Age-related changes in radiation-induced micronuclei among healthy adults

The aim of the present study was to establish the extent of in vitro radioresponse of lymphocytes among 62 healthy adults of both genders and to estimate the distribution of baseline micronuclei and radiosensitivity among individuals of the study population using the cytochalasin block micronucleus test. A younger study group consisted of 10 males (mean age, 22.4 years; range, 21-27) and 12 females (mean age, 24.8 years; range, 20-29), whereas an older study group consisted of 18 males (mean age, 35.1 years; range, 30-44) and 22 females (mean age, 38.5 years; range, 30-48). For evaluation of radiosensitivity blood samples were irradiated in vitro using 60Co g-ray source. The radiation dose employed was 2 Gy, the dose rate 0.45 Gy/min. The study revealed a significant gender effect on baseline micronuclei favoring females (Z = 3.25, P < 0.001), while yields of radiation-induced micronuclei did not differ significantly (Z = 0.56, P < 0.56) between genders. The distribution of baseline micronuclei among the individuals tested followed Poisson distribution in both study groups and in both genders, whereas the distribution of radiosensitivity among individuals of the older study group did not fulfill Poisson expectations (Kolmogorov-Smirnof test, P < 0.01). In contrast to a nonsignificant difference in radiosensitivity between males and females of the same age group (Z = 1.97, P < 0.56), a statistically significant difference in radiosensitivity between younger and older group for both genders was found (Z = 3.03, P < 0.03). Since the individuals tested were healthy, the observed variability in radiation response is considered to be an early effect of ageing.

The terrestrial Gastropoda Megalobulimus abbreviatus as a useful model for nociceptive experiments: effects of morphine and naloxone on thermal avoidance behavior

We describe the behavior of the snail Megalobulimus abbreviatus upon receiving thermal stimuli and the effects of pretreatment with morphine and naloxone on behavior after a thermal stimulus, in order to establish a useful model for nociceptive experiments. Snails submitted to non-functional (22ºC) and non-thermal hot-plate stress (30ºC) only displayed exploratory behavior. However, the animals submitted to a thermal stimulus (50ºC) displayed biphasic avoidance behavior. Latency was measured from the time the animal was placed on the hot plate to the time when the animal lifted the head-foot complex 1 cm from the substrate, indicating aversive thermal behavior. Other animals were pretreated with morphine (5, 10, 20 mg/kg) or naloxone (2.5, 5.0, 7.5 mg/kg) 15 min prior to receiving a thermal stimulus (50ºC; N = 9 in each group). The results (means ± SD) showed an extremely significant difference in response latency between the group treated with 20 mg/kg morphine (63.18 ± 14.47 s) and the other experimental groups (P < 0.001). With 2.5 mg/kg (16.26 ± 3.19 s), 5.0 mg/kg (11.53 ± 1.64 s) and 7.5 mg/kg naloxone (7.38 ± 1.6 s), there was a significant, not dose-dependent decrease in latency compared to the control (33.44 ± 8.53 s) and saline groups (29.1 ± 9.91 s). No statistically significant difference was found between the naloxone-treated groups. With naloxone plus morphine, there was a significant decrease in latency when compared to all other groups (minimum 64% in the saline group and maximum 83.2% decrease in the morphine group). These results provide evidence of the involvement of endogenous opioid peptides in the control of thermal withdrawal behavior in this snail, and reveal a stereotyped and reproducible avoidance behavior for this snail species, which could be studied in other pharmacological and neurophysiological studies.

Effects of gamma-radiation on cell growth, cycle arrest, death, and superoxide dismutase expression by DU 145 human prostate cancer cells

Gamma-irradiation (gamma-IR) is extensively used in the treatment of hormone-resistant prostate carcinoma. The objective of the present study was to investigate the effects of 60Co gamma-IR on the growth, cell cycle arrest and cell death of the human prostate cancer cell line DU 145. The viability of DU 145 cells was measured by the Trypan blue exclusion assay and the 3(4,5-dimethylthiazol-2-yl)-2,5,diphenyltetrazolium bromide test. Bromodeoxyuridine incorporation was used for the determination of cell proliferation. Cell cycle arrest and cell death were analyzed by flow cytometry. Superoxide dismutase (SOD), specifically CuZnSOD and MnSOD protein expression, after 10 Gy gamma-IR, was determined by Western immunoblotting analysis. gamma-IR treatment had a significant (P < 0.001) antiproliferative and cytotoxic effect on DU 145 cells. Both effects were time and dose dependent. Also, the dose of gamma-IR which inhibited DNA synthesis and cell proliferation by 50% was 9.7 Gy. Furthermore, gamma-IR induced cell cycle arrest in the G2/M phase and the percentage of cells in the G2/M phase was increased from 15% (control) to 49% (IR cells), with a nonsignificant induction of apoptosis. Treatment with 10 Gy gamma-IR for 24, 48, and 72 h stimulated CuZnSOD and MnSOD protein expression in a time-dependent manner, approximately by 3- to 3.5-fold. These data suggest that CuZnSOD and MnSOD enzymes may play an important role in the gamma-IR-induced changes in DU 145 cell growth, cell cycle arrest and cell death.

Modelling the super-equilibria in thermal biomass conversion : applications and limitations of the constrained free energy method

Bioenergi ses som en viktig del av det nu- och framtida sortimentet av inhemsk energi. Svartlut, bark och skogsavfall täcker mer än en femtedel av den inhemska energianvändningen. Produktionsanläggningar kan fungera ofullständigt och en mängd gas-, partikelutsläpp och tjära produceras samtidigt och kan leda till beläggningsbildning och korrosion. Orsaken till dessa problem är ofta obalans i processen: vissa föreningar anrikas i processen och superjämviktstillstånd är bildas. I denna doktorsavhandling presenteras en ny beräkningsmetod, med vilken man kan beskriva superjämviktstillståndet, de viktigaste kemiska reaktionerna, processens värmeproduktion och tillståndsstorheter samtidigt. Beräkningsmetoden grundar sig på en unik frienergimetod med bivillkor som har utvecklats vid VTT. Den här så kallade CFE-metoden har tidigare utnyttjats i pappers-, metall- och kemiindustrin. Applikationer för bioenergi, vilka är demonstrerade i doktorsavhandlingen, är ett nytt användingsområde för metoden. Studien visade att beräkningsmetoden är väl lämpad för högtemperaturenergiprocesser. Superjämviktstillstånden kan uppstå i dessa processer och det kemiska systemet kan definieras med några bivillkor. Typiska tillämpningar är förbränning av biomassa och svartlut, förgasning av biomassa och uppkomsten av kväveoxider. Också olika sätt att definiera superjämviktstillstånd presenterades i doktorsavhandlingen: empiriska konstanter, empiriska hastighetsuttryck eller reaktionsmekanismer kan användas. Resultaten av doktorsavhandlingen kan utnyttjas i framtiden i processplaneringen och i undersökning av nya tekniska lösningar för förgasning, förbränningsteknik och biobränslen. Den presenterade metoden är ett bra alternativ till de traditionella mekanistiska och fenomenmodeller och kombinerar de bästa delarna av både. --------------------------------------------------------------- Bioenergia on tärkeä osa nykyistä ja tulevaa kotimaista energiapalettia. Mustalipeä, kuori ja metsätähteet kattavat yli viidenneksen kotimaisesta energian kulutuksesta. Tuotantolaitokset eivät kuitenkaan aina toimi täydellisesti ja niiden prosesseissa syntyy erilaisia kaasu- ja hiukkaspäästöjä, tervoja sekä prosessilaitteita kuluttavia saostumia ja ruostumista. Usein syy näihin ongelmiin on prosessissa esiintyvä epätasapainotila: tietyt yhdisteet rikastuvat prosessissa ja muodostavat supertasapainotiloja. Väitöstyössä kehitettiin uusi laskentamenetelmä, jolla voidaan kuvata nämä supertasapainotilat, tärkeimmät niihin liittyvät kemialliset reaktiot, prosessin lämmöntuotanto ja tilansuureet yhtä aikaa. Laskentamenetelmä perustuu VTT:llä kehitettyyn ainutlaatuiseen rajoitettuun vapaaenergiamenetelmään. Tätä niin kutsuttua CFE-menetelmää on aiemmin sovelluttu onnistuneesti muun muassa paperi-, metalli- ja kemianteollisuudessa. Väitöstyössä esitetyt bioenergiasovellukset ovat uusi sovellusalue menetelmälle. Työ osoitti laskentatavan soveltuvan hyvin korkealämpöisiin energiatekniikan prosesseihin, joissa kemiallista systeemiä rajoittavia tekijöitä oli rajallinen määrä ja siten super-tasapainotila saattoi muodostua prosessin aikana. Tyypillisiä sovelluskohteita ovat biomassan ja mustalipeän poltto, biomassan kaasutus ja typpioksidipäästöt. Työn aikana arvioitiin myös erilaisia tapoja määritellä super-tasapainojen muodostumista rajoittavat tekijät. Rajoitukset voitiin tehdä teollisiin mittauksiin pohjautuen, kokeellisia malleja hyödyntäen tai mekanistiseen reaktiokinetiikkaan perustuen. Tulevaisuudessa väitöstyön tuloksia voidaan hyödyntää prosessisuunnittelussa ja tutkittaessa uusia teknisiä ratkaisuja kaasutus- ja polttotekniikoissa sekä biopolttoaineiden tutkimuksessa. Kehitetty menetelmä tarjoaa hyvän vaihtoehdon perinteisille mekanistisille ja ilmiömalleille yhdistäen näiden parhaita puolia.

Agent-based management systems for many-core platforms : rigorous design and efficient implementation

Due to various advantages such as flexibility, scalability and updatability, software intensive systems are increasingly embedded in everyday life. The constantly growing number of functions executed by these systems requires a high level of performance from the underlying platform. The main approach to incrementing performance has been the increase of operating frequency of a chip. However, this has led to the problem of power dissipation, which has shifted the focus of research to parallel and distributed computing. Parallel many-core platforms can provide the required level of computational power along with low power consumption. On the one hand, this enables parallel execution of highly intensive applications. With their computational power, these platforms are likely to be used in various application domains: from home use electronics (e.g., video processing) to complex critical control systems. On the other hand, the utilization of the resources has to be efficient in terms of performance and power consumption. However, the high level of on-chip integration results in the increase of the probability of various faults and creation of hotspots leading to thermal problems. Additionally, radiation, which is frequent in space but becomes an issue also at the ground level, can cause transient faults. This can eventually induce a faulty execution of applications. Therefore, it is crucial to develop methods that enable efficient as well as resilient execution of applications. The main objective of the thesis is to propose an approach to design agentbased systems for many-core platforms in a rigorous manner. When designing such a system, we explore and integrate various dynamic reconfiguration mechanisms into agents functionality. The use of these mechanisms enhances resilience of the underlying platform whilst maintaining performance at an acceptable level. The design of the system proceeds according to a formal refinement approach which allows us to ensure correct behaviour of the system with respect to postulated properties. To enable analysis of the proposed system in terms of area overhead as well as performance, we explore an approach, where the developed rigorous models are transformed into a high-level implementation language. Specifically, we investigate methods for deriving fault-free implementations from these models into, e.g., a hardware description language, namely VHDL.

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

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

Early detection of metabolic and energy disorders by thermal time series stochastic complexity analysis

Maintenance of thermal homeostasis in rats fed a high-fat diet (HFD) is associated with changes in their thermal balance. The thermodynamic relationship between heat dissipation and energy storage is altered by the ingestion of high-energy diet content. Observation of thermal registers of core temperature behavior, in humans and rodents, permits identification of some characteristics of time series, such as autoreference and stationarity that fit adequately to a stochastic analysis. To identify this change, we used, for the first time, a stochastic autoregressive model, the concepts of which match those associated with physiological systems involved and applied in male HFD rats compared with their appropriate standard food intake age-matched male controls (n=7 per group). By analyzing a recorded temperature time series, we were able to identify when thermal homeostasis would be affected by a new diet. The autoregressive time series model (AR model) was used to predict the occurrence of thermal homeostasis, and this model proved to be very effective in distinguishing such a physiological disorder. Thus, we infer from the results of our study that maximum entropy distribution as a means for stochastic characterization of temperature time series registers may be established as an important and early tool to aid in the diagnosis and prevention of metabolic diseases due to their ability to detect small variations in thermal profile.

Analysis of heart rate control to assess thermal sensitivity responses in Brazilian toads

In anurans, changes in ambient temperature influence body temperature and, therefore, energy consumption. These changes ultimately affect energy supply and, consequently, heart rate (HR). Typically, anurans living in different thermal environments have different thermal sensitivities, and these cannot be distinguished by changes in HR. We hypothesized that Rhinella jimi (a toad from a xeric environment that lives in a wide range of temperatures) would have a lower thermal sensitivity regarding cardiac control than R. icterica (originally from a tropical forest environment with a more restricted range of ambient temperatures). Thermal sensitivity was assessed by comparing animals housed at 15° and 25°C. Cardiac control was estimated by heart rate variability (HRV) and heart rate complexity (HRC). Differences in HRV between the two temperatures were not significant (P=0.214 for R. icterica and P=0.328 for R. jimi), whereas HRC differences were. All specimens but one R. jimi had a lower HRC at 15°C (all P<0.01). These results indicate that R. jimi has a lower thermal sensitivity and that cardiac control is not completely dependent on the thermal environment because HRC was not consistently different between temperatures in all R. jimi specimens. This result indicates a lack of evolutive trade-offs among temperatures given that heart rate control at 25°C is potentially not a constraint to heart rate control at 15°C.

Reconstructive dosimetry for cutaneous radiation syndrome

According to the International Atomic Energy Agency (IAEA), a relatively significant number of radiological accidents have occurred in recent years mainly because of the practices referred to as potentially high-risk activities, such as radiotherapy, large irradiators and industrial radiography, especially in gammagraphy assays. In some instances, severe injuries have occurred in exposed persons due to high radiation doses. In industrial radiography, 80 cases involving a total of 120 radiation workers, 110 members of the public including 12 deaths have been recorded up to 2014. Radiological accidents in industrial practices in Brazil have mainly resulted in development of cutaneous radiation syndrome (CRS) in hands and fingers. Brazilian data include 5 serious cases related to industrial gammagraphy, affecting 7 radiation workers and 19 members of the public; however, none of them were fatal. Some methods of reconstructive dosimetry have been used to estimate the radiation dose to assist in prescribing medical treatment. The type and development of cutaneous manifestations in the exposed areas of a person is the first achievable gross dose estimation. This review article presents the state-of-the-art reconstructive dosimetry methods enabling estimation of local radiation doses and provides guidelines for medical handling of the exposed individuals. The review also presents the Chilean and Brazilian radiological accident cases to highlight the importance of reconstructive dosimetry.

Long-term correlation of the electrocorticogram as a bioindicator of brain exposure to ionizing radiation

Understanding the effects of radiation and its possible influence on the nervous system are of great clinical interest. However, there have been few electrophysiological studies on brain activity after exposure to ionizing radiation (IR). A new methodological approach regarding the assessment of the possible effects of IR on brain activity is the use of linear and nonlinear mathematical methods in the analysis of complex time series, such as brain oscillations measured using the electrocorticogram (ECoG). The objective of this study was to use linear and nonlinear mathematical methods as biomarkers of gamma radiation regarding cortical electrical activity. Adult Wistar rats were divided into 3 groups: 1 control and 2 irradiated groups, evaluated at 24 h (IR24) and 90 days (IR90) after exposure to 18 Gy of gamma radiation from a cobalt-60 radiotherapy source. The ECoG was analyzed using power spectrum methods for the calculation of the power of delta, theta, alpha and beta rhythms and by means of the α-exponent of the detrended fluctuation analysis (DFA). Using both mathematical methods it was possible to identify changes in the ECoG, and to identify significant changes in the pattern of the recording at 24 h after irradiation. Some of these changes were persistent at 90 days after exposure to IR. In particular, the theta wave using the two methods showed higher sensitivity than other waves, suggesting that it is a possible biomarker of exposure to IR.

Low-level red laser therapy alters effects of ultraviolet C radiation on Escherichia coli cells

Low-level lasers are used at low power densities and doses according to clinical protocols supplied with laser devices or based on professional practice. Although use of these lasers is increasing in many countries, the molecular mechanisms involved in effects of low-level lasers, mainly on DNA, are controversial. In this study, we evaluated the effects of low-level red lasers on survival, filamentation, and morphology of Escherichia colicells that were exposed to ultraviolet C (UVC) radiation. Exponential and stationary wild-type and uvrA-deficientE. coli cells were exposed to a low-level red laser and in sequence to UVC radiation. Bacterial survival was evaluated to determine the laser protection factor (ratio between the number of viable cells after exposure to the red laser and UVC and the number of viable cells after exposure to UVC). Bacterial filaments were counted to obtain the percentage of filamentation. Area-perimeter ratios were calculated for evaluation of cellular morphology. Experiments were carried out in duplicate and the results are reported as the means of three independent assays. Pre-exposure to a red laser protected wild-type and uvrA-deficient E. coli cells against the lethal effect of UVC radiation, and increased the percentage of filamentation and the area-perimeter ratio, depending on UVC fluence and physiological conditions in the cells. Therapeutic, low-level red laser radiation can induce DNA lesions at a sub-lethal level. Consequences to cells and tissues should be considered when clinical protocols based on this laser are carried out.

Antioxidant activity of rosemary and oregano ethanol extracts in soybean oil under thermal oxidation

Four experiments were conducted to measure the antioxidant activity of ethanol extracts of rosemary and oregano compared with synthetic antioxidants such as TBHQ and BHA/BHT. The antioxidant activity was determined and results differed from those of the Oven test at 63º C. Peroxide values and absorptivities at 232 nm of soybean oil under Oven test were lower in treatments with 25, 50, 75, 100 and 200 mg.Kg-1 TBHQ than in treatments with 1000 mg.Kg-1 oregano extract (O), 500 mg.Kg-1 rosemary extract (R) and their mixture R+O. All the treatments were effective in controlling the thermal oxidation of oils; the natural extracts were as effective as BHA+BHT and less effective than TBHQ. The natural extracts were mixed with 25, 50, 75 and 100 mg.Kg-1 TBHQ and then added to the oil. No improvement in antioxidative properties was observed. The best antioxidant concentration could be determined from polynomial regression and quadratic equation from the experimental data.

Natural radiation levels in powdered milk samples

The control and monitoring of radioactive elements in foodstuffs is fundamental for human health maintenance. This work presents procedures to measure radioactivity levels in powdered milk samples and also a brief discussion of radionuclide transference from the environment to mankind. The measurements were performed utilizing a high-resolution gamma-ray spectrometer using an HPGe detector. The results allowed the quantification of 40K, 137Cs and 208Tl radionuclides. For 40K the average activity was 482 ± 37 Bq/kg and for 137Cs and 208Tl the lower level of detection was, respectively, 3.7 ± 1.1 and 0.5 ± 0.2 (Bq/kg). The results obtained for the milk samples were compared to data found in the literature and to the limits established by the Brazilian National Commission of Nuclear Energy (CNEN) to assure its safety to human consuption.

Electromagnetic and thermal design of a multilevel converter with high power density and reliability

Electric energy demand has been growing constantly as the global population increases. To avoid electric energy shortage, renewable energy sources and energy conservation are emphasized all over the world. The role of power electronics in energy saving and development of renewable energy systems is significant. Power electronics is applied in wind, solar, fuel cell, and micro turbine energy systems for the energy conversion and control. The use of power electronics introduces an energy saving potential in such applications as motors, lighting, home appliances, and consumer electronics. Despite the advantages of power converters, their penetration into the market requires that they have a set of characteristics such as high reliability and power density, cost effectiveness, and low weight, which are dictated by the emerging applications. In association with the increasing requirements, the design of the power converter is becoming more complicated, and thus, a multidisciplinary approach to the modelling of the converter is required. In this doctoral dissertation, methods and models are developed for the design of a multilevel power converter and the analysis of the related electromagnetic, thermal, and reliability issues. The focus is on the design of the main circuit. The electromagnetic model of the laminated busbar system and the IGBT modules is established with the aim of minimizing the stray inductance of the commutation loops that degrade the converter power capability. The circular busbar system is proposed to achieve equal current sharing among parallel-connected devices and implemented in the non-destructive test set-up. In addition to the electromagnetic model, a thermal model of the laminated busbar system is developed based on a lumped parameter thermal model. The temperature and temperature-dependent power losses of the busbars are estimated by the proposed algorithm. The Joule losses produced by non-sinusoidal currents flowing through the busbars in the converter are estimated taking into account the skin and proximity effects, which have a strong influence on the AC resistance of the busbars. The lifetime estimation algorithm was implemented to investigate the influence of the cooling solution on the reliability of the IGBT modules. As efficient cooling solutions have a low thermal inertia, they cause excessive temperature cycling of the IGBTs. Thus, a reliability analysis is required when selecting the cooling solutions for a particular application. The control of the cooling solution based on the use of a heat flux sensor is proposed to reduce the amplitude of the temperature cycles. The developed methods and models are verified experimentally by a laboratory prototype.

Permanent magnet synchronous generator design solution for large directdrive wind turbines: Thermal behavior of the LC DD-PMSG

Wind is one of the most compelling forms of indirect solar energy. Available now, the conversion of wind power into electricity is and will continue to be an important element of energy self-sufficiency planning. This paper is one in a series intended to report on the development of a new type of generator for wind energy; a compact, high-power, direct-drive permanent magnet synchronous generator (DD-PMSG) that uses direct liquid cooling (LC) of the stator windings to manage Joule heating losses. The main param-eters of the subject LC DD-PMSG are 8 MW, 3.3 kV, and 11 Hz. The stator winding is cooled directly by deionized water, which flows through the continuous hollow conductor of each stator tooth-coil winding. The design of the machine is to a large degree subordinate to the use of these solid-copper tooth-coils. Both steady-state and timedependent temperature distributions for LC DD-PMSG were examined with calculations based on a lumpedparameter thermal model, which makes it possible to account for uneven heat loss distribution in the stator conductors and the conductor cooling system. Transient calculations reveal the copper winding temperature distribution for an example duty cycle during variable-speed wind turbine operation. The cooling performance of the liquid cooled tooth-coil design was predicted via finite element analysis. An instrumented cooling loop featuring a pair of LC tooth-coils embedded in a lamination stack was built and laboratory tested to verify the analytical model. Predicted and measured results were in agreement, confirming the predicted satisfactory operation of the LC DD-PMSG cooling technology approach as a whole.