contrast, bacitracin inhibited the incorporation of [14C]acetate into acid-insoluble material more effectively 2 h after myxospore induction than during vegetative growth. Chloramphenicol added to cells 90 min after induction blocked further increase in the rate of [14C]acetate incorporation. Since the myxospore coat contains glycine, polymer synthesis was also measured by chloramphenicol-insensitive [14C]glycine incorporation into acid-insoluble material. Although protein synthesis decreased after glycerol induction, glycine incorporation increased. Two hours after induction, glycine incorporation was only 75% inhibited by chloramphenicol and rifampin. The chloramphenicol-insensitive rate of incorporation of [14C]glycine increased during the first hour after myxospore induction and reached a peak rate after 2 to 3 h. The chloramphenicol-resistant incorporation of [14C]glycine was resistant to penicillin but sensitive to bacitracin. PMID:408325

Comparison of febrile responsiveness of rats and rabbits to endogenous pyrogen.

PubMed

Stitt, J T; Shimada, S G; Bernheim, H A

1985-12-01

The fever responses of rats and rabbits were compared in detail using a single common source of semipurified endogenous pyrogen prepared from human monocytes. The characteristics and dynamics of the fever-response curves for each species were examined and their dose-response curves were determined and compared. The fevers displayed by rats were qualitatively similar to those of rabbits, but, typically, they developed and terminated more rapidly than those of rabbits. Rabbits were much more sensitive to the endogenous pyrogen than rats. The threshold dose of pyrogen required to elicit a fever was 5 times lower in the rabbit, and the slope of the rabbit's dose-response curve was 1.5 times steeper than that of the rat. The maximum fevers attainable in rabbits were approximately twice those attainable in rats. It was also shown that the more rapid febrile responses of the rat were not due to the 10-fold smaller mass of the rat; instead, we proposed that this difference was more likely due to a closer diffusional proximity of the pyrogen receptor sites to the circulation in rats. The lower sensitivity of the rat to endogenous pyrogen was attributed to a relative insensitivity of the pyrogen receptor sites in rats in the translation of the endogenous pyrogen stimulus into fever.

Parametric study of irradiation effects on the ductile damage and flow stress behavior in ferritic-martensitic steels

NASA Astrophysics Data System (ADS)

Chakraborty, Pritam; Biner, S. Bulent

2015-10-01

Ferritic-martensitic steels are currently being considered as structural materials in fusion and Gen-IV nuclear reactors. These materials are expected to experience high dose radiation, which can increase their ductile to brittle transition temperature and susceptibility to failure during operation. Hence, to estimate the safe operational life of the reactors, precise evaluation of the ductile to brittle transition temperatures of ferritic-martensitic steels is necessary. Owing to the scarcity of irradiated samples, particularly at high dose levels, micro-mechanistic models are being employed to predict the shifts in the ductile to brittle transition temperatures. These models consider the ductile damage evolution, in the form of nucleation, growth and coalescence of voids; and the brittle fracture, in the form of probabilistic cleavage initiation, to estimate the influence of irradiation on the ductile to brittle transition temperature. However, the assessment of irradiation dependent material parameters is challenging and influences the accuracy of these models. In the present study, the effects of irradiation on the overall flow stress and ductile damage behavior of two ferritic-martensitic steels is parametrically investigated. The results indicate that the ductile damage model parameters are mostly insensitive to irradiation levels at higher dose levels though the resulting flow stress behavior varies significantly.

SU-E-T-657: Quantitative Assessment of Plan Robustness for Helical Tomotherapy for Head and Neck Cancer Radiotherapy

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

Matney, J; Lian, J; Chera, B

2015-06-15

Introduction: Geometric uncertainties in daily patient setup can lead to variations in the planned dose, especially when using highly conformal techniques such as helical Tomotherapy. To account for the potential effect of geometric uncertainty, our clinical practice is to expand critical structures by 3mm expansion into planning risk volumes (PRV). The PRV concept assumes the spatial dose cloud is insensitive to patient positioning. However, no tools currently exist to determine if a Tomotherapy plan is robust to the effects of daily setup variation. We objectively quantified the impact of geometric uncertainties on the 3D doses to critical normal tissues duringmore » helical Tomotherapy. Methods: Using a Matlab-based program created and validated by Accuray (Madison, WI), the planned Tomotherapy delivery sinogram recalculated dose on shifted CT datasets. Ten head and neck patients were selected for analysis. To simulate setup uncertainty, the patient anatomy was shifted ±3mm in the longitudinal, lateral and vertical axes. For each potential shift, the recalculated doses to various critical normal tissues were compared to the doses delivered to the PRV in the original plan Results: 18 shifted scenarios created from Tomotherapy plans for three patients with head and neck cancers were analyzed. For all simulated setup errors, the maximum doses to the brainstem, spinal cord, parotids and cochlea were no greater than 0.6Gy of the respective original PRV maximum. Despite 3mm setup shifts, the minimum dose delivered to 95% of the CTVs and PTVs were always within 0.4Gy of the original plan. Conclusions: For head and neck sites treated with Tomotherapy, the use of a 3mm PRV expansion provide a reasonable estimate of the dosimetric effects of 3mm setup uncertainties. Similarly, target coverage appears minimally effected by a 3mm setup uncertainty. Data from a larger number of patients will be presented. Future work will include other anatomical sites.« less

Radiation dose-rate meter using an energy-sensitive counter

DOEpatents

Kopp, Manfred K.

1988-01-01

A radiation dose-rate meter is provided which uses an energy-sensitive detector and combines charge quantization and pulse-rate measurement to monitor radiation dose rates. The charge from each detected photon is quantized by level-sensitive comparators so that the resulting total output pulse rate is proportional to the dose-rate.

The susceptibility of TaO x-based memristors to high dose rate ionizing radiation and total ionizing dose

DOE PAGES

McLain, Michael Lee; Sheridan, Timothy J.; Hjalmarson, Harold Paul; ...

2014-11-11

This paper investigates the effects of high dose rate ionizing radiation and total ionizing dose (TID) on tantalum oxide (TaO x) memristors. Transient data were obtained during the pulsed exposures for dose rates ranging from approximately 5.0 ×10 7 rad(Si)/s to 4.7 ×10 8 rad(Si)/s and for pulse widths ranging from 50 ns to 50 μs. The cumulative dose in these tests did not appear to impact the observed dose rate response. Static dose rate upset tests were also performed at a dose rate of ~3.0 ×10 8 rad(Si)/s. This is the first dose rate study on any type ofmore » memristive memory technology. In addition to assessing the tolerance of TaO x memristors to high dose rate ionizing radiation, we also evaluated their susceptibility to TID. The data indicate that it is possible for the devices to switch from a high resistance off-state to a low resistance on-state in both dose rate and TID environments. The observed radiation-induced switching is dependent on the irradiation conditions and bias configuration. Furthermore, the dose rate or ionizing dose level at which a device switches resistance states varies from device to device; the enhanced susceptibility observed in some devices is still under investigation. As a result, numerical simulations are used to qualitatively capture the observed transient radiation response and provide insight into the physics of the induced current/voltages.« less

Effects of experimentally sustained elevated testosterone on incubation behaviour and reproductive success in female great tits (Parus major).

PubMed

de Jong, Berber; Lens, Luc; Amininasab, Seyed Mehdi; van Oers, Kees; Darras, Veerle M; Eens, Marcel; Pinxten, Rianne; Komdeur, Jan; Groothuis, Ton G G

2016-05-01

In many seasonally breeding birds, female and male testosterone (T) levels peak at the start of the breeding season, coinciding with pair bonding and nesting activities. Shortly after the onset of egg laying, T levels slowly decline to baseline levels in both sexes, but more rapidly so in females. During this period, T in males may still function to facilitate territorial behaviour, mate guarding and extra pair copulations, either via short lasting peaks or elevated basal levels of the hormone. In some species, however, males become insensitive to increased T after the onset of egg laying. It has been postulated that in these species bi-parental care is essential for offspring survival, as T is known to inhibit paternal care. However, only very few studies have analysed this for females. As females are heavily involved in parental care, they too might become insensitive to T after egg laying. Alternatively, because territorial defence, mate guarding and extra pair copulations are expected to be less important for females than for males, they may not have had the need to evolve a mechanism to become insensitive to T during the period of maternal care, because their natural T levels are never elevated during this part of the breeding season anyway. We tested these alternative hypotheses in female great tits (Parus major). Male great tits have previously been shown to be insensitive to T after egg laying with regard to nestling feeding behaviour (but not song rate). When females had started nest building, we experimentally elevated their T levels up to the nestling feeding phase, and measured incubation behaviour (only females incubate) and reproductive success. T did not significantly affect nest building or egg laying behaviour, although egg laying tended to be delayed in T females. Females with experimentally enhanced T maintained lower temperature during incubation but did not spend less time incubating. This might explain the reduced hatching success of their eggs, smaller brood size and lower number of fledglings we found in this study. As in this species T-dependent behaviour by females during the phase of parental care is not needed, the results support the hypothesis that in this species the need for selection in favour of T-insensitivity did not occur. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis of a new class of carbon-bonded anionic sigma complexes with 1,3-dimethyl-2,6-dioxo-5-(2,4,6-trinitrophenyl)-1,2,3,6-tetrahydropyrimidin-4-olate moiety as insensitive high energy density materials -- implications from impact sensitivity and thermal testings.

PubMed

Kulandaiya, Rajamani; Doraisamyraja, Kalaivani

2015-01-01

Poly nitro aromatic compounds are high energy density materials. Carbon-bonded anionic sigma complexes derived from them have remarkable thermal stability. At present there is a strong requirement for thermally stable insensitive high energy density materials (IHEDMs) in the energetic field which necessitates the present investigation. Three new carbon-bonded anionic sigma complexes were synthesized from 2-chloro-1,3,5-trinitrobenzene, 1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (1,3-dimethylbarbituric acid) and bases such as triethanolamine, pyridine and N,N-diethylaniline, characterized by UV-VIS, IR, (1)H NMR, (13)C NMR and elemental analysis data. Their molecular structures were further ascertained through single crystal X-ray diffraction studies. TGA/DTA testings were undertaken at four different heating rates (5, 10, 20 and 40 K/min) and energy of activation was determined employing Ozawa and Kissinger plots. The reported carbon-bonded anionic sigma complexes were prepared through single pot synthesis in good yield with high purity. These complexes are molecular salts comprise of cation and anion moieties. Because of the salt-like nature, they are highly stable upto 300°C and decompose in two stages on further heating. They are stable towards impact of 2 kg mass hammer upto height limit (160 cm) of the instrument. The delocalization of the negative charge and various hydrogen bonds noticed in their crystals are the added factors of their thermal stability. The new insensitive high energy density materials of the present findings may receive attention in the field of energetics in future. Graphical AbstractA new class of carbon-bonded anionic sigma complexes as insensitive high energy density materials.

Biological samples on the ISS-EXPOSE facility for the ROSE/PUR experiment

NASA Astrophysics Data System (ADS)

Rontó, Gy.; Bérces, A.; Fekete, A.; Kerékgyártó, T.; Lammer, H.; Kargl, G.; Kömle, N. I.

2002-11-01

Three types of samples, bacteriophage T7, isolated phage DNA, polycrystalline uracil thin films were prepared in sandwich form that were closed vacuum-tightly with inert gaseous environment. The response of the samples to the following selected space environmental conditions was investigated: temperature (-20 - +40°C), vacuum, short wavelength UV irradiation. Uracil thin layer samples proved to be insensitive for temperature. In the vacuum chamber the structure of the samples in sandwich arrangement did not change. Irradiation with germicidal and Deuterium lamps caused a decrease in the optical density of the uracil layers and the decrease showed a saturation tendency in both cases. The dose-effect curves at germicidal lamp possess a saturation level at a lower optical density than at Deuterium.

[Brachytherapy for head and neck cancers].

PubMed

Peiffert, D; Coche-Dequéant, B; Lapeyre, M; Renard, S

2018-05-29

The main indications of the brachytherapy of head and neck cancers are the limited tumours of the lip, the nose, the oral cavity and the oropharynx. Nasopharynx tumours are nowadays treated by intensity-modulated radiotherapy. This technique can be exclusive, associated with external radiotherapy or postoperative. It can also be a salvage treatment for the second primaries in previously irradiated areas. If the low dose rate brachytherapy rules remain the reference, the pulse dose rate technique allows the prescription of the dose rate and the optimisation of the dose distribution. Results of high dose rate brachytherapy are now published. This paper reports the recommendations of the Gec-ESTRO, published in 2017, and takes into account the data of the historical low dose rate series, and is upgraded with the pulsed-dose rate and high dose rate series. Copyright © 2018. Published by Elsevier SAS.

An accurate derivation of the air dose-rate and the deposition concentration distribution by aerial monitoring in a low level contaminated area

NASA Astrophysics Data System (ADS)

Nishizawa, Yukiyasu; Sugita, Takeshi; Sanada, Yukihisa; Torii, Tatsuo

2015-04-01

Since 2011, MEXT (Ministry of Education, Culture, Sports, Science and Technology, Japan) have been conducting aerial monitoring to investigate the distribution of radioactive cesium dispersed into the atmosphere after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FDNPP), Tokyo Electric Power Company. Distribution maps of the air dose-rate at 1 m above the ground and the radioactive cesium deposition concentration on the ground are prepared using spectrum obtained by aerial monitoring. The radioactive cesium deposition is derived from its dose rate, which is calculated by excluding the dose rate of the background radiation due to natural radionuclides from the air dose-rate at 1 m above the ground. The first step of the current method of calculating the dose rate due to natural radionuclides is calculate the ratio of the total count rate of areas where no radioactive cesium is detected and the count rate of regions with energy levels of 1,400 keV or higher (BG-Index). Next, calculate the air dose rate of radioactive cesium by multiplying the BG-Index and the integrated count rate of 1,400 keV or higher for the area where the radioactive cesium is distributed. In high dose-rate areas, however, the count rate of the 1,365-keV peak of Cs-134, though small, is included in the integrated count rate of 1,400 keV or higher, which could cause an overestimation of the air dose rate of natural radionuclides. We developed a method for accurately evaluating the distribution maps of natural air dose-rate by excluding the effect of radioactive cesium, even in contaminated areas, and obtained the accurate air dose-rate map attributed the radioactive cesium deposition on the ground. Furthermore, the natural dose-rate distribution throughout Japan has been obtained by this method.

Leuco-crystal-violet micelle gel dosimeters: Component effects on dose-rate dependence

NASA Astrophysics Data System (ADS)

Xie, J. C.; Katz, E. A. B.; Alexander, K. M.; Schreiner, L. J.; McAuley, K. B.

2017-05-01

Designed experiments were performed to produce empirical models for the dose sensitivity, initial absorbance, and dose-rate dependence respectively for leucocrystal violet (LCV) micelle gel dosimeters containing cetyltrimethylammonium bromide (CTAB) and 2,2,2-trichloroethanol (TCE). Previous gels of this type showed dose-rate dependent behaviour, producing an ˜18% increase in dose sensitivity between dose rates of 100 and 600 cGy min-1. Our models predict that the dose rate dependence can be reduced by increasing the concentration of TCE, CTAB and LCV. Increasing concentrations of LCV and CTAB produces a significant increase in dose sensitivity with a corresponding increase in initial absorbance. An optimization procedure was used to determine a nearly dose-rate independent gel which maintained high sensitivity and low initial absorbance. This gel which contains 33 mM CTAB, 1.25 mM LCV, and 96 mM TCE in 25 mM trichloroacetic acid and 4 wt% gelatin showed an increase in dose sensitivity of only 4% between dose rates of 100 and 600 cGy min-1, and provides an 80% greater dose sensitivity compared to Jordan’s standard gels with similar initial absorbance.

Dose and dose rate effects of whole-body gamma-irradiation: I. Lymphocytes and lymphoid organs

NASA Technical Reports Server (NTRS)

Pecaut, M. J.; Nelson, G. A.; Gridley, D. S.

2001-01-01

The major goal of part I of this study was to compare varying doses and dose rates of whole-body gamma-radiation on lymphoid cells and organs. C57BL/6 mice (n = 75) were exposed to 0, 0.5, 1.5, and 3.0 Gy gamma-rays (60Co) at 1 cGy/min (low-dose rate, LDR) and 80 cGy/min (high-dose rate, HDR) and euthanized 4 days later. A significant dose-dependent loss of spleen mass was observed with both LDR and HDR irradiation; for the thymus this was true only with HDR. Decreasing leukocyte and lymphocyte numbers occurred with increasing dose in blood and spleen at both dose rates. The numbers (not percentages) of CD3+ T lymphocytes decreased in the blood in a dose-dependent manner at both HDR and LDR. Splenic T cell counts decreased with dose only in HDR groups; percentages increased with dose at both dose rates. Dose-dependent decreases occurred in CD4+ T helper and CD8+ T cytotoxic cell counts at HDR and LDR. In the blood the percentages of CD4+ cells increased with increasing dose at both dose rates, whereas in the spleen the counts decreased only in the HDR groups. The percentages of the CD8+ population remained stable in both blood and spleen. CD19+ B cell counts and percentages in both compartments declined markedly with increasing HDR and LDR radiation. NK1.1+ natural killer cell numbers and proportions remained relatively stable. Overall, these data indicate that the observed changes were highly dependent on the dose, but not dose rate, and that cells in the spleen are more affected by dose rate than those in blood. The results also suggest that the response of lymphocytes in different body compartments may be variable.

Estimation of the Dose and Dose Rate Effectiveness Factor

NASA Technical Reports Server (NTRS)

Chappell, L.; Cucinotta, F. A.

2013-01-01

Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.

Using RADFET for the real-time measurement of gamma radiation dose rate

NASA Astrophysics Data System (ADS)

Andjelković, Marko S.; Ristić, Goran S.; Jakšić, Aleksandar B.

2015-02-01

RADFETs (RADiation sensitive Field Effect Transistors) are integrating ionizing radiation dosimeters operating on the principle of conversion of radiation-induced threshold voltage shift into absorbed dose. However, one of the major drawbacks of RADFETs is the inability to provide the information on the dose rate in real-time using the conventional absorbed dose measurement technique. The real-time monitoring of dose rate and absorbed dose can be achieved with the current mode dosimeters such as PN and PIN diodes/photodiodes, but these dosimeters have some limitations as absorbed dose meters and hence they are often not a suitable replacement for RADFETs. In that sense, this paper investigates the possibility of using the RADFET as a real-time dose rate meter so that it could be applied for simultaneous online measurement of the dose rate and absorbed dose. A RADFET sample, manufactured by Tyndall National Institute, Cork, Ireland, was tested as a dose rate meter under gamma irradiation from a Co-60 source. The RADFET was configured as a PN junction, such that the drain, gate and source terminals were grounded, while the radiation-induced current was measured at the bulk terminal, whereby the bulk was successively biased with 0 , 10 , 20  and 30 V. In zero-bias mode the radiation-induced current was unstable, but in the biased mode the current response was stable for the investigated dose rates from 0.65  to 32.1 Gy h-1 and up to the total absorbed dose of 25 Gy. The current increased with the dose rate in accordance with the power law, whereas the sensitivity of the current read-out was linear with respect to the applied bias voltage. Comparison with previously analyzed PIN photodiodes has shown that the investigated RADFET is competitive with PIN photodiodes as a gamma radiation dose rate meter and therefore has the potential to be employed for the real-time monitoring of the dose rate and absorbed dose.

Dose Rate Effects in Linear Bipolar Transistors

NASA Technical Reports Server (NTRS)

Johnston, Allan; Swimm, Randall; Harris, R. D.; Thorbourn, Dennis

2011-01-01

Dose rate effects are examined in linear bipolar transistors at high and low dose rates. At high dose rates, approximately 50% of the damage anneals at room temperature, even though these devices exhibit enhanced damage at low dose rate. The unexpected recovery of a significant fraction of the damage after tests at high dose rate requires changes in existing test standards. Tests at low temperature with a one-second radiation pulse width show that damage continues to increase for more than 3000 seconds afterward, consistent with predictions of the CTRW model for oxides with a thickness of 700 nm.

Thermal Decomposition of IMX-104: Ingredient Interactions Govern Thermal Insensitivity

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

Maharrey, Sean; Wiese-Smith, Deneille; Highley, Aaron M.

2015-04-01

This report summarizes initial studies into the chemical basis of the thermal insensitivity of INMX-104. The work follows upon similar efforts investigating this behavior for another DNAN-based insensitive explosive, IMX-101. The experiments described demonstrate a clear similarity between the ingredient interactions that were shown to lead to the thermal insensitivity observed in IMX-101 and those that are active in IMX-104 at elevated temperatures. Specifically, the onset of decomposition of RDX is shifted to a lower temperature based on the interaction of the RDX with liquid DNAN. This early onset of decomposition dissipates some stored energy that is then unavailable formore » a delayed, more violent release.« less

Effects of ultraviolet-B radiation on the growth, physiology and cannabinoid production of Cannabis sativa L

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

Lydon, J.

The concentration of cannabinoids in Cannabis sativa L. is correlated with high ultraviolet-B (UV-B) radiation environments. ..delta../sup 9/-Tetrahydrocannabinolic acid and cannabidiolic acid, both major secondary products of C. sativa, absorb UV-B radiation and may function as solar screens. The object of this study was to test the effects of UV-B radiation on the physiology and cannabinoid production of C. sativa. Drug and fiber-type C. sativa were irradiated with three levels of UV-B radiation for 40 days in greenhouse experiments. Physiological measurements on leaf tissues were made by infra-red gas analysis. Drug and fiber-type control plants had similar CO/sub 2/ assimilationmore » rates from 26 to 32/sup 0/C. Drug-type control plant had higher dark respiration rates and stomatal conductances than fiber-type control plants. The concentration of ..delta../sup 9/-THC, but not of other cannabinoids) in both vegetative and reproductive tissues increased with UV-B dose in drug-type plants. None of the cannabinoids in fiber-type plants were affected by UV-B radiation. The increased level of ..delta../sup 9/-THC found in leaves after irradiation may account for the physiological and morphological insensitivity to UV-B radiation in the drug-type plants. However, fiber plants showed no comparable change in the level of cannabidoil (CBD). Resin stripped form fresh fiber-type floral tissue by sonication was spotted on filter paper and irradiated continuously for 7 days. Cannabidiol (CBD) gradually decreased when irradiated but ..delta../sup 9/-THC and cannabichromene did not.« less

Pharmacologically induced alcohol craving in treatment seeking alcoholics correlates with alcoholism severity, but is insensitive to acamprosate

PubMed Central

Umhau, John C; Schwandt, Melanie L; Usala, Julie; Geyer, Christopher; Singley, Erick; George, David T; Heilig, Markus

2011-01-01

Modulation of alcohol craving induced by challenge stimuli may predict the efficacy of new pharmacotherapies for alcoholism. We evaluated two pharmacological challenges, the α2-adrenergic antagonist yohimbine, which reinstates alcohol seeking in rats, and the serotonergic compound meta-chlorophenylpiperazine (mCPP), previously reported to increase alcohol craving in alcoholics. To assess the predictive validity of this approach, the approved alcoholism medication acamprosate was evaluated for its ability to modulate challenge-induced cravings. A total of 35 treatment seeking alcohol dependent inpatients in early abstinence were randomized to placebo or acamprosate (2997 mg daily). Following two weeks of medication, subjects underwent three challenge sessions with yohimbine, mCPP or saline infusion under double blind conditions, carried out in counterbalanced order, and separated by at least 5 days. Ratings of cravings and anxiety, as well as biochemical measures were obtained. In all, 25 subjects completed all three sessions and were included in the analysis. Cravings were modestly, but significantly higher following both yohimbine and mCPP challenge compared with saline infusion. The mCPP, but not yohimbine significantly increased anxiety ratings. Both challenges produced robust ACTH, cortisol and prolactin responses. There was a significant correlation between craving and the degree of alcoholism severity. Acamprosate administration did not influence craving. Both yohimbine and mCPP challenges lead to elevated alcohol craving in a clinical population of alcoholics, and these cravings correlate with alcoholism severity. Under the experimental conditions used, alcohol cravings induced by these two stimuli are not sensitive to acamprosate at clinically used doses. PMID:21289601

Steroids alter ion transport and absorptive capacity in proximal and distal colon.

PubMed

Sellin, J H; DeSoignie, R C

1985-07-01

Steroids are potent absorbagogues, increasing Na and fluid absorption in a variety of epithelia. This study characterizes the in vitro effects of pharmacological doses of gluco- and mineralocorticoids on transport parameters of rabbit proximal and distal colon. Treatment with methylprednisolone (MP, 40 mg im for 2 days) and desoxycortone acetate (DOCA, 12.5 mg im for 3 days) resulted in a significant increase in short-circuit current (Isc) in distal colon, suggesting an increase in basal Na absorption. Amiloride (10(-4) M) caused a significantly negative Isc in MP-treated tissue, demonstrating a steroid-induced, amiloride-insensitive electrogenic ion transport in distal colon. The effect of two absorbagogues, impermeant anions (SO4-Ringer) and amphotericin, were compared in control and steroid-treated distal colon. In controls, both absorbagogues increased Isc. Impermeant anions caused a rise in Isc in both MP and DOCA tissues, suggesting that the high rate of basal Na absorption had not caused a saturation of the Na pump. The steroid-treated colons, however, did not consistently respond to amphotericin. Amiloride inhibited the entire Isc in MP-treated distal colon that had been exposed to amphotericin; this suggested that amphotericin had not exerted its characteristic effect on the apical membrane of steroid-treated colon. In proximal colon, steroids did not alter basal rates of transport; however, epinephrine-induced Na-Cl absorption was significantly greater in MP-treated vs control (P less than 0.005). Steroids increase the absorptive capacity of both proximal and distal colon for Na, while increasing basal Na absorption only in the distal colon.(ABSTRACT TRUNCATED AT 250 WORDS)

RBF kernel based support vector regression to estimate the blood volume and heart rate responses during hemodialysis.

PubMed

Javed, Faizan; Chan, Gregory S H; Savkin, Andrey V; Middleton, Paul M; Malouf, Philip; Steel, Elizabeth; Mackie, James; Lovell, Nigel H

2009-01-01

This paper uses non-linear support vector regression (SVR) to model the blood volume and heart rate (HR) responses in 9 hemodynamically stable kidney failure patients during hemodialysis. Using radial bias function (RBF) kernels the non-parametric models of relative blood volume (RBV) change with time as well as percentage change in HR with respect to RBV were obtained. The e-insensitivity based loss function was used for SVR modeling. Selection of the design parameters which includes capacity (C), insensitivity region (e) and the RBF kernel parameter (sigma) was made based on a grid search approach and the selected models were cross-validated using the average mean square error (AMSE) calculated from testing data based on a k-fold cross-validation technique. Linear regression was also applied to fit the curves and the AMSE was calculated for comparison with SVR. For the model based on RBV with time, SVR gave a lower AMSE for both training (AMSE=1.5) as well as testing data (AMSE=1.4) compared to linear regression (AMSE=1.8 and 1.5). SVR also provided a better fit for HR with RBV for both training as well as testing data (AMSE=15.8 and 16.4) compared to linear regression (AMSE=25.2 and 20.1).

LDR brachytherapy: can low dose rate hypersensitivity from the "inverse" dose rate effect cause excessive cell killing to peripherial connective tissues and organs?

PubMed

Leonard, B E; Lucas, A C

2009-02-01

Examined here are the possible effects of the "inverse" dose rate effect (IDRE) on low dose rate (LDR) brachytherapy. The hyper-radiosensitivity and induced radioresistance (HRS/IRR) effect benefits cell killing in radiotherapy, and IDRE and HRS/IRR seem to be generated from the same radioprotective mechanisms. We have computed the IDRE excess cell killing experienced in LDR brachytherapy using permanent seed implants. We conclude, firstly, that IDRE is a dose rate-dependent manifestation of HRS/IRR. Secondly, the presence of HRS/IRR or IDRE in a cell species or tissue must be determined by direct dose-response measurements. Thirdly, a reasonable estimate is that 50-80% of human adjoining connective and organ tissues experience IDRE from permanent implanted LDR brachytherapy. If IDRE occurs for tissues at point A for cervical cancer, the excess cell killing will be about a factor of 3.5-4.0 if the initial dose rate is 50-70 cGy h(-1). It is greater for adjacent tissues at lower dose rates and higher for lower initial dose rates at point A. Finally, higher post-treatment complications are observed in LDR brachytherapy, often for unknown reasons. Some of these are probably a result of IDRE excess cell killing. Measurements of IDRE need be performed for connective and adjacent organ tissues, i.e. bladder, rectum, urinary tract and small bowels. The measured dose rate-dependent dose responses should extended to <10 cGy h(-1) and involve multiple patients to detect patient variability. Results may suggest a preference for high dose rate brachytherapy or LDR brachytherapy without permanent retention of the implant seeds (hence the dose rates in peripheral tissues and organs remain above IDRE thresholds).

Neutralizing antibody fails to impact the course of Ebola virus infection in monkeys.

PubMed

Oswald, Wendelien B; Geisbert, Thomas W; Davis, Kelly J; Geisbert, Joan B; Sullivan, Nancy J; Jahrling, Peter B; Parren, Paul W H I; Burton, Dennis R

2007-01-01

Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. In this study, we have investigated the ability of the neutralizing human monoclonal antibody, KZ52, to protect against Ebola virus in rhesus macaques. This antibody was previously shown to fully protect guinea pigs from infection. Four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody KZ52 intravenously 1 d before challenge with 1,000 plaque-forming units of Ebola virus, followed by a second dose of 50 mg/kg antibody 4 d after challenge. A control animal was exposed to virus in the absence of antibody treatment. Passive transfer of the neutralizing human monoclonal antibody not only failed to protect macaques against challenge with Ebola virus but also had a minimal effect on the explosive viral replication following infection. We show that the inability of antibody to impact infection was not due to neutralization escape. It appears that Ebola virus has a mechanism of infection propagation in vivo in macaques that is uniquely insensitive even to high concentrations of neutralizing antibody.

Solid state neutron dosimeter for space applications

NASA Technical Reports Server (NTRS)

Entine, Gerald; Nagargar, Vivek; Sharif, Daud

1990-01-01

Personnel engaged in space flight are exposed to significant flux of high energy neutrons arising from both primary and secondary sources of ionizing radiation. Presently, there exist no compact neutron sensor capable of being integrated in a flight instrument to provide real time measurement of this radiation flux. A proposal was made to construct such an instrument using special PIN silicon diode which has the property of being insensitive to the other forms of ionizing radiation. Studies were performed to determine the design and construction of a better reading system to allow the PIN diode to be read with high precision. The physics of the device was studied, especially with respect to those factors which affect the sensitivity and reproducibility of the neutron response. This information was then used to develop methods to achieve high sensitivity at low neutron doses. The feasibility was shown of enhancing the PIN diode sensitivity to make possible the measurement of the low doses of neutrons encountered in space flights. The new PIN diode will make possible the development of a very compact, accurate, personal neutron dosimeter.

Comparative effects of kainic, quisqualic, and ibotenic acids on phenylethanolamine-N-methyltransferase-containing cells of rat retina.

PubMed

Cohen, J

1989-02-01

Phenylethanolamine-N-methyltransferase (PNMT) activity is located in a subpopulation of amacrine cells in the inner nuclear layer of the rat retina. Kainic, quisqualic, and ibotenic acids, all of which are analogues of glutamic acid, were injected intravitreally to the right and saline to the contralateral left eyes of adult male rats in order to determine the effect of these agents upon retinal PNMT activity. Animals were sacrificed 1 week later for tissue removal. The effect of these agents was measured by radiometric assay for PNMT. The fall in PNMT activity was used to measure the sensitivity of the PNMT-containing cells to these agents. Kainic acid was the most potent, producing the greatest reduction in PNMT activity in the smallest doses. Quisqualic acid was intermediate in potency to that of kainic and ibotenic acids. Ibotenic acid reduced PNMT activity only in extremely high doses. The PNMT-containing cells are sensitive to the toxic actions of kainic and quisqualic acids, but relatively insensitive to the actions of ibotenic acid.

Comparing phase-sensitive and phase-insensitive echolocation target images using a monaural audible sonar.

PubMed

Kuc, Roman

2018-04-01

This paper describes phase-sensitive and phase-insensitive processing of monaural echolocation waveforms to generate target maps. Composite waveforms containing both the emission and echoes are processed to estimate the target impulse response using an audible sonar. Phase-sensitive processing yields the composite signal envelope, while phase-insensitive processing that starts with the composite waveform power spectrum yields the envelope of the autocorrelation function. Analysis and experimental verification show that multiple echoes form an autocorrelation function that produces near-range phantom-reflector artifacts. These artifacts interfere with true target echoes when the first true echo occurs at a time that is less than the total duration of the target echoes. Initial comparison of phase-sensitive and phase-insensitive maps indicates that both display important target features, indicating that phase is not vital. A closer comparison illustrates the improved resolution of phase-sensitive processing, the near-range phantom-reflectors produced by phase-insensitive processing, and echo interference and multiple reflection artifacts that were independent of the processing.

Reactive flow calibration for diaminoazoxyfurazan (DAAF) and comparison with experiment

NASA Astrophysics Data System (ADS)

Johnson, Carl; Francois, Elizabeth Green; Morris, John

2012-03-01

Diaminoazoxyfurazan (DAAF) has a number of desirable properties; it is sensitive to shock while being insensitive to initiation by low level impact or friction, it has a small failure diameter, and its manufacturing process is inexpensive with minimal environmental impact. In light of its unique properties, DAAF based materials have gained interest for possible applications in insensitive munitions. In order to facilitate hydrocode modeling of DAAF and DAAF based formulations, we have developed a set of reactive flow parameters which were calibrated using published experimental data as well as recent experiments at LANL. Hydrocode calculations using the DAAF reactive flow parameters developed in the course of this work were compared to rate stick experiments, small scale gap tests, as well as the Onionskin experiment. Hydrocode calculations were compared directly to streak image results using numerous tracer points in conjunction with an external algorithm to match the data sets. The calculations display a reasonable agreement with experiment with the exception of effects related to shock desensitization of explosive.

Perceived and actual social discrimination: the case of overweight and social inclusion.

PubMed

Hartung, Freda-Marie; Renner, Britta

2013-01-01

The present study examined the correspondence between perceived and actual social discrimination of overweight people. In total, 77 first-year students provided self-ratings about their height, weight, and perceived social inclusion. To capture actual social inclusion, each participant nominated those fellow students (a) she/he likes and dislikes and (b) about whom she/he is likely to hear social news. Students with lower Body Mass Index (BMI) felt socially included, irrespective of their actual social inclusion. In contrast, students with higher BMI felt socially included depending on the degree of their actual social inclusion. Specifically, their felt social inclusion accurately reflected whether they were actually liked/disliked, but only when they were part of social news. When not part of social news, they also showed insensitivity to their actual social inclusion status. Thus, students with a lower BMI tended to be insensitive, while students with a higher BMI showed a differential sensitivity to actual social discrimination.

Potential application of a homogeneous and anisotropic slab as an angle insensitive absorbing material

NASA Astrophysics Data System (ADS)

Wang, Fang; Liu, Chang; Liu, Xiaoning; Niu, Tiaoming; Wang, Jing; Mei, Zhonglei; Qin, Jiayong

2017-06-01

In this paper, a flat and incident angle independence absorbing material is proposed and numerically verified in the optical spectrum. A homogeneous and anisotropic dielectric slab as a non-reflecting layer is first reviewed, and a feasible realization strategy of the slab is then given by using layered isotropic materials. When the loss components of the constitutive materials are not zero, the slab will work as an angle insensitive absorbing layer, and the absorption rate augments with increase of the losses. As the numerical verifications, the field distributions of a metallic cylinder and a triangular metallic object individually covered by the designed absorbing layer are demonstrated. The simulation results show that the designed absorbing layer can efficiently absorb the incident waves with the property of incident angle independence at the operation frequency. This homogeneous slab can be used in one and two dimensional situations for the realization of an invisibility cloak, a carpet cloak and even a skin cloak, if it is used to conformally cover target objects.

Rapid Acute Dose Assessment Using MCNP6

NASA Astrophysics Data System (ADS)

Owens, Andrew Steven

Acute radiation doses due to physical contact with a high-activity radioactive source have proven to be an occupational hazard. Multiple radiation injuries have been reported due to manipulating a radioactive source with bare hands or by placing a radioactive source inside a shirt or pants pocket. An effort to reconstruct the radiation dose must be performed to properly assess and medically manage the potential biological effects from such doses. Using the reference computational phantoms defined by the International Commission on Radiological Protection (ICRP) and the Monte Carlo N-Particle transport code (MCNP6), dose rate coefficients are calculated to assess doses for common acute doses due to beta and photon radiation sources. The research investigates doses due to having a radioactive source in either a breast pocket or pants back pocket. The dose rate coefficients are calculated for discrete energies and can be used to interpolate for any given energy of photon or beta emission. The dose rate coefficients allow for quick calculation of whole-body dose, organ dose, and/or skin dose if the source, activity, and time of exposure are known. Doses are calculated with the dose rate coefficients and compared to results from the International Atomic Energy Agency (IAEA) reports from accidents that occurred in Gilan, Iran and Yanango, Peru. Skin and organ doses calculated with the dose rate coefficients appear to agree, but there is a large discrepancy when comparing whole-body doses assessed using biodosimetry and whole-body doses assessed using the dose rate coefficients.

AREA RADIATION MONITOR

DOEpatents

Manning, F.W.; Groothuis, S.E.; Lykins, J.H.; Papke, D.M.

1962-06-12

S>An improved area radiation dose monitor is designed which is adapted to compensate continuously for background radiation below a threshold dose rate and to give warning when the dose integral of the dose rate of an above-threshold radiation excursion exceeds a selected value. This is accomplished by providing means for continuously charging an ionization chamber. The chamber provides a first current proportional to the incident radiation dose rate. Means are provided for generating a second current including means for nulling out the first current with the second current at all values of the first current corresponding to dose rates below a selected threshold dose rate value. The second current has a maximum value corresponding to that of the first current at the threshold dose rate. The excess of the first current over the second current, which occurs above the threshold, is integrated and an alarm is given at a selected integrated value of the excess corresponding to a selected radiation dose. (AEC)

The rate of charge tunneling is insensitive to polar terminal groups in self-assembled monolayers in Ag(TS)S(CH2)(n)M(CH2)(m)T//Ga2O3/EGaIn junctions.

PubMed

Yoon, Hyo Jae; Bowers, Carleen M; Baghbanzadeh, Mostafa; Whitesides, George M

2014-01-08

This paper describes a physical-organic study of the effect of uncharged, polar, functional groups on the rate of charge transport by tunneling across self-assembled monolayer (SAM)-based large-area junctions of the form Ag(TS)S(CH2)(n)M(CH2)(m)T//Ga2O3/EGaIn. Here Ag(TS) is a template-stripped silver substrate, -M- and -T are "middle" and "terminal" functional groups, and EGaIn is eutectic gallium-indium alloy. Twelve uncharged polar groups (-T = CN, CO2CH3, CF3, OCH3, N(CH3)2, CON(CH3)2, SCH3, SO2CH3, Br, P(O)(OEt)2, NHCOCH3, OSi(OCH3)3), having permanent dipole moments in the range 0.5 < μ < 4.5, were incorporated into the SAM. A comparison of the electrical characteristics of these junctions with those of junctions formed from n-alkanethiolates led to the conclusion that the rates of charge tunneling are insensitive to the replacement of terminal alkyl groups with the terminal polar groups in this set. The current densities measured in this work suggest that the tunneling decay parameter and injection current for SAMs terminated in nonpolar n-alkyl groups, and polar groups selected from common polar organic groups, are statistically indistinguishable.

Method to determine the position-dependant metal correction factor for dose-rate equivalent laser testing of semiconductor devices

DOEpatents

Horn, Kevin M.

2013-07-09

A method reconstructs the charge collection from regions beneath opaque metallization of a semiconductor device, as determined from focused laser charge collection response images, and thereby derives a dose-rate dependent correction factor for subsequent broad-area, dose-rate equivalent, laser measurements. The position- and dose-rate dependencies of the charge-collection magnitude of the device are determined empirically and can be combined with a digital reconstruction methodology to derive an accurate metal-correction factor that permits subsequent absolute dose-rate response measurements to be derived from laser measurements alone. Broad-area laser dose-rate testing can thereby be used to accurately determine the peak transient current, dose-rate response of semiconductor devices to penetrating electron, gamma- and x-ray irradiation.

Impact of the Amount of Liquid Intake on the Dose Rate of Patients Treated with Radioiodine.

PubMed

Haghighatafshar, Mahdi; Banani, Aida; Zeinali-Rafsanjani, Banafsheh; Etemadi, Zahra; Ghaedian, Tahereh

2018-01-01

Despite therapeutic effects of radioiodine in patients with differentiated thyroid cancer, there are some disadvantages due to harmful radiation to other tissues. According to the current guidelines, patients are recommended to drink lots of water and frequent voiding to reduce the amount of 131 I in the body. This study was designed to assess the impact of the amount of liquid intake on reduction of the measured dose rate of radioiodine-treated patients. A total of 42 patients with differentiated thyroid cancer without metastasis who had undergone total thyroidectomy and had been treated with radioiodine were selected. The patients were divided into two groups according to the amount of their fluid intake which was measured during the first 48 h after 131 I administration. In all patients, the dose rate was measured immediately and 48 h after iodine administration. Each group included 21 patients. Dose rate ratio (the ratio of the second dose rate to the first dose rate) and dose rate difference ratio (the ratio of the difference between the two measured dose rates to the first dose rate) were calculated for each patient. Despite the significant difference in the amount of the liquid drunk, no statistically significant difference was seen between the different groups in parameters of dose-rate ratio and dose-rate difference ratio. Higher fluid intake (>60 ml/h in our study) alone would not effectively reduce the patient's radiation dose rate at least not more than a well-hydrated state. It seems that other interfering factors in the thyroidectomized patients may also have some impacts on this physiologic process.

Time-division multiplexing of polarization-insensitive fiber-optic Michelson interferometric sensors

NASA Astrophysics Data System (ADS)

Huang, S. C.; Lin, W. W.; Chen, M. H.

1995-06-01

A system of time-division multiplexing of polarization-insensitive fiber-optic Michelson interferometric sensors that uses Faraday rotator mirror elements is demonstrated. This system is constructed with conventional low-birefringence single-mode fiber and is able to solve the polarization-fading problem by a combination of Faraday rotator mirrors with unbalanced Michelson interferometers. The system is lead-fiber insensitive and has potentials for practical field applications.

Cognitive insensitivity and cognitive impulsivity as mediators of bullying continuity: Extending the psychological inertia construct to bullying behavior.

PubMed

Walters, Glenn D; Espelage, Dorothy L

2018-06-21

Psychological inertia, the process by which social-cognitive variables help maintain behavioral patterns over time, has been found to explain crime continuity. The present study sought to determine whether psychological inertia can also be used to explain continuity in bullying behavior. A group of 1,161 youth (567 male) from the Illinois Study of Bullying and Sexual Violence were surveyed 3 times over a period of 1 year in an effort to determine which of two dimensions of precriminal cognition-cognitive insensitivity (callous, self-serving) or cognitive impulsivity (reckless, emotional)-mediated the past bullying-future bullying relationship. Consistent with research on crime continuity, cognitive impulsivity mediated bullying continuity, but cognitive insensitivity did not. Congruent with research on psychological inertia and crime continuity, the main reason why cognitive insensitivity did not mediate bullying continuity was that prior bullying behavior failed to predict subsequent cognitive insensitivity. In addition to providing support for a 2-dimensional (insensitivity, impulsivity) model of bullying development, these results suggest that 1 way bullying behavior can be managed is by challenging and reducing cognitive impulsivity, which in the current study was found to be a major contributor to bullying continuity. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Recommended de minimis radiation dose rates for Canada. Report No. INFO-0355

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

Not Available

1990-01-01

A de minimis dose or dose rate as used in this report represents a level of risk which is generally accepted as being of no significance to an individual, or in the case of a population, of no significance to society. The report describes the risk of biological effects from radiation; radiation from natural and man-made sources; normal incidences of cancer and genetic defects; initiatives by other agencies in the U.S., the U.K. and internationally; the importance of collective dose and dose rate; assigning values to the de minimis dose rates; and application of the de minimis dose rates.

Molecular basis for the toxin insensitivity of scorpion voltage-gated potassium channel MmKv1.

PubMed

Zhang, Chuangeng; Xie, Zili; Li, Xinxin; Chen, Jing; Feng, Jing; Lang, Yange; Yang, Weishan; Li, Wenxin; Chen, Zongyun; Yao, Jing; Cao, Zhijian; Wu, Yingliang

2016-05-01

Scorpions are insensitive to their own venoms, which contain various neurotoxins specific for mammalian or insect ion channels, whose molecular mechanism remains unsolved. Using MmKv1, a potassium channel identified from the genome of the scorpion Mesobuthus martensii, channel kinetic experiments showed that MmKv1 was a classical voltage-gated potassium channel with a voltage-dependent fast activation and slow inactivation. Compared with the human Kv1.3 channel (hKv1.3), the MmKv1 channel exhibited a remarkable insensitivity to both scorpion venom and toxin. The chimaeric channels of MmKv1 and hKv1.3 revealed that both turret and filter regions of the MmKv1 channel were critical for the toxin insensitivity of MmKv1. Furthermore, mutagenesis of the chimaeric channel indicated that two basic residues (Arg(399) and Lys(403)) in the MmKv1 turret region and Arg(425) in the MmKv1 filter region significantly affected its toxin insensitivity. Moreover, when these three basic residues of MmKv1 were simultaneously substituted with the corresponding residues from hKv1.3, the MmKv1-R399T/K403S/R425H mutant channels exhibited similar sensitivity to both scorpion venom and toxin to hKv1.3, which revealed the determining role of these three basic residues in the toxin insensitivity of the MmKv1 channel. More strikingly, a similar triad sequence structure is present in all Shaker-like channels from venomous invertebrates, which suggested a possible convergent functional evolution of these channels to enable them to resist their own venoms. Together, these findings first illustrate the mechanism by which scorpions are insensitive to their own venoms at the ion channel receptor level and enrich our knowledge of the insensitivity of scorpions and other venomous animals to their own venoms. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

beta subunits influence the biophysical and pharmacological differences between P- and Q-type calcium currents expressed in a mammalian cell line.

PubMed

Moreno, H; Rudy, B; Llinás, R

1997-12-09

Human epithelial kidney cells (HEK) were prepared to coexpress alpha1A, alpha2delta with different beta calcium channel subunits and green fluorescence protein. To compare the calcium currents observed in these cells with the native neuronal currents, electrophysiological and pharmacological tools were used conjointly. Whole-cell current recordings of human epithelial kidney alpha1A-transfected cells showed small inactivating currents in 80 mM Ba2+ that were relatively insensitive to calcium blockers. Coexpression of alpha1A, betaIb, and alpha2delta produced a robust inactivating current detected in 10 mM Ba2+, reversibly blockable with low concentration of omega-agatoxin IVA (omega-Aga IVA) or synthetic funnel-web spider toxin (sFTX). Barium currents were also supported by alpha1A, beta2a, alpha2delta subunits, which demonstrated the slowest inactivation and were relatively insensitive to omega-Aga IVA and sFTX. Coexpression of beta3 with the same combination as above produced inactivating currents also insensitive to low concentration of omega-Aga IVA and sFTX. These data indicate that the combination alpha1A, betaIb, alpha2delta best resembles P-type channels given the rate of inactivation and the high sensitivity to omega-Aga IVA and sFTX. More importantly, the specificity of the channel blocker is highly influenced by the beta subunit associated with the alpha1A subunit.

Study of the dose rate effect of 180 nm nMOSFETs

NASA Astrophysics Data System (ADS)

He, Bao-Ping; Yao, Zhi-Bin; Sheng, Jiang-Kun; Wang, Zu-Jun; Huang, Shao-Yan; Liu, Min-Bo; Xiao, Zhi-Gang

2015-01-01

Radiation induced offstate leakage in the shallow trench isolation regions of SIMC 0.18 μm nMOSFETs is studied as a function of dose rate. A “true” dose rate effect (TDRE) is observed. Increased damage is observed at low dose rate (LDR) than at high dose rate (HDR) when annealing is taken into account. A new method of simulating radiation induced degradation in shallow trench isolation (STI) is presented. A comparison of radiation induced offstate leakage current in test nMOSFETs between total dose irradiation experiments and simulation results exhibits excellent agreement. The investigation results imply that the enhancement of the leakage current may be worse for the dose rate encountered in the environment of space.

Proximal renal tubular injury in rats sub-chronically exposed to low fluoride concentrations

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

Cárdenas-González, Mariana C.; Del Razo, Luz M.; Barrera-Chimal, Jonatan

2013-11-01

Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25 ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15 ppm) and high (50 ppm) fluoride concentrations in drinking water for a period of 40 days. At the end ofmore » the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary β-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride. - Highlights: • Exposure to low concentrations of fluoride induced proximal tubular injury • Increase in urinary Kim-1, Clu, OPN and Hsp72 in 50 ppm fluoride-exposed group • Increase in urinary B2M and CysC in 15 and 50 ppm fluoride-exposed groups • Fluoride exposure increased renal Kim, Clu and OPN mRNA expression levels. • Fluoride increased kidney injury biomarkers at stages where eGFR was unaltered.« less

TCH346 as a neuroprotective drug in Parkinson's disease: a double-blind, randomised, controlled trial.

PubMed

Olanow, C Warren; Schapira, Anthony H V; LeWitt, Peter A; Kieburtz, Karl; Sauer, Dirk; Olivieri, Gianfranco; Pohlmann, Harald; Hubble, Jean

2006-12-01

There is an important unmet medical need in Parkinson's disease for a neuroprotective treatment that slows or stops disease progression. TCH346 is a potent anti-apoptotic drug that protects against loss of dopaminergic neurons in laboratory models. Our aim was to assess TCH346 as a neuroprotective drug in patients with Parkinson's disease. Patients presenting at 45 international movement disorder clinics with early untreated Parkinson's disease were assessed as part of this parallel-group, double-blind, randomised controlled trial. 301 eligible patients were randomly assigned 12-18 months' treatment with TCH346 at a daily dose of 0.5 mg (n=78), 2.5 mg (n=79), or 10 mg (n=73), or placebo (n=71), followed by a 4 week washout period. The primary outcome measure was time to development of a disability requiring dopaminergic treatment. Secondary outcome measures were the annual rate of change in the unified Parkinson's disease rating scale (UPDRS) and the PDQ-39, a measure of quality of life. Analyses were by intention-to-treat. This study is pending registration with . 255 patients completed the study. TCH346 did not differ from placebo for any of the study outcomes. Treatment was needed in 26 (34%) patients in the TCH346 0.5 mg group, 30 (38%) in the TCH346 2.5 mg group, 24 (33%) in the TCH346 10 mg group, and 23 (32%) in the placebo group. There were no significant differences between groups. There were no differences between groups in the annual change in the UPDRS or PDQ-39 either. Few patients withdrew because of adverse events and none was judged to be related to the study intervention. TCH346 did not show evidence of a neuroprotective effect. The discrepancy between the preclinical promise of TCH346 and the clinical outcome could have arisen because of the use of laboratory models that do not accurately reflect the pathogenesis of Parkinson's disease, the doses of study drug used, insensitive clinical endpoints, and the patient population selected for study.

The threshold vs LNT showdown: Dose rate findings exposed flaws in the LNT model part 1. The Russell-Muller debate

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

Calabrese, Edward J., E-mail: edwardc@schoolph.uma

This paper assesses the discovery of the dose-rate effect in radiation genetics and how it challenged fundamental tenets of the linear non-threshold (LNT) dose response model, including the assumptions that all mutational damage is cumulative and irreversible and that the dose-response is linear at low doses. Newly uncovered historical information also describes how a key 1964 report by the International Commission for Radiological Protection (ICRP) addressed the effects of dose rate in the assessment of genetic risk. This unique story involves assessments by two leading radiation geneticists, Hermann J. Muller and William L. Russell, who independently argued that the report'smore » Genetic Summary Section on dose rate was incorrect while simultaneously offering vastly different views as to what the report's summary should have contained. This paper reveals occurrences of scientific disagreements, how conflicts were resolved, which view(s) prevailed and why. During this process the Nobel Laureate, Muller, provided incorrect information to the ICRP in what appears to have been an attempt to manipulate the decision-making process and to prevent the dose-rate concept from being adopted into risk assessment practices. - Highlights: • The discovery of radiation dose rate challenged the scientific basis of LNT. • Radiation dose rate occurred in males and females. • The dose rate concept supported a threshold dose-response for radiation.« less

Thermo-elasto-viscoplastic analysis of problems in extension and shear

NASA Technical Reports Server (NTRS)

Riff, R.; Simitses, G. J.

1987-01-01

The problems of extension and shear behavior of structural elements made of carbon steel and subjected to large thermomechanical loads are investigated. The analysis is based on nonlinear geometric and constitutive relations, and is expressed in a rate form. The material constitutive equations are capable of reproducing all nonisothermal, elasto-viscoplastic characteristics. The results of the test problems show that: (1) the formulation can accommodate very large strains and rotations; (2) the model incorporates the simplification associated with rate-insensitive elastic response without losing the ability to model a rate-temperature dependent yield strength and plasticity; and (3) the formulation does not display oscillatory behavior in the stresses for the simple shear problem.

Impact of the Revised 10 CFR 835 on the Neutron Dose Rates at LLNL

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

Radev, R

2009-01-13

In June 2007, 10 CFR 835 [1] was revised to include new radiation weighting factors for neutrons, updated dosimetric models, and dose terms consistent with the newer ICRP recommendations. A significant aspect of the revised 10 CFR 835 is the adoption of the recommendations outlined in ICRP-60 [2]. The recommended new quantities demand a review of much of the basic data used in protection against exposure to sources of ionizing radiation. The International Commission on Radiation Units and Measurements has defined a number of quantities for use in personnel and area monitoring [3,4,5] including the ambient dose equivalent H*(d) tomore » be used for area monitoring and instrument calibrations. These quantities are used in ICRP-60 and ICRP-74. This report deals only with the changes in the ambient dose equivalent and ambient dose rate equivalent for neutrons as a result of the implementation of the revised 10 CFR 835. In the report, the terms neutron dose and neutron dose rate will be used for convenience for ambient neutron dose and ambient neutron dose rate unless otherwise stated. This report provides a qualitative and quantitative estimate of how much the neutron dose rates at LLNL will change with the implementation of the revised 10 CFR 835. Neutron spectra and dose rates from selected locations at the LLNL were measured with a high resolution spectroscopic neutron dose rate system (ROSPEC) as well as with a standard neutron rem meter (a.k.a., a remball). The spectra obtained at these locations compare well with the spectra from the Radiation Calibration Laboratory's (RCL) bare californium source that is currently used to calibrate neutron dose rate instruments. The measurements obtained from the high resolution neutron spectrometer and dose meter ROSPEC and the NRD dose meter compare within the range of {+-}25%. When the new radiation weighting factors are adopted with the implementation of the revised 10 CFR 835, the measured dose rates will increase by up to 22%. The health physicists should consider this increase for any areas that have dose rates near a posting limit, such as near the 100 mrem/hr for a high radiation area, as this increase in measured dose rate may result in some changes to postings and consequent radiological controls.« less

Comparison in vivo Study of Genotoxic Action of High- Versus Very Low Dose-Rate γ-Irradiation

PubMed Central

Osipov, A. N.; Klokov, D. Y.; Elakov, A. L.; Rozanova, O. M.; Zaichkina, S. I.; Aptikaeva, G. F.; Akhmadieva, A. Kh.

2004-01-01

The aim of the present study was to compare genotoxicity induced by high- versus very low dose-rate exposure of mice to γ-radiation within a dose range of 5 to 61 cGy using the single-cell gel electrophoresis (comet) assay and the micronucleus test. CBA/lac male mice were irradiated at a dose rate of 28.2 Gy/h (high dose rate) or 0.07 mGy/h (very low dose rate). The comet assay study on spleen lymphocytes showed that very low dose-rate irradiation resulted in a statistically significant increase in nucleoid relaxation (DNA breaks), starting from a dose of 20 cGy. Further prolongation of exposure time and, hence, increase of a total dose did not, however, lead to further increase in the extent of nucleoid relaxation. Doses of 20 and 61 cGy were equal in inducing DNA breaks in mouse spleen lymphocytes as assayed by the comet assay. Of note, the level of DNA damage by 20–61 cGy doses of chronic irradiation (0.07 mGy/h) was similar to that an induced by an acute (28.2 Gy/h) dose of 14 cGy. The bone marrow micronucleus test revealed that an increase in polychromatic erythrocytes with micronuclei over a background level was induced by very low-level γ-irradiation with a dose of 61 cGy only, with the extent of the cytogenetic effect being similar to that of 10 cGy high-dose-rate exposure. In summary, presented results support the hypothesis of the nonlinear threshold nature of mutagenic action of chronic low dose-rate irradiation. PMID:19330145

The estimation of galactic cosmic ray penetration and dose rates

NASA Technical Reports Server (NTRS)

Burrell, M. O.; Wright, J. J.

1972-01-01

This study is concerned with approximation methods that can be readily applied to estimate the absorbed dose rate from cosmic rays in rads - tissue or rems inside simple geometries of aluminum. The present work is limited to finding the dose rate at the center of spherical shells or behind plane slabs. The dose rate is calculated at tissue-point detectors or for thin layers of tissue. This study considers cosmic-rays dose rates for both free-space and earth-orbiting missions.

Estimation of ambient dose equivalent distribution in the 18F-FDG administration room using Monte Carlo simulation.

PubMed

Nagamine, Shuji; Fujibuchi, Toshioh; Umezu, Yoshiyuki; Himuro, Kazuhiko; Awamoto, Shinichi; Tsutsui, Yuji; Nakamura, Yasuhiko

2017-03-01

In this study, we estimated the ambient dose equivalent rate (hereafter "dose rate") in the fluoro-2-deoxy-D-glucose (FDG) administration room in our hospital using Monte Carlo simulations, and examined the appropriate medical-personnel locations and a shielding method to reduce the dose rate during FDG injection using a lead glass shield. The line source was assumed to be the FDG feed tube and the patient a cube source. The dose rate distribution was calculated with a composite source that combines the line and cube sources. The dose rate distribution was also calculated when a lead glass shield was placed in the rear section of the lead-acrylic shield. The dose rate behind the automatic administration device decreased by 87 % with respect to that behind the lead-acrylic shield. Upon positioning a 2.8-cm-thick lead glass shield, the dose rate behind the lead-acrylic shield decreased by 67 %.

Comparison of Monoenergetic Photon Organ Dose Rate Coefficients for the Female Stylized and Voxel Phantoms Submerged in Air

DOE PAGES

Hiller, Mauritius; Dewji, Shaheen Azim

2017-02-16

Dose rate coefficients computed using the International Commission on Radiological Protection (ICRP) reference adult female voxel phantom were compared with values computed using the Oak Ridge National Laboratory (ORNL) adult female stylized phantom in an air submersion exposure geometry. This is a continuation of previous work comparing monoenergetic organ dose rate coefficients for the male adult phantoms. With both the male and female data computed, effective dose rate as defined by ICRP Publication 103 was compared for both phantoms. Organ dose rate coefficients for the female phantom and ratios of organ dose rates for the voxel and stylized phantoms aremore » provided in the energy range from 30 to 5 MeV. Analysis of the contribution of the organs to effective dose is also provided. Lastly, comparison of effective dose rates between the voxel and stylized phantoms was within 8% at 100 keV and is <5% between 200 and 5000 keV.« less

Comparison of Monoenergetic Photon Organ Dose Rate Coefficients for the Female Stylized and Voxel Phantoms Submerged in Air

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

Hiller, Mauritius; Dewji, Shaheen Azim

Dose rate coefficients computed using the International Commission on Radiological Protection (ICRP) reference adult female voxel phantom were compared with values computed using the Oak Ridge National Laboratory (ORNL) adult female stylized phantom in an air submersion exposure geometry. This is a continuation of previous work comparing monoenergetic organ dose rate coefficients for the male adult phantoms. With both the male and female data computed, effective dose rate as defined by ICRP Publication 103 was compared for both phantoms. Organ dose rate coefficients for the female phantom and ratios of organ dose rates for the voxel and stylized phantoms aremore » provided in the energy range from 30 to 5 MeV. Analysis of the contribution of the organs to effective dose is also provided. Lastly, comparison of effective dose rates between the voxel and stylized phantoms was within 8% at 100 keV and is <5% between 200 and 5000 keV.« less

Guidance on the Assessment and Development of Insensitive Munitions (MURAT)

DTIC Science & Technology

2006-05-01

theoretical modelling . For this reason it is the best understood of all the areas on the flowchart. If the charge is already shocked by a previous impact...the initiation of heterogeneous high explosives due to shock waves are finite rate chemical reactions involved in the conversion of solid explosive ... explosive , increasing the chance of shock initiation (N26) Such an impact would have to take account of case material ahead of the fragment

Evaluation of experimental parameters for growth of homogeneous solid solutions

NASA Astrophysics Data System (ADS)

Scheel, Hans J.; Swendsen, Robert H.

2001-12-01

In this paper, we discuss the experimental conditions required to grow large two-component crystals from homogeneous solid solutions. Building on the work of Burton, Prim, and Slichter and that of Van Erk, we are able to establish that the concentration fluctuations for diffusion-limited growth are rather insensitive to hydrodynamic fluctuations. This enables a crystal grower to take advantage of forced convection to optimize growth rates without aggravating the striation problem.

Self-compensating fiber optic flow sensor having an end of a fiber optics element and a reflective surface within a tube

DOEpatents

Peng, Wei; Qi, Bing; Wang, Anbo

2006-05-16

A flow rate fiber optic transducer is made self-compensating for both temperature and pressure by using preferably well-matched integral Fabry-Perot sensors symmetrically located around a cantilever-like structure. Common mode rejection signal processing of the outputs allows substantially all effects of both temperature and pressure to be compensated. Additionally, the integral sensors can individually be made insensitive to temperature.

Proposals for Codaer (Combat Data Exchange Relay)

DTIC Science & Technology

1949-04-22

Target Reporting 6 CODAER INDICATORS 7 SHAFT POSITION TRANSMISSION AND CODING 9 OPERATIONS CONTROL 10 AA FIRE COORDINATION 10 INTERSHIP PLOTS 12 RELAY...of providing tactical data on at least 500 different targets or friends. The link should be insensitive to jamming and have a high degree of security...gyrations of high speed air targets. This sets the minimum data repetition rate at about 5 reports per second. Better results, particularly in view of

Poster — Thur Eve — 27: Flattening Filter Free VMAT Quality Assurance: Dose Rate Considerations for Detector Response

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

Viel, Francis; Duzenli, Cheryl; British Columbia Cancer Agency, Department of Medical Physics, Vancouver Centre

2014-08-15

Introduction: Radiation detector responses can be affected by dose rate. Due to higher dose per pulse and wider range of mu rates in FFF beams, detector responses should be characterized prior to implementation of QA protocols for FFF beams. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. This study looks at the dose per pulse variation throughout a 3D volume for typical VMAT plans and the response characteristics for a variety of detectors, and makes recommendations on the design of QA protocols for FFF VMAT QA. Materials and Methods: Linac log file data andmore » a simplified dose calculation algorithm are used to calculate dose per pulse for a variety of clinical VMAT plans, on a voxel by voxel basis, as a function of time in a cylindrical phantom. Diode and ion chamber array responses are characterized over the relevant range of dose per pulse and dose rate. Results: Dose per pulse ranges from <0.1 mGy/pulse to 1.5 mGy/pulse in a typical VMAT treatment delivery using the 10XFFF beam. Diode detector arrays demonstrate increased sensitivity to dose (+./− 3%) with increasing dose per pulse over this range. Ion chamber arrays demonstrate decreased sensitivity to dose (+/− 1%) with increasing dose rate over this range. Conclusions: QA protocols should be designed taking into consideration inherent changes in detector sensitivity with dose rate. Neglecting to account for changes in detector response with dose per pulse can lead to skewed QA results.« less

Whole-exome sequencing gives additional benefits compared to candidate gene sequencing in the molecular diagnosis of children with growth hormone or IGF-1 insensitivity.

PubMed

Shapiro, Lucy; Chatterjee, Sumana; Ramadan, Dina G; Davies, Kate M; Savage, Martin O; Metherell, Louise A; Storr, Helen L

2017-12-01

GH insensitivity (GHI) is characterised by short stature, IGF-1 deficiency and normal/elevated serum GH. IGF-1 insensitivity results in pre- and post-natal growth failure with normal/high IGF-1 levels. The prevalence of genetic defects is unknown. To identify the underlying genetic diagnoses in a paediatric cohort with GH or IGF-1 insensitivity using candidate gene (CGS) and whole-exome sequencing (WES) and assess factors associated with the discovery of a genetic defect. We undertook a prospective study of 132 patients with short stature and suspected GH or IGF-1 insensitivity referred to our centre for genetic analysis. 107 (96 GHI, 88 probands; 11 IGF-1 insensitivity, 9 probands) underwent CGS. WES was performed in those with no defined genetic aetiology following CGS. A genetic diagnosis was discovered 38/107 (36%) patients (32% probands) by CGS. WES revealed 11 patients with genetic variants in genes known to cause short stature. A further 2 patients had hypomethylation in the H19/IGF2 region or mUPD7 consistent with Silver-Russell Syndrome (total with genetic diagnosis 51/107, 48% or 41/97, 42% probands). WES also identified homozygous putative variants in FANCA and PHKB in 2 patients. Low height SDS and consanguinity were highly predictive for identifying a genetic defect. Comprehensive genetic testing confirms the genetic heterogeneity of GH/IGF-1 insensitivity and successfully identified the genetic aetiology in a significant proportion of cases. WES is rapid and may isolate genetic variants that have been missed by traditional clinically driven genetic testing. This emphasises the benefits of specialist diagnostic centres. © 2017 European Society of Endocrinology.

A pseudo-response regulator is misexpressed in the photoperiod insensitive Ppd-D1a mutant of wheat (Triticum aestivum L.).

PubMed

Beales, James; Turner, Adrian; Griffiths, Simon; Snape, John W; Laurie, David A

2007-09-01

Ppd-D1 on chromosome 2D is the major photoperiod response locus in hexaploid wheat (Triticum aestivum). A semi-dominant mutation widely used in the "green revolution" converts wheat from a long day (LD) to a photoperiod insensitive (day neutral) plant, providing adaptation to a broad range of environments. Comparative mapping shows Ppd-D1 to be colinear with the Ppd-H1 gene of barley (Hordeum vulgare) which is a member of the pseudo-response regulator (PRR) gene family. To investigate the relationship between wheat and barley photoperiod genes we isolated homologues of Ppd-H1 from a 'Chinese Spring' wheat BAC library and compared them to sequences from other wheat varieties with known Ppd alleles. Varieties with the photoperiod insensitive Ppd-D1a allele which causes early flowering in short (SD) or LDs had a 2 kb deletion upstream of the coding region. This was associated with misexpression of the 2D PRR gene and expression of the key floral regulator FT in SDs, showing that photoperiod insensitivity is due to activation of a known photoperiod pathway irrespective of day length. Five Ppd-D1 alleles were found but only the 2 kb deletion was associated with photoperiod insensitivity. Photoperiod insensitivity can also be conferred by mutation at a homoeologous locus on chromosome 2B (Ppd-B1). No candidate mutation was found in the 2B PRR gene but polymorphism within the 2B PRR gene cosegregated with the Ppd-B1 locus in a doubled haploid population, suggesting that insensitivity on 2B is due to a mutation outside the sequenced region or to a closely linked gene.

Acute changes in the central nervous system of monkeys exposed to protons.

NASA Technical Reports Server (NTRS)

Haymaker, W.; Ibrahim, M. Z. M.; Miquel, J.; Call, N.; Noden, P.; Ashley, W.; Ballinger, E. R.; Ghidoni, J.; Lindsay, I. R.; Behar, A. J.

1972-01-01

Study of the changes occurring in simian brain exposed to protons of varied energy, given in wide dose and dose-rate ranges. Results show that inflammatory reaction and glycogen accumulation in astrocytes occurred practically in all animals. Cerebral cortical necrosis, granule cell pyknosis, and inflammatory reaction occurred at doses far lower than effective for high-energy gamma radiation given other series of monkeys at comparable dose rates. Metallic impregnation, carried out in virtually all the animals tested, revealed a wide variation in glial response even at equal doses and dose rates in the same proton energy series. Proton energy effect, dose effect, dose-time effect, and dose-rate effect were evident in the various morphological categories investigated, but inconsistencies were encountered.

Absorbed dose thresholds and absorbed dose rate limitations for studies of electron radiation effects on polyetherimides

NASA Technical Reports Server (NTRS)

Long, Edward R., Jr.; Long, Sheila Ann T.; Gray, Stephanie L.; Collins, William D.

1989-01-01

The threshold values of total absorbed dose for causing changes in tensile properties of a polyetherimide film and the limitations of the absorbed dose rate for accelerated-exposure evaluation of the effects of electron radiation in geosynchronous orbit were studied. Total absorbed doses from 1 kGy to 100 MGy and absorbed dose rates from 0.01 MGy/hr to 100 MGy/hr were investigated, where 1 Gy equals 100 rads. Total doses less than 2.5 MGy did not significantly change the tensile properties of the film whereas doses higher than 2.5 MGy significantly reduced elongation-to-failure. There was no measurable effect of the dose rate on the tensile properties for accelerated electron exposures.

WE-FG-BRA-05: Potential Clinical Benefit of LINAC Flattening-Filter-Free (FFF) Mode - Improvement of Treatment Therapeutic Ratio

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

Chang, S; Department of Biomedical Engineering, University of North Carolina- Chapel Hill/ North Carolina State University, Chapel Hill, North Carolina; Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC

Purpose: Ultrahigh dose-rate radiation at >40Gy/s has demonstrated astonishing normal-tissue sparing and tumor control in recent preclinical naive and tumor-bearing rodent studies when compared to the same radiation dose at a conventional dose-rate. The working mechanism of this fascinating dose-rate effect is currently under investigation. The aims of this work include investigating 1) whether LINAC FFF mode radiation at approximately 1Gy/s also has an improved therapeutic ratio compared to the same radiation dose at the conventional dose-rate of 0.05Gy/s, and 2) the dose-rate effect’s potential working mechanism by studying the expression of the P53 gene, linked to tumor suppression andmore » cell regulation after radiation damage. Methods: We used mouse model C57BL/6J, the same as that used in the ultrahigh dose-rate studies, and exposed them to total body irradiation (TBI) using the Elekta Versa accelerator 10MV photons. Mice (N=20) were given a total dose of 12Gy in both the high dose-rate group (n=10) using the FFF-mode and the conventional dose-rate group (n=10) using the conventional does rate mode. The FFF-mode treatment setup consisted of a 15cm×15cm field size setting at 53.2cm SSD while the conventional-mode set-up consisted of a 10cm×10cm field size at 100SSD. Post-radiation, animals were monitored daily for survival analysis and signs of moribundity requiring euthanasia. In addition, mouse spleens were harvested for P53 analysis at different time points. Results: For 12Gy TBI, the 1.3Gy/s FFF-mode high dose-rate produced a statistically significant (p=0.02) improvement in mouse survival compared to the 0.05Gy/s conventional dose-rate. An initial P53 study at the time of death time-point indicates that high dose-rate radiation induced a stronger expression of P53 than conventional dose-rate radiation. Conclusion: Our pilot study indicates that the FFF-mode high dose-rate radiation, which has been used largely to improve clinical throughput, may provide the added clinical benefit of improving treatment therapeutic ratio. Animal Studies were performed within the LCCC Animal Studies Core Facility at the University of North Carolina at Chapel Hill. The LCCC Animal Studies Core is supported in part by an NCI Center Core Support Grant (CA16086) to the UNC Lineberger Comprehensive Cancer Center.« less

Slipped Distal Femoral Epiphysis in Congenital Insensitivity to Pain.

PubMed

Shaikh, M Javed; Rex, C; Vignesh, R; Chavan, Madhav

2016-01-01

Congenital insensitivity to pain (CIP) is a rare disorder, and often presents to an orthopaedic surgeon as recurrent fractures, dislocations, pseudoarthrosis, osteomyelitis etc. Here, we report a case of congenital insensitivity to pain presenting with distal femoral physeal separation in a child. A 12-year-old girl child came with complaints of limp while walking and swelling in the left knee for past 5 weeks. Mother gave a history that the girl is a known case of congenital insensitivity to pain with clear history of no pain on intramuscular injection since birth. She was born of consanguineous marriage and had no significant trauma, fever, other joint involvement or any features of rheumatism. On local examination, she had no bony tenderness, mild warmth, and moderate knee effusion with restricted range of movement. Plain radiograph showed epiphysiolysis of distal femur with widening of physis. Examination under anaesthesia demonstrated gross movement indicating lower femoral physeal separation. This unstable distal femoral epiphysis was treated under general anaesthesia with closed reduction, percutaneous cross pinning and above knee plaster cast. Congenital insensitivity to pain (CIP) is a rare disorder to diagnose. Emphasis is given on early diagnosis of orthopaedic problems and prompt treatment, educating parents and prevention of accidents. Physeal separation without significant trauma must prompt an orthopaedic surgeon to think about congenital insensitivity to pain as a differential diagnosis.

DNA methylation pattern of Photoperiod-B1 is associated with photoperiod insensitivity in wheat (Triticum aestivum).

PubMed

Sun, Han; Guo, Zhiai; Gao, Lifeng; Zhao, Guangyao; Zhang, Wenping; Zhou, Ronghua; Wu, Yongzhen; Wang, Haiyang; An, Hailong; Jia, Jizeng

2014-11-01

As one of the three key components of the 'Green Revolution', photoperiod insensitivity is vital for improved adaptation of wheat (Triticum aestivum) cultivars to a wider geographical range. Photoperiod-B1a (Ppd-B1a) is one of the major genes that confers photoperiod insensitivity in 'Green Revolution' varieties, and has made a significant contribution to wheat yield improvement. In this study, we investigated the mechanisms underlying the photoperiod insensitivity of Ppd-B1a alleles from an epigenetic perspective using a combination of bisulfite genomic sequencing, orthologous comparative analysis, association analysis, linkage analysis and gene expression analysis. Based on the study of a large collection of wheat germplasm, we report two methylation haplotypes of Ppd-B1 and demonstrate that the higher methylation haplotype (haplotype a) was associated with increased copy numbers and higher expression levels of the Ppd-B1 gene, earlier heading and photoperiod insensitivity. Furthermore, assessment of the distribution frequency of the different methylation haplotypes suggested that the methylation patterns have undergone selection during the wheat breeding process. Our study suggests that DNA methylation in the regulatory region of the Ppd-B1 alleles, which is closely related to copy number variation, plays a significant role in wheat breeding, to confer photoperiod insensitivity and better adaptation to a wider geographical range. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Verticalization of behavior elicited by dopaminergic mobilization is qualitatively different between C57BL/6J and DBA/2J mice.

PubMed

Tirelli, E; Witkin, J M

1994-10-01

Behavioral effects of dopaminergic stimulation were evaluated in C57BL/6J mice and compared to the effects occurring in DBA/2J mice, an inbred strain with reduced densities of striatal dopamine receptors. Effects of apomorphine (0.5-64 mg/kg) alone and in combination with cocaine (30 mg/kg) were assessed using a time-sampling technique that classified climbing and leaning in separate categories. Locomotion was also assessed in a separate experiment. Climbing occurred in DBA/2J mice only at doses of apomorphine that were 16 times higher than the smallest effective dose in C57BL/6J mice; nevertheless, relative to baseline values, effects were fairly comparable. By contrast, whereas DBA/2J mice showed dose-dependent leaning under apomorphine, C57BL/6J mice exhibited little leaning even at doses not producing climbing, and only after the highest apomorphine dose was leaning significantly increased. Apomorphine was equipotent in inducing gnawing across strains, although somewhat less efficacious in DBA/2J mice. When given alone, cocaine produced significant climbing, but not leaning or gnawing, in either strain. Whereas cocaine potentiated apomorphine-induced climbing and gnawing in both strains, apomorphine-induced leaning was not consistently changed by cocaine in either strain. These effects were not indirectly due to hyperkinesia, since neither apomorphine alone nor apomorphine and cocaine in combination was stimulant; apomorphine alone reduced locomotor activity and attenuated cocaine-induced hyperkinesia. The present data do not support a unitary, purely quantitative, account of insensitivity to dopaminergic stimulation based upon low densities of striatal dopamine receptors in DBA/2J mice. Rather, this constellation of results is suggestive of qualitative interstrain dissimilarities in dopaminergic responsiveness that could reflect organizational differences in receptor populations.

Dose rate effect on micronuclei induction in human blood lymphocytes exposed to single pulse and multiple pulses of electrons.

PubMed

Acharya, Santhosh; Bhat, N N; Joseph, Praveen; Sanjeev, Ganesh; Sreedevi, B; Narayana, Y

2011-05-01

The effects of single pulses and multiple pulses of 7 MV electrons on micronuclei (MN) induction in cytokinesis-blocked human peripheral blood lymphocytes (PBLs) were investigated over a wide range of dose rates per pulse (instantaneous dose rate). PBLs were exposed to graded doses of 2, 3, 4, 6, and 8 Gy of single electron pulses of varying pulse widths at different dose rates per pulse, ranging from 1 × 10(6) Gy s(-1) to 3.2 × 10(8) Gy s(-1). Different dose rates per pulse were achieved by changing the dose per electron pulse by adjusting the beam current and pulse width. MN yields per unit absorbed dose after irradiation with single electron pulses were compared with those of multiple pulses of electrons. A significant decrease in the MN yield with increasing dose rates per pulse was observed, when dose was delivered by a single electron pulse. However, no reduction in the MN yield was observed when dose was delivered by multiple pulses of electrons. The decrease in the yield at high dose rates per pulse suggests possible radical recombination, which leads to decreased biological damage. Cellular response to the presence of very large numbers of chromosomal breaks may also alter the damage.

Comparative performance analysis for computer aided lung nodule detection and segmentation on ultra-low-dose vs. standard-dose CT

NASA Astrophysics Data System (ADS)

Wiemker, Rafael; Rogalla, Patrik; Opfer, Roland; Ekin, Ahmet; Romano, Valentina; Bülow, Thomas

2006-03-01

The performance of computer aided lung nodule detection (CAD) and computer aided nodule volumetry is compared between standard-dose (70-100 mAs) and ultra-low-dose CT images (5-10 mAs). A direct quantitative performance comparison was possible, since for each patient both an ultra-low-dose and a standard-dose CT scan were acquired within the same examination session. The data sets were recorded with a multi-slice CT scanner at the Charite university hospital Berlin with 1 mm slice thickness. Our computer aided nodule detection and segmentation algorithms were deployed on both ultra-low-dose and standard-dose CT data without any dose-specific fine-tuning or preprocessing. As a reference standard 292 nodules from 20 patients were visually identified, each nodule both in ultra-low-dose and standard-dose data sets. The CAD performance was analyzed by virtue of multiple FROC curves for different lower thresholds of the nodule diameter. For nodules with a volume-equivalent diameter equal or larger than 4 mm (149 nodules pairs), we observed a detection rate of 88% at a median false positive rate of 2 per patient in standard-dose images, and 86% detection rate in ultra-low-dose images, also at 2 FPs per patient. Including even smaller nodules equal or larger than 2 mm (272 nodules pairs), we observed a detection rate of 86% in standard-dose images, and 84% detection rate in ultra-low-dose images, both at a rate of 5 FPs per patient. Moreover, we observed a correlation of 94% between the volume-equivalent nodule diameter as automatically measured on ultra-low-dose versus on standard-dose images, indicating that ultra-low-dose CT is also feasible for growth-rate assessment in follow-up examinations. The comparable performance of lung nodule CAD in ultra-low-dose and standard-dose images is of particular interest with respect to lung cancer screening of asymptomatic patients.

Sensitivity of Photosynthesis in a C4 Plant, Maize, to Heat Stress

PubMed Central

Crafts-Brandner, Steven J.; Salvucci, Michael E.

2002-01-01

Our objective was to determine the sensitivity of components of the photosynthetic apparatus of maize (Zea mays), a C4 plant, to high temperature stress. Net photosynthesis (Pn) was inhibited at leaf temperatures above 38°C, and the inhibition was much more severe when the temperature was increased rapidly rather than gradually. Transpiration rate increased progressively with leaf temperature, indicating that inhibition was not associated with stomatal closure. Nonphotochemical fluorescence quenching (qN) increased at leaf temperatures above 30°C, indicating increased thylakoid energization even at temperatures that did not inhibit Pn. Compared with CO2 assimilation, the maximum quantum yield of photosystem II (Fv/Fm) was relatively insensitive to leaf temperatures up to 45°C. The activation state of phosphoenolpyruvate carboxylase decreased marginally at leaf temperatures above 40°C, and the activity of pyruvate phosphate dikinase was insensitive to temperature up to 45°C. The activation state of Rubisco decreased at temperatures exceeding 32.5°C, with nearly complete inactivation at 45°C. Levels of 3-phosphoglyceric acid and ribulose-1,5-bisphosphate decreased and increased, respectively, as leaf temperature increased, consistent with the decrease in Rubisco activation. When leaf temperature was increased gradually, Rubisco activation acclimated in a similar manner as Pn, and acclimation was associated with the expression of a new activase polypeptide. Rates of Pn calculated solely from the kinetics of Rubisco were remarkably similar to measured rates if the calculation included adjustment for temperature effects on Rubisco activation. We conclude that inactivation of Rubisco was the primary constraint on the rate of Pn of maize leaves as leaf temperature increased above 30°C. PMID:12177490

Deuterium chemistry in the young massive protostellar core NGC 2264 CMM3

NASA Astrophysics Data System (ADS)

Awad, Z.; Shalabiea, O. M.

2018-01-01

In this work we present the first attempt of modelling the deuterium chemistry in the massive young protostellar core NGC 2264 CMM3. We investigated the sensitivity of this chemistry to the physical conditions in its surrounding environment. The results showed that deuteration, in the protostellar gas, is affected by variations in the core density, the amount of gas depletion onto grain surfaces, the CR ionisation rate, but it is insensitive to variations in the H2 ortho-to-para ratio. Our results, also, showed that deuteration is often enhanced in less-dense, partially depleted (<85%), or cores that are exerted to high CR ionisation rates (≥6.5×10^{-17} s^{-1}). However, in NGC 2264 CMM3, decreasing the amount of gas depleted onto grains and enhancing the CR ionisation rate are often overestimating the observed values in the core. The best fit time to observations occurs around (1-5) × 104 yrs for core densities in the range (1-5)×106 cm^{-3} with CR ionisation rate between (1.7-6.5)×10^{-17} s^{-1}. These values are in agreement with the results of the most recent theoretical chemical model of CMM3, and the time range of best fit is, also, in-line with the estimated age of young protostellar objects. We conclude that deuterium chemistry in protostellar cores is: (i) sensitive to variations in the physical conditions in its environment, (ii) insensitive to changes in the H2 ortho-to-para ratio. We also conclude that the core NGC 2264 CMM3 is in its early stages of chemical evolution with an estimated age of (1-5)×104 yrs.

Photochemical transformation of the insensitive munitions compound 2,4-dinitroanisole.

PubMed

Rao, Balaji; Wang, Wei; Cai, Qingsong; Anderson, Todd; Gu, Baohua

2013-01-15

The insensitive munitions compound 2,4-dinitroanisole (DNAN) is increasingly being used as a replacement for traditional, sensitive munitions compounds (e.g., trinitrotoluene [TNT]), but the environmental fate and photo-transformation of DNAN in natural water systems are currently unknown. In this study, we investigated the photo-transformation rates of DNAN with both ultraviolet (UV) and sunlight irradiation under different environmentally relevant conditions. Sunlight photo-transformation of DNAN in water was found to follow predominantly pseudo-first-order decay kinetics with an average half-life (t(1/2)) of approximately 0.70 d and activation energy (E(a)) of 53 kJ mol(-1). Photo-transformation rates of DNAN were dependent on the wavelength of the light source: irradiation with UV-B light (280-315 nm) resulted in a greater quantum yield of transformation (φ(UV-B)=3.7×10(-4)) than rates obtained with UV-A light (φ(UV-A)=2.9×10(-4) at 316-400 nm) and sunlight (φ(sun)=1.1×10(-4)). Photo-oxidation was the dominant mechanism for DNAN photo-transformation, based on the formation of nitrite (NO(2)(-)) and nitrate (NO(3)(-)) as major N species and 2,4-dinitrophenol as the minor species. Environmental factors (e.g., temperature, pH, and the presence or absence of naturally dissolved organic matter) displayed modest to little effects on the rate of DNAN photo-transformation. These observations indicate that sunlight-induced photo-transformation of DNAN may represent a significant abiotic degradation pathway in surface water, which may have important implications in evaluating the potential impacts and risks of DNAN in the environment. Published by Elsevier B.V.

Temperature insensitive refractive index sensor based on concatenated long period fiber gratings

NASA Astrophysics Data System (ADS)

Tripathi, Saurabh M.; Bock, Wojtek J.; Mikulic, Predrag

2013-10-01

We propose and demonstrate a temperature immune biosensor based on two concatenated LPGs incorporating a suitable inter-grating-space (IGS). Compensating the thermal induced phase changes in the grating region by use of an appropriate length of the IGS the temperature insensitivity has been achieved. Using standard telecommunication grade single-mode fibers we show that a length ratio of ~8.2 is sufficient to realize the proposed temperature insensitivity. The resulting sensor shows a refractive index sensitivity of 423.28 nm/RIU displaying the capability of detecting an index variation of 2.36 × 10-6 RIU in the bio-samples. The sensor can also be applied as a temperature insensitive WMD channel isolation filter in the optical communication systems, removing the necessity of any external thermal insulation packaging.

Timescales of AMOC decline in response to fresh water forcing

NASA Astrophysics Data System (ADS)

Jackson, Laura C.; Wood, Richard A.

2017-12-01

The Atlantic meridional overturning circulation (AMOC) is predicted to weaken over the coming century due to warming from greenhouse gases and increased input of fresh water into the North Atlantic, however there is considerable uncertainty as to the amount and rate of AMOC weakening. Understanding what controls the rate and timescale of AMOC weakening may help to reduce this uncertainty and hence reduce the uncertainty surrounding associated impacts. As a first step towards this we consider the timescales associated with weakening in response to idealized freshening scenarios. Here we explore timescales of AMOC weakening in response to a freshening of the North Atlantic in a suite of experiments with an eddy-permitting global climate model (GCM). When the rate of fresh water added to the North Atlantic is small (0.1 Sv; 1 Sv =1× 10^6 m^3 /s), the timescale of AMOC weakening depends mainly on the rate of fresh water input itself and can be longer than a century. When the rate of fresh water added is large (≥ 0.3 Sv) however, the timescale is a few decades and is insensitive to the actual rate of fresh water input. This insensitivity is because with a greater rate of fresh water input the advective feedbacks become more important at exporting fresh anomalies, so the rate of freshening is similar. We find advective feedbacks from: an export of fresh anomalies by the mean flow; less volume import through the Bering Strait; a weakening AMOC transporting less subtropical water northwards; and anomalous subtropical circulations which amplify export of the fresh anomalies. This latter circulation change is driven itself by the presence of fresh anomalies exported from the subpolar gyre through geostrophy. This feedback has not been identified in previous model studies and when the rate of freshening is strong it is found to dominate the total export of fresh anomalies, and hence the timescale of AMOC decline. Although results may be model dependent, qualitatively similar mechanisms are also found in a single experiment with a different GCM.

Total dose bias dependency and ELDRS effects in bipolar linear devices

NASA Technical Reports Server (NTRS)

Yui, C. C.; McClure, S. S.; Rex, B. G.; Lehman, J. M.; Minto, T. D.; Wiedeman, M.

2002-01-01

Total dose tests of several bipolar linear devices show sensitivity to both dose rate and bias during exposure. All devices exhibited Enhanced Low Dose Rate Sensitivity (ELDRS). An accelerated ELDRS test method for three different devices demonstrate results similar to tests at low dose rate. Behavior and critical parameters from these tests are compared and discussed.

The Impact of Dose Rate on the Accuracy of Step-and-Shoot Intensity-modulated Radiation Therapy Quality Assurance Using Varian 2300CD.

PubMed

Njeh, Christopher F; Salmon, Howard W; Schiller, Claire

2017-01-01

Intensity-modulated radiation therapy (IMRT) delivery using "step-and-shoot" technique on Varian C-Series linear accelerator (linac) is influenced by the communication frequency between the multileaf collimator and linac controllers. Hence, the dose delivery accuracy is affected by the dose rate. Our aim was to quantify the impact of using two dose rates on plan quality assurance (QA). Twenty IMRT patients were selected for this study. The plan QA was measured at two different dose rates. A gamma analysis was performed, and the degree of plan modulation on the QA pass rate was also evaluated in terms of average monitor unit per segment (MU/segment) and the total number of segments. The mean percentage gamma pass rate of 94.9% and 93.5% for 300 MU/min and 600 MU/min dose rate, respectively, was observed. There was a significant ( P = 0.001) decrease in percentage gamma pass rate when the dose rate was increased from 300 MU/min to 600 MU/min. There was a weak, but significant association between the percentage pass rate at both dose rate and total number of segments. The total number of MU was significantly correlated to the total number of segments ( r = 0.59). We found a positive correlation between the percentage pass rate and mean MU/segment, r = 0.52 and r = 0.57 for 300 MU/min and 600 MU/min, respectively. IMRT delivery using step-and-shoot technique on Varian 2300CD is impacted by the dose rate and the total amount of segments.

Enhanced Low Dose Rate Effects in Bipolar Circuits: A New Hardness Assurance Problem for NASA

NASA Technical Reports Server (NTRS)

Johnston, A.; Barnes, C.

1995-01-01

Many bipolar integrated circuits are much more susceptible to ionizing radiation at low dose rates than they are at high dose rates typically used for radiation parts testing. Since the low dose rate is equivalent to that seen in space, the standard lab test no longer can be considered conservative and has caused the Air Force to issue an alert. Although a reliable radiation hardness assurance test has not yet been designed, possible mechanisms for low dose rate enhancement and hardness assurance tests are discussed.

Is the Pharmacological Mode of Action of Chromium(III) as a Second Messenger?

PubMed

Vincent, John B

2015-07-01

Although recent studies have shown that chromium (as the trivalent ion) is not an essential trace element, it has been demonstrated to generate beneficial effects at pharmacologically relevant doses on insulin sensitivity and cholesterol levels of rodent models of insulin insensitivity, including models of type 2 diabetes. The mode of action of Cr(III) at a molecular level is still an area of active debate; however, the movement of Cr(III) in the body, particularly in response to changes in insulin concentration, suggests that Cr(III) could act as a second messenger, amplifying insulin signaling. The evidence for the pharmacological mechanism of Cr(III)'s ability to increase insulin sensitivity by acting as a second messenger is reviewed, and proposals for testing this hypothesis are described.

Development of a high precision dosimetry system for the measurement of surface dose rate distribution for eye applicators.

PubMed

Eichmann, Marion; Flühs, Dirk; Spaan, Bernhard

2009-10-01

The therapeutic outcome of the therapy with ophthalmic applicators is highly dependent on the application of a sufficient dose to the tumor, whereas the dose applied to the surrounding tissue needs to be minimized. The goal for the newly developed apparatus described in this work is the determination of the individual applicator surface dose rate distribution with a high spatial resolution and a high precision in dose rate with respect to time and budget constraints especially important for clinical procedures. Inhomogeneities of the dose rate distribution can be detected and taken into consideration for the treatment planning. In order to achieve this, a dose rate profile as well as a surface profile of the applicator are measured and correlated with each other. An instrumental setup has been developed consisting of a plastic scintillator detector system and a newly designed apparatus for guiding the detector across the applicator surface at a constant small distance. It performs an angular movement of detector and applicator with high precision. The measurements of surface dose rate distributions discussed in this work demonstrate the successful operation of the measuring setup. Measuring the surface dose rate distribution with a small distance between applicator and detector and with a high density of measuring points results in a complete and gapless coverage of the applicator surface, being capable of distinguishing small sized spots with high activities. The dosimetrical accuracy of the measurements and its analysis is sufficient (uncertainty in the dose rate in terms of absorbed dose to water is <7%), especially when taking the surgical techniques in positioning of the applicator on the eyeball into account. The method developed so far allows a fully automated quality assurance of eye applicators even under clinical conditions. These measurements provide the basis for future calculation of a full 3D dose rate distribution, which then can be used as input for a refined clinical treatment planning system. The improved dose rate measurements will facilitate a clinical study, which could correlate the therapeutic outcome of a brachytherapy treatment with an applicator and its individual dose rate distribution.

Development of a high precision dosimetry system for the measurement of surface dose rate distribution for eye applicators

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

Eichmann, Marion; Fluehs, Dirk; Spaan, Bernhard

2009-10-15

Purpose: The therapeutic outcome of the therapy with ophthalmic applicators is highly dependent on the application of a sufficient dose to the tumor, whereas the dose applied to the surrounding tissue needs to be minimized. The goal for the newly developed apparatus described in this work is the determination of the individual applicator surface dose rate distribution with a high spatial resolution and a high precision in dose rate with respect to time and budget constraints especially important for clinical procedures. Inhomogeneities of the dose rate distribution can be detected and taken into consideration for the treatment planning. Methods: Inmore » order to achieve this, a dose rate profile as well as a surface profile of the applicator are measured and correlated with each other. An instrumental setup has been developed consisting of a plastic scintillator detector system and a newly designed apparatus for guiding the detector across the applicator surface at a constant small distance. It performs an angular movement of detector and applicator with high precision. Results: The measurements of surface dose rate distributions discussed in this work demonstrate the successful operation of the measuring setup. Measuring the surface dose rate distribution with a small distance between applicator and detector and with a high density of measuring points results in a complete and gapless coverage of the applicator surface, being capable of distinguishing small sized spots with high activities. The dosimetrical accuracy of the measurements and its analysis is sufficient (uncertainty in the dose rate in terms of absorbed dose to water is <7%), especially when taking the surgical techniques in positioning of the applicator on the eyeball into account. Conclusions: The method developed so far allows a fully automated quality assurance of eye applicators even under clinical conditions. These measurements provide the basis for future calculation of a full 3D dose rate distribution, which then can be used as input for a refined clinical treatment planning system. The improved dose rate measurements will facilitate a clinical study, which could correlate the therapeutic outcome of a brachytherapy treatment with an applicator and its individual dose rate distribution.« less

In vitro biotransformation rates in fish liver S9: effect of dosing techniques.

PubMed

Lee, Yung-Shan; Lee, Danny H Y; Delafoulhouze, Maximilien; Otton, S Victoria; Moore, Margo M; Kennedy, Chris J; Gobas, Frank A P C

2014-08-01

In vitro biotransformation assays are currently being explored to improve estimates of bioconcentration factors of potentially bioaccumulative organic chemicals in fish. The present study compares thin-film and solvent-delivery dosing techniques as well as single versus multiple chemical dosing for measuring biotransformation rates of selected polycyclic aromatic hydrocarbons in rainbow trout (Oncorhynchus mykiss) liver S9. The findings show that biotransformation rates of very hydrophobic substances can be accurately measured in thin-film sorbent-dosing assays from concentration-time profiles in the incubation medium but not from those in the sorbent phase because of low chemical film-to-incubation-medium mass-transfer rates at the incubation temperature of 13.5 °C required for trout liver assays. Biotransformation rates determined by thin-film dosing were greater than those determined by solvent-delivery dosing for chrysene (octanol-water partition coefficient [KOW ] =10(5.60) ) and benzo[a]pyrene (KOW  =10(6.04) ), whereas there were no statistical differences in pyrene (KOW  =10(5.18) ) biotransformation rates between the 2 methods. In sorbent delivery-based assays, simultaneous multiple-chemical dosing produced biotransformation rates that were not statistically different from those measured in single-chemical dosing experiments for pyrene and benzo[a]pyrene but not for chrysene. In solvent-delivery experiments, multiple-chemical dosing produced biotransformation rates that were much smaller than those in single-chemical dosing experiments for all test chemicals. While thin-film sorbent-phase and solvent delivery-based dosing methods are both suitable methods for measuring biotransformation rates of substances of intermediate hydrophobicity, thin-film sorbent-phase dosing may be more suitable for superhydrophobic chemicals. © 2014 SETAC.

A novel growth hormone receptor gene deletion mutation in a patient with primary growth hormone insensitivity syndrome (Laron syndrome).

PubMed

Yamamoto, Hiroyasu; Kouhara, Haruhiko; Iida, Keiji; Chihara, Kazuo; Kasayama, Soji

2008-04-01

Growth hormone (GH) insensitivity syndrome (Laron syndrome) is known to be caused by genetic disorders of the GH-IGF-1 axis. Although many mutations in the GH receptor have been identified, there have been only a few reports of deletions of the GH receptor gene. A Japanese adult female patient with Laron syndrome was subjected to chromosome analysis with basic G-banding and also with a high accuracy technique. Each exon of the GH receptor gene was amplified by means of PCR. Since this patient was diagnosed with osteoporosis, the effects of alendronate on bone mineral density (BMD) were also examined. The chromosome analysis with the high accuracy technique demonstrated a large deletion of the short arm in one allele of chromosome 5 from p11 to p13.1 [46, XX, del (5) (p11-p13.1)]. PCR amplification of exons of the GH receptor gene showed that only exons 2 and 3 were amplified. Low-dose IGF-1 administration (30microg/kg body weight) failed to increase her BMD, whereas alendronate administration resulted in an increase associated with a decrease in urinary deoxypyridinoline (DPD) and serum osteocalcin concentrations. The GH receptor gene of the patient was shown to lack exons 4-10. To the best of our knowledge, this is the third case report of Laron syndrome with large GH receptor deletion. Alendronate was effective for the enhancement of BMD.

Steinach and Young, Discoverers of the Effects of Estrogen on Male Sexual Behavior and the “Male Brain”1,2

PubMed Central

2015-01-01

Abstract In the 1930s, Eugen Steinach’s group found that estradiol induces lordosis in castrated rats and reduces the threshold dose of testosterone that is necessary for the induction of ejaculation, and that estradiol-treated intact rats display lordosis as well as mounting and ejaculation. The bisexual, estrogen-sensitive male had been demonstrated. Another major, albeit contrasting, discovery was made in the 1950s, when William Young’s group reported that male guinea pigs and prenatally testosterone-treated female guinea pigs are relatively insensitive to estrogen when tested for lordosis as adults. Reduced estrogen sensitivity was part of the new concept of organization of the neural tissues mediating the sexual behavior of females into tissues similar to those of males. The importance of neural organization by early androgen stimulation was realized immediately and led to the discovery of a variety of sex differences in the brains of adult animals. By contrast, the importance of the metabolism of testosterone into estrogen in the male was recognized only after a delay. While the finding that males are sensitive to estrogen was based on Bernhard Zondek’s discovery in 1934 that testosterone is metabolized into estrogen in males, the finding that males are insensitive to estrogen was based on the hypothesis that testosterone–male sexual behavior is the typical relationship in the male. It is suggested that this difference in theoretical framework explains the discrepancies in some of the reported results. PMID:26601123

Steinach and Young, Discoverers of the Effects of Estrogen on Male Sexual Behavior and the "Male Brain".

PubMed

Södersten, Per

2015-01-01

In the 1930s, Eugen Steinach's group found that estradiol induces lordosis in castrated rats and reduces the threshold dose of testosterone that is necessary for the induction of ejaculation, and that estradiol-treated intact rats display lordosis as well as mounting and ejaculation. The bisexual, estrogen-sensitive male had been demonstrated. Another major, albeit contrasting, discovery was made in the 1950s, when William Young's group reported that male guinea pigs and prenatally testosterone-treated female guinea pigs are relatively insensitive to estrogen when tested for lordosis as adults. Reduced estrogen sensitivity was part of the new concept of organization of the neural tissues mediating the sexual behavior of females into tissues similar to those of males. The importance of neural organization by early androgen stimulation was realized immediately and led to the discovery of a variety of sex differences in the brains of adult animals. By contrast, the importance of the metabolism of testosterone into estrogen in the male was recognized only after a delay. While the finding that males are sensitive to estrogen was based on Bernhard Zondek's discovery in 1934 that testosterone is metabolized into estrogen in males, the finding that males are insensitive to estrogen was based on the hypothesis that testosterone-male sexual behavior is the typical relationship in the male. It is suggested that this difference in theoretical framework explains the discrepancies in some of the reported results.

Integrated molecular analysis indicates undetectable change in DNA damage in mice after continuous irradiation at ~ 400-fold natural background radiation.

PubMed

Olipitz, Werner; Wiktor-Brown, Dominika; Shuga, Joe; Pang, Bo; McFaline, Jose; Lonkar, Pallavi; Thomas, Aline; Mutamba, James T; Greenberger, Joel S; Samson, Leona D; Dedon, Peter C; Yanch, Jacquelyn C; Engelward, Bevin P

2012-08-01

In the event of a nuclear accident, people are exposed to elevated levels of continuous low dose-rate radiation. Nevertheless, most of the literature describes the biological effects of acute radiation. DNA damage and mutations are well established for their carcinogenic effects. We assessed several key markers of DNA damage and DNA damage responses in mice exposed to low dose-rate radiation to reveal potential genotoxic effects associated with low dose-rate radiation. We studied low dose-rate radiation using a variable low dose-rate irradiator consisting of flood phantoms filled with 125Iodine-containing buffer. Mice were exposed to 0.0002 cGy/min (~ 400-fold background radiation) continuously over 5 weeks. We assessed base lesions, micronuclei, homologous recombination (HR; using fluorescent yellow direct repeat mice), and transcript levels for several radiation-sensitive genes. We did not observe any changes in the levels of the DNA nucleobase damage products hypoxanthine, 8-oxo-7,8-dihydroguanine, 1,N6-ethenoadenine, or 3,N4-ethenocytosine above background levels under low dose-rate conditions. The micronucleus assay revealed no evidence that low dose-rate radiation induced DNA fragmentation, and there was no evidence of double strand break-induced HR. Furthermore, low dose-rate radiation did not induce Cdkn1a, Gadd45a, Mdm2, Atm, or Dbd2. Importantly, the same total dose, when delivered acutely, induced micronuclei and transcriptional responses. These results demonstrate in an in vivo animal model that lowering the dose-rate suppresses the potentially deleterious impact of radiation and calls attention to the need for a deeper understanding of the biological impact of low dose-rate radiation.

Daily radionuclide ingestion and internal radiation doses in Aomori prefecture, Japan.

PubMed

Ohtsuka, Yoshihito; Kakiuchi, Hideki; Akata, Naofumi; Takaku, Yuichi; Hisamatsu, Shun'ichi

2013-10-01

To assess internal annual dose in the general public in Aomori Prefecture, Japan, 80 duplicate cooked diet samples, equivalent to the food consumed over a 400-d period by one person, were collected from 100 volunteers in Aomori City and the village of Rokkasho during 2006–2010 and were analyzed for 11 radionuclides. To obtain average rates of ingestion of radionuclides, the volunteers were selected from among office, fisheries, agricultural, and livestock farm workers. Committed effective doses from ingestion of the diet over a 1-y period were calculated from the analytical results and from International Commission on Radiological Protection dose coefficients; for 40K, an internal effective dose rate from the literature was used. Fisheries workers had significantly higher combined internal annual dose than the other workers, possibly because of high rates of ingestion of marine products known to have high 210Po concentrations. The average internal dose rate, weighted by the numbers of households in each worker group in Aomori Prefecture, was estimated at 0.47 mSv y-1. Polonium-210 contributed 49% of this value. The sum of committed effective dose rates for 210Po, 210Pb, 228Ra, and 14C and the effective dose rate of 40K accounted for approximately 99% of the average internal dose rate.

[Dose rate-dependent cellular and molecular effects of ionizing radiation].

PubMed

Przybyszewski, Waldemar M; Wideł, Maria; Szurko, Agnieszka; Maniakowski, Zbigniew

2008-09-11

The aim of radiation therapy is to kill tumor cells while minimizing damage to normal cells. The ultimate effect of radiation can be apoptotic or necrotic cell death as well as cytogenetic damage resulting in genetic instability and/or cell death. The destructive effects of radiation arise from direct and indirect ionization events leading to peroxidation of macromolecules, especially those present in lipid-rich membrane structures as well as chromatin lipids. Lipid peroxidative end-products may damage DNA and proteins. A characteristic feature of radiation-induced peroxidation is an inverse dose-rate effect (IDRE), defined as an increase in the degree of oxidation(at constant absorbed dose) accompanying a lower dose rate. On the other hand, a low dose rate can lead to the accumulation of cells in G2, the radiosensitive phase of the cell cycle since cell cycle control points are not sensitive to low dose rates. Radiation dose rate may potentially be the main factor improving radiotherapy efficacy as well as affecting the intensity of normal tissue and whole-body side effects. A better understanding of dose rate-dependent biological effects may lead to improved therapeutic intervention and limit normal tissue reaction. The study reviews basic biological effects that depend on the dose rate of ionizing radiation.

Dose rate effects on array CCDs exposed by Co-60 γ rays induce saturation output degradation and annealing tests

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

Wang, Zujun, E-mail: wangzujun@nint.ac.cn; Chen, Wei; He, Baoping

The experimental tests of dose rate and annealing effects on array charge-coupled devices (CCDs) are presented. The saturation output voltage (V{sub S}) versus the total dose at the dose rates of 0.01, 0.1, 1.0, 10.0 and 50 rad(Si)/s are compared. Annealing tests are performed to eliminate the time-dependent effects. The V{sub S} degradation levels depend on the dose rates. The V{sub S} degradation mechanism induced by dose rate and annealing effects is analyzed. The V{sub S} at 20 krad(Si) with the dose rate of 0.03 rad(Si)/s are supplemented to assure the degradation curves between the dose rates of 0.1 andmore » 0.01 rad(Si)/s. The CCDs are divided into two groups, with one group biased and the other unbiased during {sup 60}Co γ radiation. The V{sub S} degradation levels of the biased CCDs during radiation are more severe than that of the unbiased CCDs.« less

Reward deficits in behavioural variant frontotemporal dementia include insensitivity to negative stimuli.

PubMed

Perry, David C; Datta, Samir; Sturm, Virginia E; Wood, Kristie A; Zakrzewski, Jessica; Seeley, William W; Miller, Bruce L; Kramer, Joel H; Rosen, Howard J

2017-12-01

During reward processing individuals weigh positive and negative features of a stimulus to determine whether they will pursue or avoid it. Though patients with behavioural variant frontotemporal dementia display changes in their pursuit of rewards, such as food, alcohol, money, and sex, the basis for these shifts is not clearly established. In particular, it is unknown whether patients' behaviour results from excessive focus on rewards, insensitivity to punishment, or to dysfunction in a particular stage of reward processing, such as anticipation, consumption, or action selection. Our goal was to determine the nature of the reward deficit in behavioural variant frontotemporal dementia and its underlying anatomy. We devised a series of tasks involving pleasant, unpleasant, and neutral olfactory stimuli, designed to separate distinct phases of reward processing. In a group of 25 patients with behavioural variant frontotemporal dementia and 21 control subjects, diagnosis by valence interactions revealed that patients with behavioural variant frontotemporal dementia rated unpleasant odours as less aversive than did controls and displayed lower skin conductance responses when anticipating an upcoming aversive odour. Subjective pleasantness ratings and skin conductance responses did not differ between behavioural variant frontotemporal dementia and controls for pleasant or neutral smells. In a task designed to measure the effort subjects would expend to smell or avoid smelling a stimulus, patients with behavioural variant frontotemporal dementia were less motivated, and therefore less successful than control subjects, at avoiding what they preferred not to smell, but had equivalent success at obtaining stimuli they found rewarding. Voxel-based morphometry of patients with behavioural variant frontotemporal dementia revealed that the inability to subjectively differentiate the valence of pleasant and unpleasant odours correlated with atrophy in right ventral mid-insula and right amygdala. High pleasantness ratings of unpleasant stimuli correlated with left dorsal anterior insula and frontal pole atrophy. These findings indicate that insensitivity to negative information may be a key component of the reward-seeking behaviours in behavioural variant frontotemporal dementia, and may relate to degeneration of structures that are involved in representing the emotional salience of sensory information. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Improved growth velocity of a patient with Noonan-like syndrome with loose anagen hair (NS/LAH) without growth hormone deficiency by low-dose growth hormone therapy.

PubMed

Takasawa, Kei; Takishima, Shigeru; Morioka, Chikako; Nishioka, Masato; Ohashi, Hirofumi; Aoki, Yoko; Shimohira, Masayuki; Kashimada, Kenichi; Morio, Tomohiro

2015-10-01

Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM 607721) is caused by a heterozygous c.4A>G mutation in SHOC2. Most cases exhibit both growth hormone deficiency (GHD) and growth hormone insensitivity (GHI) and thus require a high dose of growth hormone (GH) therapy (e.g., 35-40 µg/kg/day). We report on a genetically diagnosed NS/LAH patient manifesting severe short stature (-3.85 SDs) with low serum level of IGF1, 30 ng/ml. The peak levels of GH stimulation tests were within the normal range, and GHI was not observed in the IGF1 generation test. However, with low-dose GH therapy (25 µg/kg/day) for two years, IGF1 level and height were remarkably improved (IGF1: 117 ng/ml, height SDs: -2.20 SDs). Further, catch-up of motor development and improvement of the proportion of extending limbs to trunk were observed (the Developmental Quotient score increased from 68 to 98 points, and the relative sitting height ratio decreased from 0.62 to 0.57). Our results suggest that endocrinological causes for short stature are variable in NS/LAH and that GH therapy should be considered as a possible treatment for delayed development in NS/LAH. © 2015 Wiley Periodicals, Inc.

Measurement of ambient dose equivalent rates by walk survey around Fukushima Dai-ichi Nuclear Power Plant using KURAMA-II until 2016.

PubMed

Andoh, Masaki; Yamamoto, Hideaki; Kanno, Takashi; Saito, Kimiaki

2018-05-17

Ambient dose equivalent rates in various environments related to human lives were measured by walk surveys using the KURAMA-II systems from 2013 to 2016 within an 80-km radius of the Fukushima Dai-ichi Nuclear Power Plant. The dose rate of the locations where the walk survey was performed decreased to about 38% of its initial value in the 42 months from June 2013 to the December 2016, which was beyond that attributable to the physical decay of radiocaesium. The ecological half-life of the slow decreasing component was evaluated to be 4.1 ± 0.2 y. The air dose rates decreased depending on the level of the evacuation areas, and the decrease in the dose rates was slightly larger in populated areas where humans are active. The dose rates as measured by walk surveys exhibited a good correlation with those by car-borne surveys, suggesting that car-borne survey data are reflecting the air dose rates in living environments surrounding roads. The comparison of walk survey data with car-borne survey data indicated that the air dose rate varies largely even within a 100 m square area, and the variation is enhanced by human activities. The dose rates measured by the walk surveys were estimated to be medial of those along roads and those of undisturbed flat ground, and they were found to be decreasing quickly compared with the air dose rate from the flat ground fixed-point measurements. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Characteristics and verification of a car-borne survey system for dose rates in air: KURAMA-II.

PubMed

Tsuda, S; Yoshida, T; Tsutsumi, M; Saito, K

2015-01-01

The car-borne survey system KURAMA-II, developed by the Kyoto University Research Reactor Institute, has been used for air dose rate mapping after the Fukushima Dai-ichi Nuclear Power Plant accident. KURAMA-II consists of a CsI(Tl) scintillation detector, a GPS device, and a control device for data processing. The dose rates monitored by KURAMA-II are based on the G(E) function (spectrum-dose conversion operator), which can precisely calculate dose rates from measured pulse-height distribution even if the energy spectrum changes significantly. The characteristics of KURAMA-II have been investigated with particular consideration to the reliability of the calculated G(E) function, dose rate dependence, statistical fluctuation, angular dependence, and energy dependence. The results indicate that 100 units of KURAMA-II systems have acceptable quality for mass monitoring of dose rates in the environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Immediate effects of 33 to 180 rad/min (60)Co exposure on performance and blood pressure in monkeys. Topical report

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

Bruner, A.

1976-09-01

Four groups of monkeys received 1000 rads (60)Co at 33, 50, 75, or 180 rad/min wholebody irradiation while performing a delayed matching-to-sample task. Systematic dose rate effects were observed on performance and blood pressure within the initial 20 min postirradiation. The incidence and severity of performance decrement (PD) increased with higher dose rate. The appearance of postirradiation hypotension was systematically delayed and its rate of fall prolonged as dose rate was lower. The hypotension likewise appeared less deep with lower dose rate exposure. Based on the calculated cumulative dose absorbed at the time of symptom appearance two coactive thresholds weremore » proposed to exist: a total dose threshold of approximately 300 rads (midbody measurement), and a dose rate threshold of about 25 rad/min.« less

Characterization and prediction of monomer-based dose rate effects in electron-beam polymerization

NASA Astrophysics Data System (ADS)

Schissel, Sage M.; Lapin, Stephen C.; Jessop, Julie L. P.

2017-12-01

Properties of some materials produced by electron-beam (EB) induced polymerization appear dependent upon the rate at which the initiating dose was delivered. However, the magnitude of these dose rate effects (DREs) can vary greatly with different monomer formulations, suggesting DREs are dependent on chemical structure. The relationship among dose, dose rate, conversion, and the glass transition temperature (Tg) of the cured material was explored for an acrylate monomer series. A strong correlation was determined between the DRE magnitude and monomer size, and this correlation may be attributed to chain transfer. Using the Tg shift caused by changes in dose, a preliminary predictive relationship was developed to estimate the magnitude of the Tg DRE, enabling scale-up of process variables for polymers prone to dose rate effects.

Variation of indoor radon concentration and ambient dose equivalent rate in different outdoor and indoor environments.

PubMed

Stojanovska, Zdenka; Boev, Blazo; Zunic, Zora S; Ivanova, Kremena; Ristova, Mimoza; Tsenova, Martina; Ajka, Sorsa; Janevik, Emilija; Taleski, Vaso; Bossew, Peter

2016-05-01

Subject of this study is an investigation of the variations of indoor radon concentration and ambient dose equivalent rate in outdoor and indoor environments of 40 dwellings, 31 elementary schools and five kindergartens. The buildings are located in three municipalities of two, geologically different, areas of the Republic of Macedonia. Indoor radon concentrations were measured by nuclear track detectors, deployed in the most occupied room of the building, between June 2013 and May 2014. During the deploying campaign, indoor and outdoor ambient dose equivalent rates were measured simultaneously at the same location. It appeared that the measured values varied from 22 to 990 Bq/m(3) for indoor radon concentrations, from 50 to 195 nSv/h for outdoor ambient dose equivalent rates, and from 38 to 184 nSv/h for indoor ambient dose equivalent rates. The geometric mean value of indoor to outdoor ambient dose equivalent rates was found to be 0.88, i.e. the outdoor ambient dose equivalent rates were on average higher than the indoor ambient dose equivalent rates. All measured can reasonably well be described by log-normal distributions. A detailed statistical analysis of factors which influence the measured quantities is reported.

Transcriptional Analysis of Four Family 4 P450s in a Puerto Rico Strain of Aedes aegypti (Diptera: Culicidae) Compared With an Orlando Strain and Their Possible Functional Roles in Permethrin Resistance

DTIC Science & Technology

2014-05-01

melanogaster expressing CYP4D24, CYP4H29, CYP4J15v1, and CYP4H33 had a survival rate of 60.0 6.7, 29.0 4.4, 64.4 9.7, and 11.0 4.4...CYP4D24 and CYP4H29 had a survival rate of 37.8 4.4 and 2.2 2.2%, respectively. Taken together, our results suggest that CYP4D24 might play an...mechanisms, including target site insensitivity, reduced penetration rate , and met- abolic detoxiÞcation. In the case of metabolic detox- iÞcation

Selective Catalytic Combustion Sensors for Reactive Organic Analysis

NASA Technical Reports Server (NTRS)

Innes, W. B.

1971-01-01

Sensors involving a vanadia-alumina catalyst bed-thermocouple assembly satisfy requirements for simple, reproducible and rapid continuous analysis or reactive organics. Responses generally increase with temperature to 400 C and increase to a maximum with flow rate/catalyst volume. Selectivity decreases with temperature. Response time decreases with flow rate and increases with catalyst volume. At chosen optimum conditions calculated response which is additive and linear agrees better with photochemical reactivity than other methods for various automotive sources, and response to vehicle exhaust is insensitive to flow rate. Application to measurement of total reactive organics in vehicle exhaust as well as for gas chromatography detection illustrate utility. The approach appears generally applicable to high thermal effect reactions involving first order kinetics.

Digital phase-lock loop

NASA Technical Reports Server (NTRS)

Thomas, Jr., Jess B. (Inventor)

1991-01-01

An improved digital phase lock loop incorporates several distinctive features that attain better performance at high loop gain and better phase accuracy. These features include: phase feedback to a number-controlled oscillator in addition to phase rate; analytical tracking of phase (both integer and fractional cycles); an amplitude-insensitive phase extractor; a more accurate method for extracting measured phase; a method for changing loop gain during a track without loss of lock; and a method for avoiding loss of sampled data during computation delay, while maintaining excellent tracking performance. The advantages of using phase and phase-rate feedback are demonstrated by comparing performance with that of rate-only feedback. Extraction of phase by the method of modeling provides accurate phase measurements even when the number-controlled oscillator phase is discontinuously updated.

Micronucleus induction in Vicia faba roots. Part 1. Absence of dose-rate, fractionation, and oxygen effect at low doses of low LET radiations.

PubMed

Marshall, I; Bianchi, M

1983-08-01

Micronucleus indication in Vicia faba roots has been evaluated after irradiation with 60Co gamma-rays. The dependence of the damage on dose, dose rate, fractionation, and oxygen has been studied. The best fit to the experimental data in the dose region between 7 and 190 cGy is represented, for single-dose exposures, by a linear + quadratic relationship. In the low-dose region, between 7 and 20 cGy, where the linear dose dependence is dominant, no dose-rate, fractionation, or oxygen effect could be observed. These effects were, however, present in the high-dose region, where the quadratic dependence is dominant.

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

Li, Xinhua; Zhang, Da; Liu, Bob, E-mail: bliu7@mgh.harvard.edu

Purpose: The knowledge of longitudinal dose distribution provides the most direct view of the accumulated dose in computed tomography (CT) scanning. The purpose of this work was to perform a comprehensive study of dose distribution width and energy absorption with a wide range of subject sizes and beam irradiated lengths. Methods: Cumulative dose distribution along the z-axis was calculated based on the previously published CT dose equilibration data by Li, Zhang, and Liu [Med. Phys. 40, 031903 (10pp.) (2013)] and a mechanism for computing dose on axial lines by Li, Zhang, and Liu [Med. Phys. 39, 5347–5352 (2012)]. Full widthmore » at half maximum (FWHM), full width at tenth maximum (FWTM), the total energy (E) absorbed in a small cylinder of unit mass per centimeter square about the central or peripheral axis, and the energy (E{sub in}) absorbed inside irradiated length (L) were subsequently extracted from the dose distribution. Results: Extensive results of FWHM, FWTM, and E{sub in}/E were presented on the central and peripheral axes of infinitely long PMMA (diameters 6–50 cm) and water (diameters 6–55 cm) cylinders with L < 100 cm. FWHM was greater than the primary beam width only on the central axes of large phantoms and also with L ranging from a few centimeter to about 33 cm. FWTM generally increased with phantom diameter, and could be up to 32 cm longer than irradiated length, depending on L, phantom diameter and axis, but was insensitive to phantom material (PMMA or water). E{sub in}/E increased with L and asymptotically approached unity for large L. As phantom diameter increased, E{sub in}/E generally decreased, but asymptotically approached constant levels on the peripheral axes of large phantoms. A heuristic explanation of dose distribution width results was presented. Conclusions: This study enables the reader to gain a comprehensive view of dose distribution width and energy absorption and provides useful data for estimating doses to organs inside or beyond the irradiated region. The dose length product (DLP) presented by CT scanners is equal to neither E nor E{sub in}. Both E and E{sub in} can be evaluated using the equations and results presented in this paper and are robust with both constant and variable tube current scanning techniques.« less

Low and high dose rate heavy ion radiation-induced intestinal and colonic tumorigenesis in APC1638N/+ mice

NASA Astrophysics Data System (ADS)

Suman, Shubhankar; Kumar, Santosh; Moon, Bo-Hyun; Fornace, Albert J.; Datta, Kamal

2017-05-01

Ionizing radiation (IR) is a recognized risk factor for colorectal cancer (CRC) and astronauts undertaking long duration space missions are expected to receive IR doses in excess of permissible limits with implications for colorectal carcinogenesis. Exposure to IR in outer space occurs at low doses and dose rates, and energetic heavy ions due to their high linear energy transfer (high-LET) characteristics remain a major concern for CRC risk in astronauts. Previously, we have demonstrated that intestinal tumorigenesis in a mouse model (APC1638N/+) of human colorectal cancer was significantly higher after exposure to high dose rate energetic heavy ions relative to low-LET γ radiation. The purpose of the current study was to compare intestinal tumorigenesis in APC1638N/+ mice after exposure to energetic heavy ions at high (50 cGy/min) and relatively low (0.33 cGy/min) dose rate. Male and female mice (6-8 weeks old) were exposed to either 10 or 50 cGy of 28Si (energy: 300 MeV/n; LET: 70 keV/μm) or 56Fe (energy: 1000 MeV/n; LET: 148 keV/μm) ions at NASA Space Radiation Laboratory in Brookhaven National Laboratory. Mice (n = 20 mice/group) were euthanized and intestinal and colon tumor frequency and size were counted 150 days after radiation exposure. Intestinal tumorigenesis in male mice exposed to 56Fe was similar for high and low dose rate exposures. Although male mice showed a decreasing trend at low dose rate relative to high dose rate exposures, the differences in tumor frequency between the two types of exposures were not statistically significant after 28Si radiation. In female mice, intestinal tumor frequency was similar for both radiation type and dose rates tested. In both male and female mice intestinal tumor size was not different after high and low dose rate radiation exposures. Colon tumor frequency in male and female mice after high and low dose rate energetic heavy ions was also not significantly different. In conclusion, intestinal and colonic tumor frequency and size was similar irrespective of energetic heavy ion radiation dose rate suggesting that carcinogenic potential of energetic heavy ions is independent of dose rate.

Biodegradation of insensitive munition formulations IMX101 and IMX104 in surface soils.

PubMed

Indest, Karl J; Hancock, Dawn E; Crocker, Fiona H; Eberly, Jed O; Jung, Carina M; Blakeney, Gary A; Brame, Jon; Chappell, Mark A

2017-07-01

The biodegradation potential of insensitive munition melt cast formulations IMX101 and IMX104 was investigated in two unamended training range soils under aerobic and anaerobic growth conditions. Changes in community profiles in soil microcosms were monitored via high-throughput 16S rRNA sequencing over the course of the experiments to infer key microbial phylotypes that may be linked to IMX degradation. Complete anaerobic biotransformation occurred for IMX101 and IMX104 constituents 2,4-dinitroanisole (DNAN) and 3-nitro-1,2,4-triazol-5-one during the 30-day incubation period with Camp Shelby (CS) soil. By comparison, soil from Umatilla chemical depot demonstrated incomplete DNAN degradation with reduced transformation rates for both IMX101 and IMX104. Aerobic soil microcosms for both soils demonstrated reduced transformation rates compared to anaerobic degradation for all IMX constituents with DNAN the most susceptible to biotransformation by CS soil. Overall, IMX constituents hexahydro-1,3,5-trinitro-1,3,5-triazine and 1-nitroguanidine did not undergo significant transformation. In CS soil, organisms that have been associated with explosives degradation, namely members of the Burkholderiaceae, Bacillaceae, and Paenibacillaceae phylotypes increased significantly in anaerobic treatments whereas Sphingomonadaceae increased significantly in aerobic treatments. Collectively, these data may be used to populate fate and transport models to provide more accurate estimates for assessing environmental costs associated with release of IMX101 and IMX104.

Kinesin-5–dependent Poleward Flux and Spindle Length Control in Drosophila Embryo Mitosis

PubMed Central

Brust-Mascher, Ingrid; Sommi, Patrizia; Cheerambathur, Dhanya K.

2009-01-01

We used antibody microinjection and genetic manipulations to dissect the various roles of the homotetrameric kinesin-5, KLP61F, in astral, centrosome-controlled Drosophila embryo spindles and to test the hypothesis that it slides apart interpolar (ip) microtubules (MT), thereby controlling poleward flux and spindle length. In wild-type and Ncd null mutant embryos, anti-KLP61F dissociated the motor from spindles, producing a spatial gradient in the KLP61F content of different spindles, which was visible in KLP61F-GFP transgenic embryos. The resulting mitotic defects, supported by gene dosage experiments and time-lapse microscopy of living klp61f mutants, reveal that, after NEB, KLP61F drives persistent MT bundling and the outward sliding of antiparallel MTs, thereby contributing to several processes that all appear insensitive to cortical disruption. KLP61F activity contributes to the poleward flux of both ipMTs and kinetochore MTs and to the length of the metaphase spindle. KLP61F activity maintains the prometaphase spindle by antagonizing Ncd and another unknown force-generator and drives anaphase B, although the rate of spindle elongation is relatively insensitive to the motor's concentration. Finally, KLP61F activity contributes to normal chromosome congression, kinetochore spacing, and anaphase A rates. Thus, a KLP61F-driven sliding filament mechanism contributes to multiple aspects of mitosis in this system. PMID:19158379

Integrative response of plant mitochondrial electron transport chain to nitrogen source.

PubMed

Hachiya, Takushi; Noguchi, Ko

2011-02-01

Nitrogen (N) availability is widely known as a determinant of plant growth and respiration rate. However, less attention has been paid to the effect of the type of N source (nitrate, nitrite or ammonium) on the respiratory system. This review summarizes the latest findings on this topic, with an emphasis on the effect of ammonium and nitric oxide (NO) on the respiratory system, and the physiological role of alternative oxidase (AOX). First, concentrated ammonium has been found to increase plant respiration rate (ammonium-dependent respiratory increase, ARI). We will introduce two hypotheses to explain ARI, futile ammonium cycling and excess reducing equivalents, and verify the validity of each hypothesis. We suggest that these two hypotheses are not necessarily mutually exclusive. Second, gene expression of AOX is suppressed when N is predominately available as nitrate instead of ammonium. We will discuss possible signaling pathways leading to this expression pattern. Third, while AOX expression is induced by NO, AOX activity itself is insensitive to NO. In contrast, activity of cytochrome c oxidase (COX) is sensitive to NO. We outline the NO production pathway, focusing on nitrite-dependent NO production, and discuss the physiological significance of the fact that AOX activity is insensitive to NO. Finally, this review aims to build an integrated scheme of the respiratory response to the type of N source, considering leaves in high light conditions or hypoxic roots.

Eating high fat chow increases the sensitivity of rats to quinpirole-induced discriminative stimulus effects and yawning

PubMed Central

Baladi, Michelle G; France, Charles P

2010-01-01

Discriminative stimulus effects of directly-acting dopamine receptor agonists (e.g. quinpirole) appear to be mediated by D3 receptors in free-feeding rats. Free access to high fat chow increases sensitivity to quinpirole-induced yawning and the current study examined whether eating high fat chow increases sensitivity to the discriminative stimulus effects of quinpirole. Five rats discriminated between 0.032 mg/kg quinpirole and vehicle while responding under a continuous reinforcement schedule of stimulus shock termination. When rats had free access to high fat chow (discrimination training was suspended), the quinpirole discrimination dose-response curve shifted leftward, possibly indicating enhanced sensitivity at D3 receptors. In the same rats, both the ascending (mediated by D3 receptors) and descending (mediated by D2 receptors) limbs of the dose- response curve for quinpirole-induced yawning shifted leftward. When rats had free access to a standard chow (discrimination training was suspended), the quinpirole discrimination and yawning dose-response curves did not change. Together with published data showing that the discriminative stimulus effects of quinpirole in free- feeding rats are mediated by D3 receptors and the insensitivity of this effect of quinpirole to food restriction (shown to increase sensitivity to D2 but not D3-mediated effects), these results suggest that the leftward shift of the discrimination dose-response curve when rats eat high fat chow is likely due to enhanced sensitivity at D3 receptors. Thus, eating high fat food enhances drug effects in a manner that might impact clinical effects of drugs or vulnerability to drug abuse. PMID:20729718

Eating high-fat chow increases the sensitivity of rats to quinpirole-induced discriminative stimulus effects and yawning.

PubMed

Baladi, Michelle G; France, Charles P

2010-10-01

Discriminative stimulus effects of direct acting dopamine receptor agonists (e.g. quinpirole) appear to be mediated by D3 receptors in free-feeding rats. Free access to high-fat chow increases sensitivity to quinpirole-induced yawning, and this study examined whether eating high-fat chow increases sensitivity to the discriminative stimulus effects of quinpirole. Five rats discriminated between 0.032 mg/kg quinpirole and vehicle while responding under a continuous reinforcement schedule of stimulus shock termination. When rats had free access to high-fat chow (discrimination training was suspended), the quinpirole discrimination dose-response curve shifted leftward, possibly indicating enhanced sensitivity at D3 receptors. In the same rats, both the ascending (mediated by D3 receptors) and descending (mediated by D2 receptors) limbs of the dose-response curve for quinpirole-induced yawning shifted leftward. When rats had free access to a standard chow (discrimination training was suspended), the quinpirole discrimination and yawning dose-response curves did not change. Together with published data showing that the discriminative stimulus effects of quinpirole in free-feeding rats are mediated by D3 receptors and the insensitivity of this effect of quinpirole to food restriction (shown to increase sensitivity to D2 but not D3-mediated effects), these results suggest that the leftward shift of the discrimination dose-response curve when rats eat high-fat chow is likely because of enhanced sensitivity at D3 receptors. Thus, eating high-fat food enhances drug effects in a manner that might impact clinical effects of drugs or vulnerability to drug abuse.

Nonmuscarinic neurotoxicity of oxotremorine.

PubMed

Witkin, J M; Alvarado-Garcia, R; Lee, M A; Witkin, K M

1987-04-01

The ability of various treatments to prevent peripheral parasympathetic actions, central effects and lethality of the muscarinic agonist oxotremorine was studied in rats. The percentage of animals exhibiting effects of oxotremorine was dose and time dependent. The ED50 for producing lacrimation, salivation, tremor, convulsions and death was 2.5, 1.3, 1.6, 3.2 and 8.3 mg/kg i.p., respectively. Pretreatment with 5 mg/kg of atropine completely prevented all observable effects of oxotremorine at doses of 5 mg/kg and below. Doses of oxotremorine in excess of 5 mg/kg produced tremor, generalized clonic convulsions and death that could not be prevented by atropine when given at up to 160 mg/kg; lacrimation and salivation were not present in atropine-treated rats. In the presence of 40 mg/kg of atropine, ED50 values for oxotremorine were shifted more than 12-fold for lacrimation, salivation and tremor, whereas convulsions and death were maximally altered by a factor of 2. Scopolamine, benactyzine and benztropine were also incapable of completely preventing tremor, convulsions and death induced by 10 or 15 mg/kg of oxotremorine. Atropine methyl nitrate had effects comparable to atropine sulfate on lacrimation, salivation and lethality induced by oxotremorine (10 or 15 mg/kg) but had no effect on tremor or convulsions. A similar profile of atropine-insensitive effects was produced by pilocarpine and arecoline. Doses of diazepam 4 times higher (4 mg/kg) than necessary to prevent tonic-clonic convulsions induced by pentylenetetrazol were ineffective against tremor, convulsions or death produced by oxotremorine (10 or 15 mg/kg) unless given in conjunction with atropine.(ABSTRACT TRUNCATED AT 250 WORDS)

Sensitivity to psychostimulants in mice bred for high and low stimulation to methamphetamine.

PubMed

Kamens, H M; Burkhart-Kasch, S; McKinnon, C S; Li, N; Reed, C; Phillips, T J

2005-03-01

Methamphetamine (MA) and cocaine induce behavioral effects primarily through modulation of dopamine neurotransmission. However, the genetic regulation of sensitivity to these two drugs may be similar or disparate. Using selective breeding, lines of mice were produced with extreme sensitivity (high MA activation; HMACT) and insensitivity (low MA activation; LMACT) to the locomotor stimulant effects of acute MA treatment. Studies were performed to determine whether there is pleiotropic genetic influence on sensitivity to the locomotor stimulant effect of MA and to other MA- and cocaine-related behaviors. The HMACT line exhibited more locomotor stimulation in response to several doses of MA and cocaine, compared to the LMACT line. Both lines exhibited locomotor sensitization to 2 mg/kg of MA and 10 mg/kg of cocaine; the magnitude of sensitization was similar in the two lines. However, the lines differed in the magnitude of sensitization to a 1 mg/kg dose of MA, a dose that did not produce a ceiling effect that may confound interpretation of studies using higher doses. The LMACT line consumed more MA and cocaine in a two-bottle choice drinking paradigm; the lines consumed similar amounts of saccharin and quinine, although the HMACT line exhibited slightly elevated preference for a low concentration of saccharin. These results suggest that some genes that influence sensitivity to the acute locomotor stimulant effect of MA have a pleiotropic influence on the magnitude of behavioral sensitization to MA and sensitivity to the stimulant effects of cocaine. Further, extreme sensitivity to MA may protect against MA and cocaine self-administration.

Genetics Home Reference: androgen insensitivity syndrome

MedlinePlus

... particular ethnic groups? Genetic Changes Mutations in the AR gene cause androgen insensitivity syndrome . This gene provides ... hair growth and sex drive. Mutations in the AR gene prevent androgen receptors from working properly, which ...

Insensitive explosive composition of halogenated copolymer and triaminotrinitrobenzene

DOEpatents

Benziger, Theodore M.

1976-01-01

A highly insensitive and heat resistant plastic-bonded explosive containing 90 wt % triaminotrinitrobenzene and 10 wt % of a fully saturated copolymer of chlorotrifluoroethylene and vinylidene fluoride is readily manufactured by the slurry process.

Angular-dependent polarization-insensitive filter fashioned with zero-contrast grating.

PubMed

Gao, Xumin; Wu, Tong; Xu, Yin; Li, Xin; Bai, Dan; Zhu, Gangyi; Zhu, Hongbo; Wang, Yongjin

2015-06-15

We report here an angular-dependent polarization-insensitive filter fashioned with a free-standing zero-contrast grating (ZCG), which is implemented on an HfO(2)/Silicon platform. The spectral characteristics are investigated by rigorous coupled-wave analysis method and measured on angular-resolved micro-reflectance system. The proposed ZCG structure experimentally shows that the polarization-insensitive resonances occur at 595nm for the incidence angle θ of 12.8° and 500nm for the incidence angle θ of 14.2°. When the incident light is normal to the grating surface, the ZCG device generates yellow and red colors for p- and s-polarization, respectively. The experimental results are in good agreement with the simulations, which indicate that the free-standing ZCG device is promising for polarization-insensitive filter and polarization-controlled tunable color filter.

Dose and dose rate extrapolation factors for malignant and non-malignant health endpoints after exposure to gamma and neutron radiation.

PubMed

Tran, Van; Little, Mark P

2017-11-01

Murine experiments were conducted at the JANUS reactor in Argonne National Laboratory from 1970 to 1992 to study the effect of acute and protracted radiation dose from gamma rays and fission neutron whole body exposure. The present study reports the reanalysis of the JANUS data on 36,718 mice, of which 16,973 mice were irradiated with neutrons, 13,638 were irradiated with gamma rays, and 6107 were controls. Mice were mostly Mus musculus, but one experiment used Peromyscus leucopus. For both types of radiation exposure, a Cox proportional hazards model was used, using age as timescale, and stratifying on sex and experiment. The optimal model was one with linear and quadratic terms in cumulative lagged dose, with adjustments to both linear and quadratic dose terms for low-dose rate irradiation (<5 mGy/h) and with adjustments to the dose for age at exposure and sex. After gamma ray exposure there is significant non-linearity (generally with upward curvature) for all tumours, lymphoreticular, respiratory, connective tissue and gastrointestinal tumours, also for all non-tumour, other non-tumour, non-malignant pulmonary and non-malignant renal diseases (p < 0.001). Associated with this the low-dose extrapolation factor, measuring the overestimation in low-dose risk resulting from linear extrapolation is significantly elevated for lymphoreticular tumours 1.16 (95% CI 1.06, 1.31), elevated also for a number of non-malignant endpoints, specifically all non-tumour diseases, 1.63 (95% CI 1.43, 2.00), non-malignant pulmonary disease, 1.70 (95% CI 1.17, 2.76) and other non-tumour diseases, 1.47 (95% CI 1.29, 1.82). However, for a rather larger group of malignant endpoints the low-dose extrapolation factor is significantly less than 1 (implying downward curvature), with central estimates generally ranging from 0.2 to 0.8, in particular for tumours of the respiratory system, vasculature, ovary, kidney/urinary bladder and testis. For neutron exposure most endpoints, malignant and non-malignant, show downward curvature in the dose response, and for most endpoints this is statistically significant (p < 0.05). Associated with this, the low-dose extrapolation factor associated with neutron exposure is generally statistically significantly less than 1 for most malignant and non-malignant endpoints, with central estimates mostly in the range 0.1-0.9. In contrast to the situation at higher dose rates, there are statistically non-significant decreases of risk per unit dose at gamma dose rates of less than or equal to 5 mGy/h for most malignant endpoints, and generally non-significant increases in risk per unit dose at gamma dose rates ≤5 mGy/h for most non-malignant endpoints. Associated with this, the dose-rate extrapolation factor, the ratio of high dose-rate to low dose-rate (≤5 mGy/h) gamma dose response slopes, for many tumour sites is in the range 1.2-2.3, albeit not statistically significantly elevated from 1, while for most non-malignant endpoints the gamma dose-rate extrapolation factor is less than 1, with most estimates in the range 0.2-0.8. After neutron exposure there are non-significant indications of lower risk per unit dose at dose rates ≤5 mGy/h compared to higher dose rates for most malignant endpoints, and for all tumours (p = 0.001), and respiratory tumours (p = 0.007) this reduction is conventionally statistically significant; for most non-malignant outcomes risks per unit dose non-significantly increase at lower dose rates. Associated with this, the neutron dose-rate extrapolation factor is less than 1 for most malignant and non-malignant endpoints, in many cases statistically significantly so, with central estimates mostly in the range 0.0-0.2.

A Non-Destructive and Direction-Insensitive Method Using a Strain Sensor and Two Single Axis Angle Sensors for Evaluating Corn Stalk Lodging Resistance.

PubMed

Guo, Qingqian; Chen, Ruipeng; Sun, Xiaoquan; Jiang, Min; Sun, Haifeng; Wang, Shun; Ma, Liuzheng; Yang, Yatao; Hu, Jiandong

2018-06-06

Corn stalk lodging is caused by different factors, including severe wind storms, stalk cannibalization, and stalk rots, and it leads to yield loss. Determining how to rapidly evaluate corn lodging resistance will assist scientists in the field of crop breeding to understand the contributing factors in managing the moisture, chemical fertilizer, and weather conditions for corn growing. This study proposes a non-destructive and direction-insensitive method, using a strain sensor and two single axis angle sensors to measure the corn stalk lodging resistance in the field. An equivalent force whose direction is perpendicular to the stalk is utilized to evaluate the corn lodging properties when a pull force is applied on the corn stalk. A novel measurement device is designed to obtain the equivalent force with the coefficient of variation (CV) of 4.85%. Five corn varieties with two different planting densities are arranged to conduct the experiment using the novel measurement device. The experimental results show that the maximum equivalent force could reach up to 44 N. A strong relationship with the square of the correlation coefficient of 0.88 was obtained between the maximum equivalent forces and the corn field’s stalk lodging rates. Moreover, the stalk lodging angles corresponding to the different pull forces over a measurement time of 20 s shift monotonically along the equivalent forces. Thus, the non-destructive and direction-insensitive method is an excellent tool for rapid analysis of stalk lodging resistance in corn, providing critical information on in-situ lodging dynamics.

Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines

NASA Technical Reports Server (NTRS)

Gridley, D. S.; Pecaut, M. J.; Miller, G. M.; Moyers, M. F.; Nelson, G. A.

2001-01-01

The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p < 0.05). Basal proliferation of leukocytes in the blood and spleen increased significantly with increasing dose (p < 0.05). Significant dose rate effects were observed only in thrombocyte counts. Plasma levels of transforming growth factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.

Object Kinetic Monte Carlo Simulations of Radiation Damage In Bulk Tungsten

NASA Astrophysics Data System (ADS)

Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard; Roche, Kenneth; Kurtz, Richard; Wirth, Brian

2015-11-01

Results are presented for the evolution of radiation damage in bulk tungsten investigated using the object KMC simulation tool, KSOME, as a function of dose, dose rate and primary knock-on atom (PKA) energies in the range of 10 to 100 keV, at temperatures of 300, 1025 and 2050 K. At 300 K, the number density of vacancies changes minimally with dose rate while the number density of vacancy clusters slightly decreases with dose rate indicating that larger clusters are formed at higher dose rates. Although the average vacancy cluster size increases slightly, the vast majority exists as mono-vacancies. At 1025 K void lattice formation was observed at all dose rates for cascades below 60 keV and at lower dose rates for higher PKA energies. After the appearance of initial features of the void lattice, vacancy cluster density increased minimally while the average vacancy cluster size increases rapidly with dose. At 2050 K, no accumulation of defects was observed over a broad range of dose rates for all PKA energies studied in this work. Further comparisons of results of irradiation simulations at various dose rates and PKA spectra, representative of the High Flux Isotope Reactor and future fusion relevant irradiation facilities will be discussed. The U.S. Department of Energy, Office of Fusion Energy Sciences (FES) and Office of Advanced Scientific Computing Research (ASCR) has supported this study through the SciDAC-3 program.

Effects of gamma irradiation dose-rate on sterile male Aedesaegypti

NASA Astrophysics Data System (ADS)

Ernawan, Beni; Tambunan, Usman Sumo Friend; Sugoro, Irawan; Sasmita, Hadian Iman

2017-06-01

Aedesaegypti is the most important vector for dengue, yellow fever and Zika viruses. Considering its medical importance, vector population control program utilizing radiation-based sterile insect technique (SIT) is one of the potential methods for preventing and limiting the dispersal of these viruses. The present study was undertaken to evaluate the dose-rates effects of γ-sterilization on quality parameters of sterile males. Males Ae.aegypti at the pupal stage were sterilized by applying 70 Gyγ-rays in varies dose-rates, i.e. 0 (control), 300, 600, 900, 1200 and 1500Gy/h utilizing panoramic irradiator. Adult males that emerged from the pupal stage were assessed for their quality parameters, which are the percentage of emergence, longevity, sterility and mating competitiveness. The results herein indicate that there was no major effect of dose-rate on the percentage of emergence, the data showedthat there were no differences between irradiated males compared with control. Generally, the longevity of irradiated males was lower compared to control. The data also demonstrated that longevity was significantly increased at the dose-rate from 300 to 900Gy/h, then decreased at the dose-rate 900 to 1500 Gy/h. Sterility of irradiated maleswas significantly different compared to control, while there was no significantly different at dose rate 300 to 1500 Gy/h. Mating competitiveness of irradiated males was increased at the dose rate from 300 to 1200 Gy/h, then the value was decreased significantly at the dose rate 1500 Gy/h. The dose-rate effects of γ-sterilization were discussed in the context genetic vector control, in particular, the SIT. The results give information and contribute to better understanding towards γ-sterilization optimization and quality parameters of sterile male Ae. aegypti on SIT methods.

CT image electron density quantification in regions with metal implants: implications for radiotherapy treatment planning

NASA Astrophysics Data System (ADS)

Jechel, Christopher Alexander

In radiotherapy planning, computed tomography (CT) images are used to quantify the electron density of tissues and provide spatial anatomical information. Treatment planning systems use these data to calculate the expected spatial distribution of absorbed dose in a patient. CT imaging is complicated by the presence of metal implants which cause increased image noise, produce artifacts throughout the image and can exceed the available range of CT number values within the implant, perturbing electron density estimates in the image. Furthermore, current dose calculation algorithms do not accurately model radiation transport at metal-tissue interfaces. Combined, these issues adversely affect the accuracy of dose calculations in the vicinity of metal implants. As the number of patients with orthopedic and dental implants grows, so does the need to deliver safe and effective radiotherapy treatments in the presence of implants. The Medical Physics group at the Cancer Centre of Southeastern Ontario and Queen's University has developed a Cobalt-60 CT system that is relatively insensitive to metal artifacts due to the high energy, nearly monoenergetic Cobalt-60 photon beam. Kilovoltage CT (kVCT) images, including images corrected using a commercial metal artifact reduction tool, were compared to Cobalt-60 CT images throughout the treatment planning process, from initial imaging through to dose calculation. An effective metal artifact reduction algorithm was also implemented for the Cobalt-60 CT system. Electron density maps derived from the same kVCT and Cobalt-60 CT images indicated the impact of image artifacts on estimates of photon attenuation for treatment planning applications. Measurements showed that truncation of CT number data in kVCT images produced significant mischaracterization of the electron density of metals. Dose measurements downstream of metal inserts in a water phantom were compared to dose data calculated using CT images from kVCT and Cobalt-60 systems with and without artifact correction. The superior accuracy of electron density data derived from Cobalt-60 images compared to kVCT images produced calculated dose with far better agreement with measured results. These results indicated that dose calculation errors from metal image artifacts are primarily due to misrepresentation of electron density within metals rather than artifacts surrounding the implants.

Dose rate dependence for different dosimeters and detectors: TLD, OSL, EBT films, and diamond detectors.

PubMed

Karsch, L; Beyreuther, E; Burris-Mog, T; Kraft, S; Richter, C; Zeil, K; Pawelke, J

2012-05-01

The use of laser accelerators in radiation therapy can perhaps increase the low number of proton and ion therapy facilities in some years due to the low investment costs and small size. The laser-based acceleration technology leads to a very high peak dose rate of about 10(11) Gy∕s. A first dosimetric task is the evaluation of dose rate dependence of clinical dosimeters and other detectors. The measurements were done at ELBE, a superconductive linear electron accelerator which generates electron pulses with 5 ps length at 20 MeV. The different dose rates are reached by adjusting the number of electrons in one beam pulse. Three clinical dosimeters (TLD, OSL, and EBT radiochromic films) were irradiated with four different dose rates and nearly the same dose. A faraday cup, an integrating current transformer, and an ionization chamber were used to control the particle flux on the dosimeters. Furthermore two diamond detectors were tested. The dosimeters are dose rate independent up to 4●10(9) Gy∕s within 2% (OSL and TLD) and up to 15●10(9) Gy∕s within 5% (EBT films). The diamond detectors show strong dose rate dependence. TLD, OSL dosimeters, and EBT films are suitable for pulsed beams with a very high pulse dose rate like laser accelerated particle beams.

Dose rate dependence for different dosimeters and detectors: TLD, OSL, EBT films, and diamond detectors

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

Karsch, L.; Beyreuther, E.; Burris-Mog, T.

Purpose: The use of laser accelerators in radiation therapy can perhaps increase the low number of proton and ion therapy facilities in some years due to the low investment costs and small size. The laser-based acceleration technology leads to a very high peak dose rate of about 10{sup 11} Gy/s. A first dosimetric task is the evaluation of dose rate dependence of clinical dosimeters and other detectors. Methods: The measurements were done at ELBE, a superconductive linear electron accelerator which generates electron pulses with 5 ps length at 20 MeV. The different dose rates are reached by adjusting the numbermore » of electrons in one beam pulse. Three clinical dosimeters (TLD, OSL, and EBT radiochromic films) were irradiated with four different dose rates and nearly the same dose. A faraday cup, an integrating current transformer, and an ionization chamber were used to control the particle flux on the dosimeters. Furthermore two diamond detectors were tested. Results: The dosimeters are dose rate independent up to 410{sup 9} Gy/s within 2% (OSL and TLD) and up to 1510{sup 9} Gy/s within 5% (EBT films). The diamond detectors show strong dose rate dependence. Conclusions: TLD, OSL dosimeters, and EBT films are suitable for pulsed beams with a very high pulse dose rate like laser accelerated particle beams.« less

DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1.

PubMed

Ogitani, Yusuke; Aida, Tetsuo; Hagihara, Katsunobu; Yamaguchi, Junko; Ishii, Chiaki; Harada, Naoya; Soma, Masako; Okamoto, Hiromi; Oitate, Masataka; Arakawa, Shingo; Hirai, Takehiro; Atsumi, Ryo; Nakada, Takashi; Hayakawa, Ichiro; Abe, Yuki; Agatsuma, Toshinori

2016-10-15

An anti-HER2 antibody-drug conjugate with a novel topoisomerase I inhibitor, DS-8201a, was generated as a new antitumor drug candidate, and its preclinical pharmacologic profile was assessed. In vitro and in vivo pharmacologic activities of DS-8201a were evaluated and compared with T-DM1 in several HER2-positive cell lines and patient-derived xenograft (PDX) models. The mechanism of action for the efficacy was also evaluated. Pharmacokinetics in cynomolgus monkeys and the safety profiles in rats and cynomolgus monkeys were assessed. DS-8201a exhibited a HER2 expression-dependent cell growth-inhibitory activity and induced tumor regression with a single dosing at more than 1 mg/kg in a HER2-positive gastric cancer NCI-N87 model. Binding activity to HER2 and ADCC activity of DS-8201a were comparable with unconjugated anti-HER2 antibody. DS-8201a also showed an inhibitory activity to Akt phosphorylation. DS-8201a induced phosphorylation of Chk1 and Histone H2A.X, the markers of DNA damage. Pharmacokinetics and safety profiles of DS-8201a were favorable and the highest non-severely toxic dose was 30 mg/kg in cynomolgus monkeys, supporting DS-8201a as being well tolerated in humans. DS-8201a was effective in a T-DM1-insensitive PDX model with high HER2 expression. DS-8201a, but not T-DM1, demonstrated antitumor efficacy against several breast cancer PDX models with low HER2 expression. DS-8201a exhibited a potent antitumor activity in a broad selection of HER2-positive models and favorable pharmacokinetics and safety profiles. The results demonstrate that DS-8201a will be a valuable therapy with a great potential to respond to T-DM1-insensitive HER2-positive cancers and low HER2-expressing cancers. Clin Cancer Res; 22(20); 5097-108. ©2016 AACR. ©2016 American Association for Cancer Research.

Maximum dose rate is a determinant of hypothyroidism after 131I therapy of Graves' disease but the total thyroid absorbed dose is not.

PubMed

Krohn, Thomas; Hänscheid, Heribert; Müller, Berthold; Behrendt, Florian F; Heinzel, Alexander; Mottaghy, Felix M; Verburg, Frederik A

2014-11-01

The determinants of successful (131)I therapy of Graves' disease (GD) are unclear. To relate dosimetry parameters to outcome of therapy to identify significant determinants eu- and/or hypothyroidism after (131)I therapy in patients with GD. A retrospective study in which 206 Patients with GD treated in University Hospital between November 1999 and January 2011. All received (131)I therapy aiming at a total absorbed dose to the thyroid of 250 Gy based on pre-therapeutic dosimetry. Post-therapy dosimetric thyroid measurements were performed twice daily until discharge. From these measurements, thyroid (131)I half-life, the total thyroid absorbed dose, and the maximum dose rate after (131)I administration were calculated. In all, 48.5% of patients were hypothyroid and 28.6% of patients were euthyroid after (131)I therapy. In univariate analysis, nonhyperthyroid and hyperthyroid patients only differed by sex. A lower thyroid mass, a higher activity per gram thyroid tissue, a shorter effective thyroidal (131)I half-life, and a higher maximum dose rate, but not the total thyroid absorbed dose, were significantly associated with hypothyroidism. In multivariate analysis, the maximum dose rate remained the only significant determinant of hypothyroidism (P < .001). Maximum dose rates of 2.2 Gy/h and higher were associated with a 100% hypothyroidism rate. Not the total thyroid absorbed dose, but the maximum dose rate is a determinant of successfully achieving hypothyroidism in Graves' disease. Dosimetric concepts aiming at a specific total thyroid absorbed dose will therefore require reconsideration if our data are confirmed prospectively.

Demagnetization of Nd 2Fe 14B, Pr 2Fe 14B, and Sm 2Co 17 Permanent Magnets in Spallation Irradiation Fields

DOE PAGES

Simos, Nikolaos; Ozaki, S.; Mokhov, N.; ...

2018-02-27

Prompted by the need for radiation-resistant permanent magnets for insertion devices (IDs) of high-brilliance next-generation synchrotrons such as the National Synchrotron Light Source II, the demagnetization of Nd 2Fe 14B and Pr 2Fe 14B was studied after exposure to a mixed irradiating field. Degradation and damage of the permanent magnetic material by components of electromagnetic showers induced in magnets by intense high-energy electron beams will alter the magnetic field structure of the IDs. Plate-like Nd 2Fe 14B magnets were irradiated to 1.8 Grad dose and were evaluated against Pr 2Fe 14B magnets irradiated to a lower dose of 20 Mrad.more » In addition, annular Sm 2Co 17 and Nd 2Fe 14B magnets integrated within a ferrofluidic feedthrough (FFFT) rotary seal were also irradiated to dose levels of 2 Grad for Sm 2Co 17 and 20 Mrad for Nd 2Fe 14B. Post-irradiation measurements of the magnetic intensity revealed that severe demagnetization exceeding 85% occurs in Nd 2Fe 14B magnets after only 50 Mrad dose and over 87% for Pr 2Fe 14B after 10 Mrad dose. The annular-shaped Sm 2Co 17 magnets of the FFFTs were almost insensitive to irradiation up to a dose of 2 Grad. Annular-shaped Nd 2Fe 14B magnets also showed resistance to demagnetization, a direct consequence of the annular shape which is characterized by the removal of the stronger demagnetizing field present at the center of a disk-like magnet. As a result, the sensitivity of boron-based permanent magnets to neutron energy (thermal versus fast) was also assessed via specifically designed experiments and discussed.« less

Demagnetization of Nd 2Fe 14B, Pr 2Fe 14B, and Sm 2Co 17 Permanent Magnets in Spallation Irradiation Fields

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

Simos, Nikolaos; Ozaki, S.; Mokhov, N.

Prompted by the need for radiation-resistant permanent magnets for insertion devices (IDs) of high-brilliance next-generation synchrotrons such as the National Synchrotron Light Source II, the demagnetization of Nd 2Fe 14B and Pr 2Fe 14B was studied after exposure to a mixed irradiating field. Degradation and damage of the permanent magnetic material by components of electromagnetic showers induced in magnets by intense high-energy electron beams will alter the magnetic field structure of the IDs. Plate-like Nd 2Fe 14B magnets were irradiated to 1.8 Grad dose and were evaluated against Pr 2Fe 14B magnets irradiated to a lower dose of 20 Mrad.more » In addition, annular Sm 2Co 17 and Nd 2Fe 14B magnets integrated within a ferrofluidic feedthrough (FFFT) rotary seal were also irradiated to dose levels of 2 Grad for Sm 2Co 17 and 20 Mrad for Nd 2Fe 14B. Post-irradiation measurements of the magnetic intensity revealed that severe demagnetization exceeding 85% occurs in Nd 2Fe 14B magnets after only 50 Mrad dose and over 87% for Pr 2Fe 14B after 10 Mrad dose. The annular-shaped Sm 2Co 17 magnets of the FFFTs were almost insensitive to irradiation up to a dose of 2 Grad. Annular-shaped Nd 2Fe 14B magnets also showed resistance to demagnetization, a direct consequence of the annular shape which is characterized by the removal of the stronger demagnetizing field present at the center of a disk-like magnet. As a result, the sensitivity of boron-based permanent magnets to neutron energy (thermal versus fast) was also assessed via specifically designed experiments and discussed.« less

Dissolution and transport of insensitive munitions formulations IMX-101 and IMX-104 in saturated soil columns.

PubMed

Arthur, Jennifer D; Mark, Noah W; Taylor, Susan; Šimůnek, Jiří; Brusseau, Mark L; Dontsova, Katerina M

2018-05-15

Military training exercises can result in deposition of energetic residues on range soils, which ultimately can contaminate groundwater with munitions constituents. Column experiments followed by HYDRUS-1D modeling were conducted to evaluate dissolution and transport of energetic constituents from the new insensitive munitions (IM) formulations IMX-101, a mixture of 3-nitro-1,2,4-triazol-5-one (NTO), nitroguanidine (NQ), and 2, 4-dinitroanisole (DNAN), and IMX-104, a mixture of NTO, 1,3,5-hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and DNAN. NTO and DNAN are emerging contaminants associated with the development of insensitive munitions as replacements for traditional munitions. Flow interruption experiments were performed to investigate dissolution kinetics and sorption non-equilibrium between soil and solution phases. The results indicated that insensitive munitions compounds dissolved in order of their aqueous solubility, consistent with prior dissolution studies conducted in the absence of soil. Initial elution of the high concentration pulse of highly soluble NTO and NQ was followed by lower concentrations, while DNAN had generally lower and more constant concentrations in leachate. The sorption of NTO and NQ was low, while RDX, 1,3,5,7-octahydro-1,3,5,7-tetranitrotetrazocine (HMX, an impurity in technical grade RDX), and DNAN all exhibited appreciable sorption. DNAN transformation was observed, with formation of amino-reduction products 2-ANAN (2-amino-4-nitroanisole) and 4-ANAN (4-amino-2-nitroanisole). HYDRUS-1D model, incorporating one-dimensional advective-dispersive transport with particle dissolution and first-order solute transformation was used to simulate the measured breakthrough curves. Optimized dissolution parameters varied widely but were correlated between compounds in the same formulation. Determined adsorption coefficients generally agreed with values determined from batch and column studies conducted with pure NTO and DNAN, while mass-loss rate coefficients were in better agreement with ones from batch than column studies possibly due to suppression of microbial transformation during elution of high concentrations of explosives. Even in the low organic matter soils selected in this study DNAN experienced significant retardation and transformation, indicating potential for its natural attenuation. Copyright © 2017 Elsevier B.V. All rights reserved.

Population pharmacokinetic modelling of non-linear brain distribution of morphine: influence of active saturable influx and P-glycoprotein mediated efflux

PubMed Central

Groenendaal, D; Freijer, J; de Mik, D; Bouw, M R; Danhof, M; de Lange, E C M

2007-01-01

Background and purpose: Biophase equilibration must be considered to gain insight into the mechanisms underlying the pharmacokinetic-pharmacodynamic (PK-PD) correlations of opioids. The objective was to characterise in a quantitative manner the non-linear distribution kinetics of morphine in brain. Experimental approach: Male rats received a 10-min infusion of 4 mg kg−1 of morphine, combined with a continuous infusion of the P-glycoprotein (Pgp) inhibitor GF120918 or vehicle, or 40 mg kg−1 morphine alone. Unbound extracellular fluid (ECF) concentrations obtained by intracerebral microdialysis and total blood concentrations were analysed using a population modelling approach. Key results: Blood pharmacokinetics of morphine was best described with a three-compartment model and was not influenced by GF120918. Non-linear distribution kinetics in brain ECF was observed with increasing dose. A one compartment distribution model was developed, with separate expressions for passive diffusion, active saturable influx and active efflux by Pgp. The passive diffusion rate constant was 0.0014 min−1. The active efflux rate constant decreased from 0.0195 min−1 to 0.0113 min−1 in the presence of GF120918. The active influx was insensitive to GF120918 and had a maximum transport (Nmax/Vecf) of 0.66 ng min−1 ml−1 and was saturated at low concentrations of morphine (C50=9.9 ng ml−1). Conclusions and implications: Brain distribution of morphine is determined by three factors: limited passive diffusion; active efflux, reduced by 42% by Pgp inhibition; low capacity active uptake. This implies blood concentration-dependency and sensitivity to drug-drug interactions. These factors should be taken into account in further investigations on PK-PD correlations of morphine. PMID:17471182

Nociceptive threshold, blood constituents and physiological values in 213 cows with locomotion scores ranging from normal to severely lame.

PubMed

Tadich, N; Tejeda, C; Bastias, S; Rosenfeld, C; Green, L E

2013-08-01

The aim of this study was to investigate associations between mechanical nociceptive threshold, blood constituents, physiological measurements and locomotion score (LS) in dairy cattle with a range of LS from 1 (normal) to 5 (severely lame). The study used 213 Friesian/Friesian cross dairy cows from 12 farms. There were 40-50 cows each with LS 1-4 and 22 cows with LS 5. Each cow was restrained and her temperature and respiratory and cardiac rates were measured. Nociceptive threshold, plasma concentrations of haptoglobin, β-hydroxybutyrate (β-HB), cortisol, glucose, lactate, creatinine kinase activity, packed cell volume and white blood cell counts were determined. Mixed effect models were used to investigate associations between the variables measured and LS. Parity and stage of lactation were forced into all analyses and the model fit was checked by investigation of residuals. After accounting for parity and stage of lactation, nociceptive threshold was significantly lower in cattle with LS 3-5 compared with LS 1 in a dose response manner, indicating increasing hyperalgesia with increasing LS. Haptoglobin concentration was raised in all cattle with LS>1, demonstrating an inflammatory response with all levels of lameness. Cortisol and glucose concentrations were lower and β-HB concentrations higher in cows with LS 2 compared with cows with other scores, possibly signifying metabolic challenge. Heart and respiratory rate and rectal temperature were significantly higher only in cows with LS 5, suggesting that these measurements were insensitive measures of pain or stress. It was concluded that hyperalgesia increases with increasing severity of lameness and that nociceptive pressure and haptoglobin were sensitive measures of pain from lameness. Copyright © 2013 Elsevier Ltd. All rights reserved.

Rates of Change in Naturalistic Psychotherapy: Contrasting Dose-Effect and Good-Enough Level Models of Change

ERIC Educational Resources Information Center

Baldwin, Scott A.; Berkeljon, Arjan; Atkins, David C.; Olsen, Joseph A.; Nielsen, Stevan L.

2009-01-01

Most research on the dose-effect model of change has combined data across patients who vary in their total dose of treatment and has implicitly assumed that the rate of change during therapy is constant across doses. In contrast, the good-enough level model predicts that rate of change will be related to total dose of therapy. In this study, the…

Assessment of dose rate to terrestrial biota in the area around coal fired power plant applying ERICA tool and RESRAD BIOTA code.

PubMed

Ćujić, Mirjana; Dragović, Snežana

2018-08-01

This paper presents the environmental radiation risk assessment based on two software program approaches ERICA Tool (version 1.2) and RESRAD BIOTA (version 1.5) to estimate dose rates to terrestrial biota in the area around the largest coal fired power plant in Serbia. For dose rate assessment software's default reference animals and plants and the best estimated values of activity concentrations of 238 U, 234 U, 234 Th, 232 Th, 230 Th, 226 Ra, 210 Pb, 210 Po, 137 Cs in soil were used. Both approaches revealed the highest contribution to the internal dose rate due to 226 Ra and 210 Po, while 137 Cs contributed the most to the external dose rate. In the investigated area total dose rate to biota derived using ERICA Tool ranged from 0.3 to 14.4 μGy h -1 . The natural radionuclides exhibited significantly higher contribution to the total dose rate than the artificial one. In the investigated area, only dose rate for lichens and bryophytes exceeded ERICA Tool screening value of total dose rate of 10 μGy h -1 suggested as confident that environmental risks are negligible. The assessed total dose rates for reference animals and plants using RESRAD BIOTA were found to be 7 and 3 μGy h -1 , respectively. In RESRAD BIOTA - Level 3, 10 species (Lumbricus terrestris, Rana lessonae, Sciurus vulgaris, Anas platyrhynchos, Lepus europaeus, Vulpes vulpes, Capreolus capreolus, Suss crofa, Quercu srobur, Tilia spp.) representative for the study area were modeled. Among them the highest total dose rate (4.5 μGy h -1 ) was obtained for large mammals. Differences in the predicted dose rates to biota using the two software programs are the consequence of the difference in the values of transfer parameters used to calculate activity concentrations in biota. Doses of ionizing radiation estimated in this study will not exhibit deterministic effects at the population level. Thus, the obtained results indicate no significant radiation impact of coal fired power plant operation on terrestrial biota. This paper confirms the use ERICA Tool and RESRAD BIOTA softwares as flexible and effective means of radiation impact assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Radiation protocols determine acute graft-versus-host disease incidence after allogeneic bone marrow transplantation in murine models.

PubMed

Schwarte, Sebastian; Bremer, Michael; Fruehauf, Joerg; Sorge, Yanina; Skubich, Susanne; Hoffmann, Matthias W

2007-09-01

Effects of radiation sources used for total body irradiation (TBI) on Graft-versus-Host Disease (GvHD) induction were examined. In a T cell receptor (TCR) transgenic mouse model, single fraction TBI was performed with different radiation devices ((60)Cobalt; (137)Cesium; 6 MV linear accelerator), dose rates (0.85; 1.5; 2.9; 5 Gy/min) and total doses before allogeneic bone marrow transplantation (BMT). Recipients were observed for 120 days. Different tissues were examined histologically. Acute GvHD was induced by a dose rate of 0.85 Gy/min ((60)Cobalt) and a total dose of 9 Gy and injection of 5 x 10(5) lymph node cells plus 5 x 10(6) bone marrow cells. Similar results were obtained using 6 MV linear accelerator- (linac-) photons with a dose rate of 1.5 Gy/min and 0.85 Gy/min, a total dose of 9.5 Gy and injection of same cell numbers. TBI with (137)Cesium (dose rate: 2.5 Gy/min) did not lead reproducibly to lethal acute GvHD. Experimental TBI in murine models may induce different immunological responses, depending on total energy, total single dose and dose rate. GvHD might also be induced by TBI with low dose rates.

Different dose rate-dependent responses of human melanoma cells and fibroblasts to low dose fast neutrons.

PubMed

Dionet, Claude; Müller-Barthélémy, Melanie; Marceau, Geoffroy; Denis, Jean-Marc; Averbeck, Dietrich; Gueulette, John; Sapin, Vincent; Pereira, Bruno; Tchirkov, Andrei; Chautard, Emmanuel; Verrelle, Pierre

2016-09-01

To analyze the dose rate influence in hyper-radiosensitivity (HRS) of human melanoma cells to very low doses of fast neutrons and to compare to the behaviour of normal human skin fibroblasts. We explored different neutron dose rates as well as possible implication of DNA double-strand breaks (DSB), apoptosis, and energy-provider adenosine-triphosphate (ATP) levels during HRS. HRS in melanoma cells appears only at a very low dose rate (VLDR), while a high dose rate (HDR) induces an initial cell-radioresistance (ICRR). HRS does not seem to be due either to DSB or to apoptosis. Both phenomena (HRS and ICRR) appear to be related to ATP availability for triggering cell repair. Fibroblast survival after neutron irradiation is also dose rate-dependent but without HRS. Melanoma cells or fibroblasts exert their own survival behaviour at very low doses of neutrons, suggesting that in some cases there is a differential between cancer and normal cells radiation responses. Only the survival of fibroblasts at HDR fits the linear no-threshold model. This new insight into human cell responses to very low doses of neutrons, concerns natural radiations, surroundings of accelerators, proton-therapy devices, flights at high altitude. Furthermore, ATP inhibitors could increase HRS during high-linear energy transfer (high-LET) irradiation.

Analysis of interlaminar stresses in thick composite laminates with and without edge delamination

NASA Technical Reports Server (NTRS)

Whitcomb, J. D.; Raju, I. S.

1984-01-01

The effect of laminate thickness on the interlaminar stresses in rectangular quasi-isotropic laminates under uniform axial strain was studied. Laminates from 8-ply to infinitely thick were analyzed. Thick laminates were synthesized by stacking (45/0/-45/90) ply groups, rather than grouping like plies. Laminates with and without delaminations were studied. In laminates without delaminations, the free-edge interlaminar normal stress distribution in the outer ply groups was insensitive to total laminate thickness. The interlaminar normal stress distribution for the interior ply groups was nearly the same as for an infinitely thick laminate. In contrast, the free-edge inter-laminar shear stress distribution was nearly the same for inner and outer ply groups and was insensitive to laminate thickness. In laminates with delaminations those delaminations near the top and bottom surfaces of a thick laminate have much larger total strain-energy-release rates (G sub t) and mode I-to-total (G sub t/G sub t) ratios than delaminations deep in the interior. Therefore, delaminations can be expected to grow more easily near the surfaces of a laminate than in the interior.

Fixed-interval performance and self-control in infants.

PubMed Central

Darcheville, J C; Rivière, V; Wearden, J H

1993-01-01

Twenty-six infants, 3 to 23 months old, were trained on fixed-interval schedules ranging from 10 s to 80 s. The operant response was touching an illuminated location on a touch-sensitive screen, and 20 s of cartoon presentation was the reinforcer. The subjects were also trained in a six-phase self-control procedure in which the critical phases involved choice between 20 s of cartoon available after a 0.5-s delay (impulsive choice) and 40 s of cartoon delayed for 40 s (self-controlled choice). All the youngest children (3 to 5 months) showed long postreinforcement pauses on the fixed-interval schedule, with most intervals involving the emission of a single, reinforced, response, and all made self-controlled choices. Older subjects (9 to 23 months) either produced the same pattern as the younger ones on the fixed-interval schedule (classified as pause-sensitive subjects) or produced short pauses and higher steady response rates (classified as pause-insensitive subjects). All pause-sensitive subjects made self-controlled choices in the self-control condition, and all pause-insensitive subjects made impulsive ones. PMID:8409821

Older Adults' Trait Impressions of Faces Are Sensitive to Subtle Resemblance to Emotions

PubMed Central

Zebrowitz, Leslie A.

2013-01-01

Younger adults (YA) attribute emotion-related traits to people whose neutral facial structure resembles an emotion (emotion overgeneralization). The fact that older adults (OA) show deficits in accurately labeling basic emotions suggests that they may be relatively insensitive to variations in the emotion resemblance of neutral expression faces that underlie emotion overgeneralization effects. On the other hand, the fact that OA, like YA, show a ‘pop-out’ effect for anger, more quickly locating an angry than a happy face in a neutral array, suggests that both age groups may be equally sensitive to emotion resemblance. We used computer modeling to assess the degree to which neutral faces objectively resembled emotions and assessed whether that resemblance predicted trait impressions. We found that both OA and YA showed anger and surprise overgeneralization in ratings of danger and naiveté, respectively, with no significant differences in the strength of the effects for the two age groups. These findings suggest that well-documented OA deficits on emotion recognition tasks may be more due to processing demands than to an insensitivity to the social affordances of emotion expressions. PMID:24058225

A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep.

PubMed

Rétey, J V; Adam, M; Khatami, R; Luhmann, U F O; Jung, H H; Berger, W; Landolt, H-P

2007-05-01

Caffeine is the most widely used stimulant in Western countries. Some people voluntarily reduce caffeine consumption because it impairs the quality of their sleep. Studies in mice revealed that the disruption of sleep after caffeine is mediated by blockade of adenosine A2A receptors. Here we show in humans that (1) habitual caffeine consumption is associated with reduced sleep quality in self-rated caffeine-sensitive individuals, but not in caffeine-insensitive individuals; (2) the distribution of distinct c.1083T>C genotypes of the adenosine A2A receptor gene (ADORA2A) differs between caffeine-sensitive and -insensitive adults; and (3) the ADORA2A c.1083T>C genotype determines how closely the caffeine-induced changes in brain electrical activity during sleep resemble the alterations observed in patients with insomnia. These data demonstrate a role of adenosine A2A receptors for sleep in humans, and suggest that a common variation in ADORA2A contributes to subjective and objective responses to caffeine on sleep.

A numerical study on the thermal initiation of a confined explosive in 2-D geometry.

PubMed

Aydemir, Erdoğan; Ulas, Abdullah

2011-02-15

Insensitive munitions design against thermal stimuli like slow or fast cook-off has become a significant requirement for today's munitions. In order to achieve insensitive munitions characteristics, the response of the energetic material needs to be predicted against heating stimuli. In this study, a 2D numerical code was developed to simulate the slow and fast cook-off heating conditions of confined munitions and to obtain the response of the energetic materials. Computations were performed in order to predict the transient temperature distribution, the ignition time, and the location of ignition in the munitions. These predictions enable the designers to have an idea of when and at which location the energetic material ignites under certain adverse surrounding conditions. In the paper, the development of the code is explained and the numerical results are compared with available experimental and numerical data in the literature. Additionally, a parametric study was performed showing the effect of dimensional scaling of munitions and the heating rate on the ignition characteristics. Copyright © 2010 Elsevier B.V. All rights reserved.

South Asians have elevated postexercise blood pressure and myocardial oxygen consumption compared to Europeans despite equivalent resting pressure.

PubMed

Chaturvedi, Nish; Bathula, Rajaram; Shore, Angela C; Panerai, Ronney; Potter, John; Kooner, Jaspal; Chambers, John; Hughes, Alun D

2012-10-01

Stroke mortality rate is higher in South Asians than in Europeans, despite equivalent or lower resting blood pressure (BP). Elevated recovery BP after exercise predicts stroke, independently of resting values. We hypothesized that South Asians would have adverse postexercise hemodynamics and sought explanations for this. A population-based sample of 147 European and 145 South Asian middle-aged men and women performed the Dundee 3-minute step test. Cardiovascular risk factors were measured. BP, heart rate, and rate-pressure product, a measure of myocardial oxygen consumption, were compared. With 90% power and 5% significance, we could detect a difference of 0.38 of a standard deviation in any outcome measure. Resting systolic BP was similar in South Asians (144 mm Hg) and Europeans (142 mm Hg) (P=0.2), as was exercise BP (P=0.4). However, recovery systolic BP at 3 minutes after exercise was higher in South Asians by 4.3 mm Hg (95% confidence interval [CI], 0.2 to 8.3 mm Hg; P=0.04). This effect persisted when adjusted for exercise BP and work effort (5.4 mm Hg [95% CI, 2.2 to 8.7 mm Hg; P=0.001]). Adjustment for baroreflex insensitivity and greater aortic stiffness in South Asians contributes greatly to attenuating this ethnic difference (1.9 mm Hg [95% CI, -0.9 to 4.6 mm Hg; P=0.4]). Similarly, rate-pressure product recovery after exercise was impaired in South Asians by 735 mm Hg/min (95% CI, 137 to 1334 mm Hg/min; P=0.02); again, adjustment for baroreflex insensitivity and aortic stiffness attenuated this difference (261 mm Hg/min [95% CI, -39 to 561 mm Hg/min; P=0.3]). Postexercise recovery of BP and rate-pressure product is impaired in South Asians compared to Europeans even though resting and exercise BP are similar. This is associated with the autonomic dysfunction and aortic stiffness in South Asians.

Radiation-Induced Carcinogenesis: Mechanistically Based Differences between Gamma-Rays and Neutrons, and Interactions with DMBA

PubMed Central

Shuryak, Igor; Brenner, David J.; Ullrich, Robert L.

2011-01-01

Different types of ionizing radiation produce different dependences of cancer risk on radiation dose/dose rate. Sparsely ionizing radiation (e.g. γ-rays) generally produces linear or upwardly curving dose responses at low doses, and the risk decreases when the dose rate is reduced (direct dose rate effect). Densely ionizing radiation (e.g. neutrons) often produces downwardly curving dose responses, where the risk initially grows with dose, but eventually stabilizes or decreases. When the dose rate is reduced, the risk increases (inverse dose rate effect). These qualitative differences suggest qualitative differences in carcinogenesis mechanisms. We hypothesize that the dominant mechanism for induction of many solid cancers by sparsely ionizing radiation is initiation of stem cells to a pre-malignant state, but for densely ionizing radiation the dominant mechanism is radiation-bystander-effect mediated promotion of already pre-malignant cell clone growth. Here we present a mathematical model based on these assumptions and test it using data on the incidence of dysplastic growths and tumors in the mammary glands of mice exposed to high or low dose rates of γ-rays and neutrons, either with or without pre-treatment with the chemical carcinogen 7,12-dimethylbenz-alpha-anthracene (DMBA). The model provides a mechanistic and quantitative explanation which is consistent with the data and may provide useful insight into human carcinogenesis. PMID:22194850

Interstitial pneumonitis following bone marrow transplantation after low dose rate total body irradiation.

PubMed

Barrett, A; Depledge, M H; Powles, R L

1983-07-01

Idiopathic and infective interstitial pneumonitis (IPn) is a common complication after bone marrow transplantation (BMT) in many centers and carries a high mortality. We report here a series of 107 patients with acute leukemia grafted at the Royal Marsden Hospital in which only 11 (10.3%) developed IPn and only 5 died (5%). Only one case of idiopathic IPn was seen. Factors which may account for this low incidence are discussed. Sixty of 107 patients were transplanted in first remission of acute myeloid leukemia (AML) and were therefore in good general condition. Lung radiation doses were carefully monitored and doses of 10.5 Gy were not exceeded except in a group of 16 patients in whom a study of escalating doses of TBI (up to 13 Gy) was undertaken. The dose rate used for total body irradiation (TBI) was lower than that used in other centers and as demonstrated elsewhere by ourselves and others, reduction of dose rate to less than 0.05 Gy/min may be expected to lead to substantial reduction in lung damage. Threshold doses of approximately 8 Gy for IPn have been reported, but within the dose range of 8 to 10.5 Gy we suggest that dose rate may significantly affect the incidence. Data so far available suggest a true improvement in therapeutic ratio for low dose rate single fraction TBI compared with high dose rate.

MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase-mediated suppression of histone deacetylase 2.

PubMed

Kim, Richard Y; Horvat, Jay C; Pinkerton, James W; Starkey, Malcolm R; Essilfie, Ama T; Mayall, Jemma R; Nair, Prema M; Hansbro, Nicole G; Jones, Bernadette; Haw, Tatt Jhong; Sunkara, Krishna P; Nguyen, Thi Hiep; Jarnicki, Andrew G; Keely, Simon; Mattes, Joerg; Adcock, Ian M; Foster, Paul S; Hansbro, Philip M

2017-02-01

Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. Steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including neutrophilic forms of disease. However, steroid-insensitive patients with eosinophil-enriched inflammation have also been described. The mechanisms that underpin infection-induced, severe steroid-insensitive asthma can be elucidated by using mouse models of disease. We sought to develop representative mouse models of severe, steroid-insensitive asthma and to use them to identify pathogenic mechanisms and investigate new treatment approaches. Novel mouse models of Chlamydia, Haemophilus influenzae, influenza, and respiratory syncytial virus respiratory tract infections and ovalbumin-induced, severe, steroid-insensitive allergic airway disease (SSIAAD) in BALB/c mice were developed and interrogated. Infection induced increases in the levels of microRNA (miRNA)-21 (miR-21) expression in the lung during SSIAAD, whereas expression of the miR-21 target phosphatase and tensin homolog was reduced. This was associated with an increase in levels of phosphorylated Akt, an indicator of phosphoinositide 3-kinase (PI3K) activity, and decreased nuclear histone deacetylase (HDAC)2 levels. Treatment with an miR-21-specific antagomir (Ant-21) increased phosphatase and tensin homolog levels. Treatment with Ant-21, or the pan-PI3K inhibitor LY294002, reduced PI3K activity and restored HDAC2 levels. This led to suppression of airway hyperresponsiveness and restored steroid sensitivity to allergic airway disease. These observations were replicated with SSIAAD associated with 4 different pathogens. We identify a previously unrecognized role for an miR-21/PI3K/HDAC2 axis in SSIAAD. Our data highlight miR-21 as a novel therapeutic target for the treatment of this form of asthma. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Ethanol modulates the VR-1 variant amiloride-insensitive salt taste receptor. I. Effect on TRC volume and Na+ flux.

PubMed

Lyall, Vijay; Heck, Gerard L; Phan, Tam-Hao T; Mummalaneni, Shobha; Malik, Shahbaz A; Vinnikova, Anna K; DeSimone, John A

2005-06-01

The effect of ethanol on the amiloride- and benzamil (Bz)-insensitive salt taste receptor was investigated by the measurement of intracellular Na(+) activity ([Na(+)](i)) in polarized rat fungiform taste receptor cells (TRCs) using fluorescence imaging and by chorda tympani (CT) taste nerve recordings. CT responses were monitored during lingual stimulation with ethanol solutions containing NaCl or KCl. CT responses were recorded in the presence of Bz (a specific blocker of the epithelial Na(+) channel [ENaC]) or the vanilloid receptor-1 (VR-1) antagonists capsazepine or SB-366791, which also block the Bz-insensitive salt taste receptor, a VR-1 variant. CT responses were recorded at 23 degrees C or 42 degrees C (a temperature at which the VR-1 variant salt taste receptor activity is maximally enhanced). In the absence of permeable cations, ethanol induced a transient decrease in TRC volume, and stimulating the tongue with ethanol solutions without added salt elicited only transient phasic CT responses that were insensitive to elevated temperature or SB-366791. Preshrinking TRCs in vivo with hypertonic mannitol (0.5 M) attenuated the magnitude of the phasic CT response, indicating that in the absence of mineral salts, transient phasic CT responses are related to the ethanol-induced osmotic shrinkage of TRCs. In the presence of mineral salts, ethanol increased the Bz-insensitive apical cation flux in TRCs without a change in cell volume, increased transepithelial electrical resistance across the tongue, and elicited CT responses that were similar to salt responses, consisting of both a transient phasic component and a sustained tonic component. Ethanol increased the Bz-insensitive NaCl CT response. This effect was further enhanced by elevating the temperature from 23 degrees C to 42 degrees C, and was blocked by SB-366791. We conclude that in the presence of mineral salts, ethanol modulates the Bz-insensitive VR-1 variant salt taste receptor.

Higher dose rate Gamma Knife radiosurgery may provide earlier and longer-lasting pain relief for patients with trigeminal neuralgia.

PubMed

Lee, John Y K; Sandhu, Sukhmeet; Miller, Denise; Solberg, Timothy; Dorsey, Jay F; Alonso-Basanta, Michelle

2015-10-01

Gamma Knife radiosurgery (GKRS) utilizes cobalt-60 as its radiation source, and thus dose rate varies as the fixed source decays over its half-life of approximately 5.26 years. This natural decay results in increasing treatment times when delivering the same cumulative dose. It is also possible, however, that the biological effective dose may change based on this dose rate even if the total dose is kept constant. Because patients are generally treated in a uniform manner, radiosurgery for trigeminal neuralgia (TN) represents a clinical model whereby biological efficacy can be tested. The authors hypothesized that higher dose rates would result in earlier and more complete pain relief but only if measured with a sensitive pain assessment tool. One hundred thirty-three patients were treated with the Gamma Knife Model 4C unit at a single center by a single neurosurgeon during a single cobalt life cycle from January 2006 to May 2012. All patients were treated with 80 Gy with a single 4-mm isocenter without blocking. Using an output factor of 0.87, dose rates ranged from 1.28 to 2.95 Gy/min. The Brief Pain Inventory (BPI)-Facial was administered before the procedure and at the first follow-up office visit 1 month from the procedure (mean 1.3 months). Phone calls were made to evaluate patients after their procedures as part of a retrospective study. Univariate and multivariate linear regression was performed on several independent variables, including sex, age in deciles, diagnosis, follow-up duration, prior surgery, and dose rate. In the short-term analysis (mean 1.3 months), patients' self-reported pain intensity at its worst was significantly correlated with dose rate on multivariate analysis (p = 0.028). Similarly, patients' self-reported interference with activities of daily living was closely correlated with dose rate on multivariate analysis (p = 0.067). A 1 Gy/min decrease in dose rate resulted in a 17% decrease in pain intensity at its worst and a 22% decrease in pain interference with activities of daily living. In longer-term follow-up (mean 1.9 years), GKRS with higher dose rates (> 2.0 Gy/min; p = 0.007) and older age in deciles (p = 0.012) were associated with a lower likelihood of recurrence of pain. Prior studies investigating the role of dose rate in Gamma Knife radiosurgical ablation for TN have not used validated outcome tools to measure pain preoperatively. Consequently, differences in pain outcomes have been difficult to measure. By administering pain scales both preoperatively as well as postoperatively, the authors have identified statistically significant differences in pain intensity and pain interference with activities of daily living when comparing higher versus lower dose rates. Radiosurgery with a higher dose rate results in more pain relief at the early follow-up evaluation, and it may result in a lower recurrence rate at later follow-up.

Commentary 2 to Cox and Little: radiation-induced oncogenic transformation: the interplay between dose, dose protraction, and radiation quality

NASA Technical Reports Server (NTRS)

Brenner, D. J.; Hall, E. J.

1992-01-01

There is now a substantial body of evidence for end points such as oncogenic transformation in vitro, and carcinogenesis and life shortening in vivo, suggesting that dose protraction leads to an increase in effectiveness relative to a single, acute exposure--at least for radiations of medium linear energy transfer (LET) such as neutrons. Table I contains a summary of the pertinent data from studies in which the effect is seen. [table: see text] This phenomenon has come to be known as the "inverse dose rate effect," because it is in marked contrast to the situation at low LET, where protraction in delivery of a dose of radiation, either by fractionation or low dose rate, results in a decreased biological effect; additionally, at medium and high LET, for radiobiological end points such as clonogenic survival, the biological effectiveness is independent of protraction. The quantity and quality of the published reports on the "inverse dose rate effect" leaves little doubt that the effect is real, but the available evidence indicates that the magnitude of the effect is due to a complex interplay between dose, dose rate, and radiation quality. Here, we first summarize the available data on the inverse dose rate effect and suggest that it follows a consistent pattern in regard to dose, dose rate, and radiation quality; second, we describe a model that predicts these features; and, finally, we describe the significance of the effect for radiation protection.

Genetics Home Reference: congenital insensitivity to pain

MedlinePlus

... insensitivity to pain is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which ... link) National Institute of Neurological Disorders and Stroke: Peripheral Neuropathy Information Page Educational Resources (5 links) Disease InfoSearch: ...

Lengthening of Insect Development on Bt Zone Results in Adult Emergence Asynchrony: Does It Influence the Effectiveness of the High Dose/Refuge Zone Strategy?

PubMed Central

Gryspeirt, Aiko; Grégoire, Jean-Claude

2012-01-01

The “High Dose/Refuge” strategy (HD/R) is the currently recommended Insect Resistance Management strategy (IRM) to limit resistance development to Bacillus thuringiensis (Bt) plants. This strategy requires planting a “refuge zone” composed of non-Bt plants suitable for the target insect and in close proximity to a “Bt zone” expressing a high toxin concentration. One of the main assumptions is that enough susceptible adults mate with resistant insects. However, previous studies have suggested that the high toxin concentration produced by Bt plants induces slower insect development, creating an asynchrony in emergence between the refuge and the Bt zone and leading to assortative mating between adults inside each zone. Here, we develop a deterministic model to estimate the impact of toxin concentration, emergence asynchrony and refuge zone size on the effectiveness of the HD/R strategy. We conclude that emergence asynchrony only affects resistance when toxin concentration is high and resistance is recessive. Resistance develops more rapidly and survival of susceptible insects is higher at lower toxin concentration, but in such situations, resistance is insensitive to emergence asynchrony. PMID:23202319

Developing a multipoint titration method with a variable dose implementation for anaerobic digestion monitoring.

PubMed

Salonen, K; Leisola, M; Eerikäinen, T

2009-01-01

Determination of metabolites from an anaerobic digester with an acid base titration is considered as superior method for many reasons. This paper describes a practical at line compatible multipoint titration method. The titration procedure was improved by speed and data quality. A simple and novel control algorithm for estimating a variable titrant dose was derived for this purpose. This non-linear PI-controller like algorithm does not require any preliminary information from sample. Performance of this controller is superior compared to traditional linear PI-controllers. In addition, simplification for presenting polyprotic acids as a sum of multiple monoprotic acids is introduced along with a mathematical error examination. A method for inclusion of the ionic strength effect with stepwise iteration is shown. The titration model is presented with matrix notations enabling simple computation of all concentration estimates. All methods and algorithms are illustrated in the experimental part. A linear correlation better than 0.999 was obtained for both acetate and phosphate used as model compounds with slopes of 0.98 and 1.00 and average standard deviations of 0.6% and 0.8%, respectively. Furthermore, insensitivity of the presented method for overlapping buffer capacity curves was shown.

Cell killing mode of liblomycin (NK313), a novel dose-survival relationship different from bleomycins.

PubMed

Kuramochi-Motegi, A; Kuramochi, H; Takahashi, K; Takeuchi, T

1991-04-01

Liblomycin (NK313) is a novel derivative of bleomycin (BLM) and peplomycin (PEP). The cell kill kinetics of NK313 on rat ascites hepatoma AH66 were compared with those of PEP. NK313 induced intracellular DNA cleavage and arrested cell cycle progression at the G2 phase similarly to PEP. The cytocidal effect of NK313, however, was found to be different from that of PEP as described below: 1) The dose-survival curve for cells exposed to PEP for 1 hour was upward concave, whereas in case of NK313, the survival curve was linear. PEP was more effective to AH66 than NK313 at lower concentration, but at higher concentration, NK313 was much more effective. 2) The time-survival curve for cells treated with either NK313 or PEP was biphasic. NK313, however, did not induce temporary resistance of AH66 cells to NK313, while PEP induced resistance to PEP. 3) NK313 was effective against the cells which became temporarily resistant to PEP by the treatment of PEP. These differences suggest that NK313 might be of value to treat PEP-insensitive tumor cells.

Acceleration of atherogenesis in ApoE-/- mice exposed to acute or low-dose-rate ionizing radiation.

PubMed

Mancuso, Mariateresa; Pasquali, Emanuela; Braga-Tanaka, Ignacia; Tanaka, Satoshi; Pannicelli, Alessandro; Giardullo, Paola; Pazzaglia, Simonetta; Tapio, Soile; Atkinson, Michael J; Saran, Anna

2015-10-13

There is epidemiological evidence for increased non-cancer mortality, primarily due to circulatory diseases after radiation exposure above 0.5 Sv. We evaluated the effects of chronic low-dose rate versus acute exposures in a murine model of spontaneous atherogenesis. Female ApoE-/- mice (60 days) were chronically irradiated for 300 days with gamma rays at two different dose rates (1 mGy/day; 20 mGy/day), with total accumulated doses of 0.3 or 6 Gy. For comparison, age-matched ApoE-/- females were acutely exposed to the same doses and sacrificed 300 days post-irradiation. Mice acutely exposed to 0.3 or 6 Gy showed increased atherogenesis compared to age-matched controls, and this effect was persistent. When the same doses were delivered at low dose rate over 300 days, we again observed a significant impact on global development of atherosclerosis, although at 0.3 Gy effects were limited to the descending thoracic aorta. Our data suggest that a moderate dose of 0.3 Gy can have persistent detrimental effects on the cardiovascular system, and that a high dose of 6 Gy poses high risks at both high and low dose rates. Our results were clearly nonlinear with dose, suggesting that lower doses may be more damaging than predicted by a linear dose response.

Estimation of low-level neutron dose-equivalent rate by using extrapolation method for a curie level Am-Be neutron source.

PubMed

Li, Gang; Xu, Jiayun; Zhang, Jie

2015-01-01

Neutron radiation protection is an important research area because of the strong radiation biological effect of neutron field. The radiation dose of neutron is closely related to the neutron energy, and the connected relationship is a complex function of energy. For the low-level neutron radiation field (e.g. the Am-Be source), the commonly used commercial neutron dosimeter cannot always reflect the low-level dose rate, which is restricted by its own sensitivity limit and measuring range. In this paper, the intensity distribution of neutron field caused by a curie level Am-Be neutron source was investigated by measuring the count rates obtained through a 3 He proportional counter at different locations around the source. The results indicate that the count rates outside of the source room are negligible compared with the count rates measured in the source room. In the source room, 3 He proportional counter and neutron dosimeter were used to measure the count rates and dose rates respectively at different distances to the source. The results indicate that both the count rates and dose rates decrease exponentially with the increasing distance, and the dose rates measured by a commercial dosimeter are in good agreement with the results calculated by the Geant4 simulation within the inherent errors recommended by ICRP and IEC. Further studies presented in this paper indicate that the low-level neutron dose equivalent rates in the source room increase exponentially with the increasing low-energy neutron count rates when the source is lifted from the shield with different radiation intensities. Based on this relationship as well as the count rates measured at larger distance to the source, the dose rates can be calculated approximately by the extrapolation method. This principle can be used to estimate the low level neutron dose values in the source room which cannot be measured directly by a commercial dosimeter. Copyright © 2014 Elsevier Ltd. All rights reserved.

SEMICONDUCTOR PHYSICS Dose-rate dependence of optically stimulated luminescence signal

NASA Astrophysics Data System (ADS)

Pingqiang, Wei; Zhaoyang, Chen; Yanwei, Fan; Yurun, Sun; Yun, Zhao

2010-10-01

Optically stimulated luminescence (OSL) is the luminescence emitted from a semiconductor during its exposure to light. The OSL intensity is a function of the total dose absorbed by the sample. The dose-rate dependence of the OSL signal of the semiconductor CaS doped Ce and Sm was studied by numerical simulation and experiments. Based on a one-trap/one-center model, the whole OSL process was represented by a series of differential equations. The dose-rate properties of the materials were acquired theoretically by solving the equations. Good coherence was achieved between numerical simulation and experiments, both of which showed that the OSL signal was independent of dose rate. This result validates that when using OSL as a dosimetry technique, the dose-rate effect can be neglected.

Detailed Distribution Map of Absorbed Dose Rate in Air in Tokatsu Area of Chiba Prefecture, Japan, Constructed by Car-Borne Survey 4 Years after the Fukushima Daiichi Nuclear Power Plant Accident.

PubMed

Inoue, Kazumasa; Arai, Moeko; Fujisawa, Makoto; Saito, Kyouko; Fukushi, Masahiro

2017-01-01

A car-borne survey was carried out in the northwestern, or Tokatsu, area of Chiba Prefecture, Japan, to make a detailed distribution map of absorbed dose rate in air four years after the Fukushima Daiichi Nuclear Power Plant accident. This area was chosen because it was the most heavily radionuclide contaminated part of Chiba Prefecture and it neighbors metropolitan Tokyo. Measurements were performed using a 3-in × 3-in NaI(Tl) scintillation spectrometer in June 2015. The survey route covered the whole Tokatsu area which includes six cities. A heterogeneous distribution of absorbed dose rate in air was observed on the dose distribution map. Especially, higher absorbed dose rates in air exceeding 80 nGy h-1 were observed along national roads constructed using high porosity asphalt, whereas lower absorbed dose rates in air were observed along local roads constructed using low porosity asphalt. The difference between these asphalt types resulted in a heterogeneous dose distribution in the Tokatsu area. The mean of the contribution ratio of artificial radionuclides to absorbed dose rate in air measured 4 years after the accident was 29% (9-50%) in the Tokatsu area. The maximum absorbed dose rate in air, 201 nGy h-1 was observed at Kashiwa City. Radiocesium was deposited in the upper 1 cm surface layer of the high porosity asphalt which was collected in Kashiwa City and the environmental half-life of the absorbed dose rate in air was estimated to be 1.7 years.

The Effects of ELDRS at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

Chen, Dakai; Forney, James; Carts, Martin; Phan, Anthony; Cox, Stephen; Kruckmeyer, Kirby; Burns, Sam; Albarian, Rafi; Holcombe, Bruce; Little, Bradley;

Assessment of ambient gamma dose rate around a prospective uranium mining area of South India - A comparative study of dose by direct methods and soil radioactivity measurements

NASA Astrophysics Data System (ADS)

Karunakara, N.; Yashodhara, I.; Sudeep Kumara, K.; Tripathi, R. M.; Menon, S. N.; Kadam, S.; Chougaonkar, M. P.

Indoor and outdoor gamma dose rates were evaluated around a prospective uranium mining region - Gogi, South India through (i) direct measurements using a GM based gamma dose survey meter, (ii) integrated measurement days using CaSO4:Dy based thermo luminescent dosimeters (TLDs), and (iii) analyses of 273 soil samples for 226Ra, 232Th, and 40K activity concentration using HPGe gamma spectrometry. The geometric mean values of indoor and outdoor gamma dose rates were 104 nGy h-1 and 97 nGy h-1, respectively with an indoor to outdoor dose ratio of 1.09. The gamma dose rates and activity concentrations of 226Ra, 232Th, and 40K varied significantly within a small area due to the highly localized mineralization of the elements. Correlation study showed that the dose estimated from the soil radioactivity is better correlated with that measured directly using the portable survey meter, when compared to that obtained from TLDs. This study showed that in a region having localized mineralization in situ measurements using dose survey meter provide better representative values of gamma dose rates.

Host perception of jasmonates promotes infection by Fusarium oxysporum formae speciales that produce isoleucine- and leucine-conjugated jasmonates

PubMed Central

Cole, Stephanie J.; Yoon, Alexander J.; Faull, Kym F.; Diener, Andrew C.

2014-01-01

Summary Three pathogenic forms, or formae speciales, of Fusarium oxysporum infect the roots of Arabidopsis thaliana belowground, instigating symptoms of wilt disease in leaves aboveground. In prior reports, Arabidopsis mutants that are deficient in the biosynthesis of abscisic acid or salicylic acid or insensitive to ethylene or jasmonates exhibit more or less wilt disease than wild type, implicating the involvement of hormones in the normal host response to F. oxysporum. Our analysis of hormone-related mutants finds no evidence that endogenous hormones contribute to infection in roots. Mutants that are deficient in abscisic acid and insensitive to ethylene have no less infection than wild type, though they exhibit less disease. Whether a mutant that is insensitive to jasmonates affects infection depends on which forma specialis is infecting roots. Insensitivity to jasmonates suppresses infection by F. oxysporum forma specialis conglutinans and F. oxysporum forma specialis matthioli, which produce isoleucine- and leucine-conjugated jasmonate (JA-Ile/Leu) in culture filtrates; whereas, insensitivity to jasmonates has no effect on infection by F. oxysporum forma specialis raphani, which produces no detectable JA-Ile/Leu. Furthermore, insensitivity to jasmonates has no effect on wilt disease of tomato, and the tomato pathogen F. oxysporum forma specialis lycopersici produces no detectable jasmonates. Thus, some but not all F. oxysporum pathogens appear to utilize jasmonates as effectors, promoting infection in roots and/or development of symptoms in shoots. Only when infection of roots is promoted by jasmonates is wilt disease enhanced in a mutant deficient in salicylic acid biosynthesis. PMID:24387225

Mechanisms that limit the light stimulus frequency following through the APB sensitive and insensitive rod Off-pathways

PubMed Central

Bai, Xia; Zhu, Junling; Yang, Jinnan; Savoie, Brian T.; Wang, Guo-Yong

2009-01-01

In the retina, rod signal pathways process scotopic visual information. Light decrements are mediated by two distinct groups of rod pathways in the dark adapted retina that can be differentiated on the basis of their sensitivity to the glutamate agonist DL-2-amino-4-phosphonobutyric acid (APB). We have found that the APB sensitive and insensitive rod Off-pathways signal different light decrement information: the APB sensitive rod Off-pathway conveys slow and low frequency light signals, whereas the APB insensitive rod Off-pathways mediate fast and high frequency light signals (Wang, 2006). However, the mechanisms which limit the frequency following through the APB sensitive and insensitive rod Off-pathways remain unknown. In the current study, whole-cell patch-clamp recordings were made from ganglion cells in dark and light adapted mouse retina to identify the mechanisms that limit the frequency following through the APB sensitive and insensitive rod Off-pathways. The results showed that the sites from AII amacrine cells to Off cone bipolar cells are the major mechanisms that limit the frequency following through the APB sensitive rod Off-pathway. In the APB insensitive rod Off-pathways, rods themselves limited the frequency following through these pathways. Moreover, ganglion cells were able to follow higher frequencies under photopic conditions than under scotopic conditions. The Off responses followed lower frequencies than On responses under photopic conditions. This finding was observed in cells that yielded On or Off responses only as well as in On-Off cells. PMID:19406212

Genetic susceptibility: radiation effects relevant to space travel.

PubMed

Peng, Yuanlin; Nagasawa, Hatsumi; Warner, Christy; Bedford, Joel S

2012-11-01

Genetic variation in the capacity to repair radiation damage is an important factor influencing both cellular and tissue radiosensitivity variation among individuals as well as dose rate effects associated with such damage. This paper consists of two parts. The first part reviews some of the available data relating to genetic components governing such variability among individuals in susceptibility to radiation damage relevant for radiation protection and discusses the possibility and extent to which these may also apply for space radiations. The second part focuses on the importance of dose rate effects and genetic-based variations that influence them. Very few dose rate effect studies have been carried out for the kinds of radiations encountered in space. The authors present here new data on the production of chromosomal aberrations in noncycling low passage human ATM+/+ or ATM+/- cells following irradiations with protons (50 MeV or 1 GeV), 1 GeV(-1) n iron ions and gamma rays, where doses were delivered at a high dose rate of 700 mGy(-1) min, or a lower dose rate of 5 mGy min(-1). Dose responses were essentially linear over the dose ranges tested and not significantly different for the two cell strains. Values of the dose rate effectiveness factor (DREF) were expressed as the ratio of the slopes of the dose-response curves for the high versus the lower (5 mGy min(-1)) dose rate exposures. The authors refer to this as the DREF5. For the gamma ray standard, DREF5 values of approximately two were observed. Similar dose rate effects were seen for both energies of protons (DREF5 ≈ 2.2 in both cases). For 1 GeV(-1) n iron ions [linear energy transfer (LET) ≈ 150 keV μ(-1)], the DREF5 was not 1 as might have been expected on the basis of LET alone but was approximately 1.3. From these results and conditions, the authors estimate that the relative biological effectiveness for 1 GeV(-1) n iron ions for high and low dose rates, respectively, were about 10 and 15 rather than around 20 for low dose rates, as has been assumed by most recommendations from radiation protection organizations for charged particles of this LET. The authors suggest that similar studies using appropriate animal models of carcinogenesis would be valuable.

Organ Dose-Rate Calculations for Small Mammals at Maralinga, the Nevada Test Site, Hanford and Fukushima: A Comparison of Ellipsoidal and Voxelized Dosimetric Methodologies.

PubMed

Caffrey, Emily A; Johansen, Mathew P; Higley, Kathryn A

2015-10-01

Radiological dosimetry for nonhuman biota typically relies on calculations that utilize the Monte Carlo simulations of simple, ellipsoidal geometries with internal radioactivity distributed homogeneously throughout. In this manner it is quick and easy to estimate whole-body dose rates to biota. Voxel models are detailed anatomical phantoms that were first used for calculating radiation dose to humans, which are now being extended to nonhuman biota dose calculations. However, if simple ellipsoidal models provide conservative dose-rate estimates, then the additional labor involved in creating voxel models may be unnecessary for most scenarios. Here we show that the ellipsoidal method provides conservative estimates of organ dose rates to small mammals. Organ dose rates were calculated for environmental source terms from Maralinga, the Nevada Test Site, Hanford and Fukushima using both the ellipsoidal and voxel techniques, and in all cases the ellipsoidal method yielded more conservative dose rates by factors of 1.2-1.4 for photons and 5.3 for beta particles. Dose rates for alpha-emitting radionuclides are identical for each method as full energy absorption in source tissue is assumed. The voxel procedure includes contributions to dose from organ-to-organ irradiation (shown here to comprise 2-50% of total dose from photons and 0-93% of total dose from beta particles) that is not specifically quantified in the ellipsoidal approach. Overall, the voxel models provide robust dosimetry for the nonhuman mammals considered in this study, and though the level of detail is likely extraneous to demonstrating regulatory compliance today, voxel models may nevertheless be advantageous in resolving ongoing questions regarding the effects of ionizing radiation on wildlife.

Radiation dose rates now and in the future for residents neighboring restricted areas of the Fukushima Daiichi Nuclear Power Plant

PubMed Central

Harada, Kouji H.; Niisoe, Tamon; Imanaka, Mie; Takahashi, Tomoyuki; Amako, Katsumi; Fujii, Yukiko; Kanameishi, Masatoshi; Ohse, Kenji; Nakai, Yasumichi; Nishikawa, Tamami; Saito, Yuuichi; Sakamoto, Hiroko; Ueyama, Keiko; Hisaki, Kumiko; Ohara, Eiji; Inoue, Tokiko; Yamamoto, Kanako; Matsuoka, Yukiyo; Ohata, Hitomi; Toshima, Kazue; Okada, Ayumi; Sato, Hitomi; Kuwamori, Toyomi; Tani, Hiroko; Suzuki, Reiko; Kashikura, Mai; Nezu, Michiko; Miyachi, Yoko; Arai, Fusako; Kuwamori, Masanori; Harada, Sumiko; Ohmori, Akira; Ishikawa, Hirohiko; Koizumi, Akio

2014-01-01

Radiation dose rates were evaluated in three areas neighboring a restricted area within a 20- to 50-km radius of the Fukushima Daiichi Nuclear Power Plant in August–September 2012 and projected to 2022 and 2062. Study participants wore personal dosimeters measuring external dose equivalents, almost entirely from deposited radionuclides (groundshine). External dose rate equivalents owing to the accident averaged 1.03, 2.75, and 1.66 mSv/y in the village of Kawauchi, the Tamano area of Soma, and the Haramachi area of Minamisoma, respectively. Internal dose rates estimated from dietary intake of radiocesium averaged 0.0058, 0.019, and 0.0088 mSv/y in Kawauchi, Tamano, and Haramachi, respectively. Dose rates from inhalation of resuspended radiocesium were lower than 0.001 mSv/y. In 2012, the average annual doses from radiocesium were close to the average background radiation exposure (2 mSv/y) in Japan. Accounting only for the physical decay of radiocesium, mean annual dose rates in 2022 were estimated as 0.31, 0.87, and 0.53 mSv/y in Kawauchi, Tamano, and Haramachi, respectively. The simple and conservative estimates are comparable with variations in the background dose, and unlikely to exceed the ordinary permissible dose rate (1 mSv/y) for the majority of the Fukushima population. Health risk assessment indicates that post-2012 doses will increase lifetime solid cancer, leukemia, and breast cancer incidences by 1.06%, 0.03% and 0.28% respectively, in Tamano. This assessment was derived from short-term observation with uncertainties and did not evaluate the first-year dose and radioiodine exposure. Nevertheless, this estimate provides perspective on the long-term radiation exposure levels in the three regions. PMID:24567380

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer.

PubMed

Martinez, Alvaro A; Gustafson, Gary; Gonzalez, José; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

2002-06-01

To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose <93 Gy (58 patients) and high-dose biologically effective dose >93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p <0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p = 0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.

Dynamic Monitoring of Blood-Brain Barrier Integrity using Water Exchange Index (WEI) During Mannitol and CO2 Challenges in Mouse Brain

PubMed Central

Huang, Shuning; Farrar, Christian T.; Dai, Guangping; Kwon, Seon Joo; Bogdanov, Alexei A.; Rosen, Bruce R.; Kim, Young R.

2012-01-01

The integrity of the blood-brain barrier (BBB) is critical to normal brain function. Traditional techniques for assessing BBB disruption rely heavily on the spatiotemporal analysis of extravasating contrast agents. But such methods based on the leakage of relatively large molecules are not suitable to detect subtle BBB impairment or to perform repeated measurements in a short time frame. Quantification of the water exchange rate constant (WER) across the BBB using strictly intravascular contrast agents could provide a much more sensitive method for quantifying the BBB integrity. For estimating the WER, we have recently devised a powerful new method using a water exchange index (WEI) biomarker and demonstrated BBB disruption in an acute stroke model. Here we confirm that the WEI is sensitive to even very subtle changes in the integrity of the BBB caused by (1) systemic hypercapnia and (2) low doses of a hyperosmolar solution. In addition, we have examined the sensitivity and accuracy of the WEI as a biomarker of the WER using computer simulation. In particular, the dependence of the WEI-WER relation on changes in vascular blood volume, T1 relaxation of cellular magnetization, and transcytolemmal water exchange was explored. The simulated WEI was found to vary linearly with the WER for typically encountered exchange rate constants (1–4 Hz) regardless of the blood volume. However, for very high WER (>5 Hz) the WEI became progressively more insensitive to increasing WER. The incorporation of transcytolemmal water exchange, using a three-compartment tissue model, helped to extend the linear WEI regime to slightly higher WER, but had no significant effect for most physiologically important water exchange rate constants (WER<4 Hz). Variation in the cellular T1 had no effect on the WEI. Using both theoretical and experimental approaches, our study validates the utility of the WEI biomarker for monitoring BBB integrity. PMID:23055278

Conversion of Propellant Grade Picrite to Spherical Nitroguanidine, an Insensitive Filler for Melt-Cast TNT Formulations

DTIC Science & Technology

1991-09-01

problem with the solvent/non-solvent process reported by ICT is the inability to recycle the mother liquors. Apparently "strawberries" or " sea urchins ...inevitable for the foreseeable future. Exceptions could include lower production rate items such as sea mines or missile warheads, or speLfic nunitions where...Leitz Orthomat 35 mm automatic camera on polaroid film type 667, Magnification ranged up to X42. 14K 1* Scanning Electron Microscopy ( SEM ) SEM was

Recrystallization of polycrystalline silicon

NASA Technical Reports Server (NTRS)

Lall, C.; Kulkarni, S. B.; Graham, C. D., Jr.; Pope, D. P.

1981-01-01

Optical metallography is used to investigate the recrystallization properties of polycrystalline semiconductor-grade silicon. It is found that polycrystalline silicon recrystallizes at 1380 C in relatively short times, provided that the prior deformation is greater than 30%. For a prior deformation of about 40%, the recrystallization process is essentially complete in about 30 minutes. Silicon recrystallizes at a substantially slower rate than metals at equivalent homologous temperatures. The recrystallized grain size is insensitive to the amount of prestrain for strains in the range of 10-50%.

More on Projectile Motion.

ERIC Educational Resources Information Center

Molina, M. I.

2000-01-01

Mathematically explains why the range of a projectile is most insensitive to aiming errors when the initial angle is close to 45 degrees, whereas other observables such as maximum height or flight time are most insensitive for near-vertical launching conditions. (WRM)

Atypical blood glucose response to continuous and interval exercise in a person with type 1 diabetes: a case report.

PubMed

Moser, Othmar; Tschakert, Gerhard; Mueller, Alexander; Groeschl, Werner; Pieber, Thomas R; Koehler, Gerd; Eckstein, Max L; Bracken, Richard M; Hofmann, Peter

2017-06-30

Therapy must be adapted for people with type 1 diabetes to avoid exercise-induced hypoglycemia caused by increased exercise-related glucose uptake into muscles. Therefore, to avoid hypoglycemia, the preexercise short-acting insulin dose must be reduced for safety reasons. We report a case of a man with long-lasting type 1 diabetes in whom no blood glucose decrease during different types of exercise with varying exercise intensities and modes was found, despite physiological hormone responses. A Caucasian man diagnosed with type 1 diabetes for 24 years performed three different continuous high-intensity interval cycle ergometer exercises as part of a clinical trial (ClinicalTrials.gov identifier NCT02075567). Intensities for both modes of exercises were set at 5% below and 5% above the first lactate turn point and 5% below the second lactate turn point. Short-acting insulin doses were reduced by 25%, 50%, and 75%, respectively. Measurements taken included blood glucose, blood lactate, gas exchange, heart rate, adrenaline, noradrenaline, cortisol, glucagon, and insulin-like growth factor-1. Unexpectedly, no significant blood glucose decreases were observed during all exercise sessions (start versus end, 12.97 ± 2.12 versus 12.61 ± 2.66 mmol L -1 , p = 0.259). All hormones showed the expected response, dependent on the different intensities and modes of exercises. People with type 1 diabetes typically experience a decrease in blood glucose levels, particularly during low- and moderate-intensity exercises. In our patient, we clearly found no decline in blood glucose, despite a normal hormone response and no history of any insulin insensitivity. This report indicates that there might be patients for whom the recommended preexercise therapy adaptation to avoid exercise-induced hypoglycemia needs to be questioned because this could increase the risk of severe hyperglycemia and ketosis.

Dedicated high dose rate 192Ir brachytherapy radiation fields for in vitro cell exposures at variable source-target cell distances: killing of mammalian cells depends on temporal dose rate fluctuation

NASA Astrophysics Data System (ADS)

Veigel, Cornelia; Hartmann, Günther H.; Fritz, Peter; Debus, Jürgen; Weber, Klaus-Josef

2017-02-01

Afterloading brachytherapy is conducted by the stepwise movement of a radioactive source through surgically implanted applicator tubes where at predefined dwell positions calculated dwell times optimize spatial dose delivery with respect to a planned dose level. The temporal exposure pattern exhibits drastic fluctuations in dose rate at a given coordinate and within a single treatment session because of the discontinuous and repeated source movement into the target volume. This could potentially affect biological response. Therefore, mammalian cells were exposed as monolayers to a high dose rate 192Ir source by utilizing a dedicated irradiation device where the distance between a planar array of radioactive source positions and the plane of the cell monolayer could be varied from 2.5 mm to 40 mm, thus varying dose rate pattern for any chosen total dose. The Gammamed IIi afterloading system equipped with a nominal 370 GBq (10 Ci) 192-Ir source was used to irradiate V79 Chinese hamster lung fibroblasts from both confluent and from exponential growth phase with dose up to 12 Gy (at room temperature, total exposure not exceeding 1 h). For comparison, V79 cells were also exposed to 6 MV x-rays from a clinical linear accelerator (dose rate of 2.5 Gy min-1). As biological endpoint, cell survival was determined by standard colony forming assay. Dose measurements were conducted with a diamond detector (sensitive area 7.3 mm2), calibrated by means of 60Co radiation. Additionally, dose delivery was simulated by Monte Carlo calculations using the EGSnrc code system. The calculated secondary electron fluence spectra at the cell location did not indicate a significant change of radiation quality (i.e. higher linear energy transfer) at the lower distances. Clonogenic cell survival curves obtained after brachytherapy exhibited an altered biological response compared to x-rays which was characterized by a significant reduction of the survival curve shoulder when dose rate fluctuations were high. Therefore, also for the time scale of the present investigation, cellular effects of radiation are not invariant to the temporal pattern in dose rate. We propose that with high dose rate variation the cells activate less efficiently their DNA damage response than after continuous irradiation.

Sexual dimorphism and the effects of the X-linked Tfm locus on hexobarbitone metabolism and action in mice.

PubMed

King, D K; Shapiro, B H

1981-09-01

1 Normal males of the testicular feminized strain of mice (Tfm) had longer hexobarbitone-induced sleeping times than females, and hepatic hexobarbitone hydroxylase activity different in that the Km was higher and the Vmax lower in the male. 2 Castration and androgen replacement studies indicated that testicular androgens were responsible for the sexual differences in drug metabolism found in this mouse strain. 3 Hepatic hexobarbitone metabolism and action were feminized in the intact, androgen-insensitive, genetically male Tfm mouse. Furthermore, hexobarbitone hydroxylase activities were less responsive to large doses of testosterone in Tfm mice than in normal males. 4 The Tfm mouse with a deficiency in androgen receptors responded to the enzyme-inductive effects of phenobarbitone and softwood bedding, indicating that these inducers do not act through the androgen receptors.

Effects of 1.9 MeV monoenergetic neutrons on Vicia faba chromosomes: microdosimetric considerations.

PubMed

Geard, C R

1980-01-01

Aerated Vicia faba root meristems were irradiated with 1.9 MeV monoenergetic neutrons. This source of neutrons optimally provides one class of particles (recoil protons) with ranges able to traverse cell nuclei at moderate to high-LET. The volumes of the Vicia faba nuclei were log-normally distributed with a mean of 1100 micrometer3. The yield of chromatid-type aberrations was linear against absorbed dose and near-constant over 5 collection periods (2-12 h), after irradiation. Energy deposition events (recoil protons) determined by microdosimetry were related to cytological changes with the finding that 19% of incident recoil protons initiate visible changes in Vicia faba chromosomes. It is probable that a substantial fraction of recoil proton track length and deposited energy is in insensitive (non-DNA containing) portions of the nuclear volume.

Measurements of air dose rates in and around houses in the Fukushima Prefecture in Japan after the Fukushima accident.

PubMed

Matsuda, Norihiro; Mikami, Satoshi; Sato, Tetsuro; Saito, Kimiaki

2017-01-01

Measurements of air dose rates for 192 houses in a less contaminated area (<0.5 μSv h -1 ) of the Fukushima Prefecture in Japan were conducted in both living rooms and/or bedrooms using optically stimulated luminescence (OSL) dosimeters and around the houses via a man-borne survey at intervals of several meters. The relation of the two air dose rates (inside and outside) for each house, including the background from natural radionuclides, was divided into several categories, determined by construction materials (light and heavy) and floor number, with the dose reduction factors being expressed as the ratio of the dose inside to that outside the house. For wooden and lightweight steel houses (classed as light), the dose rates inside and outside the houses showed a positive correlation and linear regression with a slope-intercept form due to the natural background, although the degree of correlation was not very high. The regression coefficient, i.e., the average dose reduction factor, was 0.38 on the first floor and 0.49 on the second floor. It was found that the contribution of natural radiation cannot be neglected when we consider dose reduction factors in less contaminated areas. The reductions in indoor dose rates are observed because a patch of ground under each house is not contaminated (this is the so-called uncontaminated effect) since the shielding capability of light construction materials is typically low. For reinforced steel-framed concrete houses (classed as heavy), the dose rates inside the houses did not show a correlation with those outside the houses due to the substantial shielding capability of these materials. The average indoor dose rates were slightly higher than the arithmetic mean value of the outdoor dose rates from the natural background because concrete acts as a source of natural radionuclides. The characteristics of the uncontaminated effect were clarified through Monte Carlo simulations. It was found that there is a great variation in air dose rates even within one house, depending on the height of the area and its closeness to the outside boundary. Measurements of outdoor dose rates required consideration of local variations depending on the environment surrounding each house. The representative value was obtained from detailed distributions of air dose rates around the house, as measured by a man-borne survey. Therefore, it is imperative to recognize that dose reduction factors fluctuate in response to various factors such as the size and shape of a house, construction materials acting as a shield and as sources, position (including height) within a room, floor number, total number of floors, and surrounding environment. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Concomitant use of FSH and low-dose recombinant hCG during the late follicular phase versus conventional controlled ovarian stimulation for intracytoplasmic sperm injection cycles.

PubMed

Iaconelli, Carla Andrade Rebello; Setti, Amanda Souza; Braga, Daniela Paes Almeida Ferreira; Maldonado, Luiz Guilherme Louzada; Iaconelli, Assumpto; Borges, Edson; Aoki, Tsutomu

2017-12-01

The objective of this study was to investigate the effects of low-dose hCG supplementation on ICSI outcomes and controlled ovarian stimulation (COS) cost. Three hundred and thirty patients undergoing ICSI were split into groups according to the COS protocol: (i) control group (n = 178), including patients undergoing conventional COS treatment; and (ii) low-dose hCG group (n = 152), including patients undergoing COS with low-dose hCG supplementation. Lower mean total doses of FSH administered and higher mean oestradiol level and mature oocyte rates were observed in the low-dose hCG group. A significantly higher fertilization rate, high-quality embryo rate and blastocyst formation rate were observed in the low-dose hCG group as compared to the control group. The miscarriage rate was significantly higher in the control group compared to the low-dose hCG group. A significantly lower incidence of OHSS was observed in the low-dose hCG group. There was also a significantly lower gonadotropin cost in the low-dose hCG group as compared to the control group ($1235.0 ± 239.0×$1763.0 ± 405.3, p < 0.001). The concomitant use of low-dose hCG and FSH results in a lower abortion rate and increased number of mature oocytes retrieved, as well as improved oocyte quality, embryo quality and blastocyst formation and reduced FSH requirements.

Comparative analysis of dose rates in bricks determined by neutron activation analysis, alpha counting and X-ray fluorescence analysis for the thermoluminescence fine grain dating method

NASA Astrophysics Data System (ADS)

Bártová, H.; Kučera, J.; Musílek, L.; Trojek, T.

2014-11-01

In order to evaluate the age from the equivalent dose and to obtain an optimized and efficient procedure for thermoluminescence (TL) dating, it is necessary to obtain the values of both the internal and the external dose rates from dated samples and from their environment. The measurements described and compared in this paper refer to bricks from historic buildings and a fine-grain dating method. The external doses are therefore negligible, if the samples are taken from a sufficient depth in the wall. However, both the alpha dose rate and the beta and gamma dose rates must be taken into account in the internal dose. The internal dose rate to fine-grain samples is caused by the concentrations of natural radionuclides 238U, 235U, 232Th and members of their decay chains, and by 40K concentrations. Various methods can be used for determining trace concentrations of these natural radionuclides and their contributions to the dose rate. The dose rate fraction from 238U and 232Th can be calculated, e.g., from the alpha count rate, or from the concentrations of 238U and 232Th, measured by neutron activation analysis (NAA). The dose rate fraction from 40K can be calculated from the concentration of potassium measured, e.g., by X-ray fluorescence analysis (XRF) or by NAA. Alpha counting and XRF are relatively simple and are accessible for an ordinary laboratory. NAA can be considered as a more accurate method, but it is more demanding regarding time and costs, since it needs a nuclear reactor as a neutron source. A comparison of these methods allows us to decide whether the time- and cost-saving simpler techniques introduce uncertainty that is still acceptable.

Assessment of doses to game animals in Finland.

PubMed

Vetikko, Virve; Kostiainen, Eila

2013-11-01

A study was carried out to assess the dose rates to game animals in Finland affected by the radioactive caesium deposition that occurred after the accident at the Chernobyl nuclear power plant in Ukraine in 1986. The aim of this assessment was to obtain new information on the dose rates to mammals and birds under Finnish conditions. Dose rates were calculated using the ERICA Assessment Tool developed within the EC 6th Framework Programme. The input data consisted of measured activity concentrations of (137)Cs and (134)Cs in soil and lake water samples and in flesh samples of selected animal species obtained for environmental monitoring. The study sites were located in the municipality of Lammi, Southern Finland, where the average (137)Cs deposition was 46.5 kBq m(-2) (1 October 1987). The study sites represented the areas receiving the highest deposition in Finland after the Chernobyl accident. The selected species included moose (Alces alces), arctic hare (Lepus timidus) and several bird species: black grouse (Tetrao tetrix), hazel hen (Bonasia bonasia), mallard (Anas platurhynchos), goldeneye (Bucephala clangula) and teal (Anas crecca). For moose, dose rates were calculated for the years 1986-1990 and for the 2000s. For all other species, maximal measured activity concentrations were used. The results showed that the dose rates to these species did not exceed the default screening level of 10 μGy h(-1) used as a protection criterion. The highest total dose rate (internal and external summed), 3.7 μGy h(-1), was observed for the arctic hare in 1986. Although the dose rate of 3.7 μGy h(-1) cannot be considered negligible given the uncertainties involved in predicting the dose rates, the possible harmful effects related to this dose rate are too small to be assessed based on current knowledge on the biological effects of low doses in mammals. Copyright © 2013 Elsevier Ltd. All rights reserved.

The rate of decay of fresh fission products from a nuclear reactor

NASA Astrophysics Data System (ADS)

Dolan, David J.

Determining the rate of decay of fresh fission products from a nuclear reactor is complex because of the number of isotopes involved, different types of decay, half-lives of the isotopes, and some isotopes decay into other radioactive isotopes. Traditionally, a simplified rule of 7s and 10s is used to determine the dose rate from nuclear weapons and can be to estimate the dose rate from fresh fission products of a nuclear reactor. An experiment was designed to determine the dose rate with respect to time from fresh fission products of a nuclear reactor. The experiment exposed 0.5 grams of unenriched Uranium to a fast and thermal neutron flux from a TRIGA Research Reactor (Lakewood, CO) for ten minutes. The dose rate from the fission products was measured by four Mirion DMC 2000XB electronic personal dosimeters over a period of six days. The resulting dose rate following a rule of 10s: the dose rate of fresh fission products from a nuclear reactor decreases by a factor of 10 for every 10 units of time.

Surfactant for dye-penetrant inspection is insensitive to liquid oxygen

NASA Technical Reports Server (NTRS)

1966-01-01

LOX insensitive solvent is blended into a mixture of commercially available surfactants to clean metal surfaces which are to be investigated by the dye-penetrant method. The surfactant mixture is applied before and after application of the dye.

Evidence of Nicotine-Induced, Curare-Insensitive, Behavior in Planarians.

PubMed

Pagán, Oné R; Montgomery, Erica; Deats, Sean; Bach, Daniel; Baker, Debra

2015-10-01

Planarians are rapidly developing into very useful research subjects in pharmacology and neuroscience research. Here we report that curare, a cholinergic nicotinic receptor antagonist, alleviates the nicotine-induced planarian seizure-like movements (pSLM) by up to 50 % at equimolar concentrations of nicotine and curare (1 mM), while curare alone does not induce significant pSLMs. The simplest interpretation of our data is that there are nicotine induced behaviors insensitive to curare in our experimental organism. To the best of our knowledge, this is the first report on curare-insensitive, nicotine-induced effects in any organism.

New Insight into the Angle Insensitivity of Ultrathin Planar Optical Absorbers for Broadband Solar Energy Harvesting.

PubMed

Liu, Dong; Yu, Haitong; Duan, Yuanyuan; Li, Qiang; Xuan, Yimin

2016-09-01

Two challenging problems still remain for optical absorbers consisting of an ultrathin planar semiconductor film on top of an opaque metallic substrate. One is the angle-insensitive mechanism and the other is the system design needed for broadband solar energy harvesting. Here, first we theoretically demonstrates that the high refractive index, instead of the ultrathin feature as reported in previous studies, is the physical origin of the angle insensitivity for ultrathin planar optical absorbers. They exhibit omnidirectional resonance for TE polarization due to the high complex refractive index difference between the semiconductor and the air, while for TM polarization the angle insensitivity persists up to an incident angle related to the semiconductor refractive index. These findings were validated by fabricating and characterizing an 18 nm Ge/Ag absorber sample (representative of small band gap semiconductors for photovoltaic applications) and a 22 nm hematite/Ag sample (representative of large band gap semiconductors for photoelectrochemical applications). Then, we took advantage of angle insensitivity and designed a spectrum splitting configuration for broadband solar energy harvesting. The cascaded solar cell and unassisted solar water splitting systems have photovoltaic and photoelectrochemical cells that are also spectrum splitters, so an external spectrum splitting element is not needed.

Root Formation in Ethylene-Insensitive Plants1

PubMed Central

Clark, David G.; Gubrium, Erika K.; Barrett, James E.; Nell, Terril A.; Klee, Harry J.

1999-01-01

Experiments with ethylene-insensitive tomato (Lycopersicon esculentum) and petunia (Petunia × hybrida) plants were conducted to determine if normal or adventitious root formation is affected by ethylene insensitivity. Ethylene-insensitive Never ripe (NR) tomato plants produced more belowground root mass but fewer aboveground adventitious roots than wild-type Pearson plants. Applied auxin (indole-3-butyric acid) increased adventitious root formation on vegetative stem cuttings of wild-type plants but had little or no effect on rooting of NR plants. Reduced adventitious root formation was also observed in ethylene-insensitive transgenic petunia plants. Applied 1-aminocyclopropane-1-carboxylic acid increased adventitious root formation on vegetative stem cuttings from NR and wild-type plants, but NR cuttings produced fewer adventitious roots than wild-type cuttings. These data suggest that the promotive effect of auxin on adventitious rooting is influenced by ethylene responsiveness. Seedling root growth of tomato in response to mechanical impedance was also influenced by ethylene sensitivity. Ninety-six percent of wild-type seedlings germinated and grown on sand for 7 d grew normal roots into the medium, whereas 47% of NR seedlings displayed elongated taproots, shortened hypocotyls, and did not penetrate the medium. These data indicate that ethylene has a critical role in various responses of roots to environmental stimuli. PMID:10482660

Some cosmic radiation dose measurements aboard flights connecting Zagreb Airport.

PubMed

Vuković, B; Radolić, V; Lisjak, I; Vekić, B; Poje, M; Planinić, J

2008-02-01

When primary particles from space, mainly protons, enter the atmosphere, they produce interactions with air nuclei, and cosmic-ray showers are induced. The radiation field at aircraft altitude is complex, with different types of particles, mainly photons, electrons, positrons and neutrons, with a large energy range. The non-neutron component of cosmic radiation dose aboard A320 and ATR40 aircraft was measured with TLD-100 (LiF:Mg,Ti) detectors and the Mini 6100 semiconductor dosimeter; the neutron dose was measured with the neutron dosimeter consisted of LR-115 track detector and boron foil BN-1 or 10B converter. The estimated occupational effective dose for the aircraft crew (A320) working 500 h per year was 1.64 mSv. Another experiment was performed at the flights Zagreb-Paris-Buenos Aires and reversely, when one measured non-neutron cosmic radiation dose; for 26.7 h of flight, the MINI 6100 dosimeter gave an average dose rate of 2.3 microSv/h and the TLD dosimeter registered the dose equivalent of 75 microSv or the average dose rate of 2.7 microSv/h; the neutron dosimeter gave the dose rate of 2.4 microSv/h. In the same month, February 2005, a traveling to Japan (24-h-flight: Zagreb-Frankfurt-Tokyo and reversely) and the TLD-100 measurement showed the average dose rate of 2.4microSv/h; the neutron dosimeter gave the dose rate of 2.5 microSv/h. Comparing dose rates of the non-neutron component (low LET) and the neutron one (high LET) of the radiation field at the aircraft flight level, we could conclude that the neutron component carried about 50% of the total dose, that was near other known data.

SU-F-T-266: Dynalogs Based Evaluation of Different Dose Rate IMRT Using DVH and Gamma Index

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

Ahmed, S; Ahmed, S; Ahmed, F

2016-06-15

Purpose: This work investigates the impact of low and high dose rate on IMRT through Dynalogs by evaluating Gamma Index and Dose Volume Histogram. Methods: The Eclipse™ treatment planning software was used to generate plans on prostate and head and neck sites. A range of dose rates 300 MU/min and 600 MU/min were applied to each plan in order to investigate their effect on the beam ON time, efficiency and accuracy. Each plan had distinct monitor units per fraction, delivery time, mean dose rate and leaf speed. The DVH data was used in the assessment of the conformity and planmore » quality.The treatments were delivered on Varian™ Clinac 2100C accelerator equipped with 120 leaf millennium MLC. Dynalogs of each plan were analyzed by MATLAB™ program. Fluence measurements were performed using the Sun Nuclear™ 2D diode array and results were assessed, based on Gamma analysis of dose fluence maps, beam delivery statistics and Dynalogs data. Results: Minor differences found by adjusted R-squared analysis of DVH’s for all the plans with different dose rates. It has been also found that more and larger fields have greater time reduction at high dose rate and there was a sharp decrease in number of control points observed in dynalog files by switching dose rate from 300 MU/min to 600 MU/min. Gamma Analysis of all plans passes the confidence limit of ≥95% with greater number of passing points in 300 MU/min dose rate plans. Conclusion: The dynalog files are compatible tool for software based IMRT QA. It can work perfectly parallel to measurement based QA setup and stand-by procedure for pre and post delivery of treatment plan.« less

Detailed Distribution Map of Absorbed Dose Rate in Air in Tokatsu Area of Chiba Prefecture, Japan, Constructed by Car-Borne Survey 4 Years after the Fukushima Daiichi Nuclear Power Plant Accident

PubMed Central

Inoue, Kazumasa; Arai, Moeko; Fujisawa, Makoto; Saito, Kyouko; Fukushi, Masahiro

2017-01-01

A car-borne survey was carried out in the northwestern, or Tokatsu, area of Chiba Prefecture, Japan, to make a detailed distribution map of absorbed dose rate in air four years after the Fukushima Daiichi Nuclear Power Plant accident. This area was chosen because it was the most heavily radionuclide contaminated part of Chiba Prefecture and it neighbors metropolitan Tokyo. Measurements were performed using a 3-in × 3-in NaI(Tl) scintillation spectrometer in June 2015. The survey route covered the whole Tokatsu area which includes six cities. A heterogeneous distribution of absorbed dose rate in air was observed on the dose distribution map. Especially, higher absorbed dose rates in air exceeding 80 nGy h-1 were observed along national roads constructed using high porosity asphalt, whereas lower absorbed dose rates in air were observed along local roads constructed using low porosity asphalt. The difference between these asphalt types resulted in a heterogeneous dose distribution in the Tokatsu area. The mean of the contribution ratio of artificial radionuclides to absorbed dose rate in air measured 4 years after the accident was 29% (9–50%) in the Tokatsu area. The maximum absorbed dose rate in air, 201 nGy h-1 was observed at Kashiwa City. Radiocesium was deposited in the upper 1 cm surface layer of the high porosity asphalt which was collected in Kashiwa City and the environmental half-life of the absorbed dose rate in air was estimated to be 1.7 years. PMID:28129382

Effect of repeated oral therapeutic doses of methylphenidate on food intake and growth rate in rats.

PubMed

Alam, Nausheen; Najam, Rahila

2015-01-01

Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose (8mg/kg/day) and at low dose (2mg/kg/day) of methylphenidate in 1(st) and 2(nd) week whereas more decreased by the above doses in 3(rd) week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed.

Changes in ambient dose equivalent rates around roads at Kawamata town after the Fukushima accident.

PubMed

Kinase, Sakae; Sato, Satoshi; Sakamoto, Ryuichi; Yamamoto, Hideaki; Saito, Kimiaki

2015-11-01

Changes in ambient dose equivalent rates noted through vehicle-borne surveys have elucidated ecological half-lives of radioactive caesium in the environment. To confirm that the ecological half-lives are appropriate for predicting ambient dose equivalent rates within living areas, it is important to ascertain ambient dose equivalent rates on/around roads. In this study, radiation monitoring on/around roads at Kawamata town, located about 37 km northwest of the Fukushima Daiichi Nuclear Power Plant, was performed using monitoring vehicles and survey meters. It was found that the ambient dose equivalent rates around roads were higher than those on roads as of October 2012. And withal the ecological half-lives on roads were essentially consistent with those around roads. With dose predictions using ecological half-lives on roads, it is necessary to make corrections to ambient dose equivalent rates through the vehicle-borne surveys against those within living areas. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Investigation of natural effective gamma dose rates case study: Ardebil Province in Iran

PubMed Central

2012-01-01

Gamma rays pose enough energy to induce chemical changes that may be biologically important for the normal functioning of body cells. The external exposure of human beings to natural environmental gamma radiation normally exceeds that from all man-made sources combined. In this research natural background gamma dose rates and corresponding annual effective doses were determined for selected cities of Ardebil province. Outdoor gamma dose rates were measured using an Ion Chamber Survey Meter in 105 locations in selected districts. Average absorbed doses for Ardebil, Sar-Ein, Germy, Neer, Shourabil Recreational Lake, and Kosar were determined as 265, 219, 344, 233, 352, and 358 nSv/h, respectively. Although dose rates recorded for Germi and Kosar are comparable with some areas with high natural radiation background, however, the dose rates in other districts are well below the levels reported for such locations. Average annual effective dose due to indoor and outdoor gamma radiation for Ardebil province was estimated as 1.73 (1.35–2.39) mSv, which is on average 2 times higher than the world population weighted average. PMID:23369115

Evaluation of ingredients for the development of new insensitive munitions.

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

Maharrey, Sean P.; Johnston, Lois A.; Behrens, Richard, Jr.

2004-12-01

Several ingredients being considered by the U.S. Army for the development of new insensitive munitions have been examined. One set of ingredients consists of 2,4-dinitrophenylhydrazine (DNPH) and hexahydro-1,3,5-trinitro-s-triazine (RDX). In this set, the decomposition of the mixture was examined to determine whether adding DNPH to RDX would generate a sufficient quantity of gas to rupture the case of a munition prior to the onset of the rapid reaction of RDX, thus mitigating the violence of reaction. The second set of ingredients consists of three different reduced sensitivity RDX (RS-RDX) powders manufactured by SNPE and Dyno-Nobel. In this set, the objectivemore » was to determine properties of RS-RDX powders that may distinguish them from normal RDX powder and may account for their reduced shock sensitivity. The decomposition reactions and sublimation properties of these materials were examined using two unique instruments: the simultaneous thermogravimetric modulated beam mass spectrometry (STMBMS) instrument and the Fourier Transform ion cyclotron resonance (FTICR) mass spectrometry instrument. These instruments provide the capability to examine the details of decomposition reactions in energetic materials. DNPH does not appear to be a good candidate to mitigate the violence of the RDX reaction in a munition. DNPH decomposes between 170 C and 180 C. When mixed with RDX it decomposes between 155 C and 170 C. It decomposes to form 1,3-dintrobenzene (DNB), ammonia, water and nitrogen. Of these compounds only nitrogen and ammonia are capable of generating high pressures within a munition. When DNPH is mixed with RDX, the DNB formed in the decomposition of DNPH interacts with RDX on the surface of the RDX powder leading to a higher rate of formation of CH2O and N2O. The CH2O is consumed by reaction with DNPH to form 2-methylene-1-(2,4-dintrophenyl)hydrazine. As a result, DNPH does not generate a large quantity of gas that will lead to rupture of a munition case. Another compound to consider as an additive is 2-oxo-1,3,5-trinitro-1,3,5-triazacyclohexane (K-6), which generates more gas in the required temperature range. Examination of several different RS-RDX materials has shown that their sublimation rates and decomposition behavior differ from Holston grade RDX. The results suggest that insensitive RDX materials from both SNPE and Dyno-Nobel may have a shell-like structure of RDX on the surface of the particles that is less stable and more reactive than the material in the core of the particles. The origin of this shell-like RDX structure is uncertain, but may be due to some aspect of the manufacturing process. It is possible that this less stable RDX on the surface of the particles may be more fluid than the interior of the particles, allowing more slip between the surface of the particles under impact or shock. This may play a role in the reduced shock sensitivity of the insensitive RDX materials. The results of over 50 experiments with DNPH, mixtures of DNPH and RDX and insensitive RDX are presented. The results characterize the decomposition behavior of each of these materials.« less

MAGIC with formaldehyde applied to dosimetry of HDR brachytherapy source

NASA Astrophysics Data System (ADS)

Marques; T; Fernandes; J; Barbi; G; Nicolucci; P; Baffa; O

2009-05-01

The use of polymer gel dosimeters in brachytherapy can allow the determination of three-dimensional dose distributions in large volumes and with high spatial resolution if an adequate calibration process is performed. One of the major issues in these experiments is the polymer gel response dependence on dose rate when high dose rate sources are used and the doses in the vicinity of the sources are to be determinated. In this study, the response of a modified MAGIC polymer gel with formaldehyde around an Iridium-192 HDR brachytherapy source is presented. Experimental results obtained with this polymer gel were compared with ionization chamber measurements and with Monte Carlo simulation with PENELOPE. A maximum difference of 3.10% was found between gel dose measurements and Monte Carlo simulation at a radial distance of 18 mm from the source. The results obtained show that the gel's response is strongly influenced by dose rate and that a different calibration should be used for the vicinity of the source and for regions of lower dose rates. The results obtained in this study show that, provided the proper calibration is performed, MAGIC with formaldehyde can be successfully used to accurate determinate dose distributions form high dose rate brachytherapy sources.

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.

Analysis of Potassium in Bricks--Determining the Dose Rate from {sup 40}K for Thermoluminescence Dating

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

Musilek, Ladislav; Polach, Tomas; Trojek, Tomas

2008-08-07

Thermoluminescence (TL) dating is based on accumulating the natural radiation dose in the material of a dated artefact (brick, pottery, etc.), and comparing the dose accumulated during the lifetime of the object with the dose rate within the sample collected for TL measurement. Determining the dose rate from natural radionuclides in materials is one of the most important and most difficult parts of the technique. The most important radionuclides present are usually nuclides of the uranium and thorium decay series and {sup 40}K. An analysis of the total potassium concentration enables us to determine the {sup 40}K content effectively, andmore » from this it is possible to calculate the dose rate originating from this radiation source. X-ray fluorescence (XRF) analysis can be used to determine the potassium concentration in bricks rapidly and efficiently. The procedure for analysing potassium, examples of results of dose rate calculation and possible sources of error are described here.« less

Dose-rate effect of ultrashort electron beam radiation on DNA damage and repair in vitro.

PubMed

Babayan, Nelly; Hovhannisyan, Galina; Grigoryan, Bagrat; Grigoryan, Ruzanna; Sarkisyan, Natalia; Tsakanova, Gohar; Haroutiunian, Samvel; Aroutiounian, Rouben

2017-11-01

Laser-generated electron beams are distinguished from conventional accelerated particles by ultrashort beam pulses in the femtoseconds to picoseconds duration range, and their application may elucidate primary radiobiological effects. The aim of the present study was to determine the dose-rate effect of laser-generated ultrashort pulses of 4 MeV electron beam radiation on DNA damage and repair in human cells. The dose rate was increased via changing the pulse repetition frequency, without increasing the electron energy. The human chronic myeloid leukemia K-562 cell line was used to estimate the DNA damage and repair after irradiation, via the comet assay. A distribution analysis of the DNA damage was performed. The same mean level of initial DNA damages was observed at low (3.6 Gy/min) and high (36 Gy/min) dose-rate irradiation. In the case of low-dose-rate irradiation, the detected DNA damages were completely repairable, whereas the high-dose-rate irradiation demonstrated a lower level of reparability. The distribution analysis of initial DNA damages after high-dose-rate irradiation revealed a shift towards higher amounts of damage and a broadening in distribution. Thus, increasing the dose rate via changing the pulse frequency of ultrafast electrons leads to an increase in the complexity of DNA damages, with a consequent decrease in their reparability. Since the application of an ultrashort pulsed electron beam permits us to describe the primary radiobiological effects, it can be assumed that the observed dose-rate effect on DNA damage/repair is mainly caused by primary lesions appearing at the moment of irradiation. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Effects of breast-air and breast-lung interfaces on the dose rate at the planning target volume of a MammoSite catheter for Yb-169 and Ir-192 HDR sources

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

Cazeca, Mario J.; Medich, David C.; Munro, John J. III

2010-08-15

Purpose: To study the effects of the breast-air and breast-lung interfaces on the absorbed dose within the planning target volume (PTV) of a MammoSite balloon dose delivery system as well as the effect of contrast material on the dose rate in the PTV. Methods: The Monte Carlo MCNP5 code was used to simulate dose rate in the PTV of a 2 cm radius MammoSite balloon dose delivery system. The simulations were carried out using an average female chest phantom (AFCP) and a semi-infinite water phantom for both Yb-169 and Ir-192 high dose rate sources for brachytherapy application. Gastrografin was introducedmore » at varying concentrations to study the effect of contrast material on the dose rate in the PTV. Results: The effect of the density of the materials surrounding the MammoSite balloon containing 0% contrast material on the calculated dose rate at different radial distances in the PTV was demonstrated. Within the PTV, the ratio of the calculated dose rate for the AFCP and the semi-infinite water phantom for the point closest to the breast-air interface (90 deg.) is less than that for the point closest to the breast-lung interface (270 deg.) by 11.4% and 4% for the HDR sources of Yb-169 and Ir-192, respectively. When contrast material was introduced into the 2 cm radius MammoSite balloon at varying concentrations, (5%, 10%, 15%, and 20%), the dose rate in the AFCP at 3.0 cm radial distance at 90 deg. was decreased by as much as 14.8% and 6.2% for Yb-169 and Ir-192, respectively, when compared to that of the semi-infinite water phantom with contrast concentrations of 5%, 10%, 15%, and 20%, respectively. Conclusions: Commercially available software used to calculate dose rate in the PTV of a MammoSite balloon needs to account for patient anatomy and density of surrounding materials in the dosimetry analyses in order to avoid patient underdose.« less

49 CFR 173.50 - Class 1-Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... insensitive that there is very little probability of initiation or of transition from burning to detonation under normal conditions of transport. 1 The probability of transition from burning to detonation is... contain only extremely insensitive detonating substances and which demonstrate a negligible probability of...

Pricing index-based catastrophe bonds: Part 2: Object-oriented design issues and sensitivity analysis

NASA Astrophysics Data System (ADS)

Unger, André J. A.

2010-02-01

This work is the second installment in a two-part series, and focuses on object-oriented programming methods to implement an augmented-state variable approach to aggregate the PCS index and introduce the Bermudan-style call feature into the proposed CAT bond model. The PCS index is aggregated quarterly using a discrete Asian running-sum formulation. The resulting aggregate PCS index augmented-state variable is used to specify the payoff (principle) on the CAT bond based on reinsurance layers. The purpose of the Bermudan-style call option is to allow the reinsurer to minimize their interest rate risk exposure on making fixed coupon payments under prevailing interest rates. A sensitivity analysis is performed to determine the impact of uncertainty in the frequency and magnitude of hurricanes on the price of the CAT bond. Results indicate that while the CAT bond is highly sensitive to the natural variability in the frequency of landfalling hurricanes between El Ninõ and non-El Ninõ years, it remains relatively insensitive to uncertainty in the magnitude of damages. In addition, results indicate that the maximum price of the CAT bond is insensitive to whether it is engineered to cover low frequency high magnitude events in a 'high' reinsurance layer relative to high frequency low magnitude events in a 'low' reinsurance layer. Also, while it is possible for the reinsurer to minimize their interest rate risk exposure on the fixed coupon payments, the impact of this risk on the price of the CAT bond appears small relative to the natural variability in the CAT bond price, and consequently catastrophic risk, due to uncertainty in the frequency and magnitude of landfalling hurricanes.

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

Ritter, Boyd

Insensitive high explosives (IHEs) based on 1,3,5-triamino 2,4,6-trinitro-benzene (TATB) are the IHEs of choice for use in nuclear warheads over conventional high explosives when safety is the only consideration, because they are very insensitive to thermal or mechanical initiation stimuli. It is this inherent insensitivity to high temperatures, shock, and impact, which provides detonation design challenges when designing TATB explosive systems while at the same time providing a significant level of protection against accidental initiation. Although classified as IHE, over the past few years the focus on explosive safety has demonstrated that the shock sensitivity of TATB is influenced withmore » respect to temperature. A number of studies have been performed on TATB and TATB formulations, plastic bonded explosives (PBX) 9502, and LX-17-01 (LX-17), which demonstrates the increase in shock sensitivity of the explosive after it has been preheated or thermally cycled over various temperature ranges. Many studies suggest the change in sensitivity is partly due to the decomposition rates of the temperature elevated TATB. Others point to the coefficient of thermal expansion, the crystalline structures of TATB and/or the combination of all factors, which create voids which can become active hot spots. During thermal cycling, TATB is known to undergo an irreversible increase in specific volume called ratchet growth. This increase in specific volume correlates to a decrease in density. This decrease in density and increase in volume, demonstrate the creations of additional void spaces which could serve as potential new initiation hot spots thus, increasing the overall sensitivity of the HE. This literature review evaluates the published works to understand why the shock sensitivity of TATB-based plastic bonded explosives (PBXs) changes with temperature.« less

The regulatory properties of Rubisco activase differ among species and affect photosynthetic induction during light transitions.

PubMed

Carmo-Silva, A Elizabete; Salvucci, Michael E

2013-04-01

Rubisco's catalytic chaperone, Rubisco activase (Rca), uses the energy from ATP hydrolysis to restore catalytic competence to Rubisco. In Arabidopsis (Arabidopsis thaliana), inhibition of Rca activity by ADP is fine tuned by redox regulation of the α-isoform. To elucidate the mechanism for Rca regulation in species containing only the redox-insensitive β-isoform, the response of activity to ADP was characterized for different Rca forms. When assayed in leaf extracts, Rubisco activation was significantly inhibited by physiological ratios of ADP to ATP in species containing both α-Rca and β-Rca (Arabidopsis and camelina [Camelina sativa]) or just the β-Rca (tobacco [Nicotiana tabacum]). However, Rca activity was insensitive to ADP inhibition in an Arabidopsis transformant, rwt43, which expresses only Arabidopsis β-Rca, although not in a transformant of Arabidopsis that expresses a tobacco-like β-Rca. ATP hydrolysis by recombinant Arabidopsis β-Rca was much less sensitive to inhibition by ADP than recombinant tobacco β-Rca. Mutation of 17 amino acids in the tobacco β-Rca to the corresponding Arabidopsis residues reduced ADP sensitivity. In planta, Rubisco deactivated at low irradiance except in the Arabidopsis rwt43 transformant containing an ADP-insensitive Rca. Induction of CO2 assimilation after transition from low to high irradiance was much more rapid in the rwt43 transformant compared with plants containing ADP-sensitive Rca forms. The faster rate of photosynthetic induction and a greater enhancement of growth under a fluctuating light regime by the rwt43 transformant compared with wild-type Arabidopsis suggests that manipulation of Rca regulation might provide a strategy for enhancing photosynthetic performance in certain variable light environments.

Cell cycle-tailored targeting of metastatic melanoma: Challenges and opportunities.

PubMed

Haass, Nikolas K; Gabrielli, Brian

2017-07-01

The advent of targeted therapies of metastatic melanoma, such as MAPK pathway inhibitors and immune checkpoint antagonists, has turned dermato-oncology from the "bad guy" to the "poster child" in oncology. Current targeted therapies are effective, although here is a clear need to develop combination therapies to delay the onset of resistance. Many antimelanoma drugs impact on the cell cycle but are also dependent on certain cell cycle phases resulting in cell cycle phase-specific drug insensitivity. Here, we raise the question: Have combination trials been abandoned prematurely as ineffective possibly only because drug scheduling was not optimized? Firstly, if both drugs of a combination hit targets in the same melanoma cell, cell cycle-mediated drug insensitivity should be taken into account when planning combination therapies, timing of dosing schedules and choice of drug therapies in solid tumors. Secondly, if the combination is designed to target different tumor cell subpopulations of a heterogeneous tumor, one drug effective in a particular subpopulation should not negatively impact on the other drug targeting another subpopulation. In addition to the role of cell cycle stage and progression on standard chemotherapeutics and targeted drugs, we discuss the utilization of cell cycle checkpoint control defects to enhance chemotherapeutic responses or as targets themselves. We propose that cell cycle-tailored targeting of metastatic melanoma could further improve therapy outcomes and that our real-time cell cycle imaging 3D melanoma spheroid model could be utilized as a tool to measure and design drug scheduling approaches. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Multiple Interactions between Glucose and Brassinosteroid Signal Transduction Pathways in Arabidopsis Are Uncovered by Whole-Genome Transcriptional Profiling1

PubMed Central

2015-01-01

Brassinosteroid (BR) and glucose (Glc) regulate many common responses in plants. Here, we demonstrate that under etiolated growth conditions, extensive interdependence/overlap occurs between BR- and Glc-regulated gene expression as well as physiological responses. Glc could regulate the transcript level of 72% of BR-regulated genes at the whole-genome level, of which 58% of genes were affected synergistically and 42% of genes were regulated antagonistically. Presence of Glc along with BR in medium could affect BR induction/repression of 85% of BR-regulated genes. Glc could also regulate several genes involved in BR metabolism and signaling. Both BR and Glc coregulate a large number of genes involved in abiotic/biotic stress responses and growth and development. Physiologically, Glc and BR interact to regulate hypocotyl elongation growth of etiolated Arabidopsis (Arabidopsis thaliana) seedlings in a dose-dependent manner. Glc may interact with BR via a HEXOKINASE1 (HXK1)-mediated pathway to regulate etiolated hypocotyl elongation. BRASSINOSTEROID INSENSITIVE1 (BRI1) is epistatic to HXK1, as the Glc insensitive2bri1-6 double mutant displayed severe defects in hypocotyl elongation growth similar to its bri1-6 parent. Analysis of Glc and BR sensitivity in mutants defective in auxin response/signaling further suggested that Glc and BR signals may converge at S-phase kinase-associated protein1-Cullin-F-box-TRANSPORT INHIBITOR RESPONSE1/AUXIN-RELATED F-BOX-AUXIN/INDOLE-3-ACETIC ACID-mediated auxin-signaling machinery to regulate etiolated hypocotyl elongation growth in Arabidopsis. PMID:26034265

( sup 3 H)RO15-4513 binding to cerebellar diazepam-sensitive and insensitive GABAA receptors is unchanged by one week of ethanol intake

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

Martin, M.W.; Chen, J.P.; Wallis, C.

1992-02-26

({sup 3}H)RO15-4513, a partial inverse agonist at GABAA receptors, binds to two sites in cerebellar membranes, one sensitive (DZ-S) and one insensitive (DZ-IS) to inhibition by diazepam. These binding sites may represent different isoforms of the GABAA receptor and may play a role in ethanol (EtOH) dependence. The authors tested the hypothesis that chronic intake of EtOH induces changes in the binding properties of one or both of these putative GABBA receptors. Rats were fed a liquid diet of 4.5% EtOH for 7 d, gavaged with a 3g/kg dose of EtOH, and then sacrificed after 2 h, 12 h, ormore » 4.5 d. Binding of ({sup 3}H)RO15-4513 to cerebellar membranes was performed in the absence or presence of 10{mu}M diazepam (DZ-IS binding); DZ-S binding was calculated as the difference between total and DZ-IS. Nonlinear regression analysis showed that each class of binding site fit a model of mass action binding to a single, noninteractive population of sites. No significant difference was observed between any of the treatment groups in the apparent affinity (Kd) for ({sup 3}H)RO15-4513 at total, DZ-S, or DZ-IS sites following chronic EtOH intake or withdrawal. In addition, no significant difference was observed in the apparent number of DZ-S or DZ-IS binding sites or the ratio of DZ-S to DZ-IS.« less

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

Devic, Slobodan; Tomic, Nada; Aldelaijan, Saad

Purpose: Despite numerous advantages of radiochromic film dosimeter (high spatial resolution, near tissue equivalence, low energy dependence) to measure a relative dose distribution with film, one needs to first measure an absolute dose (following previously established reference dosimetry protocol) and then convert measured absolute dose values into relative doses. In this work, we present result of our efforts to obtain a functional form that would linearize the inherently nonlinear dose-response curve of the radiochromic film dosimetry system. Methods: Functional form [{zeta}= (-1){center_dot}netOD{sup (2/3)}/ln(netOD)] was derived from calibration curves of various previously established radiochromic film dosimetry systems. In order to testmore » the invariance of the proposed functional form with respect to the film model used we tested it with three different GAFCHROMIC Trade-Mark-Sign film models (EBT, EBT2, and EBT3) irradiated to various doses and scanned on a same scanner. For one of the film models (EBT2), we tested the invariance of the functional form to the scanner model used by scanning irradiated film pieces with three different flatbed scanner models (Epson V700, 1680, and 10000XL). To test our hypothesis that the proposed functional argument linearizes the response of the radiochromic film dosimetry system, verification tests have been performed in clinical applications: percent depth dose measurements, IMRT quality assurance (QA), and brachytherapy QA. Results: Obtained R{sup 2} values indicate that the choice of the functional form of the new argument appropriately linearizes the dose response of the radiochromic film dosimetry system we used. The linear behavior was insensitive to both film model and flatbed scanner model used. Measured PDD values using the green channel response of the GAFCHROMIC Trade-Mark-Sign EBT3 film model are well within {+-}2% window of the local relative dose value when compared to the tabulated Cobalt-60 data. It was also found that criteria of 3%/3 mm for an IMRT QA plan and 3%/2 mm for a brachytherapy QA plan are passing 95% gamma function points. Conclusions: In this paper, we demonstrate the use of functional argument to linearize the inherently nonlinear response of a radiochromic film based reference dosimetry system. In this way, relative dosimetry can be conveniently performed using radiochromic film dosimetry system without the need of establishing calibration curve.« less

Dose and dose rate effects of whole-body proton-irradiation on lymphocyte blastogenesis and hematological variables: part II

NASA Technical Reports Server (NTRS)

Pecaut, Michael J.; Gridley, Daila S.; Smith, Anna L.; Nelson, Gregory A.

2002-01-01

The goal of part II of this study was to evaluate functional characteristics of leukocytes and circulating blood cell parameters after whole-body proton irradiation at varying doses and at low- and high-dose-rates (LDR and HDR, respectively). C57BL/6 mice (n=51) were irradiated and euthanized at 4 days post-exposure for assay. Significant radiation dose- (but not dose-rate-) dependent decreases were observed in splenocyte responses to T and B cell mitogens when compared to sham-irradiated controls (P<0.001). Spontaneous blastogenesis, also significantly dose-dependent, was increased in both blood and spleen (P<0.001). Red blood cell counts, hemoglobin concentration, and hematocrit were decreased in a dose-dependent manner (P<0.05), whereas thrombocyte numbers were only slightly affected. Comparison of proton- and gamma-irradiated groups (both receiving 3 Gy at HDR) showed a higher level of spontaneous blastogenesis in blood leukocytes and a lower splenocyte response to concanavalin A following proton irradiation (P<0.05). There were no dose rate effects. Collectively, the data demonstrate that the measurements in blood and spleen were largely dependent upon the total dose of proton radiation and that an 80-fold difference in the dose rate was not a significant factor. A difference, however, was found between protons and gamma-rays in the degree of change induced in some of the measurements.

The Schwarzschild effect of the dosimetry film Kodak EDR 2.

PubMed

Djouguela, A; Kollhoff, R; Rubach, A; Harder, D; Poppe, B

2005-11-07

The magnitude of the Schwarzschild effect or failure of the reciprocity law has been experimentally investigated for the dosimetry film EDR 2 from Kodak. When the dose rate applied to achieve a given dose was reduced by a factor of 12, the net optical density was reduced by up to 5%. The clinical importance of this effect is negligible as long as the films are calibrated at a value of the dose rate approximately representative of the dose rates occurring in the target volume, but in target regions of strongly reduced dose rate the Schwarzschild effect should be allowed for by a correction of the net optical density.

Investigation of insecticide-resistance status of Cydia pomonella in Chinese populations.

PubMed

Yang, X-Q; Zhang, Y-L

2015-06-01

The codling moth Cydia pomonella (L.) is an economically important fruit pest and it has been directly targeted by insecticides worldwide. Serious resistance to insecticides has been reported in many countries. As one of the most serious invasive pest, the codling moth has populated several areas in China. However, resistance to insecticides has not been reported in China. We investigated the insecticide-resistance status of four field populations from Northwestern China by applying bioassays, enzyme activities, and mutation detections. Diagnostic concentrations of lambda-cyhalothrin, chlorpyrifos-ethyl, carbaryl, and imidacloprid were determined and used in bioassays. Field populations were less susceptible to chlorpyrifos-ethyl and carbaryl than laboratory strain. Insensitive populations displayed an elevated glutathione S-transferases (GSTs) activity. Reduced carboxylesterase (CarE) activity was observed in some insecticide insensitive populations and reduced acetylcholinesterase activity was observed only in the Wuw population. The cytochrome P450 polysubstrate monooxygenases activities in four field populations were not found to be different from susceptible strains. Neither the known-resistance mutation F399V in the acetylcholinesterase (AChE) gene, ace1, nor mutations in CarE gene CpCE-1 were found in adult individuals from our field populations. Native-PAGE revealed that various CarE isozymes and AChE insensitivity were occurring among Chinese populations. Our results indicate that codling moth populations from Northwestern China were insensitivity to chlorpyrifos-ethyl and carbaryl. Increased GST activity was responsible for insecticides insensitivity. Decreased CarE activity, as well as the presence of CarE and AChE polymorphisms might also be involved in insecticides insensitivity. New management strategies for managing this pest are discussed.

Host perception of jasmonates promotes infection by Fusarium oxysporum formae speciales that produce isoleucine- and leucine-conjugated jasmonates.

PubMed

Cole, Stephanie J; Yoon, Alexander J; Faull, Kym F; Diener, Andrew C

2014-08-01

Three pathogenic forms, or formae speciales (f. spp.), of Fusarium oxysporum infect the roots of Arabidopsis thaliana below ground, instigating symptoms of wilt disease in leaves above ground. In previous reports, Arabidopsis mutants that are deficient in the biosynthesis of abscisic acid or salicylic acid or insensitive to ethylene or jasmonates exhibited either more or less wilt disease, than the wild-type, implicating the involvement of hormones in the normal host response to F. oxysporum. Our analysis of hormone-related mutants finds no evidence that endogenous hormones contribute to infection in roots. Mutants that are deficient in abscisic acid and insensitive to ethylene show no less infection than the wild-type, although they exhibit less disease. Whether a mutant that is insensitive to jasmonates affects infection depends on which forma specialis (f. sp.) is infecting the roots. Insensitivity to jasmonates suppresses infection by F. oxysporum f. sp. conglutinans and F. oxysporum f. sp. matthioli, which produce isoleucine- and leucine-conjugated jasmonate (JA-Ile/Leu), respectively, in culture filtrates, whereas insensitivity to jasmonates has no effect on infection by F. oxysporum f. sp. raphani, which produces no detectable JA-Ile/Leu. Furthermore, insensitivity to jasmonates has no effect on wilt disease of tomato, and the tomato pathogen F. oxysporum f. sp. lycopersici produces no detectable jasmonates. Thus, some, but not all, F. oxysporum pathogens appear to utilize jasmonates as effectors, promoting infection in roots and/or the development of symptoms in shoots. Only when the infection of roots is promoted by jasmonates is wilt disease enhanced in a mutant deficient in salicylic acid biosynthesis. © 2014 BSPP AND JOHN WILEY & SONS LTD.

Insensitivity to scope in contingent valuation studies: reason for dismissal of valuations?

PubMed

Søgaard, Rikke; Lindholt, Jes; Gyrd-Hansen, Dorte

2012-11-01

The credibility of contingent valuation studies has been questioned because of the potential occurrence of scope insensitivity, i.e. that respondents do not react to higher quantities or qualities of a good. The aim of this study was to examine the extent of scope insensitivity and to assess the relevance of potential explanations that may help to shed light on how to appropriately handle this problem in contingent valuation studies. We surveyed a sample of 2004 men invited for cardiovascular disease screening. Each respondent had three contingent valuation tasks from which their sensitivity to larger risk reductions (test 1) and to change in travel costs associated with participation (test 2) could be assessed. Participants were surveyed while waiting for their screening session. Non-participants were surveyed by postal questionnaire. The sample was overall found to be sensitive to scope, testing at the conventional sample-mean level. At the individual respondent level, however, more than half of the respondents failed the tests. Potential determinants for failing the tests were examined in alternative regression models but few consistent relationships were identified. One exception was the influence of more detailed information, which was positively associated with willingness to pay and negatively associated with scope sensitivity. Possible explanations for scope insensitivity are discussed; if cognitive limitations, emotional load and mental budgeting explain scope insensitivity there are grounds for rejecting valuations, whereas other factors such as the alternative theoretical framework of regret theory may render insensitivity to scope a result of rational thinking. It is concluded that future contingent valuation studies should focus more on extracting the underlying motives for the stated preferences in order to appropriately deal with responses that are seemingly irrational, and which may lead to imprecise welfare estimates.

Dose-rate effects of Co60 irradiation on performance and physiology in monkeys. Topical report

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

Bruner, A.; Bogo, V.; Henderson, E.A.

1975-07-30

One thousand rad /sup 60/Co was administered to 12 monkeys at 75 rad/min and to 8 monkeys at 50 rad/min while they performed a delayed match-to-sample, shock avoidance task. Only four at 75 rad/min and two at 50 rad/min showed early performance decrement and/or early transient incapacitation (PD-ETI), in contrast to 13 of 16 previously studied monkeys who showed PD-ETI with an average dose rate of 180 rad/min. A dose-rate effect was concluded. When these three groups were compared with an untrained group exposed to a 4000-rad gamma-neutron pulse, all showed similar degrees of hypotension postirradiation. But the onset ofmore » hypotension was delayed and its rate of fall prolonged as dose rate decreased. Tentative interpretation was that radiation thresholds for the induction of PD-ETI exist for cumulative dose (+ or - 300 rad, midbody) and dose rate (+ or - 30 rad/min). (GRA)« less

Nanocluster irradiation evolution in Fe-9%Cr ODS and ferritic-martensitic alloys

NASA Astrophysics Data System (ADS)

Swenson, M. J.; Wharry, J. P.

2017-12-01

The objective of this study is to evaluate the influence of dose rate and cascade morphology on nanocluster evolution in a model Fe-9%Cr oxide dispersion strengthened steel and the commercial ferritic/martensitic (F/M) alloys HCM12A and HT9. We present a large, systematic data set spanning the three alloys, three irradiating particle types, four orders of magnitude in dose rate, and doses ranging 1-100 displacements per atom over 400-500 °C. Nanoclusters are characterized using atom probe tomography. ODS oxide nanoclusters experience partial dissolution after irradiation due to inverse Ostwald ripening, while F/M nanoclusters undergo Ostwald ripening. Damage cascade morphology is indicative of nanocluster number density evolution. Finally, the effects of dose rate on nanocluster morphology provide evidence for a temperature dilation theory, which purports that a negative temperature shift is necessary for higher dose rate irradiations to emulate nanocluster evolution in lower dose rate irradiations.

Remanent dose rates around the collimators of the LHC beam cleaning insertions.

PubMed

Brugger, M; Roesler, S

2005-01-01

The LHC will require an extremely powerful and unprecedented collimation system. As approximately 30% of the LHC beam is lost in the cleaning insertions, these will become some of the most radioactive locations around the entire LHC ring. Thus, remanent dose rates to be expected during later repair or maintenance interventions must be considered in the design phase itself. As a consequence, the beam cleaning insertions form a unique test bed for a recently developed approach to calculate remanent dose rates. A set of simulations, different in complexity, is used in order to evaluate methods for the estimation of remanent dose rates. The scope, as well as the restrictions, of the omega-factor method are shown and compared with the explicit simulation approach. The latter is then used to calculate remanent dose rates in the beam cleaning insertions. Furthermore, a detailed example for maintenance dose planning is given.

Intrathecal application of the nimodipine slow-release microparticle system eg-1962 for prevention of delayed cerebral ischemia and improvement of outcome after aneurysmal subarachnoid hemorrhage.

PubMed

Etminan, Nima; Macdonald, R Loch; Davis, Cara; Burton, Kevin; Steiger, Hans-Jakob; Hänggi, Daniel

2015-01-01

The effective reduction of delayed cerebral ischemia (DCI), a main contributor for poor outcome following aneurysmal subarachnoid hemorrhage (SAH), remains challenging. Previous clinical trials on systemic pharmaceutical treatment of SAH mostly failed to improve outcome, probably because of insensitive pharmaceutical targets and outcome measures, small sample size, insufficient subarachnoid drug concentrations and also detrimental, systemic effects of the experimental treatment per se. Interestingly, in studies that are more recent, intrathecal administration of nicardipine pellets following surgical aneurysm repair was suggested to have a beneficial effect on DCI and neurological outcome. However, this positive effect remained restricted to patients who were treated surgically for a ruptured aneurysm. Because of the favorable results of the preclinical data on DCI and neurological outcome in the absence of neurotoxicity or systemic side effects, we are initiating clinical trials. The PROMISE (Prolonged Release nimOdipine MIcro particles after Subarachnoid hemorrhage) trial is designed as an unblinded, nonrandomized, single-center, single-dose, dose-escalation safety and tolerability phase 1 study in patients surgically treated for aSAH and will investigate the effect of intracisternal EG-1962 administration. The NEWTON (Nimodipine microparticles to Enhance recovery While reducing TOxicity after subarachNoid hemorrhage) trial is a phase 1/2a multicenter, controlled, randomized, open-label, dose-escalation, safety, tolerability, and pharmacokinetic study comparing EG-1962 and nimodipine in patients with aneurysmal SAH.

Effect of Folic Acid and Vitamin B12 on Pemetrexed Antifolate Chemotherapy in Nutrient Lung Cancer Cells

PubMed Central

Yang, Tsung-Ying; Chang, Gee-Chen; Hsu, Shih-Lan; Huang, Yi-Rou; Chiu, Ling-Yen

2013-01-01

Pemetrexed (MTA) is a multitargeted antifolate drug approved for lung cancer therapy. Clinically, supplementation with high doses of folic acid (FA) and vitamin B12 (VB12) lowers MTA cytotoxicities. An antagonistic effect of FA/VB12 on MTA efficacy has been proposed. However, patients who receive FA/VB12 show better tolerance to MTA with improved survival. The aims of this study are to investigate the modulation of FA and VB12 on MTA drug efficacy in human nonsmall cell lung cancer (NSCLC) cell lines. The sensitivities of cells, apoptosis, and MTA-regulated proteins were characterized to determine the possible effects of high doses of FA and VB12 on MTA efficacy. MTA has the lowest efficacy under 10% serum conditions. However, supplementation with FA and VB12 individually and additively reversed the insensitivity of NSCLC cells to MTA treatment with 10% serum. The enhanced sensitivities of cells following FA/VB12 treatment were correlated with increasing apoptosis and were specific to MTA but not to 5-fluorouracil (5-FU). Enhanced sensitivity was also associated with p21WAF1/Cip1 expression level. Our results revealed no antagonistic effect of high doses of FA/VB12 on MTA efficacy in cancer cells grown in nutrient medium. Furthermore, these data may partially explain why supplementation of FA and VB12 resulted in better survival in MTA-treated patients. PMID:23984356

High dose-per-pulse electron beam dosimetry - A model to correct for the ion recombination in the Advanced Markus ionization chamber.

PubMed

Petersson, Kristoffer; Jaccard, Maud; Germond, Jean-François; Buchillier, Thierry; Bochud, François; Bourhis, Jean; Vozenin, Marie-Catherine; Bailat, Claude

2017-03-01

The purpose of this work was to establish an empirical model of the ion recombination in the Advanced Markus ionization chamber for measurements in high dose rate/dose-per-pulse electron beams. In addition, we compared the observed ion recombination to calculations using the standard Boag two-voltage-analysis method, the more general theoretical Boag models, and the semiempirical general equation presented by Burns and McEwen. Two independent methods were used to investigate the ion recombination: (a) Varying the grid tension of the linear accelerator (linac) gun (controls the linac output) and measuring the relative effect the grid tension has on the chamber response at different source-to-surface distances (SSD). (b) Performing simultaneous dose measurements and comparing the dose-response, in beams with varying dose rate/dose-per-pulse, with the chamber together with dose rate/dose-per-pulse independent Gafchromic™ EBT3 film. Three individual Advanced Markus chambers were used for the measurements with both methods. All measurements were performed in electron beams with varying mean dose rate, dose rate within pulse, and dose-per-pulse (10 -2  ≤ mean dose rate ≤ 10 3 Gy/s, 10 2  ≤ mean dose rate within pulse ≤ 10 7  Gy/s, 10 -4  ≤ dose-per-pulse ≤ 10 1  Gy), which was achieved by independently varying the linac gun grid tension, and the SSD. The results demonstrate how the ion collection efficiency of the chamber decreased as the dose-per-pulse increased, and that the ion recombination was dependent on the dose-per-pulse rather than the dose rate, a behavior predicted by Boag theory. The general theoretical Boag models agreed well with the data over the entire investigated dose-per-pulse range, but only for a low polarizing chamber voltage (50 V). However, the two-voltage-analysis method and the Burns & McEwen equation only agreed with the data at low dose-per-pulse values (≤ 10 -2 and ≤ 10 -1  Gy, respectively). An empirical model of the ion recombination in the chamber was found by fitting a logistic function to the data. The ion collection efficiency of the Advanced Markus ionization chamber decreases for measurements in electron beams with increasingly higher dose-per-pulse. However, this chamber is still functional for dose measurements in beams with dose-per-pulse values up toward and above 10 Gy, if the ion recombination is taken into account. Our results show that existing models give a less-than-accurate description of the observed ion recombination. This motivates the use of the presented empirical model for measurements with the Advanced Markus chamber in high dose-per-pulse electron beams, as it enables accurate absorbed dose measurements (uncertainty estimation: 2.8-4.0%, k = 1). The model depends on the dose-per-pulse in the beam, and it is also influenced by the polarizing chamber voltage, with increasing ion recombination with a lowering of the voltage. © 2017 American Association of Physicists in Medicine.

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

Zhang, Y; Giebeler, A; Mascia, A

Purpose: To quantitatively evaluate dosimetric consequence of spot size variations and validate beam-matching criteria for commissioning a pencil beam model for multiple treatment rooms. Methods: A planning study was first conducted by simulating spot size variations to systematically evaluate dosimetric impact of spot size variations in selected cases, which was used to establish the in-air spot size tolerance for beam matching specifications. A beam model in treatment planning system was created using in-air spot profiles acquired in one treatment room. These spot profiles were also acquired from another treatment room for assessing the actual spot size variations between the twomore » treatment rooms. We created twenty five test plans with targets of different sizes at different depths, and performed dose measurement along the entrance, proximal and distal target regions. The absolute doses at those locations were measured using ionization chambers at both treatment rooms, and were compared against the calculated doses by the beam model. Fifteen additional patient plans were also measured and included in our validation. Results: The beam model is relatively insensitive to spot size variations. With an average of less than 15% measured in-air spot size variations between two treatment rooms, the average dose difference was −0.15% with a standard deviation of 0.40% for 55 measurement points within target region; but the differences increased to 1.4%±1.1% in the entrance regions, which are more affected by in-air spot size variations. Overall, our single-room based beam model in the treatment planning system agreed with measurements in both rooms < 0.5% within the target region. For fifteen patient cases, the agreement was within 1%. Conclusion: We have demonstrated that dosimetrically equivalent machines can be established when in-air spot size variations are within 15% between the two treatment rooms.« less

Differences in rates of decrease of environmental radiation dose rates by ground surface property in Fukushima City after the Fukushima Daiichi nuclear power plant accident.

PubMed

Kakamu, Takeyasu; Kanda, Hideyuki; Tsuji, Masayoshi; Kobayashi, Daisuke; Miyake, Masao; Hayakawa, Takehito; Katsuda, Shin-ichiro; Mori, Yayoi; Okouchi, Toshiyasu; Hazama, Akihiro; Fukushima, Tetsuhito

2013-01-01

After the Great East Japan Earthquake on 11 March 2011, the environmental radiation dose in Fukushima City increased. On 11 April, 1 mo after the earthquake, the environmental radiation dose rate at various surfaces in the same area differed greatly by surface property. Environmental radiation measurements continue in order to determine the estimated time to 50% reduction in environmental radiation dose rates by surface property in order to make suggestions for decontamination in Fukushima. The measurements were carried out from 11 April to 11 November 2011. Forty-eight (48) measurement points were selected, including four kinds of ground surface properties: grass (13), soil (5), artificial turf (7), and asphalt (23). Environmental radiation dose rate was measured at heights of 100 cm above the ground surface. Time to 50% reduction of environmental radiation dose rates was estimated for each ground surface property. Radiation dose rates on 11 November had decreased significantly compared with those on 11 April for all surface properties. Artificial turf showed the longest time to 50% reduction (544.32 d, standard error: 96.86), and soil showed the shortest (213.20 d, standard error: 35.88). The authors found the environmental radiation dose rate on artificial materials to have a longer 50% reduction time than that on natural materials. These results contribute to determining an order of priority for decontamination after nuclear disasters.

Assessment of the point-source method for estimating dose rates to members of the public from exposure to patients with 131I thyroid treatment

DOE PAGES

Dewji, Shaheen Azim; Bellamy, Michael B.; Hertel, Nolan E.; ...

2015-09-01

The U.S. Nuclear Regulatory Commission (USNRC) initiated a contract with Oak Ridge National Laboratory (ORNL) to calculate radiation dose rates to members of the public that may result from exposure to patients recently administered iodine-131 ( 131I) as part of medical therapy. The main purpose was to compare dose rate estimates based on a point source and target with values derived from more realistic simulations that considered the time-dependent distribution of 131I in the patient and attenuation of emitted photons by the patient’s tissues. The external dose rate estimates were derived using Monte Carlo methods and two representations of themore » Phantom with Movable Arms and Legs, previously developed by ORNL and the USNRC, to model the patient and a nearby member of the public. Dose rates to tissues and effective dose rates were calculated for distances ranging from 10 to 300 cm between the phantoms and compared to estimates based on the point-source method, as well as to results of previous studies that estimated exposure from 131I patients. The point-source method overestimates dose rates to members of the public in very close proximity to an 131I patient but is a broadly accurate method of dose rate estimation at separation distances of 300 cm or more at times closer to administration.« less

Characterizing regional-scale temporal evolution of air dose rates after the Fukushima Daiichi Nuclear Power Plant accident.

PubMed

Wainwright, Haruko M; Seki, Akiyuki; Mikami, Satoshi; Saito, Kimiaki

2018-09-01

In this study, we quantify the temporal changes of air dose rates in the regional scale around the Fukushima Dai-ichi Nuclear Power Plant in Japan, and predict the spatial distribution of air dose rates in the future. We first apply the Bayesian geostatistical method developed by Wainwright et al. (2017) to integrate multiscale datasets including ground-based walk and car surveys, and airborne surveys, all of which have different scales, resolutions, spatial coverage, and accuracy. This method is based on geostatistics to represent spatial heterogeneous structures, and also on Bayesian hierarchical models to integrate multiscale, multi-type datasets in a consistent manner. We apply this method to the datasets from three years: 2014 to 2016. The temporal changes among the three integrated maps enables us to characterize the spatiotemporal dynamics of radiation air dose rates. The data-driven ecological decay model is then coupled with the integrated map to predict future dose rates. Results show that the air dose rates are decreasing consistently across the region. While slower in the forested region, the decrease is particularly significant in the town area. The decontamination has contributed to significant reduction of air dose rates. By 2026, the air dose rates will continue to decrease, and the area above 3.8 μSv/h will be almost fully contained within the non-residential forested zone. Copyright © 2018 Elsevier Ltd. All rights reserved.

Long-Segment Fusion for Adult Spinal Deformity Correction Using Low-Dose Recombinant Human Bone Morphogenetic Protein-2: A Retrospective Review of Fusion Rates.

PubMed

Schmitt, Paul J; Kelleher, John P; Ailon, Tamir; Heller, Joshua E; Kasliwal, Manish K; Shaffrey, Christopher I; Smith, Justin S

2016-08-01

Although use of very high-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) has been reported to markedly improve fusion rates in adult spinal deformity (ASD) surgery, most centers use much lower doses due to cost constraints. How effective these lower doses are for fusion enhancement remains unclear. To assess fusion rates using relatively low-dose rhBMP-2 for ASD surgery. This was a retrospective review of consecutive ASD patients that underwent thoracic to sacral fusion. Patients that achieved 2-year follow-up were analyzed. Impact of patient and surgical factors on fusion rate was assessed, and fusion rates were compared with historical cohorts. Of 219 patients, 172 (78.5%) achieved 2-year follow-up and were analyzed. Using an average rhBMP-2 dose of 3.1 mg/level (average total dose = 35.9 mg/case), the 2-year fusion rate was 73.8%. Cancellous allograft, local autograft, and very limited iliac crest bone graft (<20 mL, obtained during iliac bolt placement) were also used. On multivariate analysis, female sex was associated with a higher fusion rate, whereas age, comorbidity score, deformity type, and 3-column osteotomy were not. There were no complications directly attributable to rhBMP-2. Fusion rates for ASD using low-dose rhBMP-2 were comparable to those reported for iliac crest bone graft but lower than for high-dose rhBMP-2. Importantly, there were substantial differences between patients in the present series and those in the historical comparison groups that could not be fully adjusted for based on available data. Prospective evaluation of rhBMP-2 dosing for ASD surgery is warranted to define the most appropriate dose that balances benefits, risks, and costs. ASD, adult spinal deformityICBG, iliac crest bone graftOR, odds ratiorhBMP-2, recombinant human bone morphogenetic protein-2RR, risk ratioTCO, 3-column osteotomy.

Butane dihedral angle dynamics in water is dominated by internal friction

PubMed Central

Daldrop, Jan O.; Kappler, Julian; Brünig, Florian N.; Netz, Roland R.

2018-01-01

The dihedral dynamics of butane in water is known to be rather insensitive to the water viscosity; possible explanations for this involve inertial effects or Kramers’ turnover, the finite memory time of friction, and the presence of so-called internal friction. To disentangle these factors, we introduce a method to directly extract the friction memory function from unconstrained simulations in the presence of an arbitrary free-energy landscape. By analysis of the dihedral friction in butane for varying water viscosity, we demonstrate the existence of an internal friction contribution that does not scale linearly with water viscosity. At normal water viscosity, the internal friction turns out to be eight times larger than the solvent friction and thus completely dominates the effective friction. By comparison with simulations of a constrained butane molecule that has the dihedral as the only degree of freedom, we show that internal friction comes from the six additional degrees of freedom in unconstrained butane that are orthogonal to the dihedral angle reaction coordinate. While the insensitivity of butane’s dihedral dynamics to water viscosity is solely due to the presence of internal friction, inertial effects nevertheless crucially influence the resultant transition rates. In contrast, non-Markovian effects due to the finite memory time are present but do not significantly influence the dihedral barrier-crossing rate of butane. These results not only settle the character of dihedral dynamics in small solvated molecular systems such as butane, they also have important implications for the folding of polymers and proteins. PMID:29712838

Effect of radiocesium transfer on ambient dose rate in forest environments affected by the Fukushima Nuclear Power Plant accident

NASA Astrophysics Data System (ADS)

Kato, H.

2015-12-01

We investigated the transfer of canopy-intercepted radiocesium to the forest floor during 3 years following the Fukushima Daiichi Nuclear Power Plant accident. The cesium-137 (Cs-137) contents in throughfall, stemflow, and litterfall were monitored in two coniferous stands (plantation of Japanese cedar) and a deciduous broad-leaved forest stand (Japanese oak with red pine). We also measured the ambient dose rate (ADR) at different heights in the forest using a survey meter and a portable Ge gamma-ray detector. Total Cs-137 deposition flux from the canopy to forest floor for the mature cedar, young cedar, and the mixed broad-leaved stands were 166 kBq/m2, 174 kBq/m2, and 60 kBq/m2, respectively. These values correspond to 38%, 40% and 13% of total atmospheric input after the accident. The ambient dose rate in forest exhibited height dependency and its vertical distribution varied with forest type and stand age. The ambient dose rate showed an exponential decrease with time for all the forest sites, however the decreasing trend differed depending on the height of dose measurement and forest type. The ambient dose rate at the canopy (approx. 10 m-height) decreased faster than that expected from physical decay of the two radiocesium isotopes, whereas those at the forest floor varied between the three forest stands. The radiocesium deposition via throughfall seemed to increase ambient dose rate during the first 200 days after the accident, however there was no clear relationship between litterfall and ambient dose rate since 400 days after the accident. These data suggested that the ambient dose rate in forest environment varied both spatially and temporally reflecting the transfer of radiocesium from canopy to forest floor. However, further monitoring investigation and analysis are required to determine the effect of litterfall on long-term trend of ambient dose rate in forest environments.

Methods and compositions to modulate ethylene sensitivity

DOEpatents

Stepanova, Anna N.; Ecker, Joseph R.

2007-01-30

The field of the invention relates to plants and plant genes, including both plant mutants and transgenic plants containing a gene that confers an ethylene insensitive phenotype. Also encompassed by the invention are methods of using the disclosed plant gene to confer an ethylene insensitive phenotype.

Temperature-insensitive vertical-cavity surface-emitting lasers and method for fabrication thereof

DOEpatents

Chow, W.W.; Choquette, K.D.; Gourley, P.L.

1998-01-27

A temperature-insensitive vertical-cavity surface-emitting laser (VCSEL) and method for fabrication thereof are disclosed. The temperature-insensitive VCSEL comprises a quantum-well active region within a resonant cavity, the active region having a gain spectrum with a high-order subband (n {>=} 2) contribution thereto for broadening and flattening the gain spectrum, thereby substantially reducing any variation in operating characteristics of the VCSEL over a temperature range of interest. The method for forming the temperature-insensitive VCSEL comprises the steps of providing a substrate and forming a plurality of layers thereon for providing first and second distributed Bragg reflector (DBR) mirror stacks with an active region sandwiched therebetween, the active region including at least one quantum-well layer providing a gain spectrum having a high-order subband (n {>=} 2) gain contribution, and the DBR mirror stacks having predetermined layer compositions and thicknesses for providing a cavity resonance within a predetermined wavelength range substantially overlapping the gain spectrum. 12 figs.

Characterisation and Modification of Thermally Stable High Explosives for Laser Flyer Applications

NASA Astrophysics Data System (ADS)

Parker, A.; Claridge, R. P.; Proud, W. G.; Johnson, N. A.

2007-12-01

Laser initiation offers improved weapon survivability, versatility and greater Insensitive Munitions (IM) compliance. Detonators based on laser-driven flyers are less vulnerable to electrical initiation and can be based on insensitive secondary explosives. Additionally, this technology will offer advantages in terms of improved flexibility and reliability. Hexanitrostilbene (HNS) and nonanitro-m-terphenyl (NONA) were selected for investigation at QinetiQ as their increased thermal stability over conventional explosives makes them ideal candidates for use in insensitive munition compliant applications. The response of these materials to short duration high-amplitude shock impulses provided by exploding foil initiators (EFI), the electrical equivalent of a laser-driven flyer system, was investigated. Preparation techniques including sonication and the incorporation of additives were used to sensitize the materials to flyer impact, yet maintain their insensitivity to external hazards. Sonication significantly reduced the particle size of both HNS and NONA. The reduced-size explosives exhibited increased sensitivity to EFI impact than the starting materials.

Temperature-insensitive vertical-cavity surface-emitting lasers and method for fabrication thereof

DOEpatents

Chow, Weng W.; Choquette, Kent D.; Gourley, Paul L.

1998-01-01

A temperature-insensitive vertical-cavity surface-emitting laser (VCSEL) and method for fabrication thereof. The temperature-insensitive VCSEL comprises a quantum-well active region within a resonant cavity, the active region having a gain spectrum with a high-order subband (n.gtoreq.2) contribution thereto for broadening and flattening the gain spectrum, thereby substantially reducing any variation in operating characteristics of the VCSEL over a temperature range of interest. The method for forming the temperature-insensitive VCSEL comprises the steps of providing a substrate and forming a plurality of layers thereon for providing first and second distributed Bragg reflector (DBR) mirror stacks with an active region sandwiched therebetween, the active region including at least one quantum-well layer providing a gain spectrum having a high-order subband (n.gtoreq.2) gain contribution, and the DBR mirror stacks having predetermined layer compositions and thicknesses for providing a cavity resonance within a predetermined wavelength range substantially overlapping the gain spectrum.

Comparison of the anaerobic digestion at the mesophilic and thermophilic temperature regime of organic wastes from the agribusiness.

PubMed

Almeida Streitwieser, Daniela

2017-10-01

An overall kinetic power law model has been successfully applied to study the anaerobic digestion of agricultural wastes. In this comparative kinetic study feed composition, organic load rate, residence time and process temperature have been systematically varied in an automated semi-continuous fermentation system to obtain the dependency of the rate of degradation as biogas production on the organic load rate and temperature. The results show that the overall reaction order depend only on the Chemical Oxygen Demand (COD) at values between 3.6 and 3.7. The Arrhenius approach shows a shift in the rate determining step between the mesophilic and thermophilic temperature regimes. The activation energy at the temperature insensitive mesophilic regime is very small at 8.9 (kJ/mole), while the activation energy at the temperature sensitive thermophilic regime lies around 117 (kJ/mole). Copyright © 2017 Elsevier Ltd. All rights reserved.

The circulation pattern and day-night heat transport in the atmosphere of a synchronously rotating aquaplanet: Dependence on planetary rotation rate

NASA Astrophysics Data System (ADS)

Noda, S.; Ishiwatari, M.; Nakajima, K.; Takahashi, Y. O.; Takehiro, S.; Onishi, M.; Hashimoto, G. L.; Kuramoto, K.; Hayashi, Y.-Y.

2017-01-01

In order to investigate a possible variety of atmospheric states realized on a synchronously rotating aquaplanet, an experiment studying the impact of planetary rotation rate is performed using an atmospheric general circulation model (GCM) with simplified hydrological and radiative processes. The entire planetary surface is covered with a swamp ocean. The value of planetary rotation rate is varied from zero to the Earth's, while other parameters such as planetary radius, mean molecular weight and total mass of atmospheric dry components, and solar constant are set to the present Earth's values. The integration results show that the atmosphere reaches statistically equilibrium states for all runs; none of the calculated cases exemplifies the runaway greenhouse state. The circulation patterns obtained are classified into four types: Type-I characterized by the dominance of a day-night thermally direct circulation, Type-II characterized by a zonal wave number one resonant Rossby wave over a meridionally broad westerly jet on the equator, Type-III characterized by a long time scale north-south asymmetric variation, and Type-IV characterized by a pair of mid-latitude westerly jets. With the increase of planetary rotation rate, the circulation evolves from Type-I to Type-II and then to Type-III gradually and smoothly, whereas the change from Type-III to Type-IV is abrupt and discontinuous. Over a finite range of planetary rotation rate, both Types-III and -IV emerge as statistically steady states, constituting multiple equilibria. In spite of the substantial changes in circulation, the net energy transport from the day side to the night side remains almost insensitive to planetary rotation rate, although the partition into dry static energy and latent heat energy transports changes. The reason for this notable insensitivity is that the outgoing longwave radiation over the broad area of the day side is constrained by the radiation limit of a moist atmosphere, so that the transport to the night side, which is determined as the difference between the incoming solar radiation and the radiation limit, cannot change greatly.

Determination of spatial dose distribution in UCC treatments with LDR brachytherapy using Monte Carlo methods.

PubMed

Benites-Rengifo, Jorge Luis; Vega-Carrillo, Hector Rene

2018-05-19

Using Monte Carlos methods, with the MCNP5 code, a gynecological phantom and a vaginal cylinder were modeled. The spatial distribution of absorbed dose rates in Uterine Cervical Cancer treatment through low dose rate brachytherapy was determined. A liquid water gynecology computational phantom, including a vaginal cylinder applicator made of Lucite, was designed. The applicator has a linear array of four radioactive sources of Cesium 137. Around the vaginal cylinder, 13 water spherical cells of 0.5 cm-diameter were modeled to calculate absorbed dose emulating the procedure made by the treatment planning system. The gamma-ray fluence distribution was estimated, as well as the absorbed doses resulting approximately symmetrical for cells located at upper and lower of vaginal cylinder. Obtained results allow the use of the radioactive decay law to determine dose rate for Uterine Cervical Cancer using low dose rate brachytherapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Low-energy electron effects on tensile modulus and infrared transmission properties of a polypyromellitimide film

NASA Technical Reports Server (NTRS)

Ferl, J. E.; Long, E. R., Jr.

1981-01-01

Infrared (IR) spectroscopy and tensile modulus testing were used to evaluate the importance of experimental procedure on changes in properties of pyromellitic dianhydride-p,p prime-oxydianiline film exposed to electron radiation. The radiation exposures were accelerated, approximate equivalents to the total dose expected for a 30 year mission in geosynchronous Earth orbit. The change in the tensile modulus depends more on the dose rate and the time interval between exposure and testing than on total dose. The IR data vary with both total dose and dose rate. A threshold dose rate exists below which reversible radiation effects on the IR spectra occur. Above the threshold dose rate, irreversible effects occur with the appearance of a new band. Post-irradiation and in situ IR absorption bands are significantly different. It is suggested that the electron radiation induced metastable, excites molecular states.

The correlation between elongation at break and thermal decomposition of aged EPDM cable polymer

NASA Astrophysics Data System (ADS)

Šarac, T.; Devaux, J.; Quiévy, N.; Gusarov, A.; Konstantinović, M. J.

2017-03-01

The effect of simultaneous thermal and gamma irradiation ageing on the mechanical and physicochemical properties of industrial EPDM was investigated. Accelerated ageing, covering a wide range of dose rates, doses and temperatures, was preformed in stagnant air on EPDM polymer samples extracted from the cables in use in the Belgian nuclear power plants. The mechanical properties, ultimate tensile stress and elongation at break, are found to exhibit the strong dependence on the dose, ageing temperature and dose rate. The thermal decomposition of aged polymer is observed to be the dose dependent when thermogravimetry test is performed under air atmosphere. No dose dependence is observed when thermal decomposition is performed under nitrogen atmosphere. The thermal decomposition rates are found to fully mimic the reduction of elongation at break for all dose rates and ageing temperatures. This effect is argued to be the result of thermal and radiation mediated oxidation degradation process.

Characterization of a New Fully Recycled Carbon Fiber Reinforced Composite Subjected to High Strain Rate Tension

NASA Astrophysics Data System (ADS)

Meftah, H.; Tamboura, S.; Fitoussi, J.; BenDaly, H.; Tcharkhtchi, A.

2017-08-01

The aim of this study is the complete physicochemical characterization and strain rate effect multi-scale analysis of a new fully recycled carbon fiber reinforced composites for automotive crash application. Two composites made of 20% wt short recycled carbon fibers (CF) are obtained by injection molding. The morphology and the degree of dispersion of CF in the matrixes were examined using a new ultrasonic method and SEM. High strain tensile behavior up to 100 s-1 is investigated. In order to avoid perturbation due to inertial effect and wave propagation, the specimen geometry was optimized. The elastic properties appear to be insensitive to the strain rate. However, a high strain rate effect on the local visco-plasticity of the matrix and fiber/matrix interface visco-damageable behavior is emphasized. The predominant damage mechanisms evolve from generalized matrix local ductility at low strain rate regime to fiber/matrix interface debonding and fibers pull-out at high strain rate regime.

The High Strain Rate Deformation Behavior of High Purity Magnesium and AZ31B Magnesium Alloy

NASA Astrophysics Data System (ADS)

Livescu, Veronica; Cady, Carl M.; Cerreta, Ellen K.; Henrie, Benjamin L.; Gray, George T.

The deformation in compression of pure magnesium and AZ31B magnesium alloy, both with a strong basal pole texture, has been investigated as a function of temperature, strain rate, and specimen orientation. The mechanical response of both metals is highly dependent upon the orientation of loading direction with respect to the basal pole. Specimens compressed along the basal pole direction have a high sensitivity to strain rate and temperature and display a concave down work hardening behavior. Specimens loaded perpendicularly to the basal pole have a yield stress that is relatively insensitive to strain rate and temperature and a work hardening behavior that is parabolic and then linearly upwards. Both specimen orientations display a mechanical response that is sensitive to temperature and strain rate. Post mortem characterization of the pure magnesium was conducted on a subset of specimens to determine the microstructural and textural evolution during deformation and these results are correlated with the observed work hardening behavior and strain rate sensitivities were calculated.

Characterization of a New Fully Recycled Carbon Fiber Reinforced Composite Subjected to High Strain Rate Tension

NASA Astrophysics Data System (ADS)

Meftah, H.; Tamboura, S.; Fitoussi, J.; BenDaly, H.; Tcharkhtchi, A.

2018-06-01

The aim of this study is the complete physicochemical characterization and strain rate effect multi-scale analysis of a new fully recycled carbon fiber reinforced composites for automotive crash application. Two composites made of 20% wt short recycled carbon fibers (CF) are obtained by injection molding. The morphology and the degree of dispersion of CF in the matrixes were examined using a new ultrasonic method and SEM. High strain tensile behavior up to 100 s-1 is investigated. In order to avoid perturbation due to inertial effect and wave propagation, the specimen geometry was optimized. The elastic properties appear to be insensitive to the strain rate. However, a high strain rate effect on the local visco-plasticity of the matrix and fiber/matrix interface visco-damageable behavior is emphasized. The predominant damage mechanisms evolve from generalized matrix local ductility at low strain rate regime to fiber/matrix interface debonding and fibers pull-out at high strain rate regime.

Genetic characterisation of a cohort of children clinically labelled as GH or IGF1 insensitive: diagnostic value of serum IGF1 and height at presentation.

PubMed

Storr, Helen L; Dunkel, Leo; Kowalczyk, Julia; Savage, Martin O; Metherell, Louise A

2015-02-01

GH insensitivity (GHI) encompasses growth failure, low serum IGF1 and normal/elevated serum GH. By contrast, IGF1 insensitivity results in pre- and postnatal growth failure associated with relatively high IGF1 levels. From 2008 to 2013, 72 patients from 68 families (45M), mean age 7.1 years (0.4-17.0) with short stature (mean height SDS -3.9; range -9.4 to -1.5), were referred for sequencing. As a genetics referral centre, we have sequenced appropriate candidate genes (GHR, including its pseudoexon (6Ψ), STAT5B, IGFALS, IGF1, IGF1R, OBSL1, CUL7 and CCDC8) in subjects referred with suspected GHI (n=69) or IGF1 insensitivity (n=3). Mean serum IGF1 SDS was -2.7 (range -0.9 to -8.2) in GHI patients and 2.0, 3.7 and 4.4 in patients with suspected IGF1 insensitivity. Out of 69 GHI patients, 16 (23%) (19% families) had mutations in GH-IGF1 axis genes: homozygous GHR (n=13; 6 6Ψ, two novel IVS5ds+1 G to A) and homozygous IGFALS (n=3; one novel c.1291delT). In the GHI groups, two homozygous OBSL1 mutations were also identified (height SDS -4.9 and -5.7) and two patients had hypomethylation in imprinting control region 1 in 11p15 or mUPD7 consistent with Silver-Russell syndrome (SRS) (height SDS -3.7 and -4.3). A novel heterozygous IGF1R (c.112G>A) mutation was identified in one out of three (33%) IGF1-insensitive subjects. Genotyping contributed to the diagnosis of children with suspected GHI and IGF1 insensitivity, particularly in the GHI subjects with low serum IGF1 SDS (<-2.0) and height SDS (<-2.5). Diagnoses with similar phenotypes included SRS and 3-M syndrome. In 71% patients, no diagnosis was defined justifying further genetic investigation. © 2015 European Society of Endocrinology.

Dose-related difference in progression rates of cytomegalovirus retinopathy during foscarnet maintenance therapy. AIDS Clinical Trials Group Protocol 915 Team.

PubMed

Holland, G N; Levinson, R D; Jacobson, M A

1995-05-01

A previous dose-ranging study of foscarnet maintenance therapy for cytomegalovirus retinopathy showed a positive relationship between dose and survival but could not confirm a relationship between dose and time to first progression. This retrospective analysis of data from that study was undertaken to determine whether there was a relationship between dose and progression rates, which reflects the amount of retina destroyed when progression occurs. Patients were randomly given one of two foscarnet maintenance therapy doses (90 mg/kg of body weight/day [FOS-90 group] or 120 mg/kg of body weight/day [FOS-120 group] after induction therapy. Using baseline and follow-up photographs and pre-established definitions and methodology in a masked analysis, posterior progression rates and foveal proximity rates for individual lesions, selected by prospectively defined criteria, were calculated in each patient. Rates were compared between groups. The following median rates were greater for the FOS-90 group (N = 8) than for the FOS-120 group (N = 10): greatest maximum rate at which lesions enlarged in a posterior direction (43.5 vs 12.5 microns/day; P = .002); posterior progression rate for lesions closest to the fovea (42.8 vs 5.5 microns/day; P = .010); and maximum foveal proximity rate for either eye (32.3 vs 3.4 microns/day; P = .031). Patients receiving higher doses of foscarnet have slower rates of progression and therefore less retinal tissue damage during maintenance therapy. A foscarnet maintenance therapy dose of 120 mg/kg of body weight/day instead of 90 mg/kg of body weight/day may help to preserve vision in patients with cytomegalovirus retinopathy.

A less stressful alternative to oral gavage for pharmacological and toxicological studies in mice

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

Walker, Mary K., E-mail: mwalker@salud.unm.edu; Boberg, Jason R.; Walsh, Mary T.

Oral gavage dosing can induce stress and potentially confound experimental measurements, particularly when blood pressure and heart rate are endpoints of interest. Thus, we developed a pill formulation that mice would voluntarily consume and tested the hypothesis that pill dosing would be significantly less stressful than oral gavage. C57Bl/6 male mice were singly housed and on four consecutive days were exposed to an individual walking into the room (week 1, control), a pill being placed into the cage (week 2), and a dose of water via oral gavage (week 3). Blood pressure and heart rate were recorded by radiotelemetry continuouslymore » for 5 h after treatment, and feces collected 6–10 h after treatment for analysis of corticosterone metabolites. Both pill and gavage dosing significantly increased mean arterial pressure (MAP) during the first hour, compared to control. However, the increase in MAP was significantly greater after gavage and remained elevated up to 5 h, while MAP returned to normal within 2 h after a pill. Neither pill nor gavage dosing significantly increased heart rate during the first hour, compared to control; however, pill dosing significantly reduced heart rate while gavage significantly increased heart rate 2–5 h post dosing. MAP and heart rate did not differ 24 h after dosing. Lastly, only gavage dosing significantly increased fecal corticosterone metabolites, indicating a systemic stress response via activation of the hypothalamic–pituitary–adrenal axis. These data demonstrated that this pill dosing method of mice is significantly less stressful than oral gavage. -- Highlights: ► Developed a novel oral dosing method using a pill that mice will readily consume. ► Assessed stress by blood pressure, heart rate, and fecal corticosterone metabolites. ► Demonstrated that pill dosing is significantly less stressful than oral gavage.« less

Flexible manipulation of terahertz wave reflection using polarization insensitive coding metasurfaces.

PubMed

Jiu-Sheng, Li; Ze-Jiang, Zhao; Jian-Quan, Yao

2017-11-27

In order to extend to 3-bit encoding, we propose notched-wheel structures as polarization insensitive coding metasurfaces to control terahertz wave reflection and suppress backward scattering. By using a coding sequence of "00110011…" along x-axis direction and 16 × 16 random coding sequence, we investigate the polarization insensitive properties of the coding metasurfaces. By designing the coding sequences of the basic coding elements, the terahertz wave reflection can be flexibly manipulated. Additionally, radar cross section (RCS) reduction in the backward direction is less than -10dB in a wide band. The present approach can offer application for novel terahertz manipulation devices.

Optimal mapping of terrestrial gamma dose rates using geological parent material and aerogeophysical survey data.

PubMed

Rawlins, B G; Scheib, C; Tyler, A N; Beamish, D

2012-12-01

Regulatory authorities need ways to estimate natural terrestrial gamma radiation dose rates (nGy h⁻¹) across the landscape accurately, to assess its potential deleterious health effects. The primary method for estimating outdoor dose rate is to use an in situ detector supported 1 m above the ground, but such measurements are costly and cannot capture the landscape-scale variation in dose rates which are associated with changes in soil and parent material mineralogy. We investigate the potential for improving estimates of terrestrial gamma dose rates across Northern Ireland (13,542 km²) using measurements from 168 sites and two sources of ancillary data: (i) a map based on a simplified classification of soil parent material, and (ii) dose estimates from a national-scale, airborne radiometric survey. We used the linear mixed modelling framework in which the two ancillary variables were included in separate models as fixed effects, plus a correlation structure which captures the spatially correlated variance component. We used a cross-validation procedure to determine the magnitude of the prediction errors for the different models. We removed a random subset of 10 terrestrial measurements and formed the model from the remainder (n = 158), and then used the model to predict values at the other 10 sites. We repeated this procedure 50 times. The measurements of terrestrial dose vary between 1 and 103 (nGy h⁻¹). The median absolute model prediction errors (nGy h⁻¹) for the three models declined in the following order: no ancillary data (10.8) > simple geological classification (8.3) > airborne radiometric dose (5.4) as a single fixed effect. Estimates of airborne radiometric gamma dose rate can significantly improve the spatial prediction of terrestrial dose rate.

Absorbed doses of lungs from radon retained in airway lumens of mice and rats.

PubMed

Sakoda, Akihiro; Ishimori, Yuu; Yamaoka, Kiyonori; Kataoka, Takahiro; Mitsunobu, Fumihiro

2013-08-01

This paper provides absorbed doses arising from radon gas in air retained in lung airway lumens. Because radon gas exposure experiments often use small animals, the calculation was performed for mice and rats. For reference, the corresponding computations were also done for humans. Assuming that radon concentration in airway lumens is the same as that in the environment, its progeny's production in and clearance from airways were simulated. Absorbed dose rates were obtained for three lung regions and the whole lung, considering that secretory and basal cells are sensitive to radiation. The results showed that absorbed dose rates for all lung regions and whole lung generally increase from mice to rats to humans. For example, the dose rates for the whole lung were 25.4 in mice, 41.7 in rats, and 59.9 pGy (Bq m⁻³)⁻¹ h⁻¹ in humans. Furthermore, these values were also compared with lung dose rates from two other types of exposures, that is, due to inhalation of radon or its progeny, which were already reported. It was confirmed that the direct inhalation of radon progeny in the natural environment, which is known as a cause of lung cancer, results in the highest dose rates for all species. Based on the present calculations, absorbed dose rates of the whole lung from radon gas were lower by a factor of about 550 (mice), 200 (rats), or 70 (humans) than those from radon progeny inhalation. The calculated dose rate values are comparatively small. Nevertheless, the present study is considered to contribute to our understanding of doses from inhalation of radon and its progeny.

Organ and effective dose rate coefficients for submersion exposure in occupational settings

DOE PAGES

Veinot, K. G.; Y-12 National Security Complex, Oak Ridge, TN; Dewji, S. A.; ...

2017-08-24

External dose coefficients for environmental exposure scenarios are often computed using assumption on infinite or semi-infinite radiation sources. For example, in the case of a person standing on contaminated ground, the source is assumed to be distributed at a given depth (or between various depths) and extending outwards to an essentially infinite distance. In the case of exposure to contaminated air, the person is modeled as standing within a cloud of infinite, or semi-infinite, source distribution. However, these scenarios do not mimic common workplace environments where scatter off walls and ceilings may significantly alter the energy spectrum and dose coefficients.more » In this study, dose rate coefficients were calculated using the International Commission on Radiological Protection (ICRP) reference voxel phantoms positioned in rooms of three sizes representing an office, laboratory, and warehouse. For each room size calculations using the reference phantoms were performed for photons, electrons, and positrons as the source particles to derive mono-energetic dose rate coefficients. Since the voxel phantoms lack the resolution to perform dose calculations at the sensitive depth for the skin, a mathematical phantom was developed and calculations were performed in each room size with the three source particle types. Coefficients for the noble gas radionuclides of ICRP Publication 107 (e.g., Ne, Ar, Kr, Xe, and Rn) were generated by folding the corresponding photon, electron, and positron emissions over the mono-energetic dose rate coefficients. Finally, results indicate that the smaller room sizes have a significant impact on the dose rate per unit air concentration compared to the semi-infinite cloud case. For example, for Kr-85 the warehouse dose rate coefficient is 7% higher than the office dose rate coefficient while it is 71% higher for Xe-133.« less

Organ and effective dose rate coefficients for submersion exposure in occupational settings

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

Veinot, K. G.; Y-12 National Security Complex, Oak Ridge, TN; Dewji, S. A.

External dose coefficients for environmental exposure scenarios are often computed using assumption on infinite or semi-infinite radiation sources. For example, in the case of a person standing on contaminated ground, the source is assumed to be distributed at a given depth (or between various depths) and extending outwards to an essentially infinite distance. In the case of exposure to contaminated air, the person is modeled as standing within a cloud of infinite, or semi-infinite, source distribution. However, these scenarios do not mimic common workplace environments where scatter off walls and ceilings may significantly alter the energy spectrum and dose coefficients.more » In this study, dose rate coefficients were calculated using the International Commission on Radiological Protection (ICRP) reference voxel phantoms positioned in rooms of three sizes representing an office, laboratory, and warehouse. For each room size calculations using the reference phantoms were performed for photons, electrons, and positrons as the source particles to derive mono-energetic dose rate coefficients. Since the voxel phantoms lack the resolution to perform dose calculations at the sensitive depth for the skin, a mathematical phantom was developed and calculations were performed in each room size with the three source particle types. Coefficients for the noble gas radionuclides of ICRP Publication 107 (e.g., Ne, Ar, Kr, Xe, and Rn) were generated by folding the corresponding photon, electron, and positron emissions over the mono-energetic dose rate coefficients. Finally, results indicate that the smaller room sizes have a significant impact on the dose rate per unit air concentration compared to the semi-infinite cloud case. For example, for Kr-85 the warehouse dose rate coefficient is 7% higher than the office dose rate coefficient while it is 71% higher for Xe-133.« less

Dose rate evaluation of workers on the operation floor in Fukushima-Daiichi Unit 3

NASA Astrophysics Data System (ADS)

Matsushita, Kaoru; Kurosawa, Masahiko; Shirai, Keisuke; Matsuoka, Ippei; Mukaida, Naoki

2017-09-01

At Fukushima Daiichi Nuclear Power Plant Unit 3, installation of a fuel handling machine is planned to support the removal of spent fuel. The dose rates at the workplace were calculated based on the source distribution measured using a collimator in order to confirm that the dose rates on the operation floor were within a manageable range. It was confirmed that the accuracy of the source distribution was C/M = 1.0-2.4. These dose rates were then used to plan the work on the operation floor.

Evaluation of Enhanced Low Dose Rate Sensitivity in Discrete Bipolar Junction Transistors

NASA Technical Reports Server (NTRS)

Chen, Dakai; Ladbury Raymond; LaBel, Kenneth; Topper, Alyson; Ladbury, Raymond; Triggs, Brian; Kazmakites, Tony

2012-01-01

We evaluate the low dose rate sensitivity in several families of discrete bipolar transistors across device parameter, quality assurance level, and irradiation bias configuration. The 2N2222 showed the most significant low dose rate sensitivity, with low dose rate enhancement factor of 3.91 after 100 krad(Si). The 2N2907 also showed critical degradation levels. The devices irradiated at 10 mrad(Si)/s exceeded specifications after 40 and 50 krad(Si) for the 2N2222 and 2N2907 devices, respectively.

Laser-based irradiation apparatus and method to measure the functional dose-rate response of semiconductor devices

DOEpatents

Horn, Kevin M [Albuquerque, NM

2008-05-20

A broad-beam laser irradiation apparatus can measure the parametric or functional response of a semiconductor device to exposure to dose-rate equivalent infrared laser light. Comparisons of dose-rate response from before, during, and after accelerated aging of a device, or from periodic sampling of devices from fielded operational systems can determine if aging has affected the device's overall functionality. The dependence of these changes on equivalent dose-rate pulse intensity and/or duration can be measured with the apparatus. The synchronized introduction of external electrical transients into the device under test can be used to simulate the electrical effects of the surrounding circuitry's response to a radiation exposure while exposing the device to dose-rate equivalent infrared laser light.

A New Approach for the Determination of Dose Rate and Radioactivity for Detected Gamma Nuclides Using an Environmental Radiation Monitor Based on an NaI(Tl) Detector.

PubMed

Ji, Young-Yong; Kim, Chang-Jong; Lim, Kyo-Sun; Lee, Wanno; Chang, Hyon-Sock; Chung, Kun Ho

2017-10-01

To expand the application of dose rate spectroscopy to the environment, the method using an environmental radiation monitor (ERM) based on a 3' × 3' NaI(Tl) detector was used to perform real-time monitoring of the dose rate and radioactivity for detected gamma nuclides in the ground around an ERM. Full-energy absorption peaks in the energy spectrum for dose rate were first identified to calculate the individual dose rates of Bi, Ac, Tl, and K distributed in the ground through interference correction because of the finite energy resolution of the NaI(Tl) detector used in an ERM. The radioactivity of the four natural radionuclides was then calculated from the in situ calibration factor-that is, the dose rate per unit curie-of the used ERM for the geometry of the ground in infinite half-space, which was theoretically estimated by Monte Carlo simulation. By an intercomparison using a portable HPGe and samples taken from the ground around an ERM, this method to calculate the dose rate and radioactivity of four nuclides using an ERM was experimentally verified and finally applied to remotely monitor them in real-time in the area in which the ERM had been installed.

Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

NASA Technical Reports Server (NTRS)

Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

2011-01-01

Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT cells and misrejoined breaks increased in both cell lines. The present study suggests that AT cells begin to rejoin breaks when a certain number of breaks are accumulated and an increased number of exchanges were observed in G0 AT cells, which is similar situation after high-dose-rate irradiation.

Ionizing radiation sensitivity of the ocular lens and its dose rate dependence.

PubMed

Hamada, Nobuyuki

2017-10-01

In 2011, the International Commission on Radiological Protection reduced the threshold for the lens effects of low linear energy transfer (LET) radiation. On one hand, the revised threshold of 0.5 Gy is much lower than previously recommended thresholds, but mechanisms behind high radiosensitivity remain incompletely understood. On the other hand, such a threshold is independent of dose rate, in contrast to previously recommended separate thresholds each for single and fractionated/protracted exposures. Such a change was made predicated on epidemiological evidence suggesting that a threshold for fractionated/protracted exposures is not higher than an acute threshold, and that a chronic threshold is uncertain. Thus, the dose rate dependence is still unclear. This paper therefore reviews the current knowledge on the radiosensitivity of the lens and the dose rate dependence of radiation cataractogenesis, and discusses its mechanisms. Mounting biological evidence indicates that the lens cells are not necessarily radiosensitive to cell killing, and the high radiosensitivity of the lens thus appears to be attributable to other mechanisms (e.g., excessive proliferation, abnormal differentiation, a slow repair of DNA double-strand breaks, telomere, senescence, crystallin changes, non-targeted effects and inflammation). Both biological and epidemiological evidence generally supports the lack of dose rate effects. However, there is also biological evidence for the tissue sparing dose rate (or fractionation) effect of low-LET radiation and an enhancing inverse dose fractionation effect of high-LET radiation at a limited range of LET. Emerging epidemiological evidence in chronically exposed individuals implies the inverse dose rate effect. Further biological and epidemiological studies are warranted to gain deeper knowledge on the radiosensitivity of the lens and dose rate dependence of radiation cataractogenesis.

Photodetection Characterization of SiPM Technologies for their Application in Scintillator based Neutron Detectors

NASA Astrophysics Data System (ADS)

Kumar, S.; Durini, D.; Degenhardt, C.; van Waasen, S.

2018-01-01

Small-angle neutron scattering (SANS) experiments have become one of the most important techniques in the investigation of the properties of material on the atomic scale. Until 2001, nearly exclusively 3He-based detectors were used for neutron detection in these experiments, but due to the scarcity of 3He and its steeply rising price, researchers started to look for suitable alternatives. Scintillation based solid state detectors appeared as a prominent alternative. Silicon photomultipliers (SiPM), having single photon resolution, lower bias voltages compared to photomultiplier tubes (PMT), insensitivity to magnetic fields, low cost, possibility of modular design and higher readout rates, have the potential of becoming a photon detector of choice in scintillator based neutron detectors. The major concerns for utilizing the SiPM technology in this kind of applications are the increase in their noise performance and the decrease in their photon detection efficiency (PDE) due to direct exposure to neutrons. Here, a detailed comparative analysis of the PDE performance in the range between UV and NIR parts of the spectra for three different SiPM technologies, before and after irradiation with cold neutrons, has been carried out. For this investigation, one digital and two analog SiPM arrays were irradiated with 5Å wavelength cold neutrons and up to a dose of 6×1012 n/cm2 at the KWS-1 instrument of the Heinz Maier-Leibnitz Zentrum (MLZ) in Garching, Germany.

AREA MONITORING OF AMBIENT DOSE RATES IN PARTS OF SOUTH-WESTERN NIGERIA USING A GPS-INTEGRATED RADIATION SURVEY METER.

PubMed

Okeyode, I C; Rabiu, J A; Alatise, O O; Makinde, V; Akinboro, F G; Al-Azmi, D; Mustapha, A O

2017-04-01

A radiation monitoring system comprising a Geiger-Muller counter connected to a smart phone via Bluetooth was used for a dose rate survey in some parts of south-western Nigeria. The smart phone has the Geographical Positioning System, which provides the navigation information and saves it along with the dose rate data. A large number of data points was obtained that shows the dose rate distribution within the region. The results show that the ambient dose rates in the region range from 60 to 520 nSv -1 and showed a bias that is attributable to the influence of geology on the ambient radiation dose in the region. The geology influence was demonstrated by superimposing the dose rate plot and the geological map of the area. The potential applications of the device in determining baseline information and in area monitoring, e.g. for lost or abandoned sources, radioactive materials stockpiles, etc., were discussed in the article, particularly against the background of Nigeria's plan to develop its nuclear power program. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Passive dosimetry aboard the Mir Orbital Station: internal measurements.

PubMed

Benton, E R; Benton, E V; Frank, A L

2002-10-01

Passive radiation dosimeters were exposed aboard the Mir Orbital Station over a substantial portion of the solar cycle in order to measure the change in dose and dose equivalent rates as a function of time. During solar minimum, simultaneous measurements of the radiation environment throughout the habitable volume of the Mir were made using passive dosimeters in order to investigate the effect of localized shielding on dose and dose equivalent. The passive dosimeters consisted of a combination of thermoluminescent detectors to measure absorbed dose and CR-39 PNTDs to measure the linear energy transfer (LET) spectrum from charged particles of LET infinity H2O > or = 5 keV/micrometers. Results from the two detector types were then combined to yield mean total dose rate, mean dose equivalent rate, and average quality factor. Contrary to expectations, both dose and dose equivalent rates measured during May-October 1991 near solar maximum were higher than similar measurements carried out in 1996-1997 during solar minimum. The elevated dose and dose equivalent rates measured in 1991 were probably due to a combination of intense solar activity, including a large solar particle event on 9 June 1991, and the temporary trapped radiation belt created in the slot region by the solar particle event and ensuing magnetic storm of 24 March 1991. During solar minimum, mean dose and dose equivalent rates were found to vary by factors of 1.55 and 1.37, respectively, between different locations through the interior of Mir. More heavily shielded locations tended to yield lower total dose and dose equivalent rates, but higher average quality factor than did more lightly shielding locations. However, other factors such as changes in the immediate shielding environment surrounding a given detector location, changes in the orientation of the Mir relative to its velocity vector, and changes in the altitude of the station also contributed to the variation. Proton and neutron-induced target fragment secondaries, not primary galactic cosmic rays, were found to dominate the LET spectrum above 100 keV/micrometers. This indicates that in low earth orbit, trapped protons in the South Atlantic Anomaly are responsible for the major fraction of the total dose equivalent. c2002 Elsevier Science Ltd. All rights reserved.

Progressing Insensitive Munitions: Benefits and Techniques for Proactively Addressing Environmental Regulations

DTIC Science & Technology

2012-05-01

X Worm Tubifex tubifex X X X Black worm Lumbriculus X Asiatic clam Corbicula fluminea X Estuarine/marine water column Mysid shrimp Americamysis...Objective: Characterize traditional and insensitive munitions (IMs) impacts on amphibian larvae to manage a candidate for T&E status that inhabit

Paddle-based rotating-shield brachytherapy

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

Liu, Yunlong; Xu, Weiyu; Flynn, Ryan T.

Purpose: The authors present a novel paddle-based rotating-shield brachytherapy (P-RSBT) method, whose radiation-attenuating shields are formed with a multileaf collimator (MLC), consisting of retractable paddles, to achieve intensity modulation in high-dose-rate brachytherapy. Methods: Five cervical cancer patients using an intrauterine tandem applicator were considered to assess the potential benefit of the P-RSBT method. The P-RSBT source used was a 50 kV electronic brachytherapy source (Xoft Axxent™). The paddles can be retracted independently to form multiple emission windows around the source for radiation delivery. The MLC was assumed to be rotatable. P-RSBT treatment plans were generated using the asymmetric dose–volume optimizationmore » with smoothness control method [Liu et al., Med. Phys. 41(11), 111709 (11pp.) (2014)] with a delivery time constraint, different paddle sizes, and different rotation strides. The number of treatment fractions (fx) was assumed to be five. As brachytherapy is delivered as a boost for cervical cancer, the dose distribution for each case includes the dose from external beam radiotherapy as well, which is 45 Gy in 25 fx. The high-risk clinical target volume (HR-CTV) doses were escalated until the minimum dose to the hottest 2 cm{sup 3} (D{sub 2cm{sup 3}}) of either the rectum, sigmoid colon, or bladder reached their tolerance doses of 75, 75, and 90 Gy{sub 3}, respectively, expressed as equivalent doses in 2 Gy fractions (EQD2 with α/β = 3 Gy). Results: P-RSBT outperformed the two other RSBT delivery techniques, single-shield RSBT (S-RSBT) and dynamic-shield RSBT (D-RSBT), with a properly selected paddle size. If the paddle size was angled at 60°, the average D{sub 90} increases for the delivery plans by P-RSBT on the five cases, compared to S-RSBT, were 2.2, 8.3, 12.6, 11.9, and 9.1 Gy{sub 10}, respectively, with delivery times of 10, 15, 20, 25, and 30 min/fx. The increases in HR-CTV D{sub 90}, compared to D-RSBT, were 16.6, 12.9, 7.2, 3.7, and 1.7 Gy{sub 10}, respectively. P-RSBT HR-CTV D{sub 90}-values were insensitive to the paddle size for paddles angled at less than 60°. Increasing the paddle angle from 5° to 60° resulted in only a 0.6 Gy{sub 10} decrease in HR-CTV D{sub 90} on average for five cases when the delivery times were set to 15 min/fx. The HR-CTV D{sub 90} decreased to 2.5 and 11.9 Gy{sub 10} with paddle angles of 90° and 120°, respectively. Conclusions: P-RSBT produces treatment plans that are dosimetrically and temporally superior to those of S-RSBT and D-RSBT, although P-RSBT systems may be more mechanically challenging to develop than S-RSBT or D-RSBT. A P-RSBT implementation with 4–6 shield paddles would be sufficient to outperform S-RSBT and D-RSBT if delivery times are constrained to less than 15 min/fx.« less

Wide-angle, polarization-insensitive and broadband absorber based on eight-fold symmetric SRRs metamaterial

NASA Astrophysics Data System (ADS)

Wu, Dong; Liu, Yumin; Yu, Zhongyuan; Chen, Lei; Ma, Rui; Li, Yutong; Li, Ruifang; Ye, Han

2016-12-01

In this paper, we propose a novel three dimensional metamaterial design with eight-fold rotational symmetry that shows a polarization-insensitive, wide-angle and broadband perfect absorption in the microwave band. By simulation, the polarization-insensitive absorption is over 90% between 26.9 GHz to 32.9 GHz, and the broadband absorption remains a good absorption performance to a wide incident angles for both TE and TM polarizations. The magnetic field distribution are investigated to interpret the physical mechanism of broadband absorption. The broadband absorption is based on overlapping the multiple magnetic resonances at the neighboring frequencies by coupling effects of multiple metallic split-ring resonators (SRRs). Moreover, it is demonstrate that the designed structure can be extended to other frequencies by scale down the size of the unit cell, such as the visible frequencies. The simulated results show that the absorption of the smaller absorber is above 90% in the frequency range from 467 THz to 765 THz(392-642 nm), which include orange to purple light in visible region(400-760nm). The wide-angle and polarization-insensitive stabilities of the smaller absorber is also demonstrated at visible region. The proposed work provides a new design of realization of a polarization-insensitive, wide-angle and broadband absorber ranging different frequency bands, and such a structure has potential application in the fields of solar cell, imaging and detection.

Transactional Processes in Children born Preterm: Influences of Mother-Child Interactions and Parenting Stress

PubMed Central

Gerstein, Emily D.; Poehlmann-Tynan, Julie

2016-01-01

This prospective, longitudinal study examined the transactional relations among perceived maternal parenting stress, maternal insensitivity, and child behavior across toddlerhood through age 6 within families of a child born preterm. A sample of 173 mother-child dyads were followed from just before the infant was discharged from the neonatal intensive care unit to 6 years of age, with observational measurements of maternal insensitivity and child noncompliance (24 and 36 months), maternal self-reports of perceived parenting stress (24 months, 36 months, 6 years), and maternal reports of child externalizing behavior at 6 years. Results indicated that maternal insensitivity at 36 months significantly mediated the relation between parenting stress at 24 months and externalizing behaviors at 6 years. Parenting stress was also directly associated with child noncompliance at 36 months and with child externalizing behavior at 6 years. Neonatal risk was associated with increased maternal insensitivity at 24 months, but also decreased parenting stress at 24 months. No significant “child effects” from child behavior to either maternal insensitivity or parenting stress were found. Parenting stress appears to play a critical role for children born preterm, and it is associated with children’s behavior both directly and through its influence on parenting. The role of neonatal risk needs continued investigation, as families traditionally considered to be at lower risk may still face significant challenges. PMID:26147934

Transactional processes in children born preterm: Influences of mother-child interactions and parenting stress.

PubMed

Gerstein, Emily D; Poehlmann-Tynan, Julie

2015-10-01

This prospective, longitudinal study examined the transactional relations among perceived maternal parenting stress, maternal insensitivity, and child behavior across toddlerhood through age 6 within families of a child born preterm. A sample of 173 mother-child dyads were followed from just before the infant was discharged from the neonatal intensive care unit to 6 years of age, with observational measurements of maternal insensitivity and child noncompliance (24 and 36 months), maternal self-reports of perceived parenting stress (24 months, 36 months, 6 years), and maternal reports of child externalizing behavior at 6 years. Results indicated that maternal insensitivity at 36 months significantly mediated the relation between parenting stress at 24 months and externalizing behaviors at 6 years. Parenting stress was also directly associated with child noncompliance at 36 months and with child externalizing behavior at 6 years. Neonatal risk was associated with increased maternal insensitivity at 24 months, but also decreased parenting stress at 24 months. No significant "child effects" from child behavior to either maternal insensitivity or parenting stress were found. Parenting stress appears to play a critical role for children born preterm, and it is associated with children's behavior both directly and through its influence on parenting. The role of neonatal risk needs continued investigation, as families traditionally considered to be at lower risk may still face significant challenges. (c) 2015 APA, all rights reserved).

Sensitivity to azoxystrobin in Didymella bryoniae isolates collected before and after field use of strobilurin fungicides.

PubMed

Keinath, Anthony P

2009-10-01

Isolates of Didymella bryoniae (Auersw.) Rehm, causal agent of gummy stem blight on cucurbits, developed insensitivity to azoxystrobin in the eastern United States 2 years after first commercial use in 1998. Baseline sensitivity of this fungus to azoxystrobin has never been reported. The objectives were to compare baseline sensitivities of D. bryoniae from South Carolina and other locations to sensitivities of isolates exposed to azoxystrobin for one or more seasons, and to compare sensitivity in vitro and in vivo. Sixty-one isolates of D. bryoniae collected before 1998 were sensitive. Median EC50 was 0.055 mg L(-1) azoxystrobin (range 0.005 to 0.81). Forty isolates collected after exposure during 1998 also were sensitive. Fifty-three of 64 isolates collected in South and North Carolina between 2000 and 2006 were insensitive to 10 mg L(-1) azoxystrobin. Sensitive and insensitive isolates were distinguished by disease severity on Cucumis melo L. seedlings treated with azoxystrobin (20 or 200 mg L(-1)). An azoxystrobin baseline sensitivity distribution was established in vitro for isolates of D. bryoniae never exposed to strobilurins. Baseline values were comparable with those of other ascomycetes. Insensitive isolates were found in fields with a history of strobilurin applications. An in vivo method distinguished sensitive and insensitive isolates. Copyright 2009 Society of Chemical Industry.

Distribution of photoperiod-insensitive allele Ppd-A1a and its effect on heading time in Japanese wheat cultivars.

PubMed

Seki, Masako; Chono, Makiko; Nishimura, Tsutomu; Sato, Mikako; Yoshimura, Yasuhiro; Matsunaka, Hitoshi; Fujita, Masaya; Oda, Shunsuke; Kubo, Katashi; Kiribuchi-Otobe, Chikako; Kojima, Hisayo; Nishida, Hidetaka; Kato, Kenji

2013-09-01

The Ppd-A1 genotype of 240 Japanese wheat cultivars and 40 foreign cultivars was determined using a PCR-based method. Among Japanese cultivars, only 12 cultivars, all of which were Hokkaido winter wheat, carried the Ppd-A1a allele, while this allele was not found in Hokkaido spring wheat cultivars or Tohoku-Kyushu cultivars. Cultivars with a photoperiod-insensitive allele headed 6.9-9.8 days earlier in Kanto and 2.5 days earlier in Hokkaido than photoperiod-sensitive cultivars. The lower effect of photoperiod-insensitive alleles observed in Hokkaido could be due to the longer day-length at the spike formation stage compared with that in Kanto. Pedigree analysis showed that 'Purple Straw' and 'Tohoku 118' were donors of Ppd-A1a and Ppd-D1a in Hokkaido wheat cultivars, respectively. Wheat cultivars recently developed in Hokkaido carry photoperiod-insensitive alleles at a high frequency. For efficient utilization of Ppd-1 alleles in the Hokkaido wheat-breeding program, the effect of Ppd-1 on growth pattern and grain yield should be investigated. Ppd-A1a may be useful as a unique gene source for fine tuning the heading time in the Tohoku-Kyushu region since the effect of Ppd-A1a on photoperiod insensitivity appears to differ from the effect of Ppd-B1a and Ppd-D1a.

A natural frameshift mutation in Campanula EIL2 correlates with ethylene insensitivity in flowers.

PubMed

Jensen, Line; Hegelund, Josefine Nymark; Olsen, Andreas; Lütken, Henrik; Müller, Renate

2016-05-23

The phytohormone ethylene plays a central role in development and senescence of climacteric flowers. In ornamental plant production, ethylene sensitive plants are usually protected against negative effects of ethylene by application of chemical inhibitors. In Campanula, flowers are sensitive to even minute concentrations of ethylene. Monitoring flower longevity in three Campanula species revealed C. portenschlagiana (Cp) as ethylene sensitive, C. formanekiana (Cf) with intermediate sensitivity and C. medium (Cm) as ethylene insensitive. We identified key elements in ethylene signal transduction, specifically in Ethylene Response Sensor 2 (ERS2), Constitutive Triple Response 1 (CTR1) and Ethylene Insensitive 3- Like 1 and 2 (EIL1 and EIL2) homologous. Transcripts of ERS2, CTR1 and EIL1 were constitutively expressed in all species both throughout flower development and in response to ethylene. In contrast, EIL2 was found only in Cf and Cm. We identified a natural mutation in Cmeil2 causing a frameshift which resulted in difference in expression levels of EIL2, with more than 100-fold change between Cf and Cm in young flowers. This study shows that the naturally occurring 7 bp frameshift discovered in Cmeil2, a key gene in the ethylene signaling pathway, correlates with ethylene insensitivity in flowers. We suggest that transfer of the eil2 mutation to other plant species will provide a novel tool to engineer ethylene insensitive flowers.

Multi-level effects of low dose rate ionizing radiation on southern toad, Anaxyrus [Bufo] terrestris

DOE PAGES

Stark, Karolina; Scott, David E.; Tsyusko, Olga; ...

2015-04-30

Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad ( Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development –embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of ¹³⁷Cs at 0.13, 2.4, 21, and 222 mGy d⁻¹, resulting in total doses up to 15.8 Gy. Radiation treatments didmore » not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay) in red blood cells at a dose rate of 21mGy d⁻¹ and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae.« less

Radiation dose rate affects the radiosensitization of MCF-7 and HeLa cell lines to X-rays induced by dextran-coated iron oxide nanoparticles.

PubMed

Khoshgard, Karim; Kiani, Parvaneh; Haghparast, Abbas; Hosseinzadeh, Leila; Eivazi, Mohammad Taghi

2017-08-01

The aim of radiotherapy is to deliver lethal damage to cancerous tissue while preserving adjacent normal tissues. Radiation absorbed dose of the tumoral cells can increase when high atomic nanoparticles are present in them during irradiation. Also, the dose rate is an important aspect in radiation effects that determines the biological results of a given dose. This in vitro study investigated the dose-rate effect on the induced radiosensitivity by dextran-coated iron oxide in cancer cells. HeLa and MCF-7 cells were cultured in vitro and incubated with different concentrations of dextran-coated iron oxide nanoparticles. They were then irradiated with 6 MV photons at dose rates of 43, 185 and 370 cGy/min. The MTT test was used to obtain the cells' survival after 48 h of irradiations. Incubating the cells with the nanoparticles at concentrations of 10, 40 and 80 μg/ml showed no significant cytotoxicity effect. Dextran-coated iron oxide nanoparticles showed more radiosensitivity effect by increasing the dose rate and nanoparticles concentration. Radiosensitization enhancement factors of MCF-7 and HeLa cells at a dose-rate of 370 cGy/min and nanoparticles' concentration of 80 μg/ml were 1.21 ± 0.06 and 1.19 ± 0.04, respectively. Increasing the dose rate of 6 MV photons irradiation in MCF-7 and HeLa cells increases the radiosensitization induced by the dextran-coated iron nanoparticles in these cells.

β-blocker dosage and outcomes after acute coronary syndrome.

PubMed

Allen, Jason E; Knight, Stacey; McCubrey, Raymond O; Bair, Tami; Muhlestein, Joseph Brent; Goldberger, Jeffrey J; Anderson, Jeffrey L

2017-02-01

Although β-blockers increase survival in acute coronary syndrome (ACS) patients, the doses used in trials were higher than doses used in practice, and recent data do not support an advantage of higher doses. We hypothesized that rates of major adverse cardiac events (MACE), all-cause death, myocardial infarction, and stroke are equivalent for patients on low-dose and high-dose β-blocker. Patients admitted to Intermountain Healthcare with ACS and diagnosed with ≥70% coronary stenosis between 1994 and 2013 were studied (N = 7,834). We classified low dose as ≤25% and high dose as ≥50% of an equivalent daily dose of 200 mg of metoprolol. Multivariate analyses were used to test association between low-dose versus high-dose β-blocker dosage and MACE at 0-6 months and 6-24 months. A total of 5,287 ACS subjects were discharged on β-blockers (87% low dose, 12% high dose, and 1% intermediate dose). The 6-month MACE outcomes rates for the β-blocker dosage (low versus high) were not equivalent (P = .18) (hazard ratio [HR] = 0.76; 95% CI, 0.52-1.10). However, subjects on low-dose β-blocker therapy did have a significantly decreased risk of myocardial infarction for 0-6 months (HR = 0.53; 95% CI, 0.33-0.86). The rates of MACE events during the 6-24 months after presentation with ACS were equivalent for the 2 doses (P = .009; HR = 1.03 [95% CI, 0.70-1.50]). In ACS patients, rates of MACE for high-dose and low-dose β-blocker doses are similar. These findings question the importance of achieving a high dose of β-blocker in ACS patients and highlight the need for further investigation of this clinical question. Copyright © 2016 Elsevier Inc. All rights reserved.

Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate-Dependent Manner.

PubMed

Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

2018-01-01

A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR.

Effect of dose rate on residual γ-H2AX levels and frequency of micronuclei in X-irradiated mouse lymphocytes.

PubMed

Turner, H C; Shuryak, I; Taveras, M; Bertucci, A; Perrier, J R; Chen, C; Elliston, C D; Johnson, G W; Smilenov, L B; Amundson, S A; Brenner, D J

2015-03-01

The biological risks associated with low-dose-rate (LDR) radiation exposures are not yet well defined. To assess the risk related to DNA damage, we compared the yields of two established biodosimetry end points, γ-H2AX and micronuclei (MNi), in peripheral mouse blood lymphocytes after prolonged in vivo exposure to LDR X rays (0.31 cGy/min) vs. acute high-dose-rate (HDR) exposure (1.03 Gy/min). C57BL/6 mice were total-body irradiated with 320 kVP X rays with doses of 0, 1.1, 2.2 and 4.45 Gy. Residual levels of total γ-H2AX fluorescence in lymphocytes isolated 24 h after the start of irradiation were assessed using indirect immunofluorescence methods. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to determine apoptotic cell frequency in lymphocytes sampled at 24 h. Curve fitting analysis suggested that the dose response for γ-H2AX yields after acute exposures could be described by a linear dependence. In contrast, a linear-quadratic dose-response shape was more appropriate for LDR exposure (perhaps reflecting differences in repair time after different LDR doses). Dose-rate sparing effects (P < 0.05) were observed at doses ≤2.2 Gy, such that the acute dose γ-H2AX and TUNEL-positive cell yields were significantly larger than the equivalent LDR yields. At the 4.45 Gy dose there was no difference in γ-H2AX expression between the two dose rates, whereas there was a two- to threefold increase in apoptosis in the LDR samples compared to the equivalent 4.45 Gy acute dose. Micronuclei yields were measured at 24 h and 7 days using the in vitro cytokinesis-blocked micronucleus (CBMN) assay. The results showed that MNi yields increased up to 2.2 Gy with no further increase at 4.45 Gy and with no detectable dose-rate effect across the dose range 24 h or 7 days post exposure. In conclusion, the γ-H2AX biomarker showed higher sensitivity to measure dose-rate effects after low-dose LDR X rays compared to MNi formation; however, confounding factors such as variable repair times post exposure, increased cell killing and cell cycle block likely contributed to the yields of MNi with accumulating doses of ionizing radiation.

Radiological environment within an NPP after a severe nuclear accident

NASA Astrophysics Data System (ADS)

Andgren, Karin; Fritioff, Karin; Buhr, Anna Maria Blixt; Huutoniemi, Tommi

2017-09-01

The radiological environment following a severe nuclear accident can be visualised on building layouts. The direct radiation in an area (or room) can be visualized on the layout by a colouring scheme depending on the dose rate level (for example orange for high gamma dose rate level and purple for an intermediate gamma dose rate level). Following the Fukushima accident, a need for update of these layouts has been identified at the Swedish nuclear power plant of Forsmark. Shielding calculations for areas where access is desired for severe accident management have been performed. Many different sources of radiation together with different types of shielding material contribute to the dose that would be received by a person entering the area. External radiation from radioactivity within e.g. pipes and components is considered and also external radiation from radioactivity in the air (originating from diffuse leakage of the containment atmosphere). Results are presented as dose rates for relevant dose points together with a method for estimating the dose rate levels for each of the rooms of the reactor building.

Type of fitness cost influences the rate of evolution of resistance to transgenic Bt crops.

PubMed

Hackett, Sean C; Bonsall, Michael B

2016-10-01

The evolution of resistance to pesticides by insect pests is a significant challenge for sustainable agriculture. For transgenic crops expressing Bacillus thuringiensis (Bt), crystalline (Cry) toxins resistance evolution may be delayed by the high-dose/refuge strategy in which a non-toxic refuge is planted to promote the survival of susceptible insects. The high-dose/refuge strategy may interact with fitness costs associated with resistance alleles to further delay resistance. However, while a diverse range of fitness costs are reported in the field, they are typically represented as a fixed reduction in survival or viability which is insensitive to ecological conditions such as competition. Furthermore, the potential dynamic consequences of restricting susceptible insects to a refuge which represents only a fraction of the available space have rarely been considered.We present a generalized discrete time model which utilizes dynamic programming methods to derive the optimal management decisions for the control of a theoretical insect pest population exposed to Bt crops. We consider three genotypes (susceptible homozygotes, resistant homozygotes and heterozygotes) and implement fitness costs of resistance to Bt toxins as either a decrease in the relative competitive ability of resistant insects or as a penalty on fecundity. Model analysis is repeated and contrasted for two types of density dependence: uniform density dependence which operates equally across the landscape and heterogeneous density dependence where the intensity of competition scales inversely with patch size and is determined separately for the refuge and Bt crop.When the planting of Bt is decided optimally, fitness costs to fecundity allow for the planting of larger areas of Bt crops than equivalent fitness costs that reduce the competitive ability of resistant insects.Heterogeneous competition only influenced model predictions when the proportional area of Bt planted in each season was decided optimally and resistance was not recessive. Synthesis and applications . The high-dose/refuge strategy alone is insufficient to preserve susceptibility to transgenic Bacillus thuringiensis (Bt) crops in the long term when constraints upon the evolution of resistance are not insurmountable. Fitness costs may enhance the delaying effect of the refuge, but the extent to which they do so depends upon how the cost is realized biologically. Fitness costs which apply independently of other variables may be more beneficial to resistance management than costs which are only visible to selection under a limited range of ecological conditions.

Dose equivalent rate constants and barrier transmission data for nuclear medicine facility dose calculations and shielding design.

PubMed

Kusano, Maggie; Caldwell, Curtis B

2014-07-01

A primary goal of nuclear medicine facility design is to keep public and worker radiation doses As Low As Reasonably Achievable (ALARA). To estimate dose and shielding requirements, one needs to know both the dose equivalent rate constants for soft tissue and barrier transmission factors (TFs) for all radionuclides of interest. Dose equivalent rate constants are most commonly calculated using published air kerma or exposure rate constants, while transmission factors are most commonly calculated using published tenth-value layers (TVLs). Values can be calculated more accurately using the radionuclide's photon emission spectrum and the physical properties of lead, concrete, and/or tissue at these energies. These calculations may be non-trivial due to the polyenergetic nature of the radionuclides used in nuclear medicine. In this paper, the effects of dose equivalent rate constant and transmission factor on nuclear medicine dose and shielding calculations are investigated, and new values based on up-to-date nuclear data and thresholds specific to nuclear medicine are proposed. To facilitate practical use, transmission curves were fitted to the three-parameter Archer equation. Finally, the results of this work were applied to the design of a sample nuclear medicine facility and compared to doses calculated using common methods to investigate the effects of these values on dose estimates and shielding decisions. Dose equivalent rate constants generally agreed well with those derived from the literature with the exception of those from NCRP 124. Depending on the situation, Archer fit TFs could be significantly more accurate than TVL-based TFs. These results were reflected in the sample shielding problem, with unshielded dose estimates agreeing well, with the exception of those based on NCRP 124, and Archer fit TFs providing a more accurate alternative to TVL TFs and a simpler alternative to full spectral-based calculations. The data provided by this paper should assist in improving the accuracy and tractability of dose and shielding calculations for nuclear medicine facility design.

Internal complexity and environmental sensitivity in hospitals.

PubMed

Ashmos, D P; Duchon, D; Hauge, F E; McDaniel, R R

1996-01-01

Theory suggests that organizations should respond to external complexity with internal complexity. We examine whether "environmentally sensitive" hospitals are more internally complex than "environmentally insensitive" hospitals. Results show that environmentally sensitive and insensitive hospitals differed on three of the measures of internal complexity: goal complexity, strategic complexity, and relational complexity.

Characterization of grape Gibberellin Insensitive 1 mutant alleles in transgenic Arabidopsis

USDA-ARS?s Scientific Manuscript database

We generated a dozen of different mutations in the grape Gibberellin Insensitive or GAI sequence, transformed them into Arabidopsis under the control of 35S, Arabidopsis or grape GAI promoter, and evaluated the impact of these mutant alleles on plant growth and development. These GAI sequence varian...

Wavelength-insensitive radiation coupling for multi-quantum well sensor based on intersubband absorption

NASA Technical Reports Server (NTRS)

Gunapala, Sarath D. (Inventor); Bandara, Sumith V. (Inventor); Liu, John K. (Inventor)

2006-01-01

Devices and techniques for coupling radiation to intraband quantum-well semiconductor sensors that are insensitive to the wavelength of the coupled radiation. At least one reflective surface is implemented in the quantum-well region to direct incident radiation towards the quantum-well layers.

Nuclear Radiation Degradation Study on HD Camera Based on CMOS Image Sensor at Different Dose Rates.

PubMed

Wang, Congzheng; Hu, Song; Gao, Chunming; Feng, Chang

2018-02-08

In this work, we irradiated a high-definition (HD) industrial camera based on a commercial-off-the-shelf (COTS) CMOS image sensor (CIS) with Cobalt-60 gamma-rays. All components of the camera under test were fabricated without radiation hardening, except for the lens. The irradiation experiments of the HD camera under biased conditions were carried out at 1.0, 10.0, 20.0, 50.0 and 100.0 Gy/h. During the experiment, we found that the tested camera showed a remarkable degradation after irradiation and differed in the dose rates. With the increase of dose rate, the same target images become brighter. Under the same dose rate, the radiation effect in bright area is lower than that in dark area. Under different dose rates, the higher the dose rate is, the worse the radiation effect will be in both bright and dark areas. And the standard deviations of bright and dark areas become greater. Furthermore, through the progressive degradation analysis of the captured image, experimental results demonstrate that the attenuation of signal to noise ratio (SNR) versus radiation time is not obvious at the same dose rate, and the degradation is more and more serious with increasing dose rate. Additionally, the decrease rate of SNR at 20.0, 50.0 and 100.0 Gy/h is far greater than that at 1.0 and 10.0 Gy/h. Even so, we confirm that the HD industrial camera is still working at 10.0 Gy/h during the 8 h of measurements, with a moderate decrease of the SNR (5 dB). The work is valuable and can provide suggestion for camera users in the radiation field.

Nuclear Radiation Degradation Study on HD Camera Based on CMOS Image Sensor at Different Dose Rates

PubMed Central

Wang, Congzheng; Hu, Song; Gao, Chunming; Feng, Chang

2018-01-01

In this work, we irradiated a high-definition (HD) industrial camera based on a commercial-off-the-shelf (COTS) CMOS image sensor (CIS) with Cobalt-60 gamma-rays. All components of the camera under test were fabricated without radiation hardening, except for the lens. The irradiation experiments of the HD camera under biased conditions were carried out at 1.0, 10.0, 20.0, 50.0 and 100.0 Gy/h. During the experiment, we found that the tested camera showed a remarkable degradation after irradiation and differed in the dose rates. With the increase of dose rate, the same target images become brighter. Under the same dose rate, the radiation effect in bright area is lower than that in dark area. Under different dose rates, the higher the dose rate is, the worse the radiation effect will be in both bright and dark areas. And the standard deviations of bright and dark areas become greater. Furthermore, through the progressive degradation analysis of the captured image, experimental results demonstrate that the attenuation of signal to noise ratio (SNR) versus radiation time is not obvious at the same dose rate, and the degradation is more and more serious with increasing dose rate. Additionally, the decrease rate of SNR at 20.0, 50.0 and 100.0 Gy/h is far greater than that at 1.0 and 10.0 Gy/h. Even so, we confirm that the HD industrial camera is still working at 10.0 Gy/h during the 8 h of measurements, with a moderate decrease of the SNR (5 dB). The work is valuable and can provide suggestion for camera users in the radiation field. PMID:29419782

Correlation of radiation dose and heart rate in dual-source computed tomography coronary angiography.

PubMed

Laspas, Fotios; Tsantioti, Dimitra; Roussakis, Arkadios; Kritikos, Nikolaos; Efthimiadou, Roxani; Kehagias, Dimitrios; Andreou, John

2011-04-01

Computed tomography coronary angiography (CTCA) has been widely used since the introduction of 64-slice scanners and dual-source CT technology, but the relatively high radiation dose remains a major concern. To evaluate the relationship between radiation exposure and heart rate (HR), in dual-source CTCA. Data from 218 CTCA examinations, performed with a dual-source 64-slices scanner, were statistically evaluated. Effective radiation dose, expressed in mSv, was calculated as the product of the dose-length product (DLP) times a conversion coefficient for the chest (mSv = DLPx0.017). Heart rate range and mean heart rate, expressed in beats per minute (bpm) of each individual during CTCA, were also provided by the system. Statistical analysis of effective dose and heart rate data was performed by using Pearson correlation coefficient and two-sample t-test. Mean HR and effective dose were found to have a borderline positive relationship. Individuals with a mean HR >65 bpm observed to receive a statistically significant higher effective dose as compared to those with a mean HR ≤65 bpm. Moreover, a strong correlation between effective dose and variability of HR of more than 20 bpm was observed. Dual-source CT scanners are considered to have the capability to provide diagnostic examinations even with high HR and arrhythmias. However, it is desirable to keep the mean heart rate below 65 bpm and heart rate fluctuation less than 20 bpm in order to reduce the radiation exposure.

Radiation response of industrial materials: Dose-rate and morphology implications

NASA Astrophysics Data System (ADS)

Berejka, Anthony J.

2007-08-01

Industrial uses of ionizing radiation mostly rely upon high current, high dose-rate (100 kGy/s) electron beam (EB) accelerators. To a lesser extent, industry uses low dose-rate (2.8 × 10-3 kGy/s) radioactive Cobalt-60 as a gamma source, generally for some rather specific purposes, as medical device sterilization and the treatment of food and foodstuffs. There are nearly nine times as many (∼1400) high current EB units in commercial operation than gamma sources (∼160). However, gamma sources can be easily scaled-down so that much research on materials effects is conducted using gamma radiation. Likewise, laboratories are more likely to have very low beam current and consequently low dose-rate accelerators such as Van de Graaff generators and linear accelerators. With the advent of very high current EB accelerators, X-ray processing has become an industrially viable option. With X-rays from high power sources, dose-rates can be modulated based upon accelerator power and the attenuation of the X-ray by the distance of the material from the X-ray target. Dose and dose-rate dependence has been found to be of consequence in several commercial applications which can employ the use of ionizing radiation. The combination of dose and dose-rate dependence of the polymerization and crosslinking of wood impregnants and of fiber composite matrix materials can yield more economically viable results which have promising commercial potential. Monomer and oligomer structure also play an important role in attaining these desirable results. The influence of morphology is shown on the radiation response of olefin polymers, such as ethylene, propylene and isobutylene polymers and their copolymers. Both controlled morphology and controlled dose-rate have commercial consequences. These are also impacted both by the adroit selection of materials and through the possible use of X-ray processing.

Microfluidic Thrombosis under Multiple Shear Rates and Antiplatelet Therapy Doses

PubMed Central

Ku, David N.; Forest, Craig R.

2014-01-01

The mainstay of treatment for thrombosis, the formation of occlusive platelet aggregates that often lead to heart attack and stroke, is antiplatelet therapy. Antiplatelet therapy dosing and resistance are poorly understood, leading to potential incorrect and ineffective dosing. Shear rate is also suspected to play a major role in thrombosis, but instrumentation to measure its influence has been limited by flow conditions, agonist use, and non-systematic and/or non-quantitative studies. In this work we measured occlusion times and thrombus detachment for a range of initial shear rates (500, 1500, 4000, and 10000 s−1) and therapy concentrations (0–2.4 µM for eptifibatide, 0–2 mM for acetyl-salicylic acid (ASA), 3.5–40 Units/L for heparin) using a microfluidic device. We also measured complete blood counts (CBC) and platelet activity using whole blood impedance aggregometry. Effects of shear rate and dose were analyzed using general linear models, logistic regressions, and Cox proportional hazards models. Shear rates have significant effects on thrombosis/dose-response curves for all tested therapies. ASA has little effect on high shear occlusion times, even at very high doses (up to 20 times the recommended dose). Under ASA therapy, thrombi formed at high shear rates were 4 times more prone to detachment compared to those formed under control conditions. Eptifibatide reduced occlusion when controlling for shear rate and its efficacy increased with dose concentration. In contrast, the hazard of occlusion from ASA was several orders of magnitude higher than that of eptifibatide. Our results show similar dose efficacy to our low shear measurements using whole blood aggregometry. This quantitative and statistically validated study of the effects of a wide range of shear rate and antiplatelet therapy doses on occlusive thrombosis contributes to more accurate understanding of thrombosis and to models for optimizing patient treatment. PMID:24404131

Development of a high sensitivity pinhole type gamma camera using semiconductors for low dose rate fields

NASA Astrophysics Data System (ADS)

Ueno, Yuichiro; Takahashi, Isao; Ishitsu, Takafumi; Tadokoro, Takahiro; Okada, Koichi; Nagumo, Yasushi; Fujishima, Yasutake; Yoshida, Akira; Umegaki, Kikuo

2018-06-01

We developed a pinhole type gamma camera, using a compact detector module of a pixelated CdTe semiconductor, which has suitable sensitivity and quantitative accuracy for low dose rate fields. In order to improve the sensitivity of the pinhole type semiconductor gamma camera, we adopted three methods: a signal processing method to set the discriminating level lower, a high sensitivity pinhole collimator and a smoothing image filter that improves the efficiency of the source identification. We tested basic performances of the developed gamma camera and carefully examined effects of the three methods. From the sensitivity test, we found that the effective sensitivity was about 21 times higher than that of the gamma camera for high dose rate fields which we had previously developed. We confirmed that the gamma camera had sufficient sensitivity and high quantitative accuracy; for example, a weak hot spot (0.9 μSv/h) around a tree root could be detected within 45 min in a low dose rate field test, and errors of measured dose rates with point sources were less than 7% in a dose rate accuracy test.

Nuclear mass inventory, photon dose rate and thermal decay heat of spent research reactor fuel assemblies

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

Pond, R.B.; Matos, J.E.

1996-05-01

As part of the Department of Energy`s spent nuclear fuel acceptance criteria, the mass of uranium and transuranic elements in spent research reactor fuel must be specified. These data are, however, not always known or readily determined. It is the purpose of this report to provide estimates of these data for some of the more common research reactor fuel assembly types. The specific types considered here are MTR, TRIGA and DIDO fuel assemblies. The degree of physical protection given to spent fuel assemblies is largely dependent upon the photon dose rate of the spent fuel material. These data also, aremore » not always known or readily determined. Because of a self-protecting dose rate level of radiation (dose rate greater than 100 ren-x/h at I m in air), it is important to know the dose rate of spent fuel assemblies at all time. Estimates of the photon dose rate for spent MTR, TRIGA and DIDO-type fuel assemblies are given in this report.« less

Development of Rotational Accelerometers Final Report CRADA No. TSB-2008-99

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

Hunter, S.; Crosson, R.

One of the difficulties in fabricating an inexpensive angular rate or rotation sensor is producing a device that is insensitive to acceleration, including the constant acceleration of gravity. The majority of rate sensors are either tuning fork type devices sensing a relatively weak force (i.e., Coriolis effect) and thus not very sensitive, or gyroscopes (either rotating or fiber optic based) that are large, consume lots of power and are expensive. This project was a collaborative effort between LLNL and The Fredericks Company to develop a rotational sensor as a standardized, commercial product. The Fredericks Company possessed expertise and capabilities inmore » the technical aspects of manufacturing this type of sensor, and they were interested in collaborating with LLNL to manufacture the rotational rate sensors as a commercial product.« less

Chemistry resolved kinetic flow modeling of TATB based explosives

NASA Astrophysics Data System (ADS)

Vitello, Peter; Fried, Laurence E.; William, Howard; Levesque, George; Souers, P. Clark

2012-03-01

Detonation waves in insensitive, TATB-based explosives are believed to have multiple time scale regimes. The initial burn rate of such explosives has a sub-microsecond time scale. However, significant late-time slow release in energy is believed to occur due to diffusion limited growth of carbon. In the intermediate time scale concentrations of product species likely change from being in equilibrium to being kinetic rate controlled. We use the thermo-chemical code CHEETAH linked to an ALE hydrodynamics code to model detonations. We term our model chemistry resolved kinetic flow, since CHEETAH tracks the time dependent concentrations of individual species in the detonation wave and calculates EOS values based on the concentrations. We present here two variants of our new rate model and comparison with hot, ambient, and cold experimental data for PBX 9502.

Simulation Study of Nano Aqueous Flow Sensor Based on Amperometric Measurement

PubMed Central

Wu, Jian; Zhou, Qingli; Liu, Jun; Lou, Zhengguo

2006-01-01

In this paper, a novel nano aqueous flow sensor which consists of two closely spaced amperometric sensors is investigated by digital simulation. The simulation results indicate that the ratio of the responses of two closely spaced amperometric sensors is only related to flow rates in the channel, insensitive to the analyte concentration in the solution. By comparing the output of two amperometric sensors, the flow rate in the channel can be deduced. It is not necessary to determine the analyte concentration in advance. The simulation results show it is able to detect flow rate by in the range of several nano-liters per minute when the distance between the working electrodes of two amperometric sensors is 200 nm and the cross-section of the channel is 1 μm × 1 μm.

Uveal Melanoma Treated With Iodine-125 Episcleral Plaque: An Analysis of Dose on Disease Control and Visual Outcomes

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

Perez, Bradford A.; Mettu, Pradeep; Vajzovic, Lejla

2014-05-01

Purpose: To investigate, in the treatment of uveal melanomas, how tumor control, radiation toxicity, and visual outcomes are affected by the radiation dose at the tumor apex. Methods and Materials: A retrospective review was performed to evaluate patients treated for uveal melanoma with {sup 125}I plaques between 1988 and 2010. Radiation dose is reported as dose to tumor apex and dose to 5 mm. Primary endpoints included time to local failure, distant failure, and death. Secondary endpoints included eye preservation, visual acuity, and radiation-related complications. Univariate and multivariate analyses were performed to determine associations between radiation dose and the endpointmore » variables. Results: One hundred ninety patients with sufficient data to evaluate the endpoints were included. The 5-year local control rate was 91%. The 5-year distant metastases rate was 10%. The 5-year overall survival rate was 84%. There were no differences in outcome (local control, distant metastases, overall survival) when dose was stratified by apex dose quartile (<69 Gy, 69-81 Gy, 81-89 Gy, >89 Gy). However, increasing apex dose and dose to 5-mm depth were correlated with greater visual acuity loss (P=.02, P=.0006), worse final visual acuity (P=.02, P<.0001), and radiation complications (P<.0001, P=.0009). In addition, enucleation rates were worse with increasing quartiles of dose to 5 mm (P=.0001). Conclusions: Doses at least as low as 69 Gy prescribed to the tumor apex achieve rates of local control, distant metastasis–free survival, and overall survival that are similar to radiation doses of 85 Gy to the tumor apex, but with improved visual outcomes.« less

A Model For the Limiting Time in Vortex Ring Formation

NASA Technical Reports Server (NTRS)

Shariff, Karim; Gharib, Morteza; Rambod, Edmond; Merriam, Marshal (Technical Monitor)

1997-01-01

In another presentation, Gharib et at provide experimental results to show that when a vortex ring is created from a pipe by a piston, there is a limiting time or piston stroke length beyond which multiple rings appear. This time appeared to be insensitive to piston velocity history and Reynolds number. Nature might exploit such a. limit in different contexts to coherently deliver mass or momentum flux with the least number of strokes. Here, a simple hypothesis is considered: the limiting time occurs when the apparatus is no longer able to deliver energy at a rate compatible with the requirement, due to Kelvin, that a steady vortex ring have maximum energy given circulation and impulse. More specifically, the limit is expected to occur when the quantity alpha = E/square root of Gamma(sup 3)I delivered by the piston drops below the value, alpha(sub lim) for a limiting steady vortex ring solution. The resulting predictions agree very well with the experiments (after using alpha(sub lim) measured using the experimental flow fields). The insensitivity to piston history also emerges from the model. Finally, piston histories are designed that may extend the limiting time somewhat.

Biotransformation and Degradation of the Insensitive Munitions Compound, 3-Nitro-1,2,4-triazol-5-one, by Soil Bacterial Communities.

PubMed

Krzmarzick, Mark J; Khatiwada, Raju; Olivares, Christopher I; Abrell, Leif; Sierra-Alvarez, Reyes; Chorover, Jon; Field, James A

2015-05-05

Insensitive munitions (IM) are a new class of explosives that are increasingly being adopted by the military. The ability of soil microbial communities to degrade IMs is relatively unknown. In this study, microbial communities from a wide range of soils were tested in microcosms for their ability to degrade the IM, 3-nitro-1,2,4-triazol-5-one (NTO). All seven soil inocula tested were able to readily reduce NTO to 3-amino-1,2,4-triazol-5-one (ATO) via 3-hydroxyamino-1,2,4-triazol-5-one (HTO), under anaerobic conditions with H2 as an electron donor. Numerous other electron donors were shown to be suitable for NTO-reducing bacteria. The addition of a small amount of yeast extract (10 mg/L) was critical to diminish lag times and increased the biotransformation rate of NTO in nearly all cases indicating yeast extract provided important nutrients for NTO-reducing bacteria. The main biotransformation product, ATO, was degradable only in aerobic conditions, as evidenced by a rise in the inorganic nitrogen species nitrite and nitrate, indicative of nitrogen-mineralization. NTO was nonbiodegradable in aerobic microcosms with all soil inocula.

A Market-Basket Approach to Predict the Acute Aquatic Toxicity of Munitions and Energetic Materials.

PubMed

Burgoon, Lyle D

2016-06-01

An ongoing challenge in chemical production, including the production of insensitive munitions and energetics, is the ability to make predictions about potential environmental hazards early in the process. To address this challenge, a quantitative structure activity relationship model was developed to predict acute fathead minnow toxicity of insensitive munitions and energetic materials. Computational predictive toxicology models like this one may be used to identify and prioritize environmentally safer materials early in their development. The developed model is based on the Apriori market-basket/frequent itemset mining approach to identify probabilistic prediction rules using chemical atom-pairs and the lethality data for 57 compounds from a fathead minnow acute toxicity assay. Lethality data were discretized into four categories based on the Globally Harmonized System of Classification and Labelling of Chemicals. Apriori identified toxicophores for categories two and three. The model classified 32 of the 57 compounds correctly, with a fivefold cross-validation classification rate of 74 %. A structure-based surrogate approach classified the remaining 25 chemicals correctly at 48 %. This result is unsurprising as these 25 chemicals were fairly unique within the larger set.

Absolute x-ray dosimetry on a synchrotron medical beam line with a graphite calorimeter.

PubMed

Harty, P D; Lye, J E; Ramanathan, G; Butler, D J; Hall, C J; Stevenson, A W; Johnston, P N

2014-05-01

The absolute dose rate of the Imaging and Medical Beamline (IMBL) on the Australian Synchrotron was measured with a graphite calorimeter. The calorimetry results were compared to measurements from the existing free-air chamber, to provide a robust determination of the absolute dose in the synchrotron beam and provide confidence in the first implementation of a graphite calorimeter on a synchrotron medical beam line. The graphite calorimeter has a core which rises in temperature when irradiated by the beam. A collimated x-ray beam from the synchrotron with well-defined edges was used to partially irradiate the core. Two filtration sets were used, one corresponding to an average beam energy of about 80 keV, with dose rate about 50 Gy/s, and the second filtration set corresponding to average beam energy of 90 keV, with dose rate about 20 Gy/s. The temperature rise from this beam was measured by a calibrated thermistor embedded in the core which was then converted to absorbed dose to graphite by multiplying the rise in temperature by the specific heat capacity for graphite and the ratio of cross-sectional areas of the core and beam. Conversion of the measured absorbed dose to graphite to absorbed dose to water was achieved using Monte Carlo calculations with the EGSnrc code. The air kerma measurements from the free-air chamber were converted to absorbed dose to water using the AAPM TG-61 protocol. Absolute measurements of the IMBL dose rate were made using the graphite calorimeter and compared to measurements with the free-air chamber. The measurements were at three different depths in graphite and two different filtrations. The calorimetry measurements at depths in graphite show agreement within 1% with free-air chamber measurements, when converted to absorbed dose to water. The calorimetry at the surface and free-air chamber results show agreement of order 3% when converted to absorbed dose to water. The combined standard uncertainty is 3.9%. The good agreement of the graphite calorimeter and free-air chamber results indicates that both devices are performing as expected. Further investigations at higher dose rates than 50 Gy/s are planned. At higher dose rates, recombination effects for the free-air chamber are much higher and expected to lead to much larger uncertainties. Since the graphite calorimeter does not have problems associated with dose rate, it is an appropriate primary standard detector for the synchrotron IMBL x rays and is the more accurate dosimeter for the higher dose rates expected in radiotherapy applications.

Dosimetric characterization of the (60)Co BEBIG Co0.A86 high dose rate brachytherapy source using PENELOPE.

PubMed

Guerrero, Rafael; Almansa, Julio F; Torres, Javier; Lallena, Antonio M

2014-12-01

(60)Co sources are being used as an alternative to (192)Ir sources in high dose rate brachytherapy treatments. In a recent document from AAPM and ESTRO, a consensus dataset for the (60)Co BEBIG (model Co0.A86) high dose rate source was prepared by using results taken from different publications due to discrepancies observed among them. The aim of the present work is to provide a new calculation of the dosimetric characteristics of that (60)Co source according to the recommendations of the AAPM and ESTRO report. Radial dose function, anisotropy function, air-kerma strength, dose rate constant and absorbed dose rate in water have been calculated and compared to the results of previous works. Simulations using the two different geometries considered by other authors have been carried out and the effect of the cable density and length has been studied. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

The Effect of Compliance on the Impact of Mass Drug Administration for Elimination of Lymphatic Filariasis in Egypt

PubMed Central

El-Setouhy, Maged; Abd Elaziz, Khaled M.; Helmy, Hanan; Farid, Hoda A.; Kamal, Hussein A.; Ramzy, Reda M. R.; Shannon, William D.; Weil, Gary J.

2008-01-01

We studied effects of compliance on the impact of mass drug administration (MDA) with diethylcarbamazine and albendazole for lymphatic filariasis (LF) in an Egyptian village. Baseline microfilaremia (mf) and filarial antigenemia rates were 11.5% and 19.0%, respectively. The MDA compliance rates were excellent (> 85%). However, individual compliance was highly variable; 7.4% of those surveyed after five rounds of MDA denied having ever taken the medications and 52.4% reported that they had taken all five doses. The mf and antigenemia rates were 0.2% and 2.7% in those who reported five doses of MDA and 8.3% and 13.8% in those who reported zero doses. There was no significant difference in residual infection rates among those who had taken two or more doses. These results underscore the importance of compliance for LF elimination programs based on MDA and suggest that two ingested doses of MDA are as effective as five doses for reducing filariasis infection rates. PMID:18165524

Effective dose rate coefficients for exposure to contaminated soil

DOE PAGES

Veinot, Kenneth G.; Eckerman, Keith F.; Bellamy, Michael B.; ...

2017-05-10

The Oak Ridge National Laboratory Center for Radiation Protection Knowledge has undertaken calculations related to various environmental exposure scenarios. A previous paper reported the results for submersion in radioactive air and immersion in water using age-specific mathematical phantoms. This paper presents age-specific effective dose rate coefficients derived using stylized mathematical phantoms for exposure to contaminated soils. Dose rate coefficients for photon, electron, and positrons of discrete energies were calculated and folded with emissions of 1252 radionuclides addressed in ICRP Publication 107 to determine equivalent and effective dose rate coefficients. The MCNP6 radiation transport code was used for organ dose ratemore » calculations for photons and the contribution of electrons to skin dose rate was derived using point-kernels. Bremsstrahlung and annihilation photons of positron emission were evaluated as discrete photons. As a result, the coefficients calculated in this work compare favorably to those reported in the US Federal Guidance Report 12 as well as by other authors who employed voxel phantoms for similar exposure scenarios.« less

Effective dose rate coefficients for exposure to contaminated soil

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

Veinot, Kenneth G.; Eckerman, Keith F.; Bellamy, Michael B.

The Oak Ridge National Laboratory Center for Radiation Protection Knowledge has undertaken calculations related to various environmental exposure scenarios. A previous paper reported the results for submersion in radioactive air and immersion in water using age-specific mathematical phantoms. This paper presents age-specific effective dose rate coefficients derived using stylized mathematical phantoms for exposure to contaminated soils. Dose rate coefficients for photon, electron, and positrons of discrete energies were calculated and folded with emissions of 1252 radionuclides addressed in ICRP Publication 107 to determine equivalent and effective dose rate coefficients. The MCNP6 radiation transport code was used for organ dose ratemore » calculations for photons and the contribution of electrons to skin dose rate was derived using point-kernels. Bremsstrahlung and annihilation photons of positron emission were evaluated as discrete photons. As a result, the coefficients calculated in this work compare favorably to those reported in the US Federal Guidance Report 12 as well as by other authors who employed voxel phantoms for similar exposure scenarios.« less

Hydroxyurea-Mediated Cytotoxicity Without Inhibition of Ribonucleotide Reductase.

PubMed

Liew, Li Phing; Lim, Zun Yi; Cohen, Matan; Kong, Ziqing; Marjavaara, Lisette; Chabes, Andrei; Bell, Stephen D

2016-11-01

In many organisms, hydroxyurea (HU) inhibits class I ribonucleotide reductase, leading to lowered cellular pools of deoxyribonucleoside triphosphates. The reduced levels for DNA precursors is believed to cause replication fork stalling. Upon treatment of the hyperthermophilic archaeon Sulfolobus solfataricus with HU, we observe dose-dependent cell cycle arrest, accumulation of DNA double-strand breaks, stalled replication forks, and elevated levels of recombination structures. However, Sulfolobus has a HU-insensitive class II ribonucleotide reductase, and we reveal that HU treatment does not significantly impact cellular DNA precursor pools. Profiling of protein and transcript levels reveals modulation of a specific subset of replication initiation and cell division genes. Notably, the selective loss of the regulatory subunit of the primase correlates with cessation of replication initiation and stalling of replication forks. Furthermore, we find evidence for a detoxification response induced by HU treatment. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

The Dynamic Flow and Failure Behavior of Magnesium and Magnesium Alloys

NASA Astrophysics Data System (ADS)

Eswar Prasad, K.; Li, B.; Dixit, N.; Shaffer, M.; Mathaudhu, S. N.; Ramesh, K. T.

2014-01-01

We review the dynamic behavior of magnesium alloys through a survey of the literature and a comparison with our own high-strain-rate experiments. We describe high-strain-rate experiments (at typical strain rates of 103 s-1) on polycrystalline pure magnesium as well as two magnesium alloys, AZ31B and ZK60. Both deformation and failure are considered. The observed behaviors are discussed in terms of the fundamental deformation and failure mechanisms in magnesium, considering the effects of grain size, strain rate, and crystallographic texture. A comparison of current results with the literature studies on these and other Mg alloys reveals that the crystallographic texture, grain size, and alloying elements continue to have a profound influence on the high-strain-rate deformation behavior. The available data set suggests that those materials loaded so as to initiate extension twinning have relatively rate-insensitive strengths up to strain rates of several thousand per second. In contrast, some rate dependence of the flow stress is observed for loading orientations in which the plastic flow is dominated by dislocation mechanisms.

Chromosome aberrations in human lymphocytes induced by 250 MeV protons: effects of dose, dose rate and shielding.

PubMed

George, K; Willingham, V; Wu, H; Gridley, D; Nelson, G; Cucinotta, F A

2002-01-01

Although the space radiation environment consists predominantly of energetic protons, astronauts inside a spacecraft are chronically exposed to both primary particles as well as secondary particles that are generated when the primary particles penetrate the spacecraft shielding. Secondary neutrons and secondary charged particles can have an LET value that is greater than the primary protons and, therefore, produce a higher relative biological effectiveness (RBE). Using the accelerator facility at Loma Linda University, we exposed human lymphocytes in vitro to 250 MeV protons with doses ranging from 0 to 60 cGy at three different dose rates: a low dose rate of 7.5 cGy/h, an intermediate dose rate of 30 cGy/h and a high dose rate of 70 cGy/min. The effect of 15 g/cm2 aluminum shielding on the induction of chromosome aberrations was investigated for each dose rate. After exposure, lymphocytes were incubated in growth medium containing phytohemagglutinin (PHA) and chromosome spreads were collected using a chemical-induced premature chromosome condensation (PCC) technique. Aberrations were analyzed using the fluorescence in situ hybridization (FISH) technique with three different colored chromosome-painting probes. The frequency of reciprocal and complex-type chromosome exchanges were compared in shielded and unshielded samples. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Dose rate effects in radiation degradation of polymer-based cable materials

NASA Astrophysics Data System (ADS)

Plaček, V.; Bartoníček, B.; Hnát, V.; Otáhal, B.

2003-08-01

Cable ageing under the nuclear power plant (NPP) conditions must be effectively managed to ensure that the required plant safety and reliability are maintained throughout the plant service life. Ionizing radiation is one of the main stressors causing age-related degradation of polymer-based cable materials in air. For a given absorbed dose, radiation-induced damage to a polymer in air environment usually depends on the dose rate of the exposure. In this work, the effect of dose rate on the degradation rate has been studied. Three types of NPP cables (with jacket/insulation combinations PVC/PVC, PVC/PE, XPE/XPE) were irradiated at room temperature using 60Co gamma ray source at average dose rates of 7, 30 and 100 Gy/h with the doses up to 590 kGy. The irradiated samples have been tested for their mechanical properties, thermo-oxidative stability (using differential scanning calorimetry, DSC), and density. In the case of PVC and PE samples, the tested properties have shown evident dose rate effects, while the XPE material has shown no noticeable ones. The values of elongation at break and the thermo-oxidative stability decrease with the advanced degradation, density tends to increase with the absorbed dose. For XPE samples this effect can be partially explained by the increase of crystallinity. It was tested by the DSC determination of the crystalline phase amount.

Chromosome aberrations in human lymphocytes induced by 250 MeV protons: effects of dose, dose rate and shielding

NASA Technical Reports Server (NTRS)

George, K.; Willingham, V.; Wu, H.; Gridley, D.; Nelson, G.; Cucinotta, F. A.

2002-01-01

Although the space radiation environment consists predominantly of energetic protons, astronauts inside a spacecraft are chronically exposed to both primary particles as well as secondary particles that are generated when the primary particles penetrate the spacecraft shielding. Secondary neutrons and secondary charged particles can have an LET value that is greater than the primary protons and, therefore, produce a higher relative biological effectiveness (RBE). Using the accelerator facility at Loma Linda University, we exposed human lymphocytes in vitro to 250 MeV protons with doses ranging from 0 to 60 cGy at three different dose rates: a low dose rate of 7.5 cGy/h, an intermediate dose rate of 30 cGy/h and a high dose rate of 70 cGy/min. The effect of 15 g/cm2 aluminum shielding on the induction of chromosome aberrations was investigated for each dose rate. After exposure, lymphocytes were incubated in growth medium containing phytohemagglutinin (PHA) and chromosome spreads were collected using a chemical-induced premature chromosome condensation (PCC) technique. Aberrations were analyzed using the fluorescence in situ hybridization (FISH) technique with three different colored chromosome-painting probes. The frequency of reciprocal and complex-type chromosome exchanges were compared in shielded and unshielded samples. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

High dose-per-pulse electron beam dosimetry: Usability and dose-rate independence of EBT3 Gafchromic films.

PubMed

Jaccard, Maud; Petersson, Kristoffer; Buchillier, Thierry; Germond, Jean-François; Durán, Maria Teresa; Vozenin, Marie-Catherine; Bourhis, Jean; Bochud, François O; Bailat, Claude

2017-02-01

The aim of this study was to assess the suitability of Gafchromic EBT3 films for reference dose measurements in the beam of a prototype high dose-per-pulse linear accelerator (linac), capable of delivering electron beams with a mean dose-rate (Ḋ m ) ranging from 0.07 to 3000 Gy/s and a dose-rate in pulse (Ḋ p ) of up to 8 × 10 6 Gy/s. To do this, we evaluated the overall uncertainties in EBT3 film dosimetry as well as the energy and dose-rate dependence of their response. Our dosimetric system was composed of EBT3 Gafchromic films in combination with a flatbed scanner and was calibrated against an ionization chamber traceable to primary standard. All sources of uncertainties in EBT3 dosimetry were carefully analyzed using irradiations at a clinical radiotherapy linac. Energy dependence was investigated with the same machine by acquiring and comparing calibration curves for three different beam energies (4, 8 and 12 MeV), for doses between 0.25 and 30 Gy. Ḋ m dependence was studied at the clinical linac by changing the pulse repetition frequency (f) of the beam in order to vary Ḋ m between 0.55 and 4.40 Gy/min, while Ḋ p dependence was probed at the prototype machine for Ḋ p ranging from 7 × 10 3 to 8 × 10 6 Gy/s. Ḋ p dependence was first determined by studying the correlation between the dose measured by films and the charge of electrons measured at the exit of the machine by an induction torus. Furthermore, we compared doses from the films to independently calibrated thermo-luminescent dosimeters (TLD) that have been reported as being dose-rate independent up to such high dose-rates. We report that uncertainty below 4% (k = 2) can be achieved in the dose range between 3 and 17 Gy. Results also demonstrated that EBT3 films did not display any detectable energy dependence for electron beam energies between 4 and 12 MeV. No Ḋ m dependence was found either. In addition, we obtained excellent consistency between films and TLDs over the entire Ḋ p range attainable at the prototype linac confirming the absence of any dose-rate dependence within the investigated range (7 × 10 3 to 8 × 10 6 Gy/s). This aspect was further corroborated by the linear relationship between the dose-per-pulse (D p ) measured by films and the charge per pulse (C p ) measured at the prototype linac exit. Our study shows that the use of EBT3 Gafchromic films can be extended to reference dosimetry in pulsed electron beams with a very high dose rate. The measurement results are associated with an overall uncertainty below 4% (k = 2) and are dose-rate and energy independent. © 2016 American Association of Physicists in Medicine.

Quadrature demultiplexing using a degenerate vector parametric amplifier.

PubMed

Lorences-Riesgo, Abel; Liu, Lan; Olsson, Samuel L I; Malik, Rohit; Kumpera, Aleš; Lundström, Carl; Radic, Stojan; Karlsson, Magnus; Andrekson, Peter A

2014-12-01

We report on quadrature demultiplexing of a quadrature phase-shift keying (QPSK) signal into two cross-polarized binary phase-shift keying (BPSK) signals with negligible penalty at bit-error rate (BER) equal to 10(-9). The all-optical quadrature demultiplexing is achieved using a degenerate vector parametric amplifier operating in phase-insensitive mode. We also propose and demonstrate the use of a novel and simple phase-locked loop (PLL) scheme based on detecting the envelope of one of the signals after demultiplexing in order to achieve stable quadrature decomposition.

NDIA 2018 IM and EM Technology Symposium: Innovative Insensitive Munition Solutions for Enhanced Warfighter Effectiveness

DTIC Science & Technology

2018-04-26

decomposition of explosives, test materials and their mixtures. A DSC for each individual explosive, test material and mixture shall be run in duplicate... run in duplicate • Explosives and test materials are mixed in a 1:1 (w/w) ratio • Samples are heated at a rate of 5°C/min from room temperature to...warrants it. If a reaction occurs in ten trials, the load is reduced until there are no reactions observed in ten trials. The ESD test was run per a

Dose-rate effect was observed in T98G glioma cells following BNCT.

PubMed

Kinashi, Yuko; Okumura, Kakuji; Kubota, Yoshihisa; Kitajima, Erika; Okayasu, Ryuichi; Ono, Koji; Takahashi, Sentaro

2014-06-01

It is generally said that low LET radiation produce high dose-rate effect, on the other hand, no significant dose rate effect is observed in high LET radiation. Although high LET radiations are produced in BNCT, little is known about dose-rate effect of BNCT. T98G cells, which were tumor cells, were irradiated by neutron mixed beam with BPA. As normal tissue derived cells, Chinese hamster ovary (CHO-K1) cells and DNA double strand breaks (DNA-DSBs) repair deficient cells, xrs5 cells were irradiated by the neutrons (not including BPA). To DNA-DSBs analysis, T98G cells were stained immunochemically with 53BP1 antibody. The number of DNA-DSBs was determined by counting 53BP1 foci. There was no dose-rate effect in xrs5 cells. D0 difference between 4cGy/min and 20cGy/min irradiation were 0.5 and 5.9 at the neutron and gamma-ray irradiation for CHO-K1, and 0.3 at the neutron for T98G cells. D0 difference between 20cGy/min and 80cGy/min irradiation for T98G cells were 1.2 and 0.6 at neutron irradiation plus BPA and gamma-ray. The differences between neutron irradiations at the dose rate in T98G cells were supported by not only the cell viability but also 53BP1 foci assay at 24h following irradiation to monitor DNA-DSBs. Dose-rate effect of BNCT when T98G cells include 20ppm BPA was greater than that of gamma-ray irradiation. Moreover, Dose-rate effect of the neutron beam when CHO-K1 cells did not include BPA was less than that of gamma-ray irradiation These present results may suggest the importance of dose-rate effect for more efficient BNCT and the side effect reduction. © 2013 Published by Elsevier Ltd.

Effect of γ-dose rate and total dose interrelation on the polymeric hydrogel: A novel injectable male contraceptive

NASA Astrophysics Data System (ADS)

Jha, Pradeep K.; Jha, Rakhi; Gupta, B. L.; Guha, Sujoy K.

2010-05-01

Functional necessity to use a particular range of dose rate and total dose of γ-initiated polymerization to manufacture a novel polymeric hydrogel RISUG ® (reversible inhibition of sperm under guidance) made of styrene maleic anhydride (SMA) dissolved in dimethyl sulphoxide (DMSO), for its broad biomedical application explores new dimension of research. The present work involves 16 irradiated samples. They were tested by fourier transform infrared spectroscopy, matrix assisted laser desorption/ionization-TOF, field emission scanning electron microscopy, high resolution transmission electron microscopy, etc. to see the interrelation effect of gamma dose rates (8.25, 17.29, 20.01 and 25.00 Gy/min) and four sets of doses (1.8, 2.0, 2.2 and 2.4 kGy) on the molecular weight, molecular weight distribution and porosity analysis of the biopolymeric drug RISUG ®. The results of randomized experiment indicated that a range of 18-24 Gy/min γ-dose rate and 2.0-2.4 kGy γ-total doses is suitable for the desirable in vivo performance of the contraceptive copolymer.

The effects of perphenazine on self-administration behavior.

PubMed

Johanson, C E; Kandel, D A; Bonese, K

1976-04-01

In Experiment 1.6 rhesus monkeys prepared with intravenous catheters responded on a fixed-ratio 10 schedule for either an injection of 0.2 mg/kg of cocaine or 0.5 mg/kg of pentobarbital during a daily 3 hr session. The substitution of saline or various doses of perphenazine resulted in very low rates of responding. These results indicate that perphenazine is not a positive reinforcer. Pretreating animals maintained on 0.1 mg/kg or 0.2 mg/kg of cocaine with perphenazine resulted in increases in rate of self-administration at some doses and a decrease in rate at higher doses. The dose of perphenazine which resulted in the maximal increase in cocaine self-administration was directly related to the dose of cocaine maintaining responding. Pretreating animals maintained on 0.5 mg/kg of pentobarbital with perphenazine had no effect at doses which increased cocaine self-administration but decreased rate of pentobarbital self-administration at higher doses. These results indicate that perphenazine is capable of antagonizing some of the effects of cocaine.

[Evaluation of an Experimental Production Wireless Dose Monitoring System for Radiation Exposure Management of Medical Staff].

PubMed

Fujibuchi, Toshioh; Murazaki, Hiroo; Kuramoto, Taku; Umedzu, Yoshiyuki; Ishigaki, Yung

2015-08-01

Because of the more advanced and more complex procedures in interventional radiology, longer treatment times have become necessary. Therefore, it is important to determine the exposure doses received by operators and patients. The aim of our study was to evaluate an experimental production wireless dose monitoring system for pulse radiation in diagnostic X-ray. The energy, dose rate, and pulse fluoroscopy dependence were evaluated as the basic characteristics of this system for diagnostic X-ray using a fully digital fluoroscopy system. The error of 1 cm dose equivalent rate was less than 15% from 35.1 keV to 43.2 keV with energy correction using metal filter. It was possible to accurately measure the dose rate dependence of this system, which was highly linear until 100 μSv/h. This system showed a constant response to the pulse fluoroscopy. This system will become useful wireless dosimeter for the individual exposure management by improving the high dose rate and the energy characteristics.

Modelling evolution of air dose rates in river basins in Fukushima Prefecture affected by sediment-sorbed radiocesium redistribution

NASA Astrophysics Data System (ADS)

Malins, A.; Sakuma, K.; Nakanishi, T.; Kurikami, H.; Machida, M.; Kitamura, A.; Yamada, S.

2015-12-01

The radioactive 134Cs and 137Cs isotopes deposited over Fukushima Prefecture by the Fukushima Daiichi nuclear disaster are the predominant radiological concern for the years following the accident. This is because the energetic gamma radiation they emit on decay constitutes the majority of the elevated air dose rates that now afflict the region. Therefore, we developed a tool for calculating air dose rates from arbitrary radiocesium spatial distributions across the land surface and depth profiles within the ground. As cesium is strongly absorbed by clay soils, its primary redistribution mechanism within Fukushima Prefecture is by soil erosion and water-borne sediment transport. Each year between 0.1~1% of the total radiocesium inventory in the river basins neighboring Fukushima Daiichi is eroded from the land surface and enters into water courses, predominantly during typhoon storms. Although this is a small amount in relative terms, in absolute terms it corresponds to terabecquerels of 134Cs and 137Cs redistribution each year and this can affect the air dose rate at locations of high erosion and sediment deposition. This study inputs the results of sediment redistribution simulations into the dose rate evaluation tool to calculate the locations and magnitude of air dose rate changes due to radiocesium redistribution. The dose rate calculations are supported by handheld survey instrument results taken within the Prefecture.

Dose-rate plays a significant role in synchrotron radiation X-ray-induced damage of rodent testes.

PubMed

Chen, Heyu; Wang, Ban; Wang, Caixia; Cao, Wei; Zhang, Jie; Ma, Yingxin; Hong, Yunyi; Fu, Shen; Wu, Fan; Ying, Weihai

2016-01-01

Synchrotron radiation (SR) X-ray has significant potential for applications in medical imaging and cancer treatment. However, the mechanisms underlying SR X-ray-induced tissue damage remain unclear. Previous studies on regular X-ray-induced tissue damage have suggested that dose-rate could affect radiation damage. Because SR X-ray has exceedingly high dose-rate compared to regular X-ray, it remains to be determined if dose-rate may affect SR X-ray-induced tissue damage. We used rodent testes as a model to investigate the role of dose-rate in SR X-ray-induced tissue damage. One day after SR X-ray irradiation, we determined the effects of the irradiation of the same dosage at two different dose-rates, 0.11 Gy/s and 1.1 Gy/s, on TUNEL signals, caspase-3 activation and DNA double-strand breaks (DSBs) of the testes. Compared to those produced by the irradiation at 0.11 Gy/s, irradiation at 1.1 Gy/s produced higher levels of DSBs, TUNEL signals, and caspase-3 activation in the testes. Our study has provided the first evidence suggesting that dose-rate could be a significant factor in SR X-ray-induced tissue damage, which may establish a valuable base for utilizing this factor to manipulate the tissue damage in SR X-ray-based medical applications.

Dose-rate plays a significant role in synchrotron radiation X-ray-induced damage of rodent testes

PubMed Central

Chen, Heyu; Wang, Ban; Wang, Caixia; Cao, Wei; Zhang, Jie; Ma, Yingxin; Hong, Yunyi; Fu, Shen; Wu, Fan; Ying, Weihai

2016-01-01

Synchrotron radiation (SR) X-ray has significant potential for applications in medical imaging and cancer treatment. However, the mechanisms underlying SR X-ray-induced tissue damage remain unclear. Previous studies on regular X-ray-induced tissue damage have suggested that dose-rate could affect radiation damage. Because SR X-ray has exceedingly high dose-rate compared to regular X-ray, it remains to be determined if dose-rate may affect SR X-ray-induced tissue damage. We used rodent testes as a model to investigate the role of dose-rate in SR X-ray-induced tissue damage. One day after SR X-ray irradiation, we determined the effects of the irradiation of the same dosage at two different dose-rates, 0.11 Gy/s and 1.1 Gy/s, on TUNEL signals, caspase-3 activation and DNA double-strand breaks (DSBs) of the testes. Compared to those produced by the irradiation at 0.11 Gy/s, irradiation at 1.1 Gy/s produced higher levels of DSBs, TUNEL signals, and caspase-3 activation in the testes. Our study has provided the first evidence suggesting that dose-rate could be a significant factor in SR X-ray-induced tissue damage, which may establish a valuable base for utilizing this factor to manipulate the tissue damage in SR X-ray-based medical applications. PMID:28078052

Effects of Epoetin Alfa Titration Practices, Implemented After Changes to Product Labeling, on Hemoglobin Levels, Transfusion Use, and Hospitalization Rates.

PubMed

Molony, Julia T; Monda, Keri L; Li, Suying; Beaubrun, Anne C; Gilbertson, David T; Bradbury, Brian D; Collins, Allan J

2016-08-01

Little is known about epoetin alfa (EPO) dosing at dialysis centers after implementation of the US Medicare prospective payment system and revision of the EPO label in 2011. Retrospective cohort study. Approximately 412,000 adult hemodialysis patients with Medicare Parts A and B as primary payer in 2009 to 2012 to describe EPO dosing and hemoglobin patterns; of these, about 70,000 patients clustered in about 1,300 dialysis facilities to evaluate facility-level EPO titration practices and patient-level outcomes in 2012. Facility EPO titration practices when hemoglobin levels were <10 and >11g/dL (grouped treatment variable) determined from monthly EPO dosing and hemoglobin level patterns. Patient mean hemoglobin levels, red blood cell transfusion rates, and all-cause and cause-specific hospitalization rates using a facility-based analysis. Monthly EPO dose and hemoglobin level, red blood cell transfusion rates, and all-cause and cause-specific hospitalization rates. Monthly EPO doses declined across all hemoglobin levels, with the greatest decline in patients with hemoglobin levels < 10g/dL (July-October 2011). In 2012, nine distinct facility titration practices were identified. Across groups, mean hemoglobin levels differed slightly (10.5-10.8g/dL) but within-patient hemoglobin standard deviations were similar (∼0.68g/dL). Patients at facilities implementing greater dose reductions and smaller dose escalations had lower hemoglobin levels and higher transfusion rates. In contrast, patients at facilities that implemented greater dose escalations (and large or small dose reductions) had higher hemoglobin levels and lower transfusion rates. There were no clinically meaningful differences in all-cause or cause-specific hospitalization events across groups. Possibly incomplete claims data; excluded small facilities and those without consistent titration patterns; hemoglobin levels reported monthly; inferred facility practice from observed dosing. Following prospective payment system implementation and labeling revisions, EPO doses declined significantly. Under the new label, facility EPO titration practices were associated with mean hemoglobin levels (but not standard deviations) and transfusion use, but not hospitalization rates. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

High temperature, low-cycle fatigue of copper-base alloys in argon. Part 2: Zirconium-copper at 482, 538 and 593 C

NASA Technical Reports Server (NTRS)

Conway, J. B.; Stentz, R. H.; Berling, J. T.

1973-01-01

Zirconium-copper (1/2 hard) was tested in argon over the temperature range from 482 to 593 C in an evaluation of short-term tensile and low-cycle fatigue behavior. The effect of strain rate on the tensile properties was evaluated at 538 C and in general it was found that the yield and ultimate strengths increased as the strain rate was increased from 0.0004 to 0.01/sec. Ductility was essentially insensitive to strain rate in the case of the zirconium-copper alloy. Strain-rate and hold-time effects on the low cycle fatigue behavior of zirconium-copper were evaluated in argon at 538 C. These effects were as expected in that decreased fatigue life was noted as the strain rate decreased and when hold times were introduced into the tension portion of the strain-cycle. Hold times in compression were much less detrimental than hold times in tension.

Effect of an ozone injury-retardant chemical on isozyme profiles from alfalfa callus in vitro

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

Rier, J.P.; Sood, V.K.; Whitaker, A.

1983-01-01

Plant ozone injury retardant (EDU or ethylenediurea) at 1.0 ppm inhibited growth of callus of alfalfa cultivars Williamsburg (ozone-sensitive) and MSB-CW5An2(ozone-insensitive) germplasm of Medicago sative. The presence of EDU(0.1 ppm) in growth medium increased the number of protein and peroxidase isozyme bands in alfalfa cultivar stem callus and ozone modified their intensities. Protein profiles of MSB stem callus from media containing EDU or exposed to ozone were unchanged. Marked differences were observed between the peroxidase profiles of ozonated and control ozone-insensitive stem callus from media containing EDU. Protein profiles of ozonated ozone-insensitive leaf callus differed slightly from controls.

Broadband temperature-insensitivity of dispersion-engineered waveguides and resonators

NASA Astrophysics Data System (ADS)

Xu, Lijuan; He, Liuqing; Guo, Yuhao; Li, Guifang; Zhang, Lin

2018-02-01

Photonic circuits suffer from thermal drift of device performance, which is a key obstacle to the development of commercial optoelectronic products. Temperature-insensitive integrated waveguides and resonators have been demonstrated by using materials with a negative TOC at a single wavelength, which are not suitable for WDM devices and wideband nonlinear devices. Here, we propose a waveguide structure with temperature-insensitivity over a bandwidth of 780 nm (1280 to 2060 nm) with an ultra-small effective TOC within +/-1×10-6/K. Uniquely, the waveguide has small anomalous dispersion (from 66 to 329 ps/nm/km) over the same band and is suitable for frequency comb generation without being affected by intra-cavity thermal dynamics.

A vibration-insensitive optical cavity and absolute determination of its ultrahigh stability.

PubMed

Zhao, Y N; Zhang, J; Stejskal, A; Liu, T; Elman, V; Lu, Z H; Wang, L J

2009-05-25

We use the three-cornered-hat method to evaluate the absolute frequency stabilities of three different ultrastable reference cavities, one of which has a vibration-insensitive design that does not even require vibration isolation. An Nd:YAG laser and a diode laser are implemented as light sources. We observe approximately 1 Hz beat note linewidths between all three cavities. The measurement demonstrates that the vibration-insensitive cavity has a good frequency stability over the entire measurement time from 100 ms to 200 s. An absolute, correlation-removed Allan deviation of 1.4 x 10(-15) at s of this cavity is obtained, giving a frequency uncertainty of only 0.44 Hz.

Broad-gain (Δλ/λ0

PubMed

Fujita, Kazuue; Furuta, Shinichi; Dougakiuchi, Tatsuo; Sugiyama, Atsushi; Edamura, Tadataka; Yamanishi, Masamichi

2011-01-31

Broad-gain operation of λ~8.7 μm quantum cascade lasers based on dual-upper-state to multiple-lower-state transition design is reported. The devices exhibit surprisingly wide (~500 cm(-1)) electroluminescence spectra which are very insensitive to voltage and temperature changes above room temperature. With recourse to the temperature-insensitivity of electroluminescence spectra, the lasers demonstrate an extremely-weak temperature-dependence of laser performances: T0-value of 510 K, associated with a room temperature threshold current density of 2.6 kA/cm2. In addition, despite such wide gain spectra, room temperature, continuous wave operation of the laser with buried hetero structure is achieved.

Radiation Parameters of High Dose Rate Iridium -192 Sources

NASA Astrophysics Data System (ADS)

Podgorsak, Matthew B.

A lack of physical data for high dose rate (HDR) Ir-192 sources has necessitated the use of basic radiation parameters measured with low dose rate (LDR) Ir-192 seeds and ribbons in HDR dosimetry calculations. A rigorous examination of the radiation parameters of several HDR Ir-192 sources has shown that this extension of physical data from LDR to HDR Ir-192 may be inaccurate. Uncertainty in any of the basic radiation parameters used in dosimetry calculations compromises the accuracy of the calculated dose distribution and the subsequent dose delivery. Dose errors of up to 0.3%, 6%, and 2% can result from the use of currently accepted values for the half-life, exposure rate constant, and dose buildup effect, respectively. Since an accuracy of 5% in the delivered dose is essential to prevent severe complications or tumor regrowth, the use of basic physical constants with uncertainties approaching 6% is unacceptable. A systematic evaluation of the pertinent radiation parameters contributes to a reduction in the overall uncertainty in HDR Ir-192 dose delivery. Moreover, the results of the studies described in this thesis contribute significantly to the establishment of standardized numerical values to be used in HDR Ir-192 dosimetry calculations.

Continuous Exposure to Low-Dose-Rate Gamma Irradiation Reduces Airway Inflammation in Ovalbumin-Induced Asthma.

PubMed

Kim, Joong Sun; Son, Yeonghoon; Bae, Min Ji; Lee, Seung Sook; Park, Sun Hoo; Lee, Hae June; Lee, Soong In; Lee, Chang Geun; Kim, Sung Dae; Jo, Wol Soon; Kim, Sung Ho; Shin, In Sik

2015-01-01

Although safe doses of radiation have been determined, concerns about the harmful effects of low-dose radiation persist. In particular, to date, few studies have investigated the correlation between low-dose radiation and disease development. Asthma is a common chronic inflammatory airway disease that is recognized as a major public health problem. In this study, we evaluated the effects of low-dose-rate chronic irradiation on allergic asthma in a murine model. Mice were sensitized and airway-challenged with ovalbumin (OVA) and were exposed to continuous low-dose-rate irradiation (0.554 or 1.818 mGy/h) for 24 days after initial sensitization. The effects of chronic radiation on proinflammatory cytokines and the activity of matrix metalloproteinase-9 (MMP-9) were investigated. Exposure to low-dose-rate chronic irradiation significantly decreased the number of inflammatory cells, methylcholine responsiveness (PenH value), and the levels of OVA-specific immunoglobulin E, interleukin (IL)-4, and IL-5. Furthermore, airway inflammation and the mucus production in lung tissue were attenuated and elevated MMP-9 expression and activity induced by OVA challenge were significantly suppressed. These results indicate that low-dose-rate chronic irradiation suppresses allergic asthma induced by OVA challenge and does not exert any adverse effects on asthma development. Our findings can potentially provide toxicological guidance for the safe use of radiation and relieve the general anxiety about exposure to low-dose radiation.

[Do poor-responder patients benefit from increasing the daily gonadotropin dose from 300 to 450 IU during controlled ovarian hyperstimulation for IVF?].

PubMed

Haas, Jigal; Zilberberg, Eran; Kedem, Alon; Dar, Shir; Orvieto, Raoul

2015-02-01

We aim to evaluate the IVF-ET outcome in patients receiving a high daily dose (300 IU) of gonadotropins during controlled ovarian hyperstimulation (COH) for IVF and to assess the role of increasing the daily dose to 450 IU on improving outcome. All consecutive women admitted to our IVF unit during an 11 year period who underwent COH consisting of daily gonadotropin dose of 300 IU were included in the study. The ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate were assessed. We also evaluated the subsequent cycle, using daily gonadotropin doses of 450 IU, among those patients who did not conceive using the 300 IU daily gonadotropin dose. Nine hundred and forty-nine consecutive IVF cycles were evaluated. Patients who conceived using the daily gonadotropin dose of 300 IU (n = 133, 14% pregnancy rate) had significantly longer stimulation, yielded higher numbers of oocytes retrieved, fertilization rate and number of embryos transferred, compared to those who did not conceive. Moreover, while comparing IVF cycles using daily gonadotropin doses of 300 IU to 450 IU (n = 117), no in-between group differences were observed, except for significantly higher yields of oocytes retrieved. Moreover, cycles using daily gonadotropin doses of 450 IU resulted in a 7.7 live-birth rate. In poor responders undergoing COH with a daily gonadotropin dose of 300 IU, increasing the dose to 450 IU resulted in significantly higher oocyte yields and a reasonable live birth rate.

Testing Moderating Detection Systems with {sup 252}Cf-Based Reference Neutron Fields

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

Hertel, Nolan E.; Sweezy, Jeremy; Sauber, Jeremiah S.

Calibration measurements were carried out on a probe designed to measure ambient dose equivalent in accordance with ICRP Pub 60 recommendations. It consists of a cylindrical {sup 3}He proportional counter surrounded by a 25-cm-diameter spherical polyethylene moderator. Its neutron response is optimized for dose rate measurements of neutrons between thermal energies and 20 MeV. The instrument was used to measure the dose rate in four separate neutron fields: unmoderated {sup 252}Cf, D{sub 2}O-moderated {sup 252}Cf, polyethylene-moderated {sup 252}Cf, and WEP neutron howitzer with {sup 252}Cf at its center. Dose equivalent measurements were performed at source-detector centerline distances from 50 tomore » 200 cm. The ratio of air-scatter- and room-return-corrected ambient dose equivalent rates to ambient dose equivalent rates calculated with the code MCNP are tabulated.« less

Mapping of cosmic radiation dose in Croatia.

PubMed

Poje, M; Vuković, B; Radolić, V; Miklavčić, I; Faj, D; Varga Pajtler, M; Planinić, J

2012-01-01

The Earth is continually bombarded by high-energy particles coming from the outer space and the sun. These particles, termed cosmic radiation, interact with nuclei of atmospheric constituents and decrease in intensity with depth in the atmosphere. Measurements of photon and gamma radiation, performed with a Radiameter at 1 m above the ground, indicated dose rates of 50-100 nSv/h. The neutron dose rate was measured with the CR-39 track etch detector calibrated by the CERN-EU high-energy Reference Field (CERF) facility. Correlation between neutron dose rates and altitudes at 36 sites was examined in order to obtain a significant positive correlation coefficient; the resulting linear regression enabled estimation of a neutron dose at particular altitude. The measured neutron dose rate in Osijek (altitude of 89 m, latitude of 45.31° N) was 110 nSv/h. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

Kurnaz, Asli; Kuecuekoemeroglu, B.; Okumusoglu, N. T.

In this study, it was determined environmental gamma radiation dose rate for some counties of Trabzon-Turkey. A detailed ambient gamma dose measurement has been performed in the seven counties of Trabzon, using a portable environmental survey meter (NaI detector, INSPECTOR 1000). The measurements were performed indoor and outdoor of buildings and also at each spot, a reading was taken at 1 m above ground level. The dose rates varied from 42.69 nGy/h and 140.91 nGy/h for indoor gamma dose and 27.84 nGy/h and 121.80 nGy/h for outdoor gamma dose . Average indoor and outdoor gamma dose rates were ascertained tomore » be 71.05 nGy/h and 60.20 nGy/h, respectively. The annual effective doses were calculated from indoor and outdoor gamma doses to be 348.56 muSv/y and 73.83 muSv/y, respectively.« less

Room model based Monte Carlo simulation study of the relationship between the airborne dose rate and the surface-deposited radon progeny.

PubMed

Sun, Kainan; Field, R William; Steck, Daniel J

2010-01-01

The quantitative relationships between radon gas concentration, the surface-deposited activities of various radon progeny, the airborne radon progeny dose rate, and various residential environmental factors were investigated through a Monte Carlo simulation study based on the extended Jacobi room model. Airborne dose rates were calculated from the unattached and attached potential alpha-energy concentrations (PAECs) using two dosimetric models. Surface-deposited (218)Po and (214)Po were significantly correlated with radon concentration, PAECs, and airborne dose rate (p-values <0.0001) in both non-smoking and smoking environments. However, in non-smoking environments, the deposited radon progeny were not highly correlated to the attached PAEC. In multiple linear regression analysis, natural logarithm transformation was performed for airborne dose rate as a dependent variable, as well as for radon and deposited (218)Po and (214)Po as predictors. In non-smoking environments, after adjusting for the effect of radon, deposited (214)Po was a significant positive predictor for one dose model (RR 1.46, 95% CI 1.27-1.67), while deposited (218)Po was a negative predictor for the other dose model (RR 0.90, 95% CI 0.83-0.98). In smoking environments, after adjusting for radon and room size, deposited (218)Po was a significant positive predictor for one dose model (RR 1.10, 95% CI 1.02-1.19), while a significant negative predictor for the other model (RR 0.90, 95% CI 0.85-0.95). After adjusting for radon and deposited (218)Po, significant increases of 1.14 (95% CI 1.03-1.27) and 1.13 (95% CI 1.05-1.22) in the mean dose rates were found for large room sizes relative to small room sizes in the different dose models.

Spiromax, a New Dry Powder Inhaler: Dose Consistency under Simulated Real-World Conditions.

PubMed

Canonica, Giorgio Walter; Arp, Jan; Keegstra, Johan René; Chrystyn, Henry

2015-10-01

Spiromax(®) is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide-formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and Turbuhaler inhaler) of importance to patients with asthma or COPD. Dose-delivery studies were performed using low-, middle-, and high-strength DuoResp Spiromax. Dose consistency was assessed over inhaler life. Total emitted doses (TEDs) were measured at various flow rates, after exposure to high and low temperature or humidity, at different inhaler orientations, and after dropping the inhaler. The criterion for evaluating dose uniformity was whether mean TEDs were within the product specification limits. In separate studies, flow rates were measured after training, using the patient information leaflets, and again after enhanced training as part of a randomized, open-label, cross-over study. Mean values for both budesonide and formoterol were within 85%-115% of the label claim for each strength of DuoResp Spiromax for initial dose uniformity and for the other investigated conditions (temperature, humidity, orientation, dropping, knocking), with the exception of approximately an 80% increase in first dose after dropping the inhaler (subsequent doses not affected). In the flow rate patient study, two patients' inhalations with Spiromax and six with Turbuhaler were <30 L/min. The majority of asthma patients [91% (Spiromax) versus 82% (Turbuhaler)] achieved the preferred flow rate of >60 L/min. DuoResp Spiromax consistently meets dose uniformity criteria, under controlled laboratory conditions and with variations intended to mimic real-world use. Following enhanced training, all patients in the flow study were able to achieve the minimal inspiratory flow rate of >30 L/min, which is required for effective treatment.

The evaluation the magnitude radiation exposure dose rate in digital radiography room design

NASA Astrophysics Data System (ADS)

Dwiyanto, Agung; Setia Budi, Wahyu; Hardiman, Gagoek

2017-12-01

This study discusses the dose rate in digital radiography room, buit according to meet the provisions of KEMENKES No.1014 / Menkes / SK / XI / 2008 and Regulation of BAPETEN No. 8 / 2011. The provisions primary concern of radiation safety, not comfort, by considering the space design. There are five aspects to consider in designing the space: functionality, comfort, security, movement activities and aesthetics. However provisions only met three aspects of the design, which are a function, security and movement activity. Therefore, it is necessary to evaluate digital radiography room in terms of its ability to control external radiation exposure to be safe and comfortable The dose rate is measured by the range of primary and secondary radiation in the observation points by using Surveymeter. All data are obtained by the preliminary survey prior to the study. Furthermore, the review of digital radiography room is done based on architectural design theory. The dose rate for recommended improvement room is recalculated using the same method as the actual room with the help of computer modeling. The result of dose rate calculation at the inner and outer part of digital radiography observation room shows that in-room dose for a week at each measuring point exceeds the allowable dose limit both for staff and public. During a week of observation, the outdoor dose at some measuring points exceeds the dose limit set by the KEMENKES No.1014 / Menkes / SK / XI / 2008 and Regulation BEPETEN No 8/2011. Meanwhile, the result of dose rate calculation in the inner and outer part of the improved digital radiography room can meet the applicable regulations better.

A study on dosimetric properties of electronic portal imaging device and its use as a quality assurance tool in Volumetric Modulated Arc Therapy

PubMed Central

Sukumar, Prabakar; Padmanaban, Sriram; Jeevanandam, Prakash; Syam Kumar, S.A.; Nagarajan, Vivekanandan

2011-01-01

Aim In this study, the dosimetric properties of the electronic portal imaging device were examined and the quality assurance testing of Volumetric Modulated Arc Therapy was performed. Background RapidArc involves the variable dose rate, leaf speed and the gantry rotation. The imager was studied for the effects like dose, dose rate, field size, leaf speed and sag during gantry rotation. Materials and methods A Varian RapidArc machine equipped with 120 multileaf collimator and amorphous silicon detector was used for the study. The characteristics that are variable in RapidArc treatment were studied for the portal imager. The accuracy of a dynamic multileaf collimator position at different gantry angles and during gantry rotation was examined using the picket fence test. The control of the dose rate and gantry speed was verified using a test field irradiating seven strips of the same dose with different dose rate and gantry speeds. The control over leaf speed during arc was verified by irradiating four strips of different leaf speeds with the same dose in each strip. To verify the results, the RapidArc test procedure was compared with the X-Omat film and verified for a period of 6 weeks using EPID. Results The effect of gantry rotation on leaf accuracy was minimal. The dose in segments showed good agreement with mean deviation of 0.8% for dose rate control and 1.09% for leaf speed control over different gantry speeds. Conclusion The results provided a precise control of gantry speed, dose rate and leaf speeds during RapidArc delivery and were consistent over 6 weeks. PMID:24376989

Development, beam characterization and chromosomal effectiveness of X-rays of RBC characteristic X-ray generator.

PubMed

Endo, Satoru; Hoshi, Masaharu; Takada, Jun; Takatsuji, Toshihiro; Ejima, Yosuke; Saigusa, Shin; Tachibana, Akira; Sasaki, Masao S

2006-06-01

A characteristic hot-filament type X-ray generator was constructed for irradiation of cultured cells. The source provides copper K, iron K, chromium K, molybdenum L, aluminium K and carbon K shell characteristic X-rays. When cultured mouse m5S cells were irradiated and frequencies of dicentrics were fitted to a linear-quadratic model, Y = alphaD + betaD2, the chromosomal effectiveness was not a simple function of photon energy. The alpha-terms increased with the decrease of the photon energy and then decreased with further decrease of the energy with an inflection point at around 10 keV. The beta-terms stayed constant for the photon energy down to 10 keV and then increased with further decrease of energy. Below 10 keV, the relative biological effectiveness (RBE) at low doses was proportional to the photon energy, which contrasted to that for high energy X- or gamma-rays where the RBE was inversely related with the photon energy. The reversion of the energy dependency occurred at around 1-2 Gy, where the RBE of soft X-rays was insensitive to X-ray energy. The reversion of energy-RBE relation at a moderate dose may shed light on the controversy on energy dependency of RBE of ultrasoft X-rays in cell survival experiments.

Review of Copper Provision in the Parenteral Nutrition of Adults [Formula: see text].

PubMed

Livingstone, Callum

2017-04-01

The essential trace element copper (Cu) is required for a range of physiologic processes, including wound healing and functioning of the immune system. The correct amount of Cu must be provided in parenteral nutrition (PN) if deficiency and toxicity are to be avoided. While provision in line with the standard recommendations should suffice for most patients, Cu requirements may be higher in patients with increased gastrointestinal losses and severe burns and lower in those with cholestasis. The tests of Cu status that are currently available for clinical use are unreliable. Serum Cu concentration is the most commonly ordered test but is insensitive to Cu deficiency and toxicity and is misleadingly increased during the acute phase response. These limitations make it difficult for prescribers to assess Cu status and to decide how much Cu to provide. There is a need for better tests of Cu status to be developed to decrease uncertainty and improve individualization of Cu dosing. More information is needed on Cu requirements in disease and Cu contamination of PN components and other intravenous fluids. New multi-trace element products should be developed that provide Cu doses in line with the 2012 American Society for Parenteral and Enteral Nutrition recommendations. This article discusses the evaluation and treatment of Cu deficiency and toxicity in patients treated with PN.

Incidence of Hypoglycemia in Patients With Low eGFR Treated With Insulin and Dextrose for Hyperkalemia.

PubMed

Pierce, Dwayne A; Russell, Greg; Pirkle, James L

2015-12-01

Hyperkalemia is a potentially life-threatening condition that is common in kidney disease patients. Insulin is used to treat hyperkalemia, but may cause hypoglycemia, especially in kidney disease when insulin may be metabolized more slowly. We compared the rates of hypoglycemia in patients with low estimated glomerular filtration rate (eGFR) using high versus low doses of insulin for hyperkalemia to determine if lower doses of insulin would decrease the incidence of hypoglycemia. This was a retrospective study of hospitalized patients receiving intravenous insulin for hyperkalemia during a 6-month period. Patients with low eGFR were analyzed based on how much insulin they received: high dose (10 units, n = 78) versus low dose (5 units, n = 71). Postdose nadir blood glucose values were examined for up to 8 hours after the dose. The percentage of hypoglycemia (blood glucose ≤70 mg/dl) and a subset of severe hypoglycemia (blood glucose <50 mg/dl) were then reported for each dose group. A total of 149 doses were identified in patients with low eGFR. The rates of hypoglycemia were 16.7% and 19.7% (P = 0.79), respectively, among high-dose (n = 78) and low-dose (n = 71) groups. Rates of severe hypoglycemia were 8.9% and 7.0%, respectively (P = 0.90). More than 28% of hypoglycemic episodes with high doses occurred after 4 hours (median = 2.5 hours) compared with 14.3% with low doses (median = 2.38 hours). There was no difference in the rate of hypoglycemia or severe hypoglycemia between high or low doses of insulin in patients with low eGFR. We recommend monitoring up to 6 hours after insulin use in hyperkalemia. © The Author(s) 2015.

Radiation damage in single-particle cryo-electron microscopy: effects of dose and dose rate.

PubMed

Karuppasamy, Manikandan; Karimi Nejadasl, Fatemeh; Vulovic, Milos; Koster, Abraham J; Ravelli, Raimond B G

2011-05-01

Radiation damage is an important resolution limiting factor both in macromolecular X-ray crystallography and cryo-electron microscopy. Systematic studies in macromolecular X-ray crystallography greatly benefited from the use of dose, expressed as energy deposited per mass unit, which is derived from parameters including incident flux, beam energy, beam size, sample composition and sample size. In here, the use of dose is reintroduced for electron microscopy, accounting for the electron energy, incident flux and measured sample thickness and composition. Knowledge of the amount of energy deposited allowed us to compare doses with experimental limits in macromolecular X-ray crystallography, to obtain an upper estimate of radical concentrations that build up in the vitreous sample, and to translate heat-transfer simulations carried out for macromolecular X-ray crystallography to cryo-electron microscopy. Stroboscopic exposure series of 50-250 images were collected for different incident flux densities and integration times from Lumbricus terrestris extracellular hemoglobin. The images within each series were computationally aligned and analyzed with similarity metrics such as Fourier ring correlation, Fourier ring phase residual and figure of merit. Prior to gas bubble formation, the images become linearly brighter with dose, at a rate of approximately 0.1% per 10 MGy. The gradual decomposition of a vitrified hemoglobin sample could be visualized at a series of doses up to 5500 MGy, by which dose the sample was sublimed. Comparison of equal-dose series collected with different incident flux densities showed a dose-rate effect favoring lower flux densities. Heat simulations predict that sample heating will only become an issue for very large dose rates (50 e(-)Å(-2) s(-1) or higher) combined with poor thermal contact between the grid and cryo-holder. Secondary radiolytic effects are likely to play a role in dose-rate effects. Stroboscopic data collection combined with an improved understanding of the effects of dose and dose rate will aid single-particle cryo-electron microscopists to have better control of the outcome of their experiments.

Radiation damage in single-particle cryo-electron microscopy: effects of dose and dose rate

PubMed Central

Karuppasamy, Manikandan; Karimi Nejadasl, Fatemeh; Vulovic, Milos; Koster, Abraham J.; Ravelli, Raimond B. G.

2011-01-01

Radiation damage is an important resolution limiting factor both in macromolecular X-ray crystallography and cryo-electron microscopy. Systematic studies in macromolecular X-ray crystallography greatly benefited from the use of dose, expressed as energy deposited per mass unit, which is derived from parameters including incident flux, beam energy, beam size, sample composition and sample size. In here, the use of dose is reintroduced for electron microscopy, accounting for the electron energy, incident flux and measured sample thickness and composition. Knowledge of the amount of energy deposited allowed us to compare doses with experimental limits in macromolecular X-ray crystallography, to obtain an upper estimate of radical concentrations that build up in the vitreous sample, and to translate heat-transfer simulations carried out for macromolecular X-ray crystallography to cryo-electron microscopy. Stroboscopic exposure series of 50–250 images were collected for different incident flux densities and integration times from Lumbricus terrestris extracellular hemoglobin. The images within each series were computationally aligned and analyzed with similarity metrics such as Fourier ring correlation, Fourier ring phase residual and figure of merit. Prior to gas bubble formation, the images become linearly brighter with dose, at a rate of approximately 0.1% per 10 MGy. The gradual decomposition of a vitrified hemoglobin sample could be visualized at a series of doses up to 5500 MGy, by which dose the sample was sublimed. Comparison of equal-dose series collected with different incident flux densities showed a dose-rate effect favoring lower flux densities. Heat simulations predict that sample heating will only become an issue for very large dose rates (50 e−Å−2 s−1 or higher) combined with poor thermal contact between the grid and cryo-holder. Secondary radiolytic effects are likely to play a role in dose-rate effects. Stroboscopic data collection combined with an improved understanding of the effects of dose and dose rate will aid single-particle cryo-electron microscopists to have better control of the outcome of their experiments. PMID:21525648

GENOTOXIC ACTIVITY OF 1-CHLOROMETHYLPYRENE IN STOMACH EPITHELIUM IN VIVO: INSENSITIVITY OF THE SCINTILLATION UDS ASSAY

EPA Science Inventory

An acknowledged weakness of current testing programs for genotoxic hazard has been the potential insensitivity of the established mouse bone ma,-row micronucleus test and rat liver UDS assays to direct-acting or short lived mutagens which may be consumed at the site of initial co...

Silicon carbide/calcium aluminosilicate: A notch-insensitive ceramic-matrix composite

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

Cady, C.M.; Mackin, T.J.; Evans, A.G.

Tension experiments performed on a 0/90 laminated silicon carbide/calcium aluminosilicate composite at room temperature establish that this material is notch insensitive. Multiple matrix cracking is determined to be the stress redistribution mechanism. This mechanism is found to provide a particularly efficient means for creating local inelastic strains, which eliminate stress concentrations.

Structure sensitivity in the nonscalable regime explored via catalysed ethylene hydrogenation on supported platinum nanoclusters

DOE PAGES

Crampton, Andrew S.; Rötzer, Marian D.; Ridge, Claron J.; ...

2016-01-28

The sensitivity, or insensitivity, of catalysed reactions to catalyst structure is a commonly employed fundamental concept. Here we report on the nature of nano-catalysed ethylene hydrogenation, investigated through experiments on size-selected Pt n (n=8-15) clusters soft-landed on magnesia and first-principles simulations, yielding benchmark information about the validity of structure sensitivity/insensitivity at the bottom of the catalyst size range. Both ethylene-hydrogenation-to-ethane and the parallel hydrogenation–dehydrogenation ethylidyne-producing route are considered, uncovering that at the <1 nm size-scale the reaction exhibits characteristics consistent with structure sensitivity, in contrast to structure insensitivity found for larger particles. The onset of catalysed hydrogenation occurs for Ptmore » n (n≥10) clusters at T>150 K, with maximum room temperature reactivity observed for Pt 13. Structure insensitivity, inherent for specific cluster sizes, is induced in the more active Pt 13 by a temperature increase up to 400 K leading to ethylidyne formation. As a result, control of sub-nanometre particle size may be used for tuning catalysed hydrogenation activity and selectivity.« less

Structure sensitivity in the nonscalable regime explored via catalysed ethylene hydrogenation on supported platinum nanoclusters

PubMed Central

Crampton, Andrew S.; Rötzer, Marian D.; Ridge, Claron J.; Schweinberger, Florian F.; Heiz, Ueli; Yoon, Bokwon; Landman, Uzi

2016-01-01

The sensitivity, or insensitivity, of catalysed reactions to catalyst structure is a commonly employed fundamental concept. Here we report on the nature of nano-catalysed ethylene hydrogenation, investigated through experiments on size-selected Ptn (n=8–15) clusters soft-landed on magnesia and first-principles simulations, yielding benchmark information about the validity of structure sensitivity/insensitivity at the bottom of the catalyst size range. Both ethylene-hydrogenation-to-ethane and the parallel hydrogenation–dehydrogenation ethylidyne-producing route are considered, uncovering that at the <1 nm size-scale the reaction exhibits characteristics consistent with structure sensitivity, in contrast to structure insensitivity found for larger particles. The onset of catalysed hydrogenation occurs for Ptn (n≥10) clusters at T>150 K, with maximum room temperature reactivity observed for Pt13. Structure insensitivity, inherent for specific cluster sizes, is induced in the more active Pt13 by a temperature increase up to 400 K leading to ethylidyne formation. Control of sub-nanometre particle size may be used for tuning catalysed hydrogenation activity and selectivity. PMID:26817713

Structure sensitivity in the nonscalable regime explored via catalysed ethylene hydrogenation on supported platinum nanoclusters

NASA Astrophysics Data System (ADS)

Crampton, Andrew S.; Rötzer, Marian D.; Ridge, Claron J.; Schweinberger, Florian F.; Heiz, Ueli; Yoon, Bokwon; Landman, Uzi

2016-01-01

The sensitivity, or insensitivity, of catalysed reactions to catalyst structure is a commonly employed fundamental concept. Here we report on the nature of nano-catalysed ethylene hydrogenation, investigated through experiments on size-selected Ptn (n=8-15) clusters soft-landed on magnesia and first-principles simulations, yielding benchmark information about the validity of structure sensitivity/insensitivity at the bottom of the catalyst size range. Both ethylene-hydrogenation-to-ethane and the parallel hydrogenation-dehydrogenation ethylidyne-producing route are considered, uncovering that at the <1 nm size-scale the reaction exhibits characteristics consistent with structure sensitivity, in contrast to structure insensitivity found for larger particles. The onset of catalysed hydrogenation occurs for Ptn (n>=10) clusters at T>150 K, with maximum room temperature reactivity observed for Pt13. Structure insensitivity, inherent for specific cluster sizes, is induced in the more active Pt13 by a temperature increase up to 400 K leading to ethylidyne formation. Control of sub-nanometre particle size may be used for tuning catalysed hydrogenation activity and selectivity.

Clinical outcomes and cost minimization with an alternative dosing regimen for meropenem in a community hospital.

PubMed

Patel, Gita Wasan; Duquaine, Susan M; McKinnon, Peggy S

2007-12-01

To compare outcomes and cost for the traditional United States Food and Drug Administration-approved dosing regimen for meropenem versus an alternative dosing regimen providing similar pharmacodynamic exposure with a lower total daily dose. Retrospective cohort study with a cost-minimization analysis. A 417-bed, privately owned community hospital. One hundred patients who received meropenem 1 g every 8 or 12 hours (traditional dosing regimen) between January 1 and September 30, 2004 (historical controls), and 192 patients who received meropenem 500 mg every 6 or 8 hours (alternative dosing regimen) between October 1, 2004, and September 30, 2005. Demographic and clinical data were collected for all patients. Cost-minimization analysis was performed by using the drug acquisition cost for meropenem. Demographics, sources of infection, distributions of organisms, and Charlson Comorbidity Index scores were similar between patients in the traditionally and alternatively dosed groups. Concomitant therapy, duration of therapy, success rates, lengths of stay, and in-hospital mortality rates were also similar between groups. Median time to the resolution of symptoms was 3 days for traditional dosing and 1.5 days for alternative dosing (p<0.0001). A logistic regression model including the dosing strategy showed that only polymicrobial infections and sepsis were associated with increased failure rates. The median cost for antibiotics was $439.05/patient for traditional dosing and $234.08/patient for alternative dosing (p<0.0001). An alternative dosing regimen for meropenem with a lower total daily dose yielded patient outcomes, including success rates and duration of therapy, equivalent to those of the traditional dosing regimen. Alternative dosing decreased total drug exposure, costs for antibiotics, and time to the resolution of infections.

Outcome of stroke patients receiving different doses of recombinant tissue plasminogen activator.

PubMed

Ong, Cheung-Ter; Wong, Yi-Sin; Wu, Chi-Shun; Su, Yu-Hsiang

2017-01-01

Intravenous recombinant tissue plasminogen activator (tPA) at a dose of 0.9 mg/kg body weight is associated with a high hemorrhagic transformation (HT) rate. Low-dose tPA (0.6 mg/kg) may have a lower hemorrhage rate but the mortality and disability rates at 90 days cannot be confirmed as non-inferior to standard-dose tPA. Whether the doses 0.7 and 0.8 mg/kg have better efficacy and safety needs further investigation. Therefore, this study is to compare the efficacy and safety of each dose of tPA (0.6, 0.7, 0.8, and 0.9 mg/kg body weight) and to investigate the factors affecting early neurological improvement (ENI) and early neurological deterioration (END). For this observational study, data were obtained from 274 patients who received tPA thrombolytic therapy in Chia-Yi Christian Hospital stroke unit. The tPA dose was given at the discretion of each physician. The definition of ENI was a >8 point improvement (compared with baseline) at 24 h following thrombolytic therapy or an improvement in the National Institutes of Health Stroke Score (NIHSS) to 0 or 1 toward the end of tPA infusion. The definition of END was a >4 point increase in NIHSS (compared with baseline) within 24 h of tPA infusion. The primary objective was to investigate whether 0.7 and 0.8 mg/kg of tPA have higher ENI rate, lower END rate, and better outcome at 6 months. Poor outcome was defined as having a modified Rankin Scale of 3 to 6 (range, 0 [no symptoms] to 6 [death]). The secondary objective was to investigate whether low-dose tPA has a lower risk of intracerebral HT than that with standard-dose tPA. We also investigated the factors affecting ENI, END, HT, and 6-month outcome. A total of 274 patients were included during the study period, of whom 260 were followed up for >6 months. There was a trend for the HT rate to increase as the dose increased ( P =0.02). The symptomatic HT rate was not significantly different among the low-dose and standard-dose groups. The ENI and END ( P =0.52) were not significantly different among the four dosage groups. The clinical functional outcome at 6 months after stroke onset was poorer in the standard-dose group ( P =0.02). Stroke severity ( P <0.01), stroke type ( P =0.03), and diabetes mellitus ( P =0.04) affected the functional outcome at 6 months. Among the 274 patients receiving tPA thrombolytic therapy, the HT rate increased as dose increased. The symptomatic HT, ENI and END rates were not significantly different among the low-dose (0.6, 0.7, and 0.8 mg/kg) and standard-dose groups. Stroke severity (NIHSS >12), stroke type (cardioembolism and large artery atherosclerosis) and diabetes mellitus were associated with poor outcome at 6 months.