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Sample records for lethal damage pld

  1. Inhibition of X-ray-induced potentially lethal damage (PLD) repair in aerobic plateau-phase Chinese hamster cells by misonidazole

    International Nuclear Information System (INIS)

    Brown, D.M.

    1984-01-01

    The effect of the 2-nitroimidazole radiosensitizer misonidazole (MISO) and the hydrophilic analog SR-2508 on the repair of X-ray-induced potentially lethal damage (PLD) was studied in plateau-phase Chinese Hamster ovary (HA-1) cells. It was found that although MISO does not radiosensitize aerobic cells, it inhibits the repair of PLD. However, under hypoxic conditions, MISO has no effect on PLD repair. The major portion of the inhibition of PLD repair in aerobic cells requires the presence of MISO only during irradiation; little or no additional inhibition occurs when MISO is present during the postirradiation repair period. Also, treatment of aerobic cells with 5 mM MISO for either 5 or 30 min prior to irradiation is equally inhibitory. This suggests that the presence of MISO in some way modifies the initial lesion under aerobic conditions since it does not increase cell killing as determined by immediate plating but inhibits subsequent repair. The inhibition is concentration dependent; 0.5 mM MISO inhibits PLD repair by one-half while 5-10 mM totally inhibits the repair measured 6 hr postirradiation. This phenomenon suggests that radiosensitization of tissue in vivo by MISO and other 2-nitroimidazoles may not be unequivocal proof of the presence of hypoxic cells

  2. An inhibitor of potentially lethal damage (PLD) repair reduces the frequency of γ-ray mutations in cultured Chinese hamster V79 cells

    International Nuclear Information System (INIS)

    Yokoiyama, A.; Kada, T.; Kuroda, Y.

    1992-01-01

    Cordycepin (3'-deoxyadenosine, 3 - dA) is an RNA antimetabolite and a radiosensitizer in cultured mammalian cells. In the present paper, the effects of 3'-dA on γ-ray-induced lethality and 6-thioguanine (6TG)-resistant mutations in cultured Chinese hamster V79 cells were examined. 3'-dA had the effect of sensitizing the lethality induced by γ-rays. The potentially lethal damage (PLD) repair produced by post-incubation cells in Hanks' solution after γ-irradiation was almost completely suppressed by 5x10 -5 M 3'-dA. When cells were irradiated with 10 Gy γ-rays and incubated with 3'-dA for 5 h, the frequency of 6TG-resistant mutations induced by γ-rays decreased to 1/6 of that of the irradiated cells incubated without 3'-dA. The decrease in the frequency of γ-ray-induced mutations was dependent on the length of incubation time with 3'-dA. It is suggested that the inhibition of PLD repair by 3'-dA may be that of error-prone repair. (author). 26 refs.; 5 figs

  3. Potentially lethal damage and its repair

    International Nuclear Information System (INIS)

    Utsumi, Hiroshi

    1989-01-01

    Two forms termed fast-and slow-potentially lethal lethal damage (PLD) are introduced and discussed. The effect on the survival of x-irradiated Chinese hamster cells (V79) of two different post-treatments is examined in plateau- and in log-phases of growth. The postirradiation treatments used : a) incubation in hypertonic solution, and b) incubation in conditioned medium obtained from plateau-phase. Similar reduction in survival was caused by postirradiation treatment with hypertonic phosphate buffered saline, and similar increased in survival was effected by treatment in conditioned medium in plateau- and in log-phases cells. However, repair of PLD sensitive to hypertonic treatment was faster (half time, 5-10 min)(f-PLD repair) and independent from the repair of PLD (half time, 1-2 hour)(s-PLD repair) observed in conditioned medium. The results indicate the induction of two forms of PLD by radiation. Induction of both PLD was found to decrease with increasing LET of the radiation used. Identification of the molecular processes underlying repair and fixation of PLD is a task of particular interest, since it may allow replacement of a phenomenological definition with a molecular definition. Evidence is reviewed indicating the DNA double strand breaks (directly or indirectly induced) may be the DNA lesions underlying PLD. (author)

  4. Repair and fixation of potentially lethal damage (PLD) as demonstrated by delayed plating or incubation with araA in contact inhibited refed plateau-phase C3H mouse embryo 10T1/2 cells grown in the presence of BrdUrd

    International Nuclear Information System (INIS)

    Iliakis, G.; Wright, E.; Ngo, F.Q.H.

    1987-01-01

    CH3 mouse 10 T 1/2 cells showing strong inhibition of growth at confluency were grown under daily refeeding in the presence of BrdUrd (from 0 to 1 μM) and exposed to γ-rays either while exponentially growing or in the plateau phase. An increase in radiosensitivity was observed in both growth conditions mainly reflected by a reduction in Dq. Greater radiosensitization was observed in exponentially growing than in plateau-phase cells, and 3-4 times higher BrdUrd concentrations were required in plateau-phase cells for similar potentiation in killing. This effect could not be entirely attributed to a reduction in BrdUrd incorporation since measurements with 3 H-BrdUrd showed reductions in incorporation between only 17-47% in plateau-phase cells. The rate of repair of potentially lethal damage (PLD) as demonstrated by delayed plating was not affected by the incorporation of BrdUrd, but the amount of repair (measured as the relative increase in cell survival) was higher for BrdUrd containing cells. Post-irradiation treatment of cells in the plateau-phase (no BrdUrd) with 9-β-D-arabinofuranosyladenine (araA) caused fixation of radiation-induced PLD. AraA treatment of cells grown in the presence of various amounts of BrdUrd also caused fixation of PLD, but resulted in survival levels similar to those observed with cells growing in BrdUrd-free medium. This result indicates that BrdUrd mediated radiosensitization cannot be observed when cells are prevented from repairing PLD by postirradiation incubation with araA. Based on these findings we propose that the mechanism of radiosensitization by BrdUrd incorporation might be, by increasing probability of fixation, mediated by the postirrdiation progression of cells through the cycle, of a sector of PLD also sensitive to post-irradiation treatment with araA. For this sector of PLD the term α-PLD has been proposed. (orig.)

  5. X-ray-related potentially lethal damage expressed by chromosome condensation and the influence of caffeine

    International Nuclear Information System (INIS)

    Sasaki, H.; Nishimoto, T.

    1989-01-01

    Caffeine has been reported to induce premature chromosome condensation (PCC) in S-phase cells in the presence of an inhibitor of DNA synthesis. We found that when S-phase cells are treated with caffeine and hydroxyurea after X irradiation, substantially more potentially lethal damage (PLD) is expressed, but the addition of cycloheximide, which inhibits PCC induction in S-phase cells, in the presence of caffeine and hydroxyurea reduces the expression of PLD to the same level as seen with caffeine alone. This can be interpreted to mean that the expression of PLD seen with caffeine in the absence of an inhibitor of DNA synthesis is not associated with chromosome condensation. Evidence that PCC induction in S-phase cells and the influence of caffeine on PLD expression were suppressed by incubation at 40 degrees C of tsBN75 cells with a ts defect in ubiquitin-activating enzyme indicates the involvement of ubiquitin in these two processes. These observations as well as previous findings on ubiquitin suggest to us that caffeine induces changes in DNA-chromatin conformation, which are caused by induction of PCC or ubiquitination of chromosomal protein. Such changes occurring postirradiation would favor expression of PLD

  6. X-ray-related potentially lethal damage expressed by chromosome condensation and the influence of caffeine

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, H.; Nishimoto, T. (Kyushu Univ., Fukuoka (Japan))

    1989-10-01

    Caffeine has been reported to induce premature chromosome condensation (PCC) in S-phase cells in the presence of an inhibitor of DNA synthesis. We found that when S-phase cells are treated with caffeine and hydroxyurea after X irradiation, substantially more potentially lethal damage (PLD) is expressed, but the addition of cycloheximide, which inhibits PCC induction in S-phase cells, in the presence of caffeine and hydroxyurea reduces the expression of PLD to the same level as seen with caffeine alone. This can be interpreted to mean that the expression of PLD seen with caffeine in the absence of an inhibitor of DNA synthesis is not associated with chromosome condensation. Evidence that PCC induction in S-phase cells and the influence of caffeine on PLD expression were suppressed by incubation at 40 degrees C of tsBN75 cells with a ts defect in ubiquitin-activating enzyme indicates the involvement of ubiquitin in these two processes. These observations as well as previous findings on ubiquitin suggest to us that caffeine induces changes in DNA-chromatin conformation, which are caused by induction of PCC or ubiquitination of chromosomal protein. Such changes occurring postirradiation would favor expression of PLD.

  7. Defective recoveryfrom potentially lethal damage in some human fibroblast cell strains

    International Nuclear Information System (INIS)

    Arlett, C.F.; Priestley, A.

    1983-01-01

    The repair of potentially lethal damage following treatment by gamma radiation was investigated in human fibroblasts held in a non-cycling state by maintenance in a medium containing 0.5 per cent foetal calf serum. Variation in their capacity to repair PLD was noted between three normal cell strains. A failure to repair PLD in ataxia-telangiectasia cells (AT5BI) was confirmed. In three cell strains which were intermediate between normals and A-T cells in their sensitivity, XP3BR, 46BR and GB1142, a limited capacity for the repair of PLD was observed. Two other cell strains, 47BR and 67BR, which showed little if any hypersensitivity could be clearly distinguished from normals after a 24 hour period for the repair of PLD. Thus the technique might permit better discrimination between cell strains. One other cell strain, H15617, could be distinguished from normals by proving hypersensitive under all conditions. Here, however, the repair of PLD appeared to be normal. (author)

  8. Inhibitors of poly (ADP-ribose) synthesis inhibit the two types of repair of potentially lethal damage

    International Nuclear Information System (INIS)

    Utsumi, Hiroshi; Elkind, M.M.

    1994-01-01

    The purpose of this study was to examine whether 3-amino-benzamide (3ABA), an inhibitor of poly (ADP-ribose) synthesis, inhibits the two types of potentially lethal damage (PLD) repair, termed slow and fast. The fast-type PLD repair was measured by the decrease in survival of V79 Chinese hamster cells by postirradiation treatment with 3ABA. The slow-type PLD repair was measured by the increase in survival by posttreatment with conditioned medium (CM), which became conditioned by growing a crowed culture of cells and supports the slow-type PLD repair. Up to 1 mM 3-ABA inhibited the slow type repair; at doses of 2 mM and above, it inhibited the fast type of PLD repair. There are quantitative differences in cellular effects of 3ABA dependent on concentration. Poly (ADP-ribose) appears to play an important role in the PLD repairs and has little effect on the repair of sublethal damage. 10 refs., 2 figs

  9. Cultured cells from a severe combined immunodeficient mouse have a slower than normal rate of repair of potentially lethal damage sensitive to hypertonic treatment

    International Nuclear Information System (INIS)

    Kimura, H.; Terado, T.; Ikebuchi, M.; Aoyama, T.; Komatsu, K.; Nozawa, A.

    1995-01-01

    The effects of hypertonic 0.5 M NaCl treatment after irradiation on the repair of DNA damage were examined in fibroblasts of the severe combined immunodeficient (scid) mouse. These cells are hypersensitive to ionizing radiation because of a deficiency in the repair of double-strand breaks. Hypertonic treatment caused radiosensitization due to a fixation of potentially lethal damage (PLD) in scid cells, demonstrating that scid cells normally repair PLD. To assess the kinetics of the repair of PLD, hypertonic treatment was delayed for various times after irradiation. Potentially lethal damage was repaired during these times in isotonic medium at 37 degrees C. It was found that the rate of repair of PLD was much slower in scid cells than in BALB/c 3T3 cells, which have a open-quotes wild-typeclose quotes level of radiosensitivity. This fact indicates that the scid mutation affects the type of repair of PLD that is sensitive to 0.5 M NaCl treatment. In scid hybrid cells containing fragments of human chromosome 8, which complements the radiosensitivity of the scid cells, the rate of repair was restored to a normal level. An enzyme encoded by a gene on chromosome 8 may also be connected with PLD which is sensitive to hypertonic treatment. 29 refs., 3 figs

  10. Importance of TP53 and RB in the repair of potentially lethal damage and induction of color junctions after exposure to ionizing radiation

    NARCIS (Netherlands)

    Franken, N. A. P.; van Bree, C.; ten Cate, R.; van Oven, C. H.; Haveman, J.

    2002-01-01

    Repair of potentially lethal damage (PLD) was investigated in cells with functional G(1)-phase arrest with wild-type TP53 and wild-type RB and in cells in which G(1)-phase arrest was abrogated by inactivation of TP53 or RB. Confluent cultures of cells were plated for clonogenic survival assay either

  11. Free radical scavenging and the expression of potentially lethal damage in X-irradiated repair-deficient Escherichia coli

    International Nuclear Information System (INIS)

    Billen, D.

    1987-01-01

    When cells are exposed to ionizing radiation, they suffer lethal damage (LD), potentially lethal damage (PLD), and sublethal damage (SLD). All three forms of damage may be caused by direct or indirect radiation action or by the interaction of indirect radiation products with direct DNA damage. In this report I examine the expression of LD and PLD caused by the indirect action of X rays in isogenic, repair-deficient Escherichia coli. The radiosensitivity of a recA mutant, deficient both in pre- and post replication recombination repair and SOS induction (inducible error-prone repair), was compared to that of a recB mutant which is recombination deficient but SOS proficient and to a previously studied DNA polymerase 1-deficient mutant (polA) which lacks the excision repair pathway. Indirect damage by water radicals (primarily OH radicals) was circumvented by the presence of 2 M glycerol during irradiation. Indirect X-ray damage by water radicals accounts for at least 85% of the PLD found in exposed repair-deficient cells. The DNA polymerase 1-deficient mutant is most sensitive to indirect damage with the order of sensitivity polA1 greater than recB greater than or equal to recA greater than wild type. For the direct effects of X rays the order of sensitivity is recA greater than recB greater than polA1 greater than wild type. The significance of the various repair pathways in mitigating PLD by direct and indirect damage is discussed

  12. Reduced repair of potentially lethal radiation damage in glutathione synthetase-deficient human fibroblasts after X-irradiation

    International Nuclear Information System (INIS)

    Midander, J.; Revesz, L.; Deschavanne, P.J.; Debieu, D.; Malaise, E.P.

    1986-01-01

    Using a human fibroblast strain deficient in glutathione synthetase and a related proficient control strain, the role of glutathione (GSH) in repair of potentially lethal damage (PLD) has been investigated in determining survival by plating cells immediately or 24 h after irradiation. After oxic or hypoxic irradiation, both cell strains repair radiation-induced damage. However, under hypoxic conditions, the proficient cells repair PLD as well as under oxic conditions while the deficient cells repair less PLD after irradiation under hypoxic than under oxic conditions. Therefore, the oxygen enhancement ratio (o.e.r.) for proficient cells is similar whether the cells are plated immediately or 24 h later (2.0 and 2.13, respectively). In contrast, the o.e.r. for deficient cells is lower when the cells are plated 24 h after irradiation than when they are plated immediately thereafter (1.16 as compared to 1.55). The results indicate that GSH is involved in PLD repair and, in particular, in the repair of damage induced by radiation delivered under hypoxic conditions. (author)

  13. Repair of potentially lethal and sublethal radiation damage in x-irradiated ascites tumor cells

    International Nuclear Information System (INIS)

    Tsuboi, Atsushi; Okamoto, Mieko; Tsuchiya, Takehiko.

    1985-01-01

    The ability of cells to repair cellular radiation damage during the growth of TMT-3 ascites tumor and the effect of host reaction on the repair ability were examined by using an in vitro assay of cell clonogenicity after in situ irradiation of tumor cells. In single-dose experiments, the repair of potentially lethal radiation damage (PLD) was observed in stationary phase cells (12-day tumor) of the unirradiated host, but not in exponential phase cells (3-day tumor) of the unirradiated host animals. However, if previously irradiated host animals were used, even the exponentially growing tumor cells showed repair of PLD. In two-dose experiments, the ability to repair sublethal radiation damage (SLD) in exponential phase tumor cells was less than that of stationary phase cells in the unirradiated host. In the pre-irradiated host, the extent of the repair in exponential phase cells was somewhat enhanced. These results suggest that irradiation of host animals might suppress a factor that inhibits repair, resulting in enhancement of the repair capability of tumor cells. (author)

  14. The scid mutation does not affect slowly repairing potentially lethal damage that is sensitive to 0.23 M NaCl

    International Nuclear Information System (INIS)

    Kimura, Hiroshi; Ikebuchi, Makoto; Fushiki, Masato; Komatsu, Kenshi.

    1996-01-01

    The repair of slowly repairing potentially lethal damage (PLD) in radiosensitive cells from the severe combined immunodeficient (scid) mouse was compared with that in Balb/c 3T3 cells with ''wild-type'' radiosensitivity and that in RD13B2 cells derived from scid cells whose sensitivity is normal because of the presence of fragments of human chromosome 8. Treatment with 0.23 M NaCl was used for fixation of slowly repairing PLD. The scid cells repaired PLD sensitive to 0.23 M NaCl to a great extent whin 3-4 h, similarly to Balb/c 3T3 and RD13B2 cells. This indicates that the scid mutation hardly affects the repair of PLD sensitive to 0.23 M NaCl. On the other hand, as reported previously, the rapidly repairing PLD that is sensitive to 0.5 M NaCl was repaired only slowly (3-4 h) in scid cells, in contrast to the rapid repair (within 1 h) seen with Balb/c 3T3 and RD13B2. This suggests that scid mutation is responsible for this repair at reduced rate. To confirm the independence of repair of 0.23 M NaCl-sensitive PLD from that of 0.5 M NaCl-sensitive PLD, both treatments with 0.23 M NaCl and 0.5 M NaCl were combined in each line. It is found that the repair of either PLD was not affected by the other treatment. The scid mutation impaired only the repair of 0.5 M NaCl-sensitive PLD. (author)

  15. Repair of potentially lethal radiation damage: comparison of neutron and x-ray RBE and implications for radiation therapy

    International Nuclear Information System (INIS)

    Hall, E.J.; Kraljevic, U.

    1976-01-01

    Experiments with Chinese hamster cells have shown that neutron irradiation does not result in repair of potentially lethal damage (PLD), i.e., that which can be influenced by changes in environmental conditions following irradiation. Since PLD is presumed to be repaired in tumors but not in normal tissues, this absence of differential sparing of tumor cells relative to normal tissues--a feature characteristic of irradiation with x rays--represents an advantage of neutrons in addition to their reduced oxygen effect. At a given dose, the difference in relative biological effectiveness (RBE) between tumors and normal tissues corresponds to a 5 percent increase in tumor dose with no concomitant increase in dose to normal tissues, which could be significant in cancer therapy

  16. Differential response of human and rodent cell lines to chemical inhibition of the repair of potentially lethal damage

    Energy Technology Data Exchange (ETDEWEB)

    Little, J.B.; Ueno, A.M.; Dahlberg, W.K.

    1989-07-01

    We have examined the effects of several classes of metabolic inhibitors on the repair of potentially lethal damage in density-inhibited cultures of two rodent and two human cell systems which differ in their growth characteristics. Aphidicolin, 1-..beta..-D-arabinofuranosylcytosine (ara-C) and hydroxyurea showed no effect on PLD repair, whereas the effects of 9-..beta..-D-arabinofuranosyladenine (ara-A) and 3-aminobenzamide (3-AB) were cell line dependent. For example, 3-AB suppressed PLD repair almost completely in CHO cells, but showed no inhibitory effects in human diploid fibroblasts. These results indicate that inhibitors of DNA replication and poly(ADP-ribose) synthesis are not efficient inhibitors of cellular recovery in irradiated cells and, moreover, that such effects may be cell line dependent.

  17. Ultraviolet-B lethal damage on Pseudomonas aeruginosa

    International Nuclear Information System (INIS)

    Degiorgi, C.F.; Fernandez, R.O.; Pizarro, R.A.

    1996-01-01

    Pseudomonas aeruginosa has shown an increased sensitivity compared with that of Escherichia coli and Enterobacter cloacae, when they were exposed to 0.4 kJ/m2 of ultraviolet-B radiation. The rapid decay in cell viability observed in Pseudomonas aeruginosa after the irradiation was influenced by factors such as culture media and the presence of pyocyanine during the irradiation. The radioinduced lethal damage could be prevented by photoreactivating treatment, indicating that pyrimidine dimer formation was the mechanism causing bacterial death. The results indicate that several environmental conditions may act as protective agents against ultraviolet-B-induced damage

  18. Inhibition of potential lethal damage repair and related gene expression after carbon-ion beam irradiation to human lung cancer grown in nude mice

    International Nuclear Information System (INIS)

    Yashiro, Tomoyasu; Fujisawa, Takehiko; Koyama-Saegusa, Kumiko; Imai, Takashi; Miyamoto, Tadaaki

    2007-01-01

    Using cultured and nude mouse tumor cells (IA) derived from a human lung cancer, we previously demonstrated their radiosensitivity by focusing attention on the dynamics of tumor clonogens and the early and rapid survival recovery (potential lethal damage repair: PLD repair) occurring after X-ray irradiation. To the authors' knowledge, this is the first study demonstrating gene expression in association with PLD repair after carbon-ion beam or X-ray irradiation to cancer cells. In this study we tried to detect the mechanism of DNA damage and repair of the clonogens after X-ray or carbon-ion beam irradiation. At first, colony assay method was performed after irradiation of 12 Gy of X-ray or 5 Gy of carbon-ion beam to compare the time dependent cell survival of the IA cells after each irradiation pass. Second, to search the genes causing PLD repair after irradiation of X-ray or carbon-ion beam, we evaluated gene expressions by using semi-quantitative RT-PCR with the selected 34 genes reportedly related to DNA repair. The intervals from the irradiation were 0, 6, 12 and 24 hr for colony assay method, and 0, 3, 18 hr for RT-PCR method. From the result of survival assays, significant PLD repair was not observed in carbon-ion beam as compared to X-ray irradiation. The results of RT-PCR were as follows. The gene showing significantly higher expressions after X-ray irradiation than after carbon-ion beam irradiation was PCNA. The genes showing significantly lower expressions after X-ray irradiation rather than after carbon-ion beam irradiation were RAD50, BRCA1, MRE11A, XRCC3, CHEK1, MLH1, CCNB1, CCNB2 and LIG4. We conclude that PCNA could be a likely candidate gene for PLD repair. (author)

  19. The influence of inhibitors of poly (ADP-ribose) polymerase on X-ray induced potentially lethal damage repair

    International Nuclear Information System (INIS)

    Brown, D.M.; Evans, J.W.; Brown, J.M.

    1984-01-01

    Inhibition of repair of X-ray-induced potentially lethal damage (PLD) could enhance the curability of radioresistant tumours. We have studied the effect of inhibitors of the enzyme poly (ADP-ribose) polymerase on X-ray PLD repair. Four classes of inhibitors are known: aromatic amides (e.g., 3-aminobenzamide), thymidine, nicotinamides and methyl xanthines (e.g., caffeine). Plateau-phase Chinese hamster ovary (HA-1) cultures were exposed to 10 mM concentrations of thymidine, nicotinamide, 3-aminobenzamide (3-ABA) and caffeine prior to irradiation to 12 Gy in air, and then incubated with drug at 37 0 C for varying times (0-6 h) prior to subculture. Irradiated cells without drug exhibited a 5-6 fold increase in survival over the 6 h period compared to cultures plated immediately after irradiation. Although none of the compounds proved cytotoxic to unirradiated controls over the 6.5 h exposure, all of the compounds except thymidine reduced the capacity of the cells to repair PLD. The order of the inhibitory effect was caffeine > 3-ABA > nicotinamide, and the inhibition was concentration dependent for nicotinamide and 3-ABA. We also studied the effect of 3-ABA on the radiation response of exponentially growing cells. 5 mM 3-ABA for 2h post-irradiation resulted in a dose-multiplicative sensitization reducing the D 0 from 0.88 Gy to 0.69 Gy, indicating an involvement of poly (ADP-ribose) polymerase in the radiosensitivity of exponentially growing as well as plateau-phase cells. (author)

  20. Extra lethal damage due to residual incompletely repaired sublethal damage in hyperfractionated and continuous radiation treatment

    Energy Technology Data Exchange (ETDEWEB)

    Chen, J.; van de Geijn, J.; Goffman, T. (ROB, DCT, NCI, NIH, Bethesda, Maryland 20892 (US))

    1991-05-01

    In the conventional linear--quadratic model of single-dose response, the {alpha} and {beta} terms reflect lethal damage created {ital during} the delivery of a dose, from two different presumed molecular processes, one linear with dose, the other quadratic. With the conventional one-fraction-per-day (or less) regimens, the sublethal damage (SLD), presumably repairing exponentially over time, is essentially completely fixed by the time of the next dose of radiation. If this assumption is true, the effects of subsequent fractions of radiation should be independent, that is, there should be little, if any, reversible damage left from previous fractions, at the time of the next dose. For multiple daily fractions, or for the limiting case, continuous radiation, this simplification may overlook damaged cells that have had insufficient time for repair. A generalized method is presented for accounting for extra lethal damage (ELD) arising from such residual SLD for hyperfractionation and continuous irradiation schemes. It may help to predict differences in toxicity and tumor control, if any, obtained with unconventional'' treatment regimens. A key element in the present model is the finite size and the dynamic character of the pool of sublethal damage. Besides creating the usual linear and quadratic components of lethal damage, each new fraction converts a certain fraction of the existing SLD into ELD, and creates some new SLD.

  1. Extra lethal damage due to residual incompletely repaired sublethal damage in hyperfractionated and continuous radiation treatment

    International Nuclear Information System (INIS)

    Chen, J.; van de Geijn, J.; Goffman, T.

    1991-01-01

    In the conventional linear--quadratic model of single-dose response, the α and β terms reflect lethal damage created during the delivery of a dose, from two different presumed molecular processes, one linear with dose, the other quadratic. With the conventional one-fraction-per-day (or less) regimens, the sublethal damage (SLD), presumably repairing exponentially over time, is essentially completely fixed by the time of the next dose of radiation. If this assumption is true, the effects of subsequent fractions of radiation should be independent, that is, there should be little, if any, reversible damage left from previous fractions, at the time of the next dose. For multiple daily fractions, or for the limiting case, continuous radiation, this simplification may overlook damaged cells that have had insufficient time for repair. A generalized method is presented for accounting for extra lethal damage (ELD) arising from such residual SLD for hyperfractionation and continuous irradiation schemes. It may help to predict differences in toxicity and tumor control, if any, obtained with ''unconventional'' treatment regimens. A key element in the present model is the finite size and the dynamic character of the pool of sublethal damage. Besides creating the usual linear and quadratic components of lethal damage, each new fraction converts a certain fraction of the existing SLD into ELD, and creates some new SLD

  2. Intrinsic radiosensitivity and PLD repair in osteosarcoma cell lines

    International Nuclear Information System (INIS)

    Sugimoto, M.; Toguchida, J.; Kotoura, Y.; Yamamuro, T.; Utsumi, H.

    1992-01-01

    The response to radiation of seven osteosarcoma cell lines was analysed by in vitro colony-forming assay and compared with that of eight human fibroblast strains. The values of D 0 , the surviving fraction after 2 Gy (S2Gy), and the mean inactivation dose (D-bar) of osteosarcoma cells in log-phase culture were significantly higher than those of fibroblast strains (p<0.01). PLD (potentially lethal damage) repair of osteosarcoma cells evaluated in the plateau phase of growth showed great variation for enhancement of survival, although all of the values were maximised within 12 h after irradiation. In the osteosarcoma, intrinsic radiosensitivity in vitro reflected the clinical response to radiation. However, the capacity for PLD repair might not be a good indicator for predicting the results of radiation therapy. (author)

  3. Effects of β-arabinofuranosyladenine on potentially lethal damage induced in plateau phase mammalian cells exposed to U.V.-light

    International Nuclear Information System (INIS)

    Iliakis, G.

    1983-01-01

    The effect of β-arabinofuranosyladenine (β-araA), a specific inhibitor of DNA polymerases α and β, on the survival of plateau phase Ehrlich ascites tumour cells after U.V.-exposure has been studied. β-araA inhibited repair of U.V.-induced potentially lethal damage (PLD), when given to the cells after irradiation. An exponential survival curve (D 0 = 1 J/m 2 ) was obtained when irradiated cells were treated with β-araA at 120 μM. β-araA mainly affected the shoulder width of the survival curve but also changed the slope of the resistant 'tail' of the survival curve. The effect was irreversible at 80 μM and partly reversible at 20 μM. When β-araA was added to cultures in fresh or conditioned medium at 80 μM at various times after irradiation, there was a gradual decrease in PLD. Survival reached levels corresponding to those of untreated cells plated immediately after irradiation. If cells were incubated for additional times in fresh medium, survival increased to levels corresponding to those obtained with plateau phase cells after delayed plating, but did not occur in cells incubated in conditioned medium. The repair time constant for PLD was about 3 hours for cells incubated in fresh medium and about 6 hours incubated in conditioned medium. (author)

  4. A quick method for testing recessive lethal damage with a diploid strain of Aspergillus nidulans

    International Nuclear Information System (INIS)

    Morpurgo, G.; Puppo, S.; Gualandi, G.; Conti, L.

    1978-01-01

    A simple method capable of detecting recessive lethal damage in a diploid strain of Aspergillus nidulans is described. The method scores the recessive lethals on the 1st, the 3rd and the 5th chromosomes, which represent about 40% of the total map of A. nidulans. Two examples of induced lethals, with ultraviolet irradiation and methyl methanesulfonate are shown. The frequency of lethals may reach 36% of the total population with UV irradiation. (Auth.)

  5. Repair of potentially lethal damage following irradiation with x rays or cyclotron neutrons: response of the EMT-6/UW tumor system treated under various growth conditions in vitro and in vivo

    International Nuclear Information System (INIS)

    Rasey, J.S.; Nelson, N.J.

    1981-01-01

    Postirradiation potentially lethal damage (PLD) repair was examined in the EMT-6/UW tumor system under a variety of in vitro and in vivo growth conditions. Following x irradiation, surviving fraction increased in fed and unfed plateau cultures if subculture and plating were delayed; in exponentially growing cultures if they were covered with depleted medium for the first 6 h postirradiation; and in tumors in vivo if excision for preparation of a cell suspension was delayed. Following irradiation with 21.5 meV (d + → Be) neutrons, PLD repair was measurable only in unfed plateau cultures when subculture was delayed and in exponentially growing cells exposed to depleted culture medium immediately after irradiation. In x-irradiated EMT-6/UW cells, the greatest repair capacity and the highest surviving fraction ratios were measured in unfed plateau cultures; the least repair was observed in exponentially growing cells exposed to depleted medium. Thus post-neutron repair was not limited to situations where the amount of repair of photon PLD is large. The demonstration of PLD repair in tumors irradiated in vivo with X rays and the absence of such repair after neutrons could have important implications in radiotherapy if this is a general phenomenon

  6. Photoreactivable sector of lethal damage in ultraviolet-irradiated Escherichia coli cells

    International Nuclear Information System (INIS)

    Balgavy, P.

    1976-01-01

    The photoreactivable sector of lethal damage in Escherichia coli Bsub(s-1), Escherichia coli B/r Hcr - and Escherichia coli B/r Hcr + cells after ultraviolet irradiation at 254 nm is 0.823 +- 0.004, 0.70 +- 0.01 and 0.53 +- 0.06, respectively, at 99% confidence limits. For the low values of the photoreactivable sector in the B/r Hcr - and B/r Hcr + strains are likely to be responsible dark repair processes which eliminate lethal damage, brought about by pyrimidine dimers, preferably in comparison with lethal damage caused by photoproducts of another type. (author)

  7. Scopolamine methylbromide mitigates radiation induced damage and lethality in zebrafish

    International Nuclear Information System (INIS)

    Shrivastava, Nitisha; Joshi, Jayadev; Ghosh, Subhajit; Dimri, Manali; Prem Kumar, Indracanti; Sehgal, Neeta

    2014-01-01

    In view of the strategic importance radiation countermeasures hold, the present study was undertaken to screen a collection of small molecule clinical compounds for possible radioprotective action using zebrafish as a model system. Preliminary screening in developing zebrafish embryos (24 hour post fertilization, (hpf)) using damage manifestations and survival as end point identified scopolamine methylbromide (SMB), a muscarinic receptor antagonist, as a potential radiomitigator. It was found to be optimal (60% survival advantage after 6 th post irradiation day) at a dose of 80 μM when added 3 h post 20 Gy exposure. Mechanistic studies suggested that SMB though exhibited no significant antioxidant potential, but was found to limit radiation induced apoptosis (pre G1 population) quantified through flow cytometry (6 and 5% reduction after 8 or 24 h after treatments) and annexin V staining (8% reduction). Further, quantitative analysis, using caspase 3 assay, revealed a 2.46 fold increase in apoptosis in irradiated group and treatment of irradiated zebrafish embryos with SMB led to a significant reduction in global apoptosis (1.7 fold; p<0.05) when compared to irradiated group. In silico studies based on structural and functional similarity with known radioprotectors suggested similarities with atropine, a known anti-inflammatory agent with muscarinic antagonism and radioprotective potential. In view of this SMB was tested, in silico, for possible anti-inflammatory action. Molecular docking studies revealed that SMB interacts (B.E-8.0 Kcal/mole) with cycloxygenase-2 (COX-2). In lieu of this, anti-inflammation activity was assessed through ChIN (chemically induced inflammation) method in 3 dpf (days post fertilization) embryos and SMB was found to significantly inhibit inflammation at all doses studied from 20-200 μM at 3 and 6 hpi (hours post inflammation). Overall the result suggests that scopolamine methylbromide mitigates radiation induced injury and lethality in

  8. The effect of recovery from potentially lethal damage on the determination of repair and repopulation in a murine tumour

    International Nuclear Information System (INIS)

    Sheldon, P.W.; Fowler, J.F.

    1985-01-01

    Repair and repopulation following X irradiation of clamped-off murine anaplastic MT tumours was investigated using the established method of (Dsub(n)-D 1 )/(n-1). Repair was complete in 4 h, similar in extent to that reported in other tumours, and within the range of that reported for normal tissues. Subsequent repopulation commenced after 4 days and was equivalent to 1.8 Gy/day recovered dose, corresponding to a clonogenic cell number doubling time of 1.8 days. However, estimates of repair and repopulation may have been in error because the chronically hypoxic cells in this tumour alone have the ability to recover from potentially lethal damage (PLD) and so are more radioresistant than cells rendered acutely hypoxic by clamping. Because of this, even clamping off tumours at irradiation does not render all cell populations equally radioresistant, and so reoxygenation between fractions could result in an underestimate of repair and repopulation. Further, the differing sensitivity between acutely and chronically hypoxic cells renders the apparent OER a function of dose (i.e., oxygen not truly dose-modifying to chronically hypoxic cells). Consequently it is incorrect to assume a constant OER in order to compare repair in tumours irradiated under hypoxic conditions with that in normal tissues irradiated under aerobic conditions. (author)

  9. Recovery from UV-induced potentially lethal damage in systemic lupus erythematosus skin fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Zamansky, G B

    1986-08-01

    The repair of ultraviolet light-induced potentially lethal damage was investigated in density-inhibited skin fibroblast cell strains derived from patients with systemic lupus erythematosus. The effect of exposure to polychromatic ultraviolet light composed of environmentally relevant wavelengths or to the more commonly studied, short wavelength (254 nm) ultraviolet light was studied. Systemic lupus erythematosus cells, which are hypersensitive to ultraviolet light under growth promoting conditions, were able to repair potentially lethal damage as well as normal cells.

  10. Recovery from UV-induced potentially lethal damage in systemic lupus erythematosus skin fibroblasts

    International Nuclear Information System (INIS)

    Zamansky, G.B.

    1986-01-01

    The repair of ultraviolet light-induced potentially lethal damage was investigated in density-inhibited skin fibroblast cell strains derived from patients with systemic lupus erythematosus. The effect of exposure to polychromatic ultraviolet light composed of environmentally relevant wavelengths or to the more commonly studied, short wavelength (254 nm) ultraviolet light was studied. Systemic lupus erythematosus cells, which are hypersensitive to ultraviolet light under growth promoting conditions, were able to repair potentially lethal damage as well as normal cells. (author)

  11. Reproductive-phase and interphase lethal cell damage after irradiation and treatment with cytostatics

    International Nuclear Information System (INIS)

    Hagemann, G.

    1979-01-01

    After X-ray irradiation of manual cells, two lethal fractions occur due to reproductive and interphase death under low and high radiation doses. The damage kinetics on which this fact is based is compared with hypothetical tumour frequencies and leucemia induction caused in experiments. The reproductive-lethal damage can be manifested by means of colony size spectrometry, with the median colony size class differences (MCD) serving as measure for the damage found. The simultaneous effects of the cytostatics BLEOMYCIN or ICRF 159 and X-rays on reproductive lethal and interphase-lethal damage are measured by means of MCD and survival fraction, and the additive and intensifying effect' is judged with the help of suitably defined terms. This shows that the clinically used ICRF 159 has an additive effect on interphase-lethal and a sub-additive effect on reproductive-lethal cell damage. Thus, favourable results may be expected for the electivity factor in fractionated irradiation and with regard to delayed damage in healthy tissue. (orig.) 891 MG/orig. 892 RDG [de

  12. Damage to E. coli cells induced by tritium decay: secondary lethality under nongrowth conditions

    International Nuclear Information System (INIS)

    Koukalova, B.; Kuhrova, V.

    1980-01-01

    Cells containing incorporated 3 H-thymidine are damaged by its decay. It was found with E.coli TAU-bar cells that a small part of the damage is lethal whereas most of it is reparable and only potentially lethal. If cells are subjected to nongrowth conditions, the potentially lethal damage changes to lethal damage. This process is called secondary lethality (SL). The extent of SL and some changes in DNA under three different modes of growth inhibition were determined. It was found that: (i) SL is maximal under conditions of amino acid starvation (-AA), the viable count decreasing by two orders of magnitude. (ii) SL is 4 times lower in the presence of chloramphenicol (-AA+CLP) and 6.5 times lower under +AA+CLP conditions. Changes in the sedimentation rate of DNA determined in alkaline sucrose gradient correlate with the differences in SL: under -AA conditions the sedimentation rate of DNA decreases whereas in the presence of CLP no decrease occurs. The results suggest that certain enzymatic processes take place under -AA conditions which lead to irreparable changes in DNA. (author)

  13. Damage to E. coli cells induced by tritium decay: secondary lethality under nongrowth conditions

    Energy Technology Data Exchange (ETDEWEB)

    Koukalova, B; Kuhrova, V [Ceskoslovenska Akademie Ved, Brno. Biofysikalni Ustav

    1980-05-01

    Cells containing incorporated /sup 3/H-thymidine are damaged by its decay. It was found with E.coli TAU-bar cells that a small part of the damage is lethal whereas most of it is reparable and only potentially lethal. If cells are subjected to nongrowth conditions, the potentially lethal damage changes to lethal damage. This process is called secondary lethality (SL). The extent of SL and some changes in DNA under three different modes of growth inhibition were determined. It was found that: (i) SL is maximal under conditions of amino acid starvation (-AA), the viable count decreasing by two orders of magnitude. (ii) SL is 4 times lower in the presence of chloramphenicol (-AA+CLP) and 6.5 times lower under +AA+CLP conditions. Changes in the sedimentation rate of DNA determined in alkaline sucrose gradient correlate with the differences in SL: under -AA conditions the sedimentation rate of DNA decreases whereas in the presence of CLP no decrease occurs. The results suggest that certain enzymatic processes take place under -AA conditions which lead to irreparable changes in DNA.

  14. Quantitative aspects of repair of potentially lethal damage in mammalian cells

    International Nuclear Information System (INIS)

    Iliakis, G.; Pohlit, W.

    1979-01-01

    Stationary cultures of Ehrlich ascites tumour cells were irradiated with X-rays and then immediately or after a time interval tsub(rep) plated to measure the survival. The increase in survival observed after delayed plating was interpreted as repair of potentially lethal damage. A cybernetic model was used to analyse these data. Three states of damage were assumed for the cells. In state A the cells could grow to macrocolonies, in state B the cells suffered potentially lethal damage and could grow to macrocolonies only if they were allowed to repair the damage and in state C the cells were lethally damaged. A method of deriving the values of the parameters of the model from the experimental data was given. The dependence of the reaction rate constant of the repair potentially lethal damage on the dose D was used to derive a possible mechanism for the production of the shoulder in the dose effect curve. Finally this model was compared with other models of radiation action in living cells. (author)

  15. Lethal, potentially lethal, and nonlethal damage induction by heavy ions in cultured human cells

    International Nuclear Information System (INIS)

    Todd, P.; Wood, J.C.; Walker, J.T.; Weiss, S.J.

    1985-01-01

    In the fields of high-LET radiotherapy and space radiation safety it is important to know the relative probabilities with which a cell whose nucleus is struck by a heavy ion will be damaged or killed. Experiments were performed in which synchronous cultured human T-1 cells (presumptive HeLa) were irradiated with natural alpha particles of energy approximately 3.5 MeV at various times after mitotic selection up to the middle of S phase. Nuclear-area histograms were determined as a function of time after mitosis under conditions identical to those used for irradiation. The efficiency with which one particle passing through the nucleus killed a cell was found to be 0.14-0.20. This value was extrapolated to experimental cell survival data obtained when asynchronous cultured human cells were irradiated with He, Li, B, C, N, O, Ne, Ar ions of energy 6.58 or 5.5 MeV/amu, and the cell killing efficiency was found to be in the broad range of 0.5-1.0 under single-hit conditions. Similarly irradiated cells were examined for colony-size distribution by an image analysis technique, and it was found that the loss of large colonies was dose and LET-dependent in a systematic way. Dose-response data suggest two predominant subpopulations, resistant and sensitive cells, and it appears that the sensitive population is affected by single-hit kinetics. The single-hit coefficient for the induction of inherited slow growth varied with LET in a similar way to that for survival. The action cross section for this form of heritable damage appears to be comparable to the geometric cross section of the cell nucleus

  16. Repair of potentially lethal damage in unfed plateau phase cultures of Ehrlich ascited tumour cells

    International Nuclear Information System (INIS)

    Illiakis, G.

    1980-01-01

    Plateau phase EAT-cells have been irradiated at different times in the plateau phase and their ability to repair PLD has been measured. A large capacity to repair PLD has been observed if the cultures were kept in the plateau phase for some hours after irradiation before diluting and plating to measure the survival. In combination with theoretical considerations it is concluded that almost all the PLD produced under these conditions can be repaired. The reaction rate of this repair was independent of the dose and the age of the culture. The results also indicate that PLD repair is independent of the intercellular contact of EAT-cells. (author)

  17. Modification of the repair of potentially lethal damage in plateau-phase Chinese hamster cells by 2-chlorodeoxyadenosine

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, Kiyoshi; Hiraoka, Wakako; Kuwabara, Mikinori; Matsuda, Akira; Ueda, Tohru; Sato, Fumiaki.

    1988-09-01

    The ability of 2-chlorodeoxyadenosine, a ribonucleotide reductase inhibitor, to inhibit the repair of potentially lethal damage was demonstrated in Chinese hamster V79 cells after X irradiation in plateau-phase cultures. This ability of the drug was completely diminished when deoxycytidine was added at the same time, though this was slightly affected by the addition of adenosine, suggesting that this drug was phosphorylated by deoxycytidine kinase to serve as an inhibitor of the repair of potentially lethal damage. Compared with hydroxyurea, another ribonucleotide reductase inhibitor, this drug appeared to contain its own activity which suppressed the repair of potentially lethal damage. A combined study of post-irradiation treatment with hypertonic salt solution and with this drug on the fixation of potentially lethal damage revealed that this drug inhibited the repair of hypertonic-insensitive potentially lethal damage.

  18. Modification of the repair of potentially lethal damage in plateau-phase Chinese hamster cells by 2-chlorodeoxyadenosine

    International Nuclear Information System (INIS)

    Tanabe, Kiyoshi; Hiraoka, Wakako; Kuwabara, Mikinori; Matsuda, Akira; Ueda, Tohru; Sato, Fumiaki.

    1988-01-01

    The ability of 2-chlorodeoxyadenosine, a ribonucleotide reductase inhibitor, to inhibit the repair of potentially lethal damage was demonstrated in Chinese hamster V79 cells after X irradiation in plateau-phase cultures. This ability of the drug was completely diminished when deoxycytidine was added at the same time, though this was slightly affected by the addition of adenosine, suggesting that this drug was phosphorylated by deoxycytidine kinase to serve as an inhibitor of the repair of potentially lethal damage. Compared with hydroxyurea, another ribonucleotide reductase inhibitor, this drug appeared to contain its own activity which suppressed the repair of potentially lethal damage. A combined study of post-irradiation treatment with hypertonic salt solution and with this drug on the fixation of potentially lethal damage revealed that this drug inhibited the repair of hypertonic-insensitive potentially lethal damage. (author)

  19. A linear-quadratic model of cell survival considering both sublethal and potentially lethal radiation damage

    International Nuclear Information System (INIS)

    Rutz, H.P.; Coucke, P.A.; Mirimanoff, R.O.

    1991-01-01

    The authors assessed the dose-dependence of repair of potentially lethal damage in Chinese hamster ovary cells x-irradiated in vitro. The recovery ratio (RR) by which survival (SF) of the irradiated cells was enhanced increased exponentially with a linear and a quadratic component namely ζ and ψ: RR=exp(ζD+ψD 2 ). Survival of irradiated cells can thus be expressed by a combined linear-quadratic model considering 4 variables, namely α and β for the capacity of the cells to accumulate sublethal damage, and ζ and ψ for their capacity to repair potentially lethal damage: SF=exp((ζ-α)D+ (ψ-β)D 2 ). author. 26 refs.; 1 fig.; 1 tab

  20. Arrest of irradiated G1, S, or G2 cells at mitosis using nocodazole promotes repair of potentially lethal damage

    International Nuclear Information System (INIS)

    Iliakis, G.; Nuesse, M.

    1984-01-01

    The ability of synchronized Ehrlich ascites tumor cells, irradiated in G1, S, and G2 phases, to repair potentially lethal damage when arrested at mitosis by using 0.4 μg/ml nocodazole, a specific inhibitor of microtubule polymerization, has been studied. Cells irradiated in these phases were found to repair potentially lethal damage at mitosis. The extent of this repair was similar to that observed for cells irradiated at the same stages in the cell cycle but allowed to repair potentially lethal damage by incubating in balanced salt solution for 6 hr after X irradiation

  1. Pedigree analyses of yeast cells recovering from DNA damage allow assignment of lethal events to individual post-treatment generations

    International Nuclear Information System (INIS)

    Klein, F.; Karwan, A.; Wintersberger, U.

    1990-01-01

    Haploid cells of Saccharomyces cerevisiae were treated with different DNA damaging agents at various doses. A study of the progeny of individual such cells allowed the assignment of lethal events to distinct post treatment generations. By microscopically inspecting those cells which were not able to form visible colonies the authors could discriminate between cells dying from immediately effective lethal hits and those generating microcolonies probably as a consequence of lethal mutation(s). The experimentally obtained numbers of lethal events were mathematically transformed into mean probabilities of lethal fixations at taking place in cells of certain post treatment generations. Such analyses give detailed insight into the kinetics of lethality as a consequence of different kinds of DNA damage. For example, X-irradiated cells lost viability mainly by lethal hits, only at a higher dose also lethal mutations fixed in the cells that were in direct contact with the mutagen, but not in later generations, occurred. Ethyl methanesulfonate (EMS)-treated cells were hit by 00-fixations in a dose dependent manner. The distribution of all sorts of lethal fixations taken together, which occurred in the EMS-damaged cell families, was not random. For comparison analyses of cells treated with methyl methanesulfonate, N-methyl-N'-nitro-N-nitrosoguanidine and nitrous acid are also reported

  2. Effects of extracellular and intracellular pH on repair of potentially lethal damage, chromosome aberrations and DNA double-strand breaks in irradiated plateau-phase A549 cells

    International Nuclear Information System (INIS)

    Jayanth, V.R.; Bayne, M.T.; Varnes, M.E.

    1994-01-01

    Plateau-phage A549 cells exhibit a high capacity for repair of potentially lethal radiation damage (PLD). Previously it was found that PLD repair could be partially inhibited by increasing the extracellular pH (pH e ) of the spent medium from its normal value of 6.7-6.8 to 7.6 during postirradiation holding. This study shows that PLD repair is also inhibited by reducing the pH e of the spent medium to 6.0. The effects of altering pH e on rejoining of DNA double-strand breaks (DSBs) as measured by neutral filter elution and on mitotic delay and chromosome aberrations seen after releasing cells from the plateau phase were investigated. Neither increasing nor decreasing the pH e of the spent medium had an effect on radiation-induced mitotic delay. Rejoining of DSBs was significantly inhibited by holding at pH e 6.0 but not affected by holding at pH e 7.6. At 2 h after irradiation about 51% of unrejoined breaks remained at pH e 6.0, compared to about 15% at pH e 6.7 or 7.6. However, holding at pH e 7.6 appeared to cause a marginal change in the kinetics of rejoining of DSBs. Repair of lesions leading to dicentric and acentric chromosome aberrations did not occur when cells were held at pH e 6.0, since less than 10% of these aberrations disappeared from cells held for 24 h before subculture. In contrast, holding plateau-phase cells at pH e 7.6 vs 6.7 caused a small but significant reduction in the disappearance of dicentrics but had no effect on the rate or extent of the disappearance of acentrics. These data have led us to hypothesize that inhibition of PLD repair by holding at pH e 6.0 is related both to inhibition of pH-dependent DNA repair enzymes and to induction of changes in DNA which lead to misrepair when the cells are released from plateau phase. Inhibition of PLD repair by holding at pH e 7.6 is related primarily to changes in DNA structure which promote misrepair. 43 refs., 5 figs., 4 tabs

  3. Caffeine and D sub 2 O medium interact in affecting the expression of radiation-induced potentially lethal damage

    Energy Technology Data Exchange (ETDEWEB)

    Utsumi, H. (Kyoto Univ. (Japan). Radiation Biology Center); Elkind, M.M. (Colorado State Univ., Fort Collins, CO (United States). Dept. of Radiological Health Sciences)

    1991-10-01

    Earlier work has been extended to compare the killing of long-phase V79 Chinese hamster cells by ionizing radiation when they are treated immediately after irradiation with medium containing either caffeine or 90% D{sub 2}O. The object was to determine if the enhanced killing due to post-treatment with caffeine, or D{sub 2}O, resulted from action on the same sector of potentially lethal damage as appeared to be the case for hypertonic shock and D{sub 2}O medium. The treatments by themselves were not toxic to unirradiated cells. We found that the enhanced expression of potentially lethal damage by post-treatment with caffeine or D{sub 2}O medium is similar. For example, the kinetic of the repair of the potentially lethal damage expressible by either post-treatment was similar, and an additive enhancement of potentially lethal damage occurred when the two treatments were administered sequentially. These findings suggest that caffeine and D{sub 2}O medium affect the same sector of potentially lethal damage. When the two treatments were combined, however, they competed with each other. Thus, although caffeine and D{sub 2}O medium act on the same sector of potentially lethal damage they do so differently, suggesting that more than one pathway of the expression of radiation damage can result in the same phenotypic effect. (author).

  4. Caffeine and D2O medium interact in affecting the expression of radiation-induced potentially lethal damage

    International Nuclear Information System (INIS)

    Utsumi, H.; Elkind, M.M.

    1991-01-01

    Earlier work has been extended to compare the killing of long-phase V79 Chinese hamster cells by ionizing radiation when they are treated immediately after irradiation with medium containing either caffeine or 90% D 2 O. The object was to determine if the enhanced killing due to post-treatment with caffeine, or D 2 O, resulted from action on the same sector of potentially lethal damage as appeared to be the case for hypertonic shock and D 2 O medium. The treatments by themselves were not toxic to unirradiated cells. We found that the enhanced expression of potentially lethal damage by post-treatment with caffeine or D 2 O medium is similar. For example, the kinetic of the repair of the potentially lethal damage expressible by either post-treatment was similar, and an additive enhancement of potentially lethal damage occurred when the two treatments were administered sequentially. These findings suggest that caffeine and D 2 O medium affect the same sector of potentially lethal damage. When the two treatments were combined, however, they competed with each other. Thus, although caffeine and D 2 O medium act on the same sector of potentially lethal damage they do so differently, suggesting that more than one pathway of the expression of radiation damage can result in the same phenotypic effect. (author)

  5. Testosterone Depletion by Castration May Protect Mice from Heat-Induced Multiple Organ Damage and Lethality

    Directory of Open Access Journals (Sweden)

    Ruei-Tang Cheng

    2010-01-01

    Full Text Available When the vehicle-treated, sham-operated mice underwent heat stress, the fraction survival and core temperature at +4 h of body heating were found to be 5 of 15 and 34.4∘C±0.3∘C, respectively. Castration 2 weeks before the start of heat stress decreased the plasma levels of testosterone almost to zero, protected the mice from heat-induced death (fraction survival, 13/15 and reduced the hypothermia (core temperature, 37.3∘C. The beneficial effects of castration in ameliorating lethality and hypothermia can be significantly reduced by testosterone replacement. Heat-induced apoptosis, as indicated by terminal deoxynucleotidyl- transferase- mediatedαUDP-biotin nick end-labeling staining, were significantly prevented by castration. In addition, heat-induced neuronal damage, as indicated by cell shrinkage and pyknosis of nucleus, to the hypothalamus was also castration-prevented. Again, the beneficial effects of castration in reducing neuronal damage to the hypothalamus as well as apoptosis in multiple organs during heatstroke, were significantly reversed by testosterone replacement. The data indicate that testosterone depletion by castration may protect mice from heatstroke-induced multiple organ damage and lethality.

  6. Effects of β-arabinofuranosyladenine on the growth and repair of potentially lethal damage in Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    Iliakis, G.

    1980-01-01

    β-D-Arabinofuranosyladenine (β-araA) inhibit the growth of Ehrlich ascites tumor cells by selective inhibition of DNA polymerases. RNA and protein synthesis are not significantly affected. Addition of β-araA to the cells after irradiation resulted in a concentration-dependent decrease in survival, presumably due to the inhibition of the repair of potentially lethal damage. Since β-araA selectively inhibits DNA polymerases it is suggested that repair of potentially lethal damage involves steps at the DNA level which require some polymerization. These repair steps take place in the DNA with a velocity comparable to that of the repair of potentially lethal damage. The inhibition of the repair of potentially lethal damage by β-araA was modified by the addition of deoxyadenosine; this supports the finding that β-araA acts competitively against dATP at the molecular level. The inhibition of the repair of potentially lethal damage by β-araA, which is partly reversible, resulted in a concentration-dependent modification of the survival curve. At low concentrations of β-araA a dose-modifying decrease in survival was observed. At higher concentrations (more than 12 μM) the decrease in survival resulted in a decrease of the shoulder width of the survival curve. Eventually an exponential curve was obtained. We suggest therefore that the shoulder of the survival curve results from some repair or potentially lethal damage. Preliminary information has been obtained on the time course of this repair

  7. Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival.

    Science.gov (United States)

    Tinkum, Kelsey L; Stemler, Kristina M; White, Lynn S; Loza, Andrew J; Jeter-Jones, Sabrina; Michalski, Basia M; Kuzmicki, Catherine; Pless, Robert; Stappenbeck, Thaddeus S; Piwnica-Worms, David; Piwnica-Worms, Helen

    2015-12-22

    Short-term fasting protects mice from lethal doses of chemotherapy through undetermined mechanisms. Herein, we demonstrate that fasting preserves small intestinal (SI) architecture by maintaining SI stem cell viability and SI barrier function following exposure to high-dose etoposide. Nearly all SI stem cells were lost in fed mice, whereas fasting promoted sufficient SI stem cell survival to preserve SI integrity after etoposide treatment. Lineage tracing demonstrated that multiple SI stem cell populations, marked by Lgr5, Bmi1, or HopX expression, contributed to fasting-induced survival. DNA repair and DNA damage response genes were elevated in SI stem/progenitor cells of fasted etoposide-treated mice, which importantly correlated with faster resolution of DNA double-strand breaks and less apoptosis. Thus, fasting preserved SI stem cell viability as well as SI architecture and barrier function suggesting that fasting may reduce host toxicity in patients undergoing dose intensive chemotherapy.

  8. Repair of potentially lethal damage by introduction of T4 DNA ligase in eucaryotic cells

    International Nuclear Information System (INIS)

    Durante, M.; Grossi, G.F.; Napolitano, M.; Gialanella, G.

    1991-01-01

    The bacterial enzyme PvuII, which generates blunt-ended DNA double-strand breaks, and T4 DNA ligase, which seals adjacent DNA fragments in coupling to ATP cleavage, were introduced in mouse C3H10T1/2 fibroblasts using osmolytic shock of pinocytic vesicles. Cells were then assayed for their clonogenic ability. In agreement with previous studies by others, the authors found that PvuII restriction endonuclease simulates ionizing radiation effects by causing a dose-dependent loss of reproductive capacity. They show that concomitant treatment with DNA ligase considerably increases cell survival. Survival curves were shown to be dependent on ligase enzyme dose and on ATP concentration in the hypertonic medium. They conclude that T4 DNA ligase is able to repair some potentially lethal damage produced by restriction endonucleases in eucaryotic cells. (author)

  9. In vitro holding and PLD-repair. Pt. 2

    International Nuclear Information System (INIS)

    Stevenson, A.F.G.; Palackal, T.; Lange, C.S.

    1989-01-01

    The repair of potentially lethal damage (PLDR) in mammalian cells is expected to be better in quiescent cultures since PLD is supposedly fixed during cycle progression. Plateau phase cultures, therefore, serve as models because of assumed mitotic quiescence. Four established cell lines (V79, CHO, L5178Y and HELA) and one euploid cell strain IMR-90 have been analysed by flow cytometry and electron microscopy to address questions on quiescence in the plateau phase and the effect of holding (induction of quiescence by nutrient privation). In contrast to commonly held views, our results indicate that the quiescent fraction in cultures from transformed cells is exceedingly low (1% or less). Plateau phase cultures of transformed cells are constantly turning over. Euploid cells like the IMR-90 show true quiescence in the plateau phase. Holding causes typical cytopathological changes. These changes have been ultrastructurely characterised. Resistant sub-populations of cells can be selected out under holding-conditions. Such selected cells show completely different radiobiological characteristics, which raise questions on the interpretation of data on PLDR. (orig.)

  10. Potentially lethal damage repair in cell lines of radioresistant human tumours and normal skin fibroblasts

    International Nuclear Information System (INIS)

    Marchese, M.J.; Minarik, L.; Hall, E.J.; Zaider, M.

    1985-01-01

    Radiation cell survival data were obtained in vitro for three cell lines isolated from human tumours traditionally considered to be radioresistant-two melanomas and one osteosarcoma-as well as from a diploid skin fibroblast cell line. One melanoma cell line was much more radioresistant than the other, while the osteosarcoma and fibroblast cell lines were more radiosensitive than either. For cells growing exponentially, little potentially lethal damage repair (PLDR) could be demonstrated by comparing survival data for cells in which subculture was delayed by 6 h with those sub-cultured immediately after treatment. For the malignant cells in plateau phase, which in these cells might be better termed 'slowed growth phase', since an appreciable fraction of the cells are still cycling, a small amount of PLDR was observed, but not as much as reported by other investigators in the literature. The normal fibroblasts, which achieved a truer plateau phase in terms of noncycling cells, showed a significantly larger amount of PLDR than the tumour cells. (author)

  11. Evidence for the induction of two types of potentially lethal damage after exposure of plateau phase Chinese hamster V79 cells to γ-rays

    International Nuclear Information System (INIS)

    Iliakis, G.

    1985-01-01

    The fixation of γ-rays induced potentially damage (PLD) caused after treatment either with β-araA or in medium made hypertonic by the addition of sodium chloride was studied in plateauphase chinese hamster V79 cells. Treatment with β-araA was found to affect a sector of PLD, the fixation of which specifically reduced the shoulder width of the survival curve. The effect was maximized when cell survival reached levels corresponding to an exponential line, with a slope similar to the final slope of the survival curve of untreated cells. This effect was achieved by a four hour treatment with β-araA at concentrations above 150 μM. Longer treatment times or incubation at higher β-araA concentrations did not significantly enhance the effect. Treatment in hypertonic medium, on the other hand, enhanced cell killing in a concentration dependent (NaCl-concentration) way and the survival reached values much lower than those corresponding to an exponential line. No indication for a plateau in the effect, indicating complete fixation of the sector of PLD that reacts sensitively to this treatment, was obtained. Boht the slope and the shoulder width of the survival curve were affected, the slope first being increaseed after short treatment times (up to 10 min), followed by a decrease in the shoulder width after longer treatment times (longer than 10 min). (orig./WL)

  12. Hyperthermia radiosensitization in human glioma cells comparison of recovery of polymerase activity, survival, and potentially lethal damage repair

    International Nuclear Information System (INIS)

    Raaphorst, G.P.; Feeley, M.M.

    1994-01-01

    DNA polymerase inactivation is compared to thermal radiosensitization and inhibition of damage recovery in human glioma cells. Two human glioma cell lines (U87MG and U373MG) were exposed to hyperthermia and irradiation. Hyperthermia was given at 43 degrees C and 45 degrees C and DNA polymerase α + δ + ε and β activities were measured. Hyperthermia was given at various times before irradiation and the degree of radiosensitization and polymerase activity was assessed at various times after heating. In addition the ability of cells to undergo repair of potentially lethal radiation damage was assessed for cells irradiated at various times after heating. Polymerase α + δ + ε and polymerase β both recovered after heating but polymerase β was faster and was complete in U373MG but not in the U87MG cell lines after 48 h incubation after heating (45 degrees C, 60 min). Incubation, between hyperthermia and irradiation resulted in a loss of radiosensitization and a loss of inhibition of repair of potentially lethal damage. These changes correlated well with recovery of polymerase β but not with polymerase α + δ + ε. The correlation of polymerase β activity and thermoradiosensitization and its recovery indicate that polymerase β may be one of the mechanisms involved in thermoradiosensitization. 35 refs., 7 figs

  13. Poly(ADP-ribose) metabolism in X-irradiated Chinese hamster cells: its relation to repair of potentially lethal damage

    International Nuclear Information System (INIS)

    Ben-Hur, E.; Elkind, M.M.

    1984-01-01

    Nicotinamide-adenine dinucleotide (NAD + ) is the substrate used by cells in poly(ADP-ribose) synthesis. X-irradiation of log-phase Chinese hamster cells caused a rapid decrease in NAD + levels which was linearly dependent on radiation dose. The activity of ADP-ribosyl transferase (ADPRT) also increased linearly with radiation dose. The decrease of NAD + was slower, and the increase in ADPRT activity was less pronounced, in a radiation sensitive line, V79-AL162/S-10. An inhibitor of ADPRT, m-aminobenzamide, largely prevented the depletion of cellular NAD + and reduced the rate at which ADPRT activity disappeared during post-irradiation incubation. Post-irradiation treatment with hypertonic buffer or with medium containing D 2 O-which inhibit repair of radiation-induced potentially lethal damage-enhanced the depletion of NAD + and prevented the reduction in ADPRT activity following irradiation. The characteristics of the effects of treatment with hypertonic buffer on NAD + metabolism were qualitatively similar to the effects that such treatment has on radiation-induced cell killing. These results suggest that poly(ADP-ribose) synthesis after irradiation plays a role in the repair of potentially lethal damage. (author)

  14. DNA polymerase I is crucial for the repair of potentially lethal damage caused by the indirect effects of X irradiation in Escherichia coli

    International Nuclear Information System (INIS)

    Billen, D.

    1985-01-01

    The radiosensitivity of an Escherichia coli mutant deficient in DNA polymerase I was measured in the presence of OH radical scavengers. The extreme X-ray sensitivity of the mutant could be abolished by OH radical scavengers if a sufficiently high level of radioprotector was present. There was a direct correlation between the OH radical scavenging activity of the chemicals tested (NO 2 - , n-butanol, glycerol, t-amyl alcohol, and t-butanol) and their protective ability. The author interprets the data as showing that the indirect actions of X rays (primarily OH radicals) result in major damage to the bacterial DNA which in large part consists of potentially lethal lesions. This potentially lethal damage is repaired through an enzymatic pathway requiring DNA polymerase I. I. In the mutant lacking DNA polymerase I, these potentially lethal lesions are expressed as cell lethality

  15. Indirect effects are involved in the production of potentially lethal damage in X irradiated escherichia coli

    International Nuclear Information System (INIS)

    Billen, D.

    1985-01-01

    When living cells are exposed to low LET radiation, 60 to 70% of the resulting lethality is said to be due to indirect effects. Using the OH radical scavengers: glycerol n-butanol, t-butanol, and NO/sub 2//sup -/. The authors observed that a radiosensitive E. coli K-12 mutant (W 3110 thy/sup -/ polAl/sup -/) lacking DNA polymerase 1 displays a markedly enhanced radioresistance when exposed to X rays in the presence of these chemicals. The extent of protection afforded by these chemicals correlated with their OH radical scavenging ability over the limited range of concentrations of the chemicals studied. (Only non-toxic concentrations of the chemicals were used). The presence of 2M glycerol during irradiation of the PolAl/sup -/ cells results in a survival level higher than that seen for the unprotected parent strain (W 3110 thy polA/sup +/)

  16. Induction of lethal and genetic damage by vacuum-ultraviolet (163 nm) irradiation of aqueous suspensions of yeast cells

    International Nuclear Information System (INIS)

    Ito, T.; Kobayashi, K.

    1976-01-01

    Yeast cells suspended in distilled water were irradiated with monochromatic 163 nm photons by immersing a specially designed discharge tube into the suspension. This was thought to be a useful means of investigating in vivo effects of radiation-induced water radicals on well cells in the complete absence of ionic species, since 163 nm photons can dissociate water only via excitation. These experiments showed that the water radicals (excluding e/sub aq/ - ) exerted both lethal and genetic (gene-conversion) effects quite potently, and the characteristic protection against these effects was observable when 2-mercaptoethanol or, in particular, p-aminobenzoic acid, a specific scavenger for OH radicals, was added to the medium prior to irradiation. Nearly complete protection from both lethal and genetic effects was observed in some cases with p-aminobenzoic acid. These results establish unequivocally that the OH radical, and not the hydrogen atom (H radical), possesses the damaging potency in the cell. Comparisons with γ-ray experiments revealed several differences between 163 nm photons and γ rays in the protective actions of radical scavengers, which may be attributable to reactive species other than OH radicals produced by the γ rays

  17. The effect of sub-lethal damage repair and exchange on the final slope of cell survival curves

    International Nuclear Information System (INIS)

    Carlone, M.C.; Wilkins, D.E.; Raaphorst, G.P.

    2003-01-01

    Full text: The Lea-Catcheside dose rate protraction factor, G, is the most widely used model to describe the effects of dose rate on cell survival. In the linear quadratic formalism, this factor modifies the beta component of cell killing; G is greatest for acute irradiations while vanishing at low dose rates. We have found a simple compartmental model that can derive the Lea-Catcheside function. This compartmental model clearly shows that the G function can only be derived using a little known assumption: the diminution of sub-lethal damage due to exchange of repairable lesions is negligible compared to that due to repair. This assumption was explicitly stated by Lea, but it does not appear to have been restated or verified since very early work on cell survival. The implication of this assumption is that sub-lethal damage can be modeled without considering exchange, which is evidenced by the fact that the G function does not contain parameters relating to exchange. By using a new model that fully accounts for repair and exchange of sublethal lesions, a cell survival expression that has a modified G function, but that retains the linear quadratic formalism, can be obtained. At low doses, this new model predicts linear-quadratic behavior, but the behavior gradually changes to mono-exponential at high doses, which is consistent with experimental observations. Modeling cell survival of well-known survival curves using the modified linear quadratic model shows statistically significant improvement in the fits to the cell survival data as compared to best fits obtained with the linear quadratic model. It is shown that these improvements in fits are due to a superior representation of the high dose region of the survival curve

  18. RBE-LET relationships for different types of lethal radiation damage in mammalian cells: comparison with DNA dsb and an interpretation of differences in radiosensitivity

    NARCIS (Netherlands)

    Barendsen, G. W.

    1994-01-01

    Relative biological effectiveness (RBE), as a function of linear energy transfer (LET), is evaluated for different types of damage contributing to mammalian cell reproductive death. Survival curves are analysed assuming a linear-quadratic dose dependence of lethal lesions. The linear term represents

  19. Strand breaks and lethal damage in plasmid DNA subjected to 60CO-γirradiation

    International Nuclear Information System (INIS)

    Klimczak, U.

    1992-01-01

    Experiments with calf thymus DNA subjected to extracellular irradiation yield information on the role of direct and indirect effects in single-strand breakage, if this is evaluated with reference to the scavenger activity in respect of OH radicals. The role of the two processes in the occurrence of double-stand breaks and further damage leading to cell decay has so far remained largely obscure. It was the aim of the study described here to contribute to research in this field by performing in vitro experiments on biologically active DNA. For this purpose, DNA from pBR322 plasmids was irradiated in the presence of OH-radical scavengers. The number of single-strand and double-strand breaks was determined on the basis of the system's ability to eliminate OH radicals. In order to asses the influence of irradiation processes on the biological activity of DNA, investigations were carried out in E. coli for transformations caused by irradiated plasmid DNA. The results were interpreted in the light of theories about inhomogenous reaction kinetics put forward by Mark et al. (1989). It was finally discussed, which of the gamma-irradiation injuries occurring in DNA was to be held responsible for the inactivation of plasmid DNA and which enzymatic processes were additionally at work here. (orig./MG) [de

  20. Polar solvent modification of x ray induced potentially lethal damage in heterogeneous human colon tumor cells in vitro

    International Nuclear Information System (INIS)

    Arundel, C.M.; Leith, J.T.; Dexter, D.L.; Glicksman, A.S.

    1984-01-01

    Two subpopulations of tumor cells (clones A and D) obtained from a human colon adenocarcinoma were examined for their sensitivities to x-irradiation as unfed, early plateau phase cultures. Both the single dose survival curves and the kinetics of potentially lethal damage recovery (PLDR) were determined for the two tumor lines. Also, possible modification of PLDR by N,N-dimethylformamide (DMF), which has previously been shown to enhance the radiosensitivity of exponentially growing tumor cells, was investigated by adding DMF (0.8% v/v) to plateau phase cultures immediately after irradiation, and determining effects on the extent of PLDR. For non-DMF treated cells, the survival curve parameters of the diploid (clone D) and aneuploid (clone A) lines were very similar. Using initial survival levels of 3.5% (clone D) or 5.5% (clone A) to investigate PLDR, it was found that the increase in survival for clone D was 2.2, while the SFR for clone A was 1.6. DMF did not change either the kinetics or extent of PLDR in these two tumor lines when added to cultures immediately after irradiation. These results indicate that significant heterogeneity in PLDR exists between these closely related tumor subpopulations

  1. Detection of γ-ray-induced DNA damages in malformed dominant lethal embryos of the Japanese medaka (Oryzias latipes) using AP-PCR fingerprinting

    International Nuclear Information System (INIS)

    Kubota, Yoshiko; Shimada, Atsuko; Shima, Akihiro

    1992-01-01

    Adult male fish of the medaka HNI strain exposed to 9.5 Gy or 19 Gy (0.95 Gy/min) of γ-rays were mated with non-irradiated female fish of the Hd-rR strain. Genomic DNA was prepared from malformed individual embryos which were expected to be dominant lethal and used for AP-PCR fingerprinting. By the use of a part of the T3 promoter sequence (20 mer), which is not found in the medaka genome as an arbitrary primer, polymorphisms were found in genomic fingerprints which could distinguish the parental strains. On the other hand, fingerprints of F1 hybrids were found to be the sum of those of their parents. Based on these findings, the fingerprints of genomic DNA of each severely malformed embryo were analyzed, because it was expected that radiation-induced genomic damages resulting in severe malformation and eventually in dominant lethals should be detected as changes in paternal fingerprints of F1 hybrids. Indeed, changes were found in genomic DNA as loss of some paternal bands in fingerprints of malformed embryos. One of 10 malformed embryos obtained from 9.5 Gy γ-irradiated males had lost 5 bands. These results indicated a possibility that quantitative as well as qualitative estimation of γ-ray-induced DNA damages can be made by this method which does not require the functional selection based on a specific target gene. (author). 16 refs., 3 figs., 1 tab

  2. Protective effect of Asparagus racemosus root extract against lethal total - body electron beam radiation induced damage in Swiss albino mice

    International Nuclear Information System (INIS)

    Sharmila, K.P.; Bhandary, B. Satheesh Kumar; Suchetha Kumari, N.; Bhat, Vadish S.; Shetty, Jayaram; Peter, Alex John; Jose, Jerish M.; Fernandes, Ronald

    2016-01-01

    To investigate the protective effect of Asparagus Racemosus Root ethanolic extract (ARE) in Swiss albino mice against acute lethal total - body Electron beam irradiation. Swiss Albino mice were used for the assessment of radiation induced sickness and 30 day survival analysis. Survival studies were determined using the Kaplan-Meier survival curves. The maximum survival was observed in the experimental mice pretreated with 200 mg/kg.b.wt. of ARE which also reduced the radiation sickness characteristics. This dose was considered as an optimal dose for radioprotection. Treatment of mice with ARE before irradiation delayed the onset of mortality as compared with the untreated irradiated controls. Present findings demonstrate the potential of ARE in mitigating radiation-induced mortality, which may be attributed to its free radical scavenging and increased antioxidant potential

  3. The relationships between RBE and LET for different types of lethal damage in mammalian cells: biophysical and molecular mechanisms

    NARCIS (Netherlands)

    Barendsen, G. W.

    1994-01-01

    The relative biological effectiveness (RBE) of radiations as a function of linear energy transfer (LET) is analyzed for different types of damage causing reproductive death of mammalian cells. Survival curves are evaluated assuming a linear-quadratic dose dependence of the induction of reproductive

  4. Relationship of DNA repair and chromosome aberrations to potentially lethal damage repair in X-irradiated mammalian cells

    International Nuclear Information System (INIS)

    Fornace, A.J. Jr.; Nagasawa, H.; Little, J.B.

    1980-01-01

    By the alkaline elution technique, the repair of x-ray-induced DNA single strand breaks and DNA-protein cross-links was investigated in stationary phase, contact-inhibited mouse cells. During the first hour of repair, approximately 90% of x-ray induced single strand breaks were rejoined whereas most of the remaining breaks were rejoined more slowly during the next 5 h. The number of residual non-rejoined single strand breaks was approximately proportional to the x-ray dose at early repair times. DNA-protein cross-links were removed at a slower rate - T 1/2 approximately 10 to 12 h. Cells were subcultured at low density at various times after irradiation and scored for colony survival, and chromosome aberrations in the first mitosis after sub-culture. Both cell lethality and the frequency of chromosome aberrations decreased during the first several hours of repair, reaching a minimum level by 6 h; this decrease correlated temporally with the repair of the slowly rejoining DNA strand breaks. The possible relationship of DNA repair to changes in survival and chromosome aberrations is discussed

  5. Diet-Induced Alterations in Gut Microflora Contribute to Lethal Pulmonary Damage in TLR2/TLR4-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Yewei Ji

    2014-07-01

    Full Text Available Chronic intake of Western diet has driven an epidemic of obesity and metabolic syndrome, but how it induces mortality remains unclear. Here, we show that chronic intake of a high-fat diet (HFD, not a low-fat diet, leads to severe pulmonary damage and mortality in mice deficient in Toll-like receptors 2 and 4 (DKO. Diet-induced pulmonary lesions are blocked by antibiotic treatment and are transmissible to wild-type mice upon either cohousing or fecal transplantation, pointing to the existence of bacterial pathogens. Indeed, diet and innate deficiency exert significant impact on gut microbiota composition. Thus, chronic intake of HFD promotes severe pulmonary damage and mortality in DKO mice in part via gut dysbiosis, a finding that may be important for immunodeficient patients, particularly those on chemotherapy or radiotherapy, where gut-microbiota-caused conditions are often life threatening.

  6. A Study on Recovery from Potentially Lethal Damage induced by γ-Irradiation in Plateau-phase Vero Cells in vitro

    International Nuclear Information System (INIS)

    Kim, Il Han; Choi, Eun Kyung; Ha, Sung Whan; Park, Charn Il; Cha, Chang Yong

    1988-01-01

    Recovery from potentially lethal damage (PLDR) after irradiation was studied in plateau-phase culture of Vero cells in vitro. Unfed plateau-phase cells were irradiated with dose of 1 to 9 Gy using Cs-137 irradiator. Cells then were incubated again and left in situ for 0, 1, 2, 3, 4, 5, 6 and 24 hours and then were trypsinized, explanted, and subcultured in fresh RPMI-1640 media containing 0.33% agar. Cell survival was measured by colony forming ability. An adequate number of heavily irradiated Vero cells were added as feeder cells to make the total cell number constant in every culture dish. As the postirradiation in situ incubation time increased, surviving fraction increased saturation level at 2 to 4 hours after in situ incubation. As the radiation dose increased, the rate of PLDR also increased. In analysis of cell survival curve fitted to the linear-quadratic model, the linear inactivation coefficient (a) decreased largely and reached nearly to zero but the quadratic inactivation coefficient (b) increased minimally by increment of postirradiation in situ incubation time. So PLDR mainly affected the damage expressed as a. In the multitarget model, significant change was not obtained in D0 but in Dq. Therefore, shoulder region in cell survival curve was mainly affected by PLDR and terminal slope was not influenced at all. And dose-modifying factor by PLDR was relatively higher in shoulder region, that is, in low dose area below 3 Gy

  7. Damage to the DNA of microorganisms from decay of incorporated 125I and the relationship of DNA damage to lethal effects

    International Nuclear Information System (INIS)

    Krisch, R.E.; Krasin, F.; Sauri, C.J.

    1975-01-01

    Iodine-125 decays by electron capture and is known to cause severe molecular damage to small organic molecules via vacancy cascades. In an examination of the biological effects of this decay mode we have labelled coliphages T1 and T4, as well as E. coli, with 125 I-5-iododeoxyuridine, which is incorporated into DNA in place of thymidine. Labelled organisms are generally stored in liquid nitrogen at -196 0 C during decay and are periodically assayed for loss of viability and for breakage of DNA, using neutral and alkaline sucrose gradient sedimentation techniques. Briefly, our experiments have demonstrated drastic damage to DNA from the decay of incorporated 125 I, as would be predicted from the data for small molecules. (auth)

  8. Action of caffeine on x-irradiated HeLa cells. V. Identity of the sector of cells that expresses potentially lethal damage in G1 and G2

    International Nuclear Information System (INIS)

    Beetham, K.L.; Tolmach, L.J.

    1982-01-01

    When HeLa S3 cells are irradiated in early G 1 with 4 Gy of 220-kV x rays and are then incubated in growth medium containing up to 5 mM caffeine, survival is reduced (as reported previously), reaching a concentration-dependent plateau. Cell killing presumably occurs as a result of the fixation of a portion of the potentially lethal damage the cells contain. These cells respond to continued treatment with caffeine at concentrations greater than 2 mM during S, but less so than during G 1 . When they reach G 2 arrest, however, extensive cell killing again occurs (reported previously), presumably also the result of potentially lethal damage fixation. G 1 -irradiated cultures that are treated with caffeine either continuously at a concentration in the range 1 to 5 mM, or at 10 mM for 8 hr and subsequently with the low concentration, achieve the same survival level in G 2 , provided that the potentially lethal damage is not repaired during G 1 and S. Repair seems to be completely inhibited in the presence of 3 to 4 mM caffeine. The results indicate that fixation of potentially lethal damage occurs in the same sector of cells in G 1 and G 2 , suggesting that the same cellular lesion gives rise to cell killing in the two phases

  9. PLD$ is involved in phagocytosis of microglia: expression and localization changes of PLD4 are correlated with activation state of microglia.

    Directory of Open Access Journals (Sweden)

    Yoshinori Otani

    Full Text Available Phospholipase D4 (PLD4 is a recently identified protein that is mainly expressed in the ionized calcium binding adapter molecule 1 (Iba1-positive microglia in the early postnatal mouse cerebellar white matter. Unlike PLD1 and PLD2, PLD4 exhibits no enzymatic activity for conversion of phosphatidylcholine into choline and phosphatidic acid, and its function is completely unknown. In the present study, we examined the distribution of PLD4 in mouse cerebellar white matter during development and under pathological conditions. Immunohistochemical analysis revealed that PLD4 expression was associated with microglial activation under such two different circumstances. A primary cultured microglia and microglial cell line (MG6 showed that PLD4 was mainly present in the nucleus, except the nucleolus, and expression of PLD4 was upregulated by lipopolysaccharide (LPS stimulation. In the analysis of phagocytosis of LPS-stimulated microglia, PLD4 was co-localized with phagosomes that contained BioParticles. Inhibition of PLD4 expression using PLD4 specific small interfering RNA (siRNA in MG6 cells significantly reduced the ratio of phagocytotic cell numbers. These results suggest that the increased PLD4 in the activation process is involved in phagocytosis of activated microglia in the developmental stages and pathological conditions of white matter.

  10. Inhibition of potentially lethal radiation damage repair in normal and neoplastic human cells by 3-aminobenzamide: an inhibitor of poly(ADP-ribosylation)

    International Nuclear Information System (INIS)

    Thraves, P.J.; Mossman, K.L.; Frazier, D.T.; Dritschilo, A.

    1986-01-01

    The effect of 3-aminobenzamide (3AB), an inhibitor of poly(ADP-ribose) synthetase, on potentially lethal damage repair (PLDR) was investigated in normal human fibroblasts and four human tumor cell lines from tumors with varying degrees of radiocurability. The tumor lines selected were: Ewing's sarcoma, a bone tumor considered radiocurable and, human lung adenocarcinoma, osteosarcoma, and melanoma, three tumors considered nonradiocurable. PLDR was measured by comparing cell survival when cells were irradiated in a density-inhibited state and replated at appropriate cell numbers at specified times following irradiation to cell survival when cells were replated immediately following irradiation. 3AB was added to cultures 2 hr prior to irradiation and removed at the time of replating. Different test radiation doses were used for the various cell lines to obtain equivalent levels of cell survival. In the absence of inhibitor, PLDR was similar in all cell lines tested. In the presence of 8 mM 3AB, differential inhibition of PLDR was observed. PLDR was almost completely inhibited in Ewing's sarcoma cells and partially inhibited in normal fibroblast cells and osteosarcoma cells. No inhibition of PLDR was observed in the lung adenocarcinoma or melanoma cells. Except for the osteosarcoma cells, inhibition of PLDR by 3AB correlated well with radiocurability

  11. Action of caffeine on x-irradiated HeLa cells. VII. Evidence that caffeine enhances expression of potentially lethal radiation damage

    International Nuclear Information System (INIS)

    Beetham, K.L.; Tolmach, L.J.

    1984-01-01

    HeLa cells irradiated with 2 Gy of 220-kV X rays suffer a 60-70% loss of colony-forming ability which is increased to 90% by postirradiation treatment with 10 mM caffeine for 6 hr. The detailed postirradiation patterns of cell death and sister-cell fusion in such cultures and in cultures in which the colony-forming ability was brought to about the same level by treatment with a larger (4 Gy) X-ray dose alone or by longer (48 hr) treatment with 10 mM caffeine alone were recorded by time-lapse cinemicrography. Because the patterns of cell death and fusion differ radically in irradiated and in caffeine-treated cultures, the response of the additional cells killed by the combined treatment can be identified as X-ray induced rather than caffeine induced. The appearance of cultures after several days of incubation confirms the similarity of the post-treatment patterns of proliferation in cultures suffering enhanced killing to those occurring in cultures treated with larger doses of X rays alone. It is concluded that x rays do not sensitize cells to caffeine, but rather that caffeine enhanced the expression of potentially lethal radiation-induced damage

  12. Fixation of potentially lethal radiation damage by post-irradiation exposure of Chinese hamster cells to 0.5 M or 1.5 M NaCl solutions

    International Nuclear Information System (INIS)

    Raaphorst, G.P.; Dewey, W.C.

    1979-01-01

    The effect of 0.05 M and 1.5 M NaCl treatments on CHO cells during and after irradiation has been examined. Treatment with either hypotonic or hypertonic salt solutions during and after irradiation resulted in the fixation of radiation damage which would otherwise not be expressed. The half time for fixation was 4 to 5 min, and the increased expression of the potentially lethal damage by anisotonic solutions was mainly characterized by large decreases in the shoulder of the survival curve, as well as by decreases in Dsub(o). Fixation of radiation damage at 37 0 C occurred to a much greater extent for the hypertonic treatment than for the hypotonic treatment and was greater at 37 0 C than at 20 0 C. Although both the hypotonic and hypertonic treatments during and after irradiation reduced or eliminated the repair of sublethal and potentially lethal damage, treatment during irradiation only, radiosensitized the cells when the treatment was hypotonic, and radioprotected the cells when the treatment was hypertonic. These observations are discussed in relation to salt treatments and different temperatures altering competition between repair and fixation of potentially lethal lesions, the number of which depends on the particular salt treatment at the time of irradiation. (author)

  13. Protective effect of hydroferrate fluid, MRN-100, against lethality and hematopoietic tissue damage in γ-radiated Nile tilapia, Oreochromis niloticus

    International Nuclear Information System (INIS)

    Ghoneum, Mamdooh; Elbaghdady, Heba Allah M.; El-Shebly, Abdallah A.; Pan, Deyu; Assanah, Edward; Lawson, Greg

    2013-01-01

    Hydroferrate fluid, MRN-100, an iron-based compound derived from bivalent and trivalent ferrates, is a potent antioxidant compound. Therefore, we examined the protective effect of MRN-100 against γ-radiation-induced lethality and damage to hematopoietic tissues in fish. A total of 216 Nile tilapia fish (Oreochromis niloticus) were randomly divided into four groups. Group 1 served as a control that was administered no radiation and no MRN-100 treatment. Group 2 was exposed only to γ-radiation (15 Gy). Groups 3 and 4 were pre-treated with MRN-100 at doses of either 1 ml/l or 3 ml/l in water for 1 week, and subsequently exposed to radiation while continuing to receive MRN-100 for 27 days. The survival rate was measured, and biochemical and histopathological analyses of hematopoietic tissues were performed for the different treatment groups at 1 and 4 weeks post-radiation. Exposure to radiation reduced the survival rate to 27.7%, while treatment with MRN-100 maintained the survival rate at 87.2%. In addition, fish exposed to γ-radiation for 1 week showed a significant decrease in the total number of white blood cells (WBCs) and red blood cells (RBCs) series. However, treatment with MRN-100 protected the total WBC count and the RBCs series when compared with irradiated fish. Furthermore, significant histological lesions were observed in the hepatopancreas, spleen and gills of irradiated fish. However, treatment with MRN-100 protected the histopathology of various organs. We conclude that MRN-100 is a radioprotective agent in fish and may be useful as an adjuvant treatment to counteract the adverse side effects associated with radiation exposure. (author)

  14. Lethal Epistaxis.

    Science.gov (United States)

    Byard, Roger W

    2016-09-01

    Epistaxis or nosebleed refers to bleeding from the nostrils, nasal cavity, or nasopharynx. Occasional cases may present with torrential lethal hemorrhage. Three cases are reported to demonstrate particular features: Case 1: A 51-year-old woman with lethal epistaxis with no obvious bleeding source; Case 2: A 77-year-old man with treated nasopharyngeal carcinoma who died from epistaxis arising from a markedly neovascularized tumor bed; Case 3: A 2-year-old boy with hemophilia B who died from epistaxis with airway obstruction in addition to gastrointestinal bleeding. Epistaxis may be associated with trauma, tumors, vascular malformations, bleeding diatheses, infections, pregnancy, endometriosis, and a variety of different drugs. Careful dissection of the nasal cavity is required to locate the site of hemorrhage and to identify any predisposing conditions. This may be guided by postmortem computerized tomographic angiography (PCTA). Despite careful dissection, however, a source of bleeding may never be identified. © 2016 American Academy of Forensic Sciences.

  15. DLC coating of textile blood vessels using PLD

    Czech Academy of Sciences Publication Activity Database

    Kocourek, Tomáš; Jelínek, Miroslav; Vorlíček, Vladimír; Zemek, Josef; Janča, T.; Žížková, V.; Podlaha, J.; Popov, C.

    2008-01-01

    Roč. 93, č. 3 (2008), s. 627-632 ISSN 0947-8396 R&D Projects: GA MPO FI-IM2/068; GA ČR GA202/06/0216 Institutional research plan: CEZ:AV0Z10100522 Keywords : blood vessels * PLD * DLC * sp2 * sp3 Subject RIV: BH - Optics, Masers, Lasers Impact factor: 1.884, year: 2008

  16. Long Gd-123 coated conductor by PLD method

    International Nuclear Information System (INIS)

    Fuji, H.; Igarashi, M.; Hanada, Y.; Miura, T.; Hanyu, S.; Kakimoto, K.; Iijima, Y.; Saitoh, T.

    2008-01-01

    We have developed long Gd-123 coated conductors by ion-beam-assisted deposition (IBAD) and pulsed-laser-deposition (PLD) method. Recently, large-scale reel-to-reel apparatus with the 110 cm x 15 cm assisting ion source was introduced to IBAD system. It was enable to produce 500 m-class IBAD-Gd 2 Zr 2 O 7 (GZO) tapes with Δφ of below 15 deg. and high throughputs of 3 m/h. Furthermore, apparatus with multi-lane and laser scanning was introduced to PLD system. As a result, end to end I c of 318 A were obtained for a 201.5 m long tape, and I c x L values were 64,077 Am. Furthermore, 500 m-class deposition was carried out by improving PLD conditions. As a result, I c x L values of 112,166 Am was obtained and it's a world record on August 2007. In the short samples, I c of over 500 A was obtained with Gd-123 thickness of 2.0 μm and over 100 A was obtained in magnetic field of 3 T, perpendicular to c-axis

  17. Fear potentiated startle increases phospholipase D (PLD) expression/activity and PLD-linked metabotropic glutamate receptor mediated post-tetanic potentiation in rat amygdala.

    Science.gov (United States)

    Krishnan, Balaji; Scott, Michael T; Pollandt, Sebastian; Schroeder, Bradley; Kurosky, Alexander; Shinnick-Gallagher, Patricia

    2016-02-01

    Long-term memory (LTM) of fear stores activity dependent modifications that include changes in amygdala signaling. Previously, we identified an enhanced probability of release of glutamate mediated signaling to be important in rat fear potentiated startle (FPS), a well-established translational behavioral measure of fear. Here, we investigated short- and long-term synaptic plasticity in FPS involving metabotropic glutamate receptors (mGluRs) and associated downstream proteomic changes in the thalamic-lateral amygdala pathway (Th-LA). Aldolase A, an inhibitor of phospholipase D (PLD), expression was reduced, concurrent with significantly elevated PLD protein expression. Blocking the PLD-mGluR signaling significantly reduced PLD activity. While transmitter release probability increased in FPS, PLD-mGluR agonist and antagonist actions were occluded. In the unpaired group (UNP), blocking the PLD-mGluR increased while activating the receptor decreased transmitter release probability, consistent with decreased synaptic potentials during tetanic stimulation. FPS Post-tetanic potentiation (PTP) immediately following long-term potentiation (LTP) induction was significantly increased. Blocking PLD-mGluR signaling prevented PTP and reduced cumulative PTP probability but not LTP maintenance in both groups. These effects are similar to those mediated through mGluR7, which is co-immunoprecipitated with PLD in FPS. Lastly, blocking mGluR-PLD in the rat amygdala was sufficient to prevent behavioral expression of fear memory. Thus, our study in the Th-LA pathway provides the first evidence for PLD as an important target of mGluR signaling in amygdala fear-associated memory. Importantly, the PLD-mGluR provides a novel therapeutic target for treating maladaptive fear memories in posttraumatic stress and anxiety disorders. Published by Elsevier Inc.

  18. Modification of the sensitivity and repair of potentially lethal damage by diethyldithiocarbamate during and following exposure of plateau-phase cultures of mammalian cells to radiation and cis-diamminedichloroplatinum(II)

    International Nuclear Information System (INIS)

    Evans, R.G.; Engel, C.; Wheatley, C.; Nielsen, J.

    1982-01-01

    Diethyldithiocarbamate (DDC), a chelating agent known to reduce levels of superoxide dismutase and glutathione peroxidase, appears to protect irradiated monolayers of mammalian cells when present for 1 hr before and during irradiation. To examine a possible cause of this modification, the repair of potentially lethal X-ray damage was examined with and without the presence of DDC in the medium overlying the cells postirradiation. Although little repair was seen in full medium alone when DDC was added to the full medium, the amount of repair was comparable to that seen under optimum repair conditions, that is, in Hanks' balanced salt solution. The t 1/2 of the repair process in Hanks' balanced salt solution or in full medium with DDC added was comparable and of the order of 1 to 1.5 hr. The cis-platinum sensitivity of the monolayers is significantly modified by the addition of DDC, and the nature of the modification is dependent upon the time at which the DDC is added to the cells following initiation of cis-platinum exposure. To investigate a possible reason for this protection by DDC, we examined the repair of potentially lethal cis-platinum damage in the cell monolayers. Minimal repair was noted in the presence of either Hanks' balanced salt solution or full medium, but when DDC was added to the full medium, the repair was tripled, and the t 1/2 of the repair process was approximately 2 hr. The ability of DDC to protect cells from exposure to both X-rays and cis-platinum, together with its augmentation of repair of potentially lethal damage following exposure to each, has broad clinical application and is being actively explored in tumor-bearing mice

  19. Development of RPS trip logic based on PLD technology

    International Nuclear Information System (INIS)

    Choi, Jong Gyun; Lee, Dong Young

    2012-01-01

    The majority of instrumentation and control (I and C) systems in today's nuclear power plants (NPPs) are based on analog technology. Thus, most existing I and C systems now face obsolescence problems. Existing NPPs have difficulty in repairing and replacing devices and boards during maintenance because manufacturers no longer produce the analog devices and boards used in the implemented I and C systems. Therefore, existing NPPs are replacing the obsolete analog I and C systems with advanced digital systems. New NPPs are also adopting digital I and C systems because the economic efficiencies and usability of the systems are higher than the analog I and C systems. Digital I and C systems are based on two technologies: a microprocessor based system in which software programs manage the required functions and a programmable logic device (PLD) based system in which programmable logic devices, such as field programmable gate arrays, manage the required functions. PLD based systems provide higher levels of performance compared with microprocessor based systems because PLD systems can process the data in parallel while microprocessor based systems process the data sequentially. In this research, a bistable trip logic in a reactor protection system (RPS) was developed using very high speed integrated circuits hardware description language (VHDL), which is a hardware description language used in electronic design to describe the behavior of the digital system. Functional verifications were also performed in order to verify that the bistable trip logic was designed correctly and satisfied the required specifications. For the functional verification, a random testing technique was adopted to generate test inputs for the bistable trip logic.

  20. Wettability modification of porous PET by atmospheric femtosecond PLD

    Science.gov (United States)

    Assaf, Youssef; Forstmann, Guillaume; Kietzig, Anne-Marie

    2018-04-01

    In this study, porous structures were created on poly(ethylene terephthalate) (PET) by femtosecond (fs) laser micromachining. While such structures offer a texture that is desirable for several applications, their wettability does not always match the application in question. The aim of this investigation is to tune the wettability of such surfaces by incorporating a controlled amount of nanoparticles into the structure. The machined PET samples were thus used as substrates for fs pulsed laser deposition (PLD) of titanium under ambient conditions. The nanoparticles were deposited as nanochain clusters due to the formation of an oxide layer between individual nanoparticles. The stability of nanoparticle incorporation was tested by placing the samples in an ultrasonic ethanol bath. Results indicated that nanoparticles were still successfully incorporated into the microstructure after sonication. Nanoparticle surface coverage was observed to be controllable through the operating fluence. The dynamic contact angles of the resulting composite surface were observed to decrease with increasing titanium incorporation. Therefore, this work highlights atmospheric fs PLD as a method for wettability modification of high surface area microstructures without undermining their topology. In addition, this technique uses almost the same equipment as the machining process by which the microstructures are initially created, further highlighting its practicality.

  1. The effect of postirradiation holding at 22 degrees C on the repair of sublethal, potentially lethal and potentially neoplastic transforming damage in gamma-irradiated HeLa x skin fibroblast human hybrid cells

    International Nuclear Information System (INIS)

    Redpath, J.L.; Antoniono, R.J.; Mendonca, M.S.; Sun, C.

    1994-01-01

    The effect of postirradiation holding at 22 degrees C on cell growth, progression of cells through the cell cycle, and the repair of sublethal, potentially lethal and potentially neoplastic transforming damage in γ-irradiated HeLa x skin fibroblast human hybrid cells has been examined. Cell growth and cell cycle progression were essentially stopped at this reduced temperature. Cell survival was dramatically reduced by holding confluent cultures for 6 h at 22 degrees C, as opposed to 37 degrees C, after 7.5 Gy γ radiation delivered at a rate of 2 Gy/min. Return of the cells to 37 degrees C for 6 h after holding at 22 degrees C did not result in increased survival. A similar effect was obtained when the cells were held at 22 degrees C between split-dose irradiation of log-phase cultures where no increase in survival was observed over a split-dose interval of 4 h. In this case a partial increase in survival was observed upon returning the cells to 37 degrees C for 3 h after holding at 22 degrees C for the first 3 h of the split-dose interval. Neoplastic transformation frequency was not enhanced by holding confluent cultures for 6 h at 22 degrees C after 7.5 Gy γ radiation. This is consistent with previous observations that misrepair of potentially neoplastic transforming damage already occurs at 37 degrees C. The overall results are interpreted in terms of the reduced temperature favoring misrepair, rather than inhibition of repair, of sublethal, potentially lethal and potentially transforming radiation damage. 24 refs., 5 figs., 3 tabs

  2. Morphological and optical properties of silicon thin films by PLD

    International Nuclear Information System (INIS)

    Ayouchi, R.; Schwarz, R.; Melo, L.V.; Ramalho, R.; Alves, E.; Marques, C.P.; Santos, L.; Almeida, R.; Conde, O.

    2009-01-01

    Silicon thin films have been prepared on sapphire substrates by pulsed laser deposition (PLD) technique. The films were deposited in vacuum from a silicon target at a base pressure of 10 -6 mbar in the temperature range from 400 to 800 deg. C. A Q-switched Nd:YAG laser (1064 nm, 5 ns duration, 10 Hz) at a constant energy density of 2 J x cm -2 has been used. The influence of the substrate temperature on the structural, morphological and optical properties of the Si thin films was investigated. Spectral ellipsometry and atomic force microscopy (AFM) were used to study the thickness and the surface roughness of the deposited films. Surface roughness values measured by AFM and ellipsometry show the same tendency of increasing roughness with increased deposition temperature

  3. Developement of multimedial web portal for PLD course tutorials

    OpenAIRE

    Fíla, Lukáš

    2009-01-01

    Tato práce popisuje principy tvorby statických webových stránek a nejpoužívanější metody používané při tvorbě stránek dynamických. Seznámíte se s jazyky HTML, CSS, PHP, JavaScript a databázemi MySQL. Dále jsou zpracovány základní informace o problematice programovatelných logických obvodů PLD a FPGA. This paper describes the principles of the creation of static Web pages and the most common methods used in creating dynamic pages. Acquainted with the languages of HTML, CSS, PHP, JavaScript ...

  4. Influence of agents that enhance lethal effects of radiation on the damage to bacterial membranes by x rays and ultraviolet light

    International Nuclear Information System (INIS)

    Cancelliere, G.; Giacchi, P.; Misiti-Dorello, P.; Quintiliani, M.

    1975-01-01

    Radiation damage to the cell membrane of E. coli B/r was evaluated by the release of intracellular K + ions as a function of radiation dose. It was found that x-ray-induced K + loss was (i) not affected by the presence of oxygen; (ii) enhanced by sodium iodide (NaI), iodoacetic acid (IAA), iodopropionic acid (IPA), and iodoacetamide (IAM) when cells were irradiated while in equilibrium with air; (iii) still enhanced by NaI, but not by IAM, when cell suspensions were bubbled with N 2 or O 2 before and during irradiation; (iv) decreased by N-ethylmaleimide (NEM) under any irradiation conditions. It was also found that both NEM and iodine-containing compounds protected cells from membrane damage caused by exposure to uv light. Parallel experiments carried out on cell survival confirmed the lack of correlation between the damage responsible for the loss of intracellular K + and that responsible for cell killing

  5. [Association of polymorphisms of NAPE-PLD and FAAH genes with schizophrenia in Chinese Han population].

    Science.gov (United States)

    Si, Peiru; Liu, Shulian; Tong, Dongxiao; Cheng, Meijin; Wang, Liwen; Cheng, Xiaoli

    2018-04-10

    To assess the association of polymorphisms of N-acyl-phosphatidylethanolamine-phospholipase D (DAPE-PLD) and fatty acid amide hydrolase (FAAH) genes, as well as their interaction, with schizophrenia. Polymorphisms of NAPE-PLD rs12540583 and FAAH rs324420, rs2295633, and rs6429600 were determined with PCR - restriction fragment length polymorphism assay and Sanger sequencing. The genotypes of 345 subjects of Han Chinese origin diagnosed with schizophrenia and a 403 controls were compared. The results were analyzed with SPSS 17.0, and the interaction of the two genes was analyzed using a multifactor dimensionality reduction (MDR) method. The frequency of NAPE-PLD rs12540583 polymorphism was significantly different between the two groups under both dominant and additive models (χ2=17.18 vs. χ2=18.94, P<0.0125). The frequencies of AC genotype and C allele of the patient group at rs12540583 were higher than those of the controls, and the interaction of NAPE-PLD and FAAH was associated with schizophrenia. A four-loci model (rs12540583, rs324420, rs2295633 and rs6429600) can best model the interaction between NAPE-PLD and FAAH. The AC genotype and C allele of NAPE-PLD rs12540583 locus are risk factors for schizophrenia, and the interaction between NAPE-PLD rs12540583 and FAAH rs324420, rs2295633 and rs6429600 is associated with schizophrenia.

  6. Manajemen Pelayanan Mahasiswa Difabel di PLD UIN Sunan Kalijaga Berbasis Komputer Job Access with Speech (JAWS

    Directory of Open Access Journals (Sweden)

    Kuzaemah

    2017-05-01

    Full Text Available This research attempt to meganalisis how management of computer service JAWS for student of blind at PLD UIN Sunan Kalijaga Yogyakarta. This research is a field research using qualitative approach. Data collection is done through observation, interview, and documentation. The results of this study indicate that JAWS Computer Service Management in PLD UIN Sunan Kalijaga Yogyakarta includes several management functions, the first, the planning of the PLD chairman determines the schedule of activities. Second, the organizing of the PLD chair divides the duties of each position. Third, the implementation of all PLD members who have been tasked by the leader perform their duties respectively. Fourth, supervision of all activities in the PLD is always monitored and held a regular meeting to find out the problems faced so that can be solved together. Benefits of the existence of JAWS computer service is to increase knowledge of technology for blind students and train the independence of blind students in doing lecture tasks that blessed with typing as well as paper assignments, thesis and so on. The factors supporting the implementation of JAWS computer service that is the spirit of learning blind students and the help of PLD volunteers. For the inhibiting factor is the number of JAWS computers are very limited so they have to take turns in using it

  7. Reconciling the conservation of the purple swamphen (Porphyrio porphyrio and its damage in Mediterranean rice fields through sustainable non-lethal techniques

    Directory of Open Access Journals (Sweden)

    Rubén Moreno-Opo

    2018-04-01

    Full Text Available Resolving human–wildlife conflicts requires the assessment and implementation of appropriate technical measures that minimize negative impacts on socio-economic uses, including agriculture, and ensure the adequate protection of biological diversity. Rice paddies are widely distributed in the western Mediterranean region. Because of their high productivity, they can be a good habitat for waterbirds, including the purple swamphen Porphyrio porphyrio, particularly in areas where natural wetlands have been removed or reduced. As a result of its population growth, there have been increasing levels of damage caused by this species in rice fields due to stem-cutting and opening of bald patches in rice fields. With the aim of reducing damage, we evaluated the effectiveness of passive and active measures that would limit access to rice fields and deter/scare away purple swamphens in affected areas of the Ebro Delta (NE Spain. We selected the techniques according to the growth phase of rice and the activity of birds in the rice fields (perimeter fences and clearing vegetation around the rice plots during sprouting and growing phases, and falconry at maturation. There were positive results during the sprouting and growing phases thanks to fences and clearing vegetation, reducing the affected area by 37.8% between treatment and control plots. This would mean an economic savings of 18,550 €/year in compensation payments by regional administrations including the investment in implementing and maintaining passive protection measures. Active deterrence through falconry did not reduce the level of damage. The analysis of purple swamphen home range, activity centers (centroids, and the proportion of locations in and outside of rice fields showed no differences before and after dissuasive practices. These results were influenced by multiple concurrent factors including weather, the structural configuration of the rice plots and their location. In summary, we

  8. Maternal Antibody-Mediated Disease Enhancement in Type I Interferon-Deficient Mice Leads to Lethal Disease Associated with Liver Damage.

    Directory of Open Access Journals (Sweden)

    Julia María Martínez Gómez

    2016-03-01

    Full Text Available Epidemiological studies have reported that most of the severe dengue cases occur upon a secondary heterologous infection. Furthermore, babies born to dengue immune mothers are at greater risk of developing severe disease upon primary infection with a heterologous or homologous dengue virus (DENV serotype when maternal antibodies reach sub-neutralizing concentrations. These observations have been explained by the antibody mediated disease enhancement (ADE phenomenon whereby heterologous antibodies or sub-neutralizing homologous antibodies bind to but fail to neutralize DENV particles, allowing Fc-receptor mediated entry of the virus-antibody complexes into host cells. This eventually results in enhanced viral replication and heightened inflammatory responses. In an attempt to replicate this ADE phenomenon in a mouse model, we previously reported that upon DENV2 infection 5-week old type I and II interferon (IFN receptors-deficient mice (AG129 born to DENV1-immune mothers displayed enhancement of disease severity characterized by increased virus titers and extensive vascular leakage which eventually led to the animals' death. However, as dengue occurs in immune competent individuals, we sought to reproduce this mouse model in a less immunocompromised background. Here, we report an ADE model that is mediated by maternal antibodies in type I IFN receptor-deficient A129 mice. We show that 5-week old A129 mice born to DENV1-immune mothers succumbed to a DENV2 infection within 4 days that was sub-lethal in mice born to naïve mothers. Clinical manifestations included extensive hepatocyte vacuolation, moderate vascular leakage, lymphopenia, and thrombocytopenia. Anti-TNFα therapy totally protected the mice and correlated with healthy hepatocytes. In contrast, blocking IL-6 did not impact the virus titers or disease outcome. This A129 mouse model of ADE may help dissecting the mechanisms involved in dengue pathogenesis and evaluate the efficacy of

  9. IZO deposited by PLD on flexible substrate for organic heterostructures

    Science.gov (United States)

    Socol, M.; Preda, N.; Stanculescu, A.; Breazu, C.; Florica, C.; Rasoga, O.; Stanculescu, F.; Socol, G.

    2017-05-01

    In:ZnO (IZO) thin films were deposited on flexible plastic substrates by pulsed laser deposition (PLD) method. The obtained layers present adequate optical and electrical properties competitive with those based on indium tin oxide (ITO). The figure of merit (9 × 10-3 Ω-1) calculated for IZO layers demonstrates that high quality coatings can be prepared by this deposition technique. A thermal annealing (150 °C for 1 h) or an oxygen plasma etching (6 mbar for 10 min.) were applied to the IZO layers to evaluate the influence of these treatments on the properties of the transparent coatings. Using vacuum evaporation, organic heterostructures based on cooper phthalocyanine (CuPc) and 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) were deposited on the untreated and treated IZO layers. The optical and electrical properties of the heterostructures were investigated by UV-Vis, FTIR and current-voltage ( I- V) measurements. For the heterostructure fabricated on IZO treated in oxygen plasma, an improvement in the current value with at least one order of magnitude was evidenced in the I- V characteristics recorded in dark conditions. Also, an increase in the current value for the heterostructure deposited on untreated IZO layer can be achieved by adding an organic layer such as tris-8-hydroxyquinoline aluminium (Alq3).

  10. PLD of X7R for thin film capacitors

    International Nuclear Information System (INIS)

    Hino, Takanori; Matsumoto, Noriyuki; Nishida, Minoru; Araki, Takao

    2008-01-01

    Thin film capacitors with a thickness of 200 nm were prepared on SrTiO 3 (1 0 0), (1 1 0) and (1 1 1) single crystal substrates at a temperature of 973 K by pulsed laser deposition (PLD) using a KrF excimer laser in an O 2 -O 3 atmosphere with a gas pressure of 1 Pa using an X7R sintered target. As a result, perovskite BaTiO 3 solid solution films were obtained. In the X7R thin films on (1 0 0) and (1 1 0) SrTiO 3 , only diffraction peaks with strong intensities from BaTiO 3 (1 0 0) and (1 1 0), respectively, were observed. X7R films on SrTiO 3 (1 1 1) were grown epitaxially oriented to the crystal plane direction of the substrate by inserting an initial homoepitaxial SrTiO 3 layer with a thickness of 4 nm. The X7R/SrTiO 3 film capacitors yielded a large volumetric efficiency of 50 μF/mm 3 and a temperature coefficient of capacitance (TCC) of -1.3% to 1.3% which satisfies the EIA standard specifications for X7R

  11. Putting the PLE into PLD: Virtual Professional Learning and Development

    Directory of Open Access Journals (Sweden)

    Hazel Owen

    2014-05-01

    Full Text Available The range of affordances that a virtual environment offers can provide opportunities for more formal Professional Learning and Development (PLD that has flexibility of choice, time and approach for educators. It was this potential that inspired the design of the Virtual Professional Learning and Development (VPLD program that was instigated in October 2009 by the NZ Ministry of Education, who also funded the project. The findings from the pilot of the VPLD program in 2010 indicated that when professional learning was situated within the practitioner's context, and with complementary, easily-accessible opportunities for sharing of practice within an online Community of Practice, participants demonstrated high levels of engagement as well as changes in their own teaching practice. The VPLD Programme was facilitated and researched again during 2011, building on findings from 2010. Findings to date suggest that the educators developed a sense of self-efficacy that motivated them to trial alternative approaches, and to initiate iterative cycles of trial, error, and improvement.

  12. Monalysin, a novel ß-pore-forming toxin from the Drosophila pathogen Pseudomonas entomophila, contributes to host intestinal damage and lethality.

    Directory of Open Access Journals (Sweden)

    Onya Opota

    2011-09-01

    Full Text Available Pseudomonas entomophila is an entomopathogenic bacterium that infects and kills Drosophila. P. entomophila pathogenicity is linked to its ability to cause irreversible damages to the Drosophila gut, preventing epithelium renewal and repair. Here we report the identification of a novel pore-forming toxin (PFT, Monalysin, which contributes to the virulence of P. entomophila against Drosophila. Our data show that Monalysin requires N-terminal cleavage to become fully active, forms oligomers in vitro, and induces pore-formation in artificial lipid membranes. The prediction of the secondary structure of the membrane-spanning domain indicates that Monalysin is a PFT of the ß-type. The expression of Monalysin is regulated by both the GacS/GacA two-component system and the Pvf regulator, two signaling systems that control P. entomophila pathogenicity. In addition, AprA, a metallo-protease secreted by P. entomophila, can induce the rapid cleavage of pro-Monalysin into its active form. Reduced cell death is observed upon infection with a mutant deficient in Monalysin production showing that Monalysin plays a role in P. entomophila ability to induce intestinal cell damages, which is consistent with its activity as a PFT. Our study together with the well-established action of Bacillus thuringiensis Cry toxins suggests that production of PFTs is a common strategy of entomopathogens to disrupt insect gut homeostasis.

  13. ETOH inhibits embryonic neural stem/precursor cell proliferation via PLD signaling

    International Nuclear Information System (INIS)

    Fujita, Yuko; Hiroyama, Masami; Sanbe, Atsushi; Yamauchi, Junji; Murase, Shoko; Tanoue, Akito

    2008-01-01

    While a mother's excessive alcohol consumption during pregnancy is known to have adverse effects on fetal neural development, little is known about the underlying mechanism of these effects. In order to investigate these mechanisms, we investigated the toxic effect of ethanol (ETOH) on neural stem/precursor cell (NSC) proliferation. In cultures of NSCs, phospholipase D (PLD) is activated following stimulation with epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2). Exposure of NSCs to ETOH suppresses cell proliferation, while it has no effect on cell death. Phosphatidic acid (PA), which is a signaling messenger produced by PLD, reverses ETOH inhibition of NSC proliferation. Blocking the PLD signal by 1-butanol suppresses the proliferation. ETOH-induced suppression of NSC proliferation and the protective effect of PA for ETOH-induced suppression are mediated through extracellular signal-regulated kinase signaling. These results indicate that exposure to ETOH impairs NSC proliferation by altering the PLD signaling pathway

  14. Quick screening for new flux pinning materials in YBCO films with the combinatorial-PLD method

    International Nuclear Information System (INIS)

    Yoshimura, T.; Ichino, Y.; Yoshida, Y.; Takai, Y.; Kita, R.; Suzuki, K.; Takeuchi, T.

    2011-01-01

    An effective way to improve the superconducting properties in REBa 2 Cu 3 O y (REBCO) films under a magnetic field is to dope artificial pinning centers (APC). The pinning performance depends on the content of the APC materials. Usually, the optimal APC content is explored by preparing films one at a time from the REBCO target using different APC material content, which is an extremely time-consuming process. The combinatorial-PLD (C-PLD) method allowed us to prepare films that continuously changed in composition across a single substrate. In this study, we used the C-PLD method to prepare BaSnO 3 (BSO)-doped YBCO films. The films were deposited on SrTiO 3 substrate using a fourth-harmonic Nd:YAG laser. From the results of the J c -B curves at 77 K and B//c, the film that contained 3.2 vol.% of BSO exhibited the best pinning performance in this study. We showed that the C-PLD method was efficient for quick screening of the optimal APC content with only one deposition. We also used the C-PLD method to explore new APC materials, and proved that it can quickly evaluate the new APC materials Ba 3 Cu 3 In 4 O 12 and BaTbO 3 .

  15. PLD2 has both enzymatic and cell proliferation-inducing capabilities, that are differentially regulated by phosphorylation and dephosphorylation

    International Nuclear Information System (INIS)

    Henkels, Karen M.; Short, Stephen; Peng, Hong-Juan; Fulvio, Mauricio Di; Gomez-Cambronero, Julian

    2009-01-01

    Phospholipase D2 (PLD2) overexpression in mammalian cells results in cell transformation. We have hypothesized that this is due to an increase of de novo DNA synthesis. We show here that overexpression of PLD2-WT leads to an increased DNA synthesis, as measured by the expression levels of the proliferation markers PCNA, p27 KIP1 and phospho-histone-3. The enhancing effect was even higher with phosphorylation-deficient PLD2-Y179F and PLD2-Y511F mutants. The mechanism for this did not involve the enzymatic activity of the lipase, but, rather, the presence of the protein tyrosine phosphatase CD45, as silencing with siRNA for CD45 abrogated the effect. The two Y→F mutants had in common a YxN consensus site that, in the phosphorylated counterparts, could be recognized by SH2-bearing proteins, such as Grb2. Even though Y179F and Y511F cannot bind Grb2, they could still find other protein partners, one of which, we have reasoned, could be CD45 itself. Affinity purified PLD2 is indeed activated by Grb2 and deactivated by CD45 in vitro. We concluded that phosphorylated PLD2, aided by Grb2, mediates lipase activity, whereas dephosphorylated PLD2 mediates an induction of cell proliferation, and the specific residues involved in this newly discovered regulation of PLD2 are Y 179 and Y 511 .

  16. Influence of ion bombardment on growth and properties of PLD created DLC films

    Czech Academy of Sciences Publication Activity Database

    Jelínek, Miroslav; Písařík, Petr; Kocourek, Tomáš; Zemek, Josef; Lukeš, J.

    2013-01-01

    Roč. 110, č. 4 (2013), s. 943-947 ISSN 0947-8396 R&D Projects: GA MŠk LD12069 Institutional research plan: CEZ:AV0Z10100522 Keywords : DLC * ion bombardment * sp3 /sp2 * thin films * PLD Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.694, year: 2013

  17. Antibacterial properties of Ag-doped hydroxyapatite layersprepared by PLD method

    Czech Academy of Sciences Publication Activity Database

    Jelínek, Miroslav; Kocourek, Tomáš; Jurek, Karel; Remsa, Jan; Mikšovský, Jan; Weiserová, Marie; Strnad, J.; Luxbacher, T.

    2010-01-01

    Roč. 101, č. 4 (2010), s. 615-620 ISSN 0947-8396 Institutional research plan: CEZ:AV0Z10100522; CEZ:AV0Z50200510 Keywords : antibacterial properties, * PLD * layers * silver -doped Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.765, year: 2010

  18. PLD prepared nanostructured Pt-CeO2 thin films containing ionic platinum

    Czech Academy of Sciences Publication Activity Database

    Vorokhta, M.; Khalakhan, I.; Matolínová, I.; Nováková, J.; Haviar, M.; Lančok, Ján; Novotný, Michal; Yoshikawa, H.; Matolín, V.

    2017-01-01

    Roč. 396, Feb (2017), s. 278-283 ISSN 0169-4332 Institutional support: RVO:68378271 Keywords : PLD * cerium oxide * ionic platinum * HAXPES Subject RIV: BM - Solid Matter Physics ; Magnetism OBOR OECD: Condensed matter physics (including formerly solid state physics, supercond.) Impact factor: 3.387, year: 2016

  19. Modified sol–gel preparation of LiNbO.sub.3./sub. target for PLD

    Czech Academy of Sciences Publication Activity Database

    Jakeš, V.; Rubešová, V.; Erben, J.; Nekvindová, P.; Jelínek, Miroslav

    2013-01-01

    Roč. 35, č. 12 (2013), s. 2540-2543 ISSN 0925-3467 R&D Projects: GA ČR(CZ) GAP106/10/1477 Institutional support: RVO:68378271 Keywords : lithium niobate * PLD * sol–gel * Pechini polyesterification * transmittance Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.075, year: 2013 http://dx.doi.org/10.1016/j.optmat.2013.07.019

  20. PLD prepared bioactive BaTiO.sub.3./sub. films on TiNb implants

    Czech Academy of Sciences Publication Activity Database

    Jelínek, Miroslav; Vaněk, Přemysl; Tolde, Z.; Buixaderas, Elena; Kocourek, Tomáš; Studnička, Václav; Drahokoupil, Jan; Petzelt, Jan; Remsa, Jan; Tyunina, Marina

    2017-01-01

    Roč. 70, Jan (2017), s. 334-339 ISSN 0928-4931 R&D Projects: GA ČR(CZ) GA15-05864S; GA ČR(CZ) GA15-01558S Institutional support: RVO:68378271 Keywords : BaTiO 3 * thin films * pld * implants * TiNb * ferroelectricity Subject RIV: BM - Solid Matter Physics ; Magnetism OBOR OECD: Condensed matter physics (including formerly solid state physics, supercond.)

  1. Remarkable progress in fabricating RE123 coated conductors by IBAD/PLD technique at Fujikura

    Energy Technology Data Exchange (ETDEWEB)

    Igarashi, M; Kakimoto, K; Hanyu, S; Tashita, C; Hayashida, T; Hanada, Y; Fujita, S; Morita, K; Nakamura, N; Sutoh, Y; Kutami, H; Iijima, Y; Saitoh, T, E-mail: m_igarashi@fujikura.co.j [Fujikura Ltd., 1440, Mutsuzaki, Sakura, Chiba, 285-8550 (Japan)

    2010-06-01

    Increase of production rate and improvement of quality for RE123 coated conductors have been tried. In-plane texturing of MgO was attempted by the IBAD system with the world largest ion source. As a result of optimizing condition in large deposition area, the dramatically high throughput of 1000 m / h was realized to obtain the IBAD-MgO with {Delta}{phi} < 10{sup 0}. Furthermore, simple buffer structure was demonstrated. Well textured CeO{sub 2} layer with {Delta}{phi} of around 4{sup 0} was obtained by directly deposited on IBAD-MgO layer in spite of large lattice mismatch of 28% between CeO{sub 2} and MgO. Several over 100 m buffer substrates with the architecture of / PLD-CeO{sub 2} (60 m / h) / IBAD-MgO (333{approx}1000 m / h) / Y{sub 2}O{sub 3} (500 m / h) / Al{sub 2}O{sub 3} (150 m / h) / Hastelloy / were already prepared. On these production substrates, GdBCO layer was deposited by the large PLD system at high throughput. The 260 m long GdBCO tape with I{sub c} > 600 A except some locations was obtained at the throughput of 15 m / h. In addition to the speed-up, the very high I{sub c} of 1040 A was also achieved by the hot-wall heating PLD system.

  2. Study on the diagnostic value of determination of serum IV-C, PC III, HA, LN and PLD concentrations for hepatic fibrosis in patients with B hepatitis of various types

    International Nuclear Information System (INIS)

    Li Zhuocheng; Chen Jianxiong; Xiong Ying

    2004-01-01

    Objective: To investigate the changes of serum levels of collagen type IV(IV-C), procollagen type III (PC III), hyaluronic acid (HA), laminin (LN) and prolidase (PLD) and their relationship with hepatic fibrosis in patients with B hepatitis of different types. Methods: Serum levels of IV-C, PC III, HA, LN and PLD were measured with RIA in 39 controls and 103 patients with HBV infection of various types (including acute hepatitis AH n=19, chronic persistent hepatitis CPH n=29, Chronic active hepatitis CAH n=25 and liver cirrhosis LH n=30. Degree of hepatic fibrosis (Grade 0-4) was ascertained with liver biopsy in 35 patients (CAH16, LC19) and correlationship with the corresponding levels of these 5 serum markers was steadied. Results: 1) Serum levels of IV-C, PC III, HA, LN and PLD were significantly higher in patients with CAH and LC than those in other patients and controls (P 0.05). 3) Serum levels of these markers were all positively correlated with the degree of hepatic fibrosis noted in the biopsy specimens obtained from patients with CAH (n=16) and LC (n=19) (r=+0.64 - + 0.89, P<0.01). Conclusion: Serum levels of these markers could reflect the degree of hepatic fibrosis and severity of liver damage; determination of which was of diagnostic and even prognostic value. HA and LN appeared to be better correlated with degree of hepatic fibrosis than the remaining three markers did. (authors)

  3. PLD-Repair after ''holding'' of rodent cell cultures: A critical annotation

    International Nuclear Information System (INIS)

    Stevenson, A.F.G.; Lange, C.S.

    1987-01-01

    The radiosensitivity of cells in vitro has been reported to be influenced by culture-conditions both before and after exposure to ionising radiations. The effect of ''Stationary-Holding'' and/or delayed plating on the repair of potentially lethal damage (PLDR) are such examples. The so-called Stationary or Plateau-Phase of commonly used cell lines like the V79 are often quiescent (non-mitotic). The authors analysis of the V79 ''Plateau-Phase'' (S-phase cytocide through VrUdR incorporation with FuDR block and light exposure) reveals that the cultures have merely reached a state of maximal permissible density and are, in fact, in kinetic equilibrium with at least half the population of cells, even in densely confluent cultures, going through cycle. Attempts at holding the cells from cycling (through nutrient-depletion and serum-privation) were unsuccessful, although the turn-over-rate was reduced. Their assays for X-irradiated clonogenic survivors after attempted holding combined with delayed plating (DP) showed differences in the survival curves for exponentially growing (Log) and confluent cultures, Although DP improved survival in general, it abolished the shoulder in Log cultures. These observations may explain why most PLDR is seen in the second and lower survival-decades. The significance of the persistent cycling fraction in the interpretation of PLDR after delayed plating must be considered

  4. Fabrication of long REBCO coated conductors by PLD process in China

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yijie, E-mail: yjli@sjtu.edu.cn [Key Laboratory of Artificial Structure and Quantum Control, Ministry of Education, Department of Physics and Astronomy, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 20040 (China); Shanghai Superconductor Technology Corporation, Ltd, 28 Jiang Chuan Road, Shanghai 200240 (China); Liu, Linfei; Wu, Xiang [Key Laboratory of Artificial Structure and Quantum Control, Ministry of Education, Department of Physics and Astronomy, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 20040 (China)

    2015-11-15

    Highlights: • SJTU fabricated 100 m long class CC tapes with over 300 A/cm on RABiTS tapes in 2011. • 100 m long CC tapes with 500 A/cm have been routinely fabricated on IBAD-MgO tapes. • The process optimization for kilometer long coated conductor tapes is underway. - Abstract: In China, the First National Key Project on CC Program started in 2009, which was focused on developing hundred meter long class CC tapes based on PLD/RABiTS processes. In this project, SJTU mainly worked on all of functional layer deposition process development. Northwest Institute for Non-ferrous Metal Research worked on RABiTS tape fabrication. At the end of the project in 2011, SJTU successfully fabricated hundred meter long CC tapes with over 300 A/cm (at 77 K, self field) on RABiTS tapes. To develop high performance CC tapes by PLD/IBAD-MgO processes, a pilot CC fabrication line was set up at Shanghai Superconductor Technology Corporation, Ltd. in 2013. High quality long REBCO coated conductors have been successfully fabricated on flexible polycrystalline metal tapes by PLD plus magnetron sputter and IBAD processes. Under optimized conditions, the IBAD-MgO layers showed pure (0 0 1) orientation and excellent in-plane texture. The in-plane phi-scan rocking curve is 4–6 degrees. AFM observation showed MgO layer had very smooth surface. The RMS is less 1 nm. On the textured MgO layer, sputter deposited single cerium oxide cap-layer showed pure (0 0 1) orientation and excellent in-plane texture of 4–6 degree. Reel-to-reel PLD process with high deposition rate was already scaled up to 100 m/h tape speed. Hundred meters long coated conductor tapes with over 500 A/cm performance have been routinely fabricated. And now, the process optimization for kilometer long coated conductor tapes is underway.

  5. Histopathological effects of lethal and sub-lethal concentrations of ...

    African Journals Online (AJOL)

    The histopathological effects of lethal and sub-lethal concentrations of glyphosate on African catfish Clarias gariepinus were investigated. C. gariepinus juveniles were assessed in a static renewal bioassay for 96 hours (acute toxicity) and 28 days (chronic toxicity) using varying concentrations (0.0 mg/l 20.0 mg/l, 30.0 mg/l, ...

  6. Suicide Lethality: A Concept Analysis.

    Science.gov (United States)

    DeBastiani, Summer; De Santis, Joseph P

    2018-02-01

    Suicide is a significant health problem internationally. Those who complete suicide may have different behaviors and risk factors than those who attempt a non-fatal suicide. The purpose of this article is to analyze the concept of suicide lethality and propose a clear definition of the concept through the identification of antecedents, attributes, and consequences. A literature search for articles published in the English language between 1970 and 2016 was conducted using MEDLINE, the Cochrane Library, Pubmed, Psychlit, Ovid, PsycINFO, and Proquest. The bibliographies of all included studies were also reviewed to identify additional relevant citations. A concept analysis was conducted on the literature findings using six stages of Walker and Avant's method. The concept analysis differentiated between suicide, lethality, suicidal behavior, and suicide lethality. Presence of a suicide plan or a written suicide note was not found to be associated with the majority of completed suicides included in the definition of suicide lethality. There are a few scales that measure the lethality of a suicide attempt, but none that attempt to measure the concept of suicide lethality as described in this analysis. Clarifying the concept of suicide lethality encourages awareness of the possibility of different suicidal behaviors associated with different suicide outcomes and will inform the development of future nursing interventions. A clearer definition of the concept of suicide lethality will guide clinical practice, research, and policy development aimed at suicide prevention.

  7. Development of long GdBCO coated conductor using the IBAD/MPMT-PLD method

    International Nuclear Information System (INIS)

    Ibi, A; Fukushima, H; Yamada, Y; Miyata, S; Kuriki, R; Takahashi, K; Shiohara, Y

    2006-01-01

    We have developed long GdBa 2 Cu 3 O 7-X (GdBCO) coated conductors by a multi-plume and multi-turn pulsed laser deposition (MPMT-PLD) method and have successfully fabricated 32 and 60.7 m long GdBCO coated conductors with a high critical current, I c , and high deposition rate. The I c of the 32 and 60.7 m long GdBCO coated conductors were 205 A (J c = 1.36 MA cm -2 ) and 183 A (J c = 1.45 MA cm -2 ), respectively, at 77 K and 0 T. In addition, they exhibited higher I c values in a magnetic field than a YBa 2 Cu 3 O 7-X (YBCO) coated conductor: typically 20 A at 77 K and 3 T while the value for a YBCO coated conductor is 8 A. These high I c values are due to the smaller number of a-axis oriented grains in GdBCO than in YBCO. Furthermore, the speed of production of the GdBCO layer was increased to 10 m h -1 while that of the former YBCO coated conductor was 3.75 m h -1 . The material yield of long GdBCO layers using the MPMT-PLD method was about 26-28%. The high I c of GdBCO in a magnetic field, the high production rate and the high material yield are promising for applications

  8. PERAN RELAWAN TERHADAP KEMANDIRIAN DIFABEL DI PLD UIN SUNAN KALIJAGA YOGYAKARTA

    Directory of Open Access Journals (Sweden)

    Neni Rosita

    2015-12-01

    Full Text Available Fakta difabel di UIN Sunan Kalijaga belum semua bisa mandiri, disebabkan ada beberapa hal yang tidak dapat dilakukan sendiri seperti mencari buku diperpustakaan, mengedit tugas untuk difabel netra. Oleh karena itu, mahasiswa difabel membutuhkan peranan relawan, dalam proses menjalankan pendidikan di perguruan tinggi, yang aksesibilitasnya belum tercipta secara holistic dan konprehensif. Berdasarkan paparan tersebut maka penting untuk dilakukannya  penelitian terkait dengan bagaimana peran relawan Pusat Layanan Difabel (PLD UIN Sunan Kalijaga dan bagaimana kemandirian yang dimiliki oleh mahasiswa difabel UIN Sunan Kalijaga yang bergabung di PLD. Penelitian ini menggunakan metode kualitatif, dengan jenis penelitian lapangan, data primier berupa observasi dan wawancara beberapa relawan dan mahasiswa difabel yang juga sebagai subjek dalam penelitian ini. Adapun hasil dari penelitian ini adalah: Pertama, Peran relawan di Pusat Layanan Difabel UIN Sunan Kalijaga yakni pendampingan kuliah untuk difabel rungu dan pendampingan ujian untuk difabel netra serta pengenalan mobilitas kampus terhadap semua difabel. Sehingga dapat memudahkan dalam mengenal lingkungan di UIN Sunan Kalijaga. Relawan berperan dalam menjembatani difabel agar dapat menyuarakan hak­haknya di hadapan publik. Kedua, Kemandirian difabel terlihat pada kemandirian belajar di kampus UIN Sunan Kalijaga yang dapat mengikuti kuliah dan pelajaran dengan baik. Baik dalam menyelesaikan dan mengedit tugas, membaca buku, dan keperpustakaan. Difabel yang mandiri mampu bersaing dan selalu optimis dalam setiap situasi yang dihadapi.

  9. Final Report and Documentation for the PLD11 Multipurpose Programmable Logic VME Board Design

    International Nuclear Information System (INIS)

    Hutchinson, Robert L.; Pierson, Lyndon G.; Robertson, Perry J.; Tarman, Thomas D.; Witzke, Edward L.

    1999-01-01

    The PLD11 board is a 9U VME board containing 11 Altera 10K100 Programmable Logic Devices, controlled impedance clock tree, VME interface, programming inteface, 0C3 (155 Mbps) interface and serial port. The 11 Altera 10K100 Programmable Logic Devices arranged to provide four 96 bit wide buses for a total of 384 parallel digital data lines in and out of the board that can operate up to 100 Mhz for a aggrigate throughput of 38.4 Gpbs. The 14.44'' X 15.75'' board has over 1.1 million programmable gates that can be programmed through a serial interace. The board contains a clock reference and 50 ohm clock distribution tree that can drive each of the eleven 10K100 devices with two critically timed clock references. Five external clock references can be used to drive five additional PLD 11 boards for a total of six boards operating all from the same synchronous clock reference. A system of six boards provides just under 7 million programmable gates

  10. Nanostructured PLD-grown gadolinia doped ceria: Chemical and structural characterization by transmission electron microscopy techniques

    DEFF Research Database (Denmark)

    Rodrigo, Katarzyna Agnieszka; Wang, Hsiang-Jen; Heiroth, Sebastian

    2011-01-01

    The morphology as well as the spatially resolved elemental and chemical characterization of 10 mol% gadolinia doped ceria (CGO10) structures prepared by pulsed laser deposition (PLD) technique are investigated by scanning transmission electron microscopy accompanied with electron energy loss spec......, indicate apparent variation of the ceria valence state across and along the film. No element segregation to the grain boundaries is detected. These results are discussed in the context of solid oxide fuel cell applications.......The morphology as well as the spatially resolved elemental and chemical characterization of 10 mol% gadolinia doped ceria (CGO10) structures prepared by pulsed laser deposition (PLD) technique are investigated by scanning transmission electron microscopy accompanied with electron energy loss...... spectroscopy and energy dispersive X-ray spectroscopy. A dense, columnar and structurally inhomogeneous CGO10 film, i.e. exhibiting grain size refinement across the film thickness, is obtained in the deposition process. The cerium M4,5 edges, used to monitor the local electronic structure of the grains...

  11. An RBS study of thin PLD and MOCVD strontium copper oxide layers

    Energy Technology Data Exchange (ETDEWEB)

    Kantor, Z. [Institute of Physics, University of Pannonia, H-8200 Veszprem (Hungary); Papadopoulou, E.L.; Aperathitis, E. [Inst. Electronic Struture and Laser, Foundation for Research and Technology - Hellas, P.O. Box 1527, Heraklion 71110 (Greece); Deschanvres, J.-L. [LMPG INP Grenoble-Minatec, BP 257, 38016 Grenoble Cedex 1 (France); Somogyi, K. [MicroVacuum Ltd., Kerekgyarto u.: 10, H-1147 Budapest (Hungary)], E-mail: karoly.somogyi@microvacuum.com; Szendro, I. [MicroVacuum Ltd., Kerekgyarto u.: 10, H-1147 Budapest (Hungary)

    2008-09-30

    Strontium copper oxide (SCO) has been studied as p-type transparent (VIS) conductive oxide material. Also theoretical studies suggested p-type conductivity of the SrCu{sub 2}O{sub 2} composition. SCO thin layers, with thicknesses of 30-2000 nm, were deposited on glass and silicon substrates both by pulsed laser deposition (PLD) and by MOCVD method. The as-grown layers showed high electrical resistance. Due to an annealing process, the resistivity significantly decreased and the layers showed p-type conductivity. Optical transparency measured on samples grown on glass substrates was found about or above 80%, including also thickness dependence. RBS measurements were applied for the determination of the chemical composition profile of the layers. A comparison revealed some specific differences between as-grown and annealed PLD samples. Due to the annealing, the ratio of oxide phases was changed and a vertical inhomogeneity in chemical composition was observed. Our measurements revealed also the influence of the deposition technique and of the substrate.

  12. Radiosensitivity and recovery from radiation damage in cultured CHO cells exposed to hyperthermia at 42.5 or 45.50C

    International Nuclear Information System (INIS)

    Raaphorst, G.P.; Freeman, M.L.; Dewey, W.C.

    1979-01-01

    The effect of hyperthermic treatments (42.5 or 45.5 0 C) on recovery from radiation damage has been examined. Recovery from sublethal damage (SLD) when heat was administered prior to irradiation was not inhibited by small heat treatments survival reduced to 80% by 30 min at 42.5 0 C or 4 min at 45.5 0 C) for either temperature, but recovery was inhibited by larger heat treatments (survival reduced to 10% by 120 min at 42.5 0 C or 15 min at 45.5 0 C). Thus, the effects of 42.5 or 45.5 0 C on recovery from SLD were similar when the heat treatments resulting in equal survival levels were used. Recovery from potentially lethal damage (PLD), as measured by incubation at 20 0 C after a combination of radiation and heat treatments was observed when a small heat treatement (30 min at 42.5 0 C) was given either before or after irradiation. The amount of radiosensitization, i.e., the thermal enhancement ratio (TER), calculated at the survival level of 10 -3 , correlated with the amount of cell killing resulting from the heat exposure alone, irrespective of the temperature at which the cells were treated

  13. Thin films of NdFeB deposited by PLD technique

    International Nuclear Information System (INIS)

    Constantinescu, C.; Scarisoreanu, N.; Moldovan, A.; Dinescu, M.; Petrescu, L.; Epureanu, G.

    2007-01-01

    Neodymium-iron-boron (NdFeB) is a material with important magnetic properties, mostly used in permanent magnet fabrication. Thin layers of NdFeB are needed for miniaturization in electrical engineering, electronics and for high-tech devices. In this paper we applied pulsed lased deposition (PLD) in vacuum for obtaining thin films of NdFeB from stoichiometric targets. The influence of different buffer layers and of the laser parameters (wavelength and fluence) on the NdFeB structures, composition and magnetic properties have been investigated. The obtained structures were characterized by atomic force microscopy (AFM) and optical microscopy. Vibrating sample magnetometry (VSM) has been performed for specific magnetic characterization

  14. Thin films of NdFeB deposited by PLD technique

    Energy Technology Data Exchange (ETDEWEB)

    Constantinescu, C. [National Institute for Laser, Plasma and Radiation Physics, P.O. Box MG 16, RO-077125 Magurele, Bucharest (Romania); Scarisoreanu, N. [National Institute for Laser, Plasma and Radiation Physics, P.O. Box MG 16, RO-077125 Magurele, Bucharest (Romania); Moldovan, A. [National Institute for Laser, Plasma and Radiation Physics, P.O. Box MG 16, RO-077125 Magurele, Bucharest (Romania); Dinescu, M. [National Institute for Laser, Plasma and Radiation Physics, P.O. Box MG 16, RO-077125 Magurele, Bucharest (Romania)]. E-mail: dinescum@ifin.nipne.ro; Petrescu, L. [Department of Electrical Engineering, ' Politehnica' University of Bucharest, 313 Spl. Independentei, 060042 Bucharest (Romania); Epureanu, G. [Department of Electrical Engineering, ' Politehnica' University of Bucharest, 313 Spl. Independentei, 060042 Bucharest (Romania)

    2007-07-31

    Neodymium-iron-boron (NdFeB) is a material with important magnetic properties, mostly used in permanent magnet fabrication. Thin layers of NdFeB are needed for miniaturization in electrical engineering, electronics and for high-tech devices. In this paper we applied pulsed lased deposition (PLD) in vacuum for obtaining thin films of NdFeB from stoichiometric targets. The influence of different buffer layers and of the laser parameters (wavelength and fluence) on the NdFeB structures, composition and magnetic properties have been investigated. The obtained structures were characterized by atomic force microscopy (AFM) and optical microscopy. Vibrating sample magnetometry (VSM) has been performed for specific magnetic characterization.

  15. Composition-ratio control of CuInS{sub 2} films using PLD

    Energy Technology Data Exchange (ETDEWEB)

    Wakita, Kazuki; Po-Han, Tseng; Yoshida, Ryo; Kyan, Issei [Department of Electrical and Electronic Engineering, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016 (Japan); Shim, Yong-Gu [Department of Physics and Electronics, Osaka Prefecture University, 1-1 Gakuencho, Naka-ku, Sakai, Osaka 599-8531 (Japan)

    2017-06-15

    A sulfur-annealing treatment was investigated to control the sulfur content of epitaxial CuInS{sub 2} films grown on GaAs substrate by PLD. The sulfur-annealing treatment improved the surface roughness and film crystallinity. Photoluminescence measurements obtained using the confocal microspectroscopy demonstrated that the annealed films show band-edge emissions over a very large area. Electron-probe microanalysis measurements indicated that the sulfur content of the annealed films was about 50 at.%, and the content of the emission area was more than 50 at.%. Therefore, the sulfur content of epitaxial CuInS{sub 2} films was successfully controlled by the sulfur-annealing treatment. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  16. A Comparison of BLISS and PLD on Low-SNR WASP-29b Spitzer Observations

    Science.gov (United States)

    Challener, Ryan; Harrington, Joseph; Cubillos, Patricio E.; Blecic, Jasmina; Deming, Drake; Hellier, Coel

    2018-01-01

    We present an analysis of Spitzer secondary eclipse observations of exoplanet WASP-29b. WASP-29b is a Saturn-sized, short-period exoplanet with mass 0.24 ± 0.02 Jupiter masses and radius 0.84 ± 0.06 Jupiter radii (Hellier et al., 2010). We measure eclipse depths and midpoints using our Photometry for Orbits, Eclipses, and Transits (POET) code, which does photometry and light-curve modeling with a BiLinearly Interpolated Subpixel Sensitivity (BLISS) map, and our Zen Eliminates Noise (ZEN) code, which takes POET photometry and applies Pixel-Level Decorrelation (PLD). BLISS creates a physical map of pixel gain variations, and is thereby independent of any astrophysical effects. PLD takes a mathematical approach, using relative variations in pixel values near the target to eliminate position-correlated noise. The results are consistent between the methods, except in one outlier observation where neither model could effectively remove correlated noise in the light curve. Using the eclipse timings, along with previous transit observations and radial velocity data, we further refine the orbit of WASP-29b, and, when excluding the outlier, determine an eccentricity between 0.037 and 0.056. We performed atmospheric retrieval with our Bayesian Atmospheric Radiative Transfer (BART) code but find that, when the outlier is discarded, the planet is consistent with a blackbody, and molecular abundances cannot be constrained. This work is based on observations made with the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory, California Institute of Technology under a contract with NASA. This work was supported by NASA Planetary Atmospheres grant NNX12AI69G and NASA Astrophysics Data Analysis Program grant NNX13AF38G.

  17. Early events of lethal action by tobramycin in Pseudomonas aeruginosa

    International Nuclear Information System (INIS)

    Raulston, J.E.

    1988-01-01

    The immediate activities of the aminoglycoside antibiotic, tobramycin, were investigated in Pseudomonas aeruginosa PAO1. The influence of carbon growth substate and the antibiotic exposure environment in the magnitude of activity were examined. Lethality by 8 μg/ml tobramycin occurred rapidly (1 to 3 minutes). The release of specific cellular components into the supernatant was associated with lethality. This material was initially detected as an increase in UV-absorbance. Magnesium in the reaction mixture provided protection against lethality and leakage, but did not reverse lethal damage after a 3 minute tobramycin treatment. Also, uptake of 3 H-tobramycin was reduced in the presence of magnesium. Cells grown with glucose as a carbon source were more susceptible than organic acid grown cells as was the rapidity and amount of cell damage. Analyses of the leakage material revealed a 2-fold increase of protein in the supernatant after a 1-3 minute treatment which paralleled lethality. A prominent 29 kDa protein was observed by SDS-PAGE in the released material, which has been identified as the periplasmic enzyme, β-lactamase. The immediate activities of tobramycin did not involve (i) release of overall cell protein, (ii) massive loss of total pool amino acids, (iii) cell lysis, (iv) inhibition of proline uptake, (v) release of lipopolysaccharide, or (vi) leakage of ATP. Electron microscopy showed no apparent damage after a 3 minute exposure. 40% inhibition of protein synthesis had occurred by 3 minutes of exposure, while release of UV-absorbing material and lethality were detectable after only 1 minute. Resistant cystic fibrosis isolates of P. aeruginosa did not leak under the same experimental conditions, but one of two susceptible strains examined did show increased UV-absorbance following treatment

  18. Towards in-situ tem analysis of PLD Pb(Zr,Ti)O3 thin film membranes

    NARCIS (Netherlands)

    Sardan Sukas, Ö.; Berenschot, Johan W.; de Boer, Meint J.; Nguyen, Duc Minh; van Zalk, M.; Abelmann, Leon

    2011-01-01

    In this paper, a novel technique for fabricating Transmission Electron Microscopy (TEM) chips for investigating structural and piezoelectric properties of Pulse Laser Deposited (PLD) Lead Zirconium Titanate (PZT) thin films is presented. The method involves silicon-on-insulator (SOI) wafer

  19. Early experience with the Occlutech PLD occluder for mitral paravalvar leak closure through a hybrid transapical approach.

    Science.gov (United States)

    Bedair, Radwa; Morgan, Gareth J; Bapat, Vinayak; Kapetanakis, Stamatis; Goreczny, Sebastian; Simpson, John; Qureshi, Shakeel A

    2016-12-10

    We sought to evaluate the feasibility and efficacy of hybrid transapical closure of paravalvar mitral leaks using a new Occlutech PLD occluder in patients with heart failure and/or haemolytic anaemia. Retrospective analysis of clinical and procedural data was undertaken for patients who had attempted closure of paravalvar mitral leaks via a hybrid transapical approach with the Occlutech PLD occluder. Eight patients (four males, median age 69 years) underwent closure of 10 mitral paravalvar leaks using eight Occlutech PLD occluders and two AMPLATZER Vascular Plugs (AVP II). Successful deployment, with significant reduction of the paravalvar leak was achieved in seven patients with short procedure (median 131 min) and fluoroscopy times (median 22 min). One patient had mechanical interference with prosthetic valve function, requiring surgery. Another patient with a high EuroSCORE (48.8%) died of multi-organ failure two days after the procedure. Clinical improvement in either heart failure or haemolysis was seen in all discharged patients. In our series of patients with challenging anatomy, the Occlutech PLD occluders performed well when implanted via a hybrid transapical approach. Further work is needed to assess this methodology fully for a wider population and to assess other deployment approaches for this promising new occluder.

  20. Recombinant M. bovis BCG expressing the PLD protein promotes survival in mice challenged with a C. pseudotuberculosis virulent strain.

    Science.gov (United States)

    Leal, Karen Silva; de Oliveira Silva, Mara Thais; de Fátima Silva Rezende, Andréa; Bezerra, Francisco Silvestre Brilhante; Begnini, Karine; Seixas, Fabiana; Collares, Tiago; Dellagostin, Odir; Portela, Ricardo Wagner; de Carvalho Azevedo, Vasco Ariston; Borsuk, Sibele

    2018-06-14

    The aim of this study was to evaluate the survival of mice inoculated with M. bovis BCG Pasteur recombinant expressing the PLD protein and challenged with a C. pseudotuberculosis virulent strain. Four groups were immunized with a sterile 0.9% saline solution (G1), 10 6  CFU of M. bovis BCG Pasteur (G2), 10 6  CFU of M. bovis BCG/pld (G3) or 10 6  CFU of M. bovis BCG/pld with a booster with rPLD (G4) and challenged with 10 4 CFU of C. pseudotuberculosis MIC-6 strain. The highest survival rate of 88% was observed in G4, followed by 77% in G3 and 66% in G2. A significant statistical difference was observed in the levels of cytokines IFN-γ and IL-10 in vaccinated groups (G3 and G4) when compared with the control group (G1) (p < 0.05). The results seem promising as the recombinant vaccine elicited a cellular immune response and provided significant survival after a high virulent challenge. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Theories of Lethal Mutagenesis: From Error Catastrophe to Lethal Defection.

    Science.gov (United States)

    Tejero, Héctor; Montero, Francisco; Nuño, Juan Carlos

    2016-01-01

    RNA viruses get extinct in a process called lethal mutagenesis when subjected to an increase in their mutation rate, for instance, by the action of mutagenic drugs. Several approaches have been proposed to understand this phenomenon. The extinction of RNA viruses by increased mutational pressure was inspired by the concept of the error threshold. The now classic quasispecies model predicts the existence of a limit to the mutation rate beyond which the genetic information of the wild type could not be efficiently transmitted to the next generation. This limit was called the error threshold, and for mutation rates larger than this threshold, the quasispecies was said to enter into error catastrophe. This transition has been assumed to foster the extinction of the whole population. Alternative explanations of lethal mutagenesis have been proposed recently. In the first place, a distinction is made between the error threshold and the extinction threshold, the mutation rate beyond which a population gets extinct. Extinction is explained from the effect the mutation rate has, throughout the mutational load, on the reproductive ability of the whole population. Secondly, lethal defection takes also into account the effect of interactions within mutant spectra, which have been shown to be determinant for the understanding the extinction of RNA virus due to an augmented mutational pressure. Nonetheless, some relevant issues concerning lethal mutagenesis are not completely understood yet, as so survival of the flattest, i.e. the development of resistance to lethal mutagenesis by evolving towards mutationally more robust regions of sequence space, or sublethal mutagenesis, i.e., the increase of the mutation rate below the extinction threshold which may boost the adaptability of RNA virus, increasing their ability to develop resistance to drugs (including mutagens). A better design of antiviral therapies will still require an improvement of our knowledge about lethal

  2. Chronic exposure of corals to fine sediments: lethal and sub-lethal impacts.

    Directory of Open Access Journals (Sweden)

    Florita Flores

    Full Text Available Understanding the sedimentation and turbidity thresholds for corals is critical in assessing the potential impacts of dredging projects in tropical marine systems. In this study, we exposed two species of coral sampled from offshore locations to six levels of total suspended solids (TSS for 16 weeks in the laboratory, including a 4 week recovery period. Dose-response relationships were developed to quantify the lethal and sub-lethal thresholds of sedimentation and turbidity for the corals. The sediment treatments affected the horizontal foliaceous species (Montipora aequituberculata more than the upright branching species (Acropora millepora. The lowest sediment treatments that caused full colony mortality were 30 mg l(-1 TSS (25 mg cm(-2 day(-1 for M. aequituberculata and 100 mg l(-1 TSS (83 mg cm(-2 day(-1 for A. millepora after 12 weeks. Coral mortality generally took longer than 4 weeks and was closely related to sediment accumulation on the surface of the corals. While measurements of damage to photosystem II in the symbionts and reductions in lipid content and growth indicated sub-lethal responses in surviving corals, the most reliable predictor of coral mortality in this experiment was long-term sediment accumulation on coral tissue.

  3. Chronic Exposure of Corals to Fine Sediments: Lethal and Sub-Lethal Impacts

    Science.gov (United States)

    Flores, Florita; Hoogenboom, Mia O.; Smith, Luke D.; Cooper, Timothy F.; Abrego, David; Negri, Andrew P.

    2012-01-01

    Understanding the sedimentation and turbidity thresholds for corals is critical in assessing the potential impacts of dredging projects in tropical marine systems. In this study, we exposed two species of coral sampled from offshore locations to six levels of total suspended solids (TSS) for 16 weeks in the laboratory, including a 4 week recovery period. Dose-response relationships were developed to quantify the lethal and sub-lethal thresholds of sedimentation and turbidity for the corals. The sediment treatments affected the horizontal foliaceous species (Montipora aequituberculata) more than the upright branching species (Acropora millepora). The lowest sediment treatments that caused full colony mortality were 30 mg l−1 TSS (25 mg cm−2 day−1) for M. aequituberculata and 100 mg l−1 TSS (83 mg cm−2 day−1) for A. millepora after 12 weeks. Coral mortality generally took longer than 4 weeks and was closely related to sediment accumulation on the surface of the corals. While measurements of damage to photosystem II in the symbionts and reductions in lipid content and growth indicated sub-lethal responses in surviving corals, the most reliable predictor of coral mortality in this experiment was long-term sediment accumulation on coral tissue. PMID:22662225

  4. Factors that determine the presence of particles in YBCO films grown by PLD

    International Nuclear Information System (INIS)

    Barrales-Guadarrama, V R; Rodríguez-Rodríguez, E M; Barrales-Guadarrama, R; Reyes Ayala, N

    2017-01-01

    The method of growing thin films PLD, is widely used in applications and possesses great potential in thin YBa 2 Cu 3 O 7-δ films production with outstanding physical properties. However, it is limited in nano and micro technology due to the presence of particles on the surface of the films. This article describes some causes that create these particles. YBa 2 Cu 3 O 7-δ films have been grown on electrolytic copper used as a variable model the distance target-substrate. The effects are studied through Scanning Electronic Microscopy. It is observed particles with a large variety of shapes and distributions. The results show that ranging the target-substrate distance, the superficial morphology is modified. An evidence of it, is that the evaporation of d B-S = 7 cm, is more coherent that d B-S = 3 cm. Therefore, exist a relation between the morphology and the parameters of growing. Also affect, the structural change that exists among the substrate and the film formation, the substrate preparation and it must not be monocrystalline, these factors define a kinetic and a mechanism of growing that promotes a heterogeneous nucleation. (paper)

  5. PLD prepared nanostructured Pt-CeO{sub 2} thin films containing ionic platinum

    Energy Technology Data Exchange (ETDEWEB)

    Vorokhta, M., E-mail: vorohtam@gmail.com [Charles University in Prague, Faculty of Mathematics and Physics, Department of Surface and Plasma Science, V Holešovičkách 2, 18000 Prague 8 (Czech Republic); Khalakhan, I.; Matolínová, I.; Nováková, J.; Haviar, S. [Charles University in Prague, Faculty of Mathematics and Physics, Department of Surface and Plasma Science, V Holešovičkách 2, 18000 Prague 8 (Czech Republic); Lančok, J.; Novotný, M. [Institute of Physics, Academy of Sciences of the Czech Republic, Na Slovance 2, 182 21 Prague, Czhech Republic (Czech Republic); Yoshikawa, H. [National Institute for Materials Science, Sengen 1-2-1, Tsukuba, Ibaraki 305-0047 (Japan); Matolín, V. [Charles University in Prague, Faculty of Mathematics and Physics, Department of Surface and Plasma Science, V Holešovičkách 2, 18000 Prague 8 (Czech Republic)

    2017-02-28

    Highlights: • Nanostructured Pt-CeO{sub 2} thin catalyst films were grown on plasma etched and non-etched carbon substrates by pulsed laser deposition. • The surface composition of the nanostructured Pt-CeO{sub 2} films was investigated by surface analysis techniques. • The effect of film roughening was separated from the effect of platinum-ceria atomic interactions. - Abstract: The composition of nanostructured Pt-CeO{sub 2} films on graphite substrates prepared by pulsed laser deposition has been investigated by means of hard X-ray photoelectron spectroscopy, scanning electron microscopy, high resolution transmission electron microscopy, and atomic force microscopy. The influence of morphology of the graphite substrates was investigated with respect to the relative concentrations of ionic and metallic Pt species in the films. It was found that the degree of Pt{sup 2+} enrichment is directly related to the surface morphology of graphite substrates. In particular, the deposition of Pt-CeO{sub 2} films on rough graphite substrate etched in oxygen plasma yielded nanostructured Pt-CeO{sub 2} catalyst films with high surface area and high Pt{sup 2+}/Pt{sup 0} ratio. The presented results demonstrate that PLD is a suitable method for the preparation of thin Pt-CeO{sub 2} catalyst films for fuel cell applications.

  6. Non-Lethal Weapons Program

    Science.gov (United States)

    Sheets Frequently Asked Questions Non-Lethal Weapons FAQs Active Denial System FAQs Human Electro -Muscular Incapacitation FAQs Related Links Business Opportunities Contact JNLWD Congressional Engagement , Wednesday, Sept 20, 2017. The Active Denial System, blunt-impact munitions, dazzling lasers, LRAD 100X

  7. Antibacterial, mechanical and surface properties of Ag-DLC films prepared by dual PLD for medical applications

    Czech Academy of Sciences Publication Activity Database

    Písařík, Petr; Jelínek, Miroslav; Remsa, Jan; Mikšovský, Jan; Zemek, Josef; Jurek, Karel; Kubinová, Šárka; Lukeš, J.; Šepitka, J.

    2017-01-01

    Roč. 77, Aug (2017), s. 955-962 ISSN 0928-4931 R&D Projects: GA ČR(CZ) GA15-05864S; GA MŠk LO1409 Institutional support: RVO:68378271 Keywords : DLC * silver doped DLC * antibacterial properties * mechanical properties * dual PLD Subject RIV: BM - Solid Matter Physics ; Magnetism OBOR OECD: Condensed matter physics (including formerly solid state physics, supercond.)

  8. Lethal mechanisms in gastric volvulus.

    Science.gov (United States)

    Omond, Kimberley J; Byard, Roger W

    2017-01-01

    A 55-year-old wheelchair-bound woman with severe cerebral palsy was found at autopsy to have marked distention of the stomach due to a volvulus. The stomach was viable, and filled with air and fluid and had pushed the left dome of the diaphragm upwards causing marked compression of the left lung with a mediastinal shift to the right (including the heart). There was no evidence of gastric perforation, ischaemic necrosis or peritonitis. Removal of the organ block revealed marked kyphoscoliosis. Histology confirmed the viability of the stomach and biochemistry showed no dehydration. Death in cases of acute gastric volvulus usually occurs because of compromise of the gastric blood supply resulting in ischaemic necrosis with distention from swallowed air and fluid resulting in perforation with lethal peritonitis. Hypovolaemic shock may also occur. However, the current case demonstrates an alternative lethal mechanism, that of respiratory compromise due to marked thoracic organ compression.

  9. Dominant-lethal mutations and heritable translocations in mice

    International Nuclear Information System (INIS)

    Generoso, W.M.

    1983-01-01

    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed

  10. Dominant-lethal mutations and heritable translocations in mice

    Energy Technology Data Exchange (ETDEWEB)

    Generoso, W.M.

    1983-01-01

    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed.

  11. Radiation-induced DNA damage and cellular lethality

    International Nuclear Information System (INIS)

    Sakai, K.; Okada, S.

    1984-01-01

    Radiation-induced DNA scissions and their repair were investigated in mammalian cells using an alkaline separation method. DNA breaks in mouse L5178Y cells and Chinese hamster V79 cells were grouped into three in terms of their repair profile; fast-reparable breaks (FRBs; T1/2 = 5 min), slow-reparable breaks (SRBs; T1/2 = 70 min) and non-reparable breaks (NRBs). The three types of DNA lesions were studied under conditions where cellular radiosensitivity was modified. The authors obtained the following results: 1. Cell cycle fluctuation: L5178Y showed maximum sensitivity at M and G/sub 1/-S boundary, and minimum sensitivity at G/sub 1/ and late S. Cycle dependency was not found for FRBs or SRBs, but NRBs showed bimodal fluctuation with peaks at M and G/sub 1/-S, and with bottoms at G/sub 1/ and late S. 2. Different sensitivity of L5178Y and V79: L5178Y cells were more sensitive to X-rays (D/sub ο/ = 0.9 Gy) than V79 (D/sub ο/ = 1.8 Gy). The amount of FRBs or SRBs was identical in the two cell lines. However, the amount of NRBs in L5178Y was greater than that in V79. 3. Split dose irradiation: The time interval between two doses resulted in a gradual decrease of NRBs. The time course of the decrease was similar to the split dose recovery in terms of cell death. The parallel relationship between NRBs and cell killing implies that NRBs could play an important role in radiation-induced cell death

  12. PLD growth of CoPd thin films and characterization of their magnetic properties by magneto optical Kerr effect

    Science.gov (United States)

    Sedrpooshan, Mehran; Ahmadvand, Hossein; Ranjbar, Mehdi; Salamati, Hadi

    2018-06-01

    CoPd alloy thin films with different thicknesses and Co/Pd ratios have been deposited on Si (100) substrate by pulsed laser deposition (PLD). The magnetic properties were investigated by using the magneto-optical Kerr effect (MOKE) in both longitudinal and polar geometries. The results show that the films with thickness in the range of 6-24 nm, deposited at a low substrate temperature of 200 °C, are mostly magnetized in the plane of film. Higher deposition temperature forces the magnetic easy axis to orient in the perpendicular direction of the films.

  13. 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality

    Directory of Open Access Journals (Sweden)

    Miriam S. N. Hohmann

    2013-01-01

    Full Text Available 5-Lipoxygenase (5-LO converts arachidonic acid into leukotrienes (LTs and is involved in inflammation. At present, the participation of 5-LO in acetaminophen (APAP-induced hepatotoxicity and liver damage has not been addressed. 5-LO deficient (5-LO-/- mice and background wild type mice were challenged with APAP (0.3–6 g/kg or saline. The lethality, liver damage, neutrophil and macrophage recruitment, LTB4, cytokine production, and oxidative stress were assessed. APAP induced a dose-dependent mortality, and the dose of 3 g/kg was selected for next experiments. APAP induced LTB4 production in the liver, the primary target organ in APAP toxicity. Histopathological analysis revealed that 5-LO-/- mice presented reduced APAP-induced liver necrosis and inflammation compared with WT mice. APAP-induced lethality, increase of plasma levels of aspartate aminotransferase and alanine aminotransferase, liver cytokine (IL-1β, TNF-α, IFN-γ, and IL-10, superoxide anion, and thiobarbituric acid reactive substances production, myeloperoxidase and N-acetyl-β-D-glucosaminidase activity, Nrf2 and gp91phox mRNA expression, and decrease of reduced glutathione and antioxidant capacity measured by 2,2′-azinobis(3-ethylbenzothiazoline 6-sulfonate assay were prevented in 5-LO-/- mice compared to WT mice. Therefore, 5-LO deficiency resulted in reduced mortality due to reduced liver inflammatory and oxidative damage, suggesting 5-LO is a promising target to reduce APAP-induced lethality and liver inflammatory/oxidative damage.

  14. Dominant lethals following administration of tritium (THO) to rat males

    International Nuclear Information System (INIS)

    Yagova, A.; Baev, I.; Bajrakova, A.

    1976-01-01

    Adult rat males were given a single intraperitoneal tritium (THO) injection at 0,01 or 0,001 mCi/g body weight (1/100 or 1/1000 of LDsub(50/30), respectively). Twelve days after treatment each male was mated to 3-5 intact females, and the latter were replaced by fresh ones every 12 following days over a 120-day period. Mated females were killed to score conceptions, corpora lutea, and live and dead embryos. Estimations were made of F 1 prenatal death rate (according to Bateman, 1958) and the frequency of induction of dominant lethal mutations (according to Roehrborn, 1970). The results observed indicated paternal exposure to tritium (THO) to produce dominant lethals both in pre- and post-meiotic germ cells in the rat. The extent of the genetic damage studied was found to depend on the amount of activity administered as well as on the time interval between treatment and conception. (author)

  15. Electroshock weapons can be lethal!

    Science.gov (United States)

    Lundquist, Marjorie

    2008-03-01

    Electroshock weapons (EWs)-stun guns, tasers, riot shields-are electroconductive devices designed to safely incapacitate healthy men neuromuscularly, so they are called nonlethal or less-lethal. EW firms seeking large nonmilitary markets targeted law enforcement and corrections personnel, who began using EWs in prisons/jails and on public patrol in 1980 in the USA. This shifted the EW-shocked population from healthy soldiers to a heterogeneous mix of both sexes, ages 6-92, in a wide variety of health conditions! An EW operates by disrupting normal physiological processes, producing transient effects in healthy people. But if a person's health is sufficiently compromised, the margin of safety can be lost, resulting in death or permanent health problems. 325 people have died after EW shock since 1980. Did the EW cause these deaths? Evidence indicates that EWs do play a causal role in most such deaths. EWs can be lethal for people in diabetic shock^1 (hypoglycemia), which may be why Robert Dziekanski-a Polish immigrant to Canada-died so quickly after he was tasered at Vancouver Airport: not having eaten for over 10 hours, he likely was severely hypoglycemic. The EW death rate in North America is 30 times higher than need be, because EW users have not been properly trained to use EWs on a heterogeneous population safely! ^1J. Clinical Engineering 30(3):111(2005).

  16. Role of catechins on ET-1 induced stimulation of PLD and NADPH oxidase activities in pulmonary smooth muscle cells: Determination of the probable mechanism by molecular docking studies.

    Science.gov (United States)

    Chakraborti, Sajal; Sarkar, Jaganmay; Bhuyan, Rajabrata; Chakraborti, Tapati

    2017-12-05

    Treatment of human pulmonary artery smooth muscle cells with ET-1 stimulated PLD and NADPH oxidase activities, which were inhibited upon pretreatment with bosentan (ET-1 receptor antagonist), FIPI (PLD inhibitor), apocynin (NADPH oxidase inhibitor) and EGCG & ECG (catechins having galloyl group), but not EGC & EC (catechins devoid of galloyl group). Herein, we determined the probable mechanism by which the galloyl group containing catechins inhibit ET-1 induced stimulation of PLD activity by molecular docking analyses based on our biochemical studies. ET-1 induced stimulation of PLD activity was inhibited by SecinH3 (inhibitor of cytohesin). Arf-6 and cytohesin-1 were associated in the cell membrane, which was not inhibited by the catechins during ET-1 treatment to the cells. However, EGCG and ECG inhibited binding of GTPγS with Arf-6 even in presence of cytohesin-1. The molecular docking analyses revealed that the galloyl group containing catechins (EGCG/ECG) with cytohesin1-Arf6GDP, but not the non-galloyl-containing catechins (EGC and EC), prevents GDP/GTP exchange in Arf-6 which seems to be an important mechanism for inhibition of ET-1 induced activation of PLD and subsequently increase in NADPH oxidase activities.

  17. THE UNCOVERING OF A NOVEL REGULATORY MECHANISM FOR PLD2: FORMATION OF A TERNARY COMPLEX WITH PROTEIN TYROSINE PHOSPHATASE PTP1B AND GROWTH FACTOR RECEPTOR-BOUND PROTEIN GRB2

    Science.gov (United States)

    Horn, Jeff; Lopez, Isabel; Miller, Mill; Gomez-Cambronero, Julian

    2011-01-01

    The regulation of PLD2 activation is poorly understood at present. Transient transfection of COS-7 with a mycPLD2 construct results in elevated levels of PLD2 enzymatic activity and tyrosyl phosphorylation. To investigate whether this phosphorylation affects PLD2 enzymatic activity, anti-myc immunoprecipitates were treated with recombinant protein tyrosine phosphatase PTP1B. Surprisingly, lipase activity and PY levels both increased over a range of PTP1B concentrations. These increases occurred in parallel to a measurable PTP1B-associated phosphatase activity. Inhibitor studies demonstrated that an EGF-receptor type kinase is involved in phosphorylation. In a COS-7 cell line created in the laboratory that stably expressed myc-PLD2, PTP1B induced a robust (>6-fold) augmentation of myc-PLD2 phosphotyrosine content. The addition of growth factor receptor-bound protein 2 (Grb2) to cell extracts also elevated PY levels of myc-PLD (>10-fold). Systematic co-immunoprecipitation-immunoblotting experiments pointed at a physical association between PLD2, Grb2 and PTP1B in both physiological conditions and in overexpressed cells. This is the first report of a demonstration of the mammalian isoform PLD2 existing in a ternary complex with a protein tyrosine phosphatase, PTP1b, and the docking protein Grb2 which greatly enhances tyrosyl phosphorylation of the lipase. PMID:15896299

  18. Efficacy of PLD-118, a novel inhibitor of candida isoleucyl-tRNA synthetase, against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant C. albicans.

    Science.gov (United States)

    Petraitis, Vidmantas; Petraitiene, Ruta; Kelaher, Amy M; Sarafandi, Alia A; Sein, Tin; Mickiene, Diana; Bacher, John; Groll, Andreas H; Walsh, Thomas J

    2004-10-01

    PLD-118, formerly BAY 10-8888, is a synthetic antifungal derivative of the naturally occurring beta-amino acid cispentacin. We studied the activity of PLD-118 in escalating dosages against experimental oropharyngeal and esophageal candidiasis (OPEC) caused by fluconazole (FLC)-resistant Candida albicans in immunocompromised rabbits. Infection was established by fluconazole-resistant (MIC > 64 microg/ml) clinical isolates from patients with refractory esophageal candidiasis. Antifungal therapy was administered for 7 days. Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v. BID injections; and animals receiving desoxycholate amphotericin B (DAMB) i.v. at 0.5 mg/kg/day. PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P PLD-118 demonstrated nonlinear plasma pharmacokinetics across the investigated dosage range, as was evident from a dose-dependent increase in plasma clearance and a dose-dependent decrease in the area under the plasma concentration-time curve. The biochemical safety profile was similar to that of FLC. In summary, PLD-118 demonstrated dosage-dependent antifungal activity and nonlinear plasma pharmacokinetics in treatment of experimental FLC-resistant oropharyngeal and esophageal candidiasis.

  19. Effect of lethal and sub-lethal concentrations of tobacco (Nicotiana ...

    African Journals Online (AJOL)

    Lethal and sub-lethal bioassays on Clarias gariepinus were conducted to evaluate the toxicity of tobacco (Nicotiana tobaccum) leaf dust on weight gain and haematological indices of Clarias gariepinus (mean weight 10.5±0.70g) in glass aquaria with aeration system. The concentrations used during the lethal exposure are: ...

  20. Molecular basis of the mutagenic and lethal effects of ultraviolet irradiation

    International Nuclear Information System (INIS)

    Grossman, L.

    1982-01-01

    Using bacteria as a model, the molecular basis of the mutagenic and lethal effects of uv radiation is being studied. Attention is focused on the mechanism of action of uv-1 specific endonucleases in the repair of damaged DNA. The isolation and identification of similar enzymes in human cells are being conducted concurrently

  1. Adenoviral gene transfer of PLD1-D4 enhances insulin sensitivity in mice by disrupting phospholipase D1 interaction with PED/PEA-15.

    Directory of Open Access Journals (Sweden)

    Angela Cassese

    Full Text Available Over-expression of phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (PED/PEA-15 causes insulin resistance by interacting with the D4 domain of phospholipase D1 (PLD1. Indeed, the disruption of this association restores insulin sensitivity in cultured cells over-expressing PED/PEA-15. Whether the displacement of PLD1 from PED/PEA-15 improves insulin sensitivity in vivo has not been explored yet. In this work we show that treatment with a recombinant adenoviral vector containing the human D4 cDNA (Ad-D4 restores normal glucose homeostasis in transgenic mice overexpressing PED/PEA-15 (Tg ped/pea-15 by improving both insulin sensitivity and secretion. In skeletal muscle of these mice, D4 over-expression inhibited PED/PEA-15-PLD1 interaction, decreased Protein Kinase C alpha activation and restored insulin induced Protein Kinase C zeta activation, leading to amelioration of insulin-dependent glucose uptake. Interestingly, Ad-D4 administration improved insulin sensitivity also in high-fat diet treated obese C57Bl/6 mice. We conclude that PED/PEA-15-PLD1 interaction may represent a novel target for interventions aiming at improving glucose tolerance.

  2. Coronin 1B regulates S1P-induced human lung endothelial cell chemotaxis: role of PLD2, protein kinase C and Rac1 signal transduction.

    Directory of Open Access Journals (Sweden)

    Peter V Usatyuk

    Full Text Available Coronins are a highly conserved family of actin binding proteins that regulate actin-dependent processes such as cell motility and endocytosis. We found that treatment of human pulmonary artery endothelial cells (HPAECs with the bioactive lipid, sphingosine-1-phosphate (S1P rapidly stimulates coronin 1B translocation to lamellipodia at the cell leading edge, which is required for S1P-induced chemotaxis. Further, S1P-induced chemotaxis of HPAECs was attenuated by pretreatment with small interfering RNA (siRNA targeting coronin 1B (∼36%, PLD2 (∼45% or Rac1 (∼50% compared to scrambled siRNA controls. Down regulation PLD2 expression by siRNA also attenuated S1P-induced coronin 1B translocation to the leading edge of the cell periphery while PLD1 silencing had no effect. Also, S1P-induced coronin 1B redistribution to cell periphery and chemotaxis was attenuated by inhibition of Rac1 and over-expression of dominant negative PKC δ, ε and ζ isoforms in HPAECs. These results demonstrate that S1P activation of PLD2, PKC and Rac1 is part of the signaling cascade that regulates coronin 1B translocation to the cell periphery and the ensuing cell chemotaxis.

  3. Factors influencing circadian rhythms in acetaminophen lethality.

    Science.gov (United States)

    Schnell, R C; Bozigian, H P; Davies, M H; Merrick, B A; Park, K S; McMillan, D A

    1984-01-01

    Experiments were conducted to examine the effects of changes in lighting schedules and food consumption on circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice. Under a normal lighting schedule (light: 06.00-18.00 h), male mice exhibited a circadian rhythm in acetaminophen lethality (peak: 18.00 h; nadir: 06.00, 10.00 h) and an inverse rhythm in hepatic glutathione concentrations (peak: 06.00, 10.00 h; nadir: 18.00 h). Under a reversed lighting schedule (light: 18.00-06.00 h) the glutathione rhythm was reversed and the rhythm in acetaminophen lethality was altered showing greater sensitivity to the drug. Under continuous light, there was a shift in the acetaminophen lethality and the hepatic glutathione rhythms. Under continuous dark, both rhythms were abolished. Under a normal lighting regimen, hepatic glutathione levels were closely correlated with food consumption; i.e., both were increased during the dark phase and decreased during the light phase. Fasting the mice for 12 h abolished the rhythms in acetaminophen lethality and hepatic glutathione levels; moreover, the lethality was increased and the hepatic glutathione levels were decreased. These experiments show that both lighting schedules and feeding can alter the circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice.

  4. Transporting Patients with Lethal Contagious Infections

    National Research Council Canada - National Science Library

    Swartz, Colleen

    2002-01-01

    .... The AIT is a unique military medical team capable of worldwide air evacuation and management of a limited number of patients who are potentially exposed to known and unknown lethal communicable...

  5. Experiences in therapy for lethal midline granuloma

    International Nuclear Information System (INIS)

    Tosaka, Kaoru; Ishikawa, Takeru

    1982-01-01

    Four cases of the lethal midline granuloma or malignant granuloma of the nose were treated by irradiation and chemotherapy, which are generally prescribed for malignant lymphomas. Clinical, histological and laboratory examination indicated that they were the lethal midline granuloma and clearly differentiated from Wegener's granulomatosis or malignant lymphoma. All of the cases exhibited primary remission. The four cases were observed up to 38, 22, 14, and 10 months since the beginning of the therapy, showing no local or general recurrence. (author)

  6. [Damage control in field surgery].

    Science.gov (United States)

    Samokhvalov, I M; Manukovskiĭ, V A; Badalov, V I; Severin, V V; Golovko, K P; Denisenko, V V

    2011-09-01

    Damage control surgery (DCS) is an important option in the store of war surgery and surgery of trauma. The main purpose of our investigation was to specify the percentage of the injured who need DCS. We performed retrospective study of the patients in the combat operations in Chechnya (1994-2002) and in peacetime (2005-2010). Total lethality in group with the standard surgical approach was 62.3%. It was significantly higher than the lethality in group of patients who underwent DCS - 50.0% (p < 0.05). Thus, the experience of DCS in War Surgery Department confirms that DCS is perspective tendency in treatment of patients with severe and extremely severe trauma, and allows decreasing lethality in 12.3%.

  7. Effect of substrate temperature and post annealing temperature on ZnO:Zn PLD thin film properties

    Science.gov (United States)

    Hasabeldaim, E.; Ntwaeaborwa, O. M.; Kroon, R. E.; Coetsee, E.; Swart, H. C.

    2017-12-01

    The pulsed laser deposition (PLD) substrate temperature and post-annealing temperature are effective methods to control the film optical and structural properties. The structure, morphology and optical properties of the deposited and post-annealed PLD ZnO:Zn films were studied. The films were deposited at different substrate temperatures of 50 °C, 200 °C and 400 °C. The films deposited at the substrate temperature of 50 °C and 200 °C were post-annealed in air at 400 °C and 600 °C for two hours. The films all had a highly preferential orientation with the hexagonal c-axis perpendicular to the substrate surface. The stress was found to be compressive stress with values -3.289 GPa, -4.864 GPa and -4.425 GPa for the film deposited at 50 °C, 200 °C and 400 °C, respectively. After post-annealing treatments, the stress of the films was almost completely released and stress-free films were obtained. The crystallite sizes were 19 nm, 25 nm and 39 nm, while the average particles sizes were 95 nm, 85 nm and 129 nm for the film deposited at 50 °C, 200 °C and 400 °C respectively. The crystallite sizes and particles sizes seemed to increase with the increase in the substrate temperature. Contrary to this, the change in crystallite sizes were inversely proportional to the particles size when increasing the post-annealing temperatures. Deconvoluted X-ray photoelectron spectroscopy peaks of the O1s binding energy region revealed that the films deposited at different substrate temperatures contained oxygen-related defects. Photoluminescence studies revealed that the films all emitted ultra-violet emission around 379 nm. The film deposited at 50 °C emitted a broad green emission centered at ∼524 nm. By increasing the substrate temperature up to 200 °C and 400 °C a new orange emission around 621 nm and 634 nm as well as a weak emission around 416 nm and 500 nm were observed, respectively. After post-annealing treatments, new bands over the visible region (blue, green

  8. Enhancement in (BHmax of PLD-made isotropic Nd-Fe-B thick film magnets deposited on Si substrates

    Directory of Open Access Journals (Sweden)

    M. Nakano

    2017-05-01

    Full Text Available Increase in Nd contents of a PLD-made isotropic Nd-Fe-B thick-film magnet enabled us to enhance the thickness of the film magnet deposited on a Si substrate because the linear expansion coefficient of Nd is an intermediate value between Nd2Fe14B and Si. The large amount of Nd, however, degraded the residual magnetic polarization and (BHmax. In the study, we reduced the Nd contents of each Nd-Fe-B film by inserting a Nd or a Nd-rich Nd-Fe-B buffer layer between a Nd-Fe-B film and a Si substrate in order to suppress the mechanical destruction together with the improvement in magnetic properties. It was found that the mechanical property of a Nd-Fe-B film comprising the Nd-Fe-B buffer layer in the thickness range from 10 to 60 μm was superior than that of a sample with the Nd buffer layer. Resultantly, an average (BHmax value of Nd-Fe-B films with each Nd-Fe-B buffer layer deposited on Si substrates could be enhanced by approximately 15 kJ/m3 compared to that of non-buffer-layered films.

  9. Lethality Index 2008-2014: Less shootings, same lethality, more opacity

    Directory of Open Access Journals (Sweden)

    Carlos Silva Forné

    2017-11-01

    Full Text Available This article evaluates the use of lethal force by Mexican federal security forces during shootings with presumed members of organized crime from 2008-2014. The authors use official data and press reports on deaths and wounded in shootings to construct indicators such as the number of dead civilians over the number of dead officials from the federal security forces and the number of dead civilians over the number of wounded civilians. In a context where certain factors that contribute to an excessive use of force become more common, the results of the study show a growing use of lethal force. This raises questions over the possible excessive use of lethal force as a normal or systematic practice. The study also shows a growing context of opacity in the information available to evaluate the use of lethal force and the general lack of a legal framework to regulate the use of lethal force in Mexico.

  10. Inhibitory action of chlorophyllin of autosome recessive lethals induced by irradiation

    International Nuclear Information System (INIS)

    Salceda, V.M.; Pimentel, P.A.E.; Cruces, M.P.

    2006-01-01

    The chlorophyllin is a sodium salt of the chlorophyll that has a strong protective action of the damage induced by different agents so much physical as chemical. In Drosophila there is reported this effect in somatic cells. In contrast, in germinal cells using tests with the sexual chromosomes has not been found such inhibitory action. For this reason, in this occasion we will refer to the effect of the lethality induced in autosome chromosomes, in particular to the chromosome II of this species. For such effect groups of males of the line Canton-S its were pre-treated for 24h with or without 69 mm of CCS and later on treaties with or without 40 Gy of gamma irradiation. The males were then subjected to the technical Cy L / Pm for the detection of recessive lethals. In the third generation the respective counts of the descendant of each one of them to determine the corresponding categories for each extracted chromosome were made. To be mendelian crosses it is expected for a normal chromosome a proportion 2:1 of individuals with genotype Cy L / +: +/+. The absence of individuals +/+ it is indicative of a lethal gene, until 10% of these individuals of each male's total descendant, it is considered that is carrying of a semi lethal gene. The sum of lethal and semi lethals constitutes the category detrimental. The obtained results indicated that the pre-treatment with CCS reduces in a significant way the frequency of induced lethals by 40 Gy of gamma rays. The fact that an effect inhibitor has not been observed in the test of recessive lethal bound to the sex obtained previously, it contrasts with the effect observed in the chromosome II, results of this study and with the one observed in the chromosome III in somatic cells. The above-mentioned shows a differential action of the CCS between sexual chromosomes and autosomal before the effect of the gamma radiation. At the moment we don't have an explanation to these evidences. To evaluate the action of the chlorophyllin

  11. Cell lethality after selective irradiation of the DNA replication fork

    International Nuclear Information System (INIS)

    Hofer, K.G.; Warters, R.L.

    1985-01-01

    It has been suggested that nascent DNA located at the DNA replication fork may exhibit enhanced sensitivity to radiation damage. To evaluate this hypothesis, Chinese hamster ovary cells (CHO) were labeled with 125 I-iododeoxyuridine ( 125 IUdR) either in the presence or absence of aphidicolin. Aphidicolin (5 μg/ml) reduced cellular 125 IUdR incorporation to 3-5% of the control value. The residual 125 I incorporation appeared to be restricted to low molecular weight (sub-replicon sized) fragments of DNA which were more sensitive to micrococcal nuclease attack and less sensitive to high salt DNase I digestion than randomly labeled DNA. These findings suggest that DNA replicated in the presence of aphidicolin remains localized at the replication fork adjacent to the nuclear matrix. Based on these observations an attempt was made to compare the lethal consequences of 125 I decays at the replication fork to that of 125 I decays randomly distributed over the entire genome. Regardless of the distribution of decay events, all treatment groups exhibited identical dose-response curves (D 0 : 101 125 I decays/cell). Since differential irradiation of the replication complex did not result in enhanced cell lethality, it can be concluded that neither the nascent DNA nor the protein components (replicative enzymes, nuclear protein matrix) associated with the DNA replication site constitute key radiosensitive targets within the cellular genome. (orig.)

  12. Introduction of Artificial Pinning Center into PLD-YBCO Coated Conductor on IBAD and Self-Epitaxial CeO2 Buffered Metal Substrate

    International Nuclear Information System (INIS)

    Kobayashi, H.; Yamada, Y.; Ishida, S.; Takahashi, K.; Konishi, M.; Ibi, A.; Miyata, S.; Kato, T.; Hirayama, T.; Shiohara, Y.

    2006-01-01

    In order to fabricate YBa2Cu3O7-x (YBCO) coated conductors with high critical current density Jc in magnetic fields, we fabricated YBCO coated conductors with artificial pinning centers by the pulsed laser deposition (PLD) method on a self epitaxial PLD-CeO2 layer and ion-beam assisted deposition (IBAD)-Gd2Zr2O7 (GZO) buffered Hastelloy tape. Artificial pinning centers were introduced by the PLD deposition using the yttria-stabilized zirconia (YSZ) oxide target (nano-dot method) and YBCO target including YSZ particles (mixed target method). In the experiments using YSZ oxide target, YSZ nano-dots were observed. They were approximately 15 nm in height and 10 nm to 70 nm in diameter. We found that the density of nano-dots was controlled by the number of laser pulses. These samples exhibited higher Jc than YBCO films in magnetic fields. Furthermore, a similar improvement of Jc was observed in the experiments using YBCO target including YSZ particles. TEM observation revealed that columnar nano-structure made of BaZrO3 was formed during YBCO deposition and it was effective for pinning. We call this new epitaxial nano-structure 'bamboo structure' from its anisotropic growth and morphology

  13. Towards the practical PLD-IBAD coated conductor fabrication - Long wire, high production rate and J c enhancement in a magnetic field

    International Nuclear Information System (INIS)

    Yamada, Yutaka; Ibi, Akira; Fukushima, Hiroyuki; Kuriki, Reiji; Miyata, Seiki; Takahashi, Kazuhiro; Kobayashi, Hirokazu; Ishida, Satoru; Konishi, Masaya; Kato, Takeharu; Hirayama, Tsukasa; Shiohara, Yuh

    2006-01-01

    SRL-Nagoya Coated Conductor Center (NCCC) have succeeded in fabricating stably long coated conductor using ion-beam assisted deposition (IBAD) and pulsed laser deposition (PLD) methods. Reel-to-reel PLD equipment with a multi-plume and multi-turn deposition system (MPMT PLD) resulted in a long coated conductor with a high critical current, I c , of 245 A and length of 212.6 m. I c x L (length) reached the record of 52,087 A m. At the same time, the effort to enhance I c and J c in a magnetic filed are also carried out using artificial pinning center and RE element: YSZ mixed Y123 target brought about a high J c especially in the magnetic field parallel to the c-axis. This was attributed to a columnar structure of the 'bamboo structure' (BaZrO 3 /Y123 layer-stacked structure) in Y123 + YSZ sample. Gd123 was also found to be effective for enhancing pinning properties, which was considered to be due to the native stacking faults in the 123 structure. The combination of Gd element and YSZ introduction were also studied and clearly demonstrated the improvement of the anisotropy of J c for a magnetic field angle

  14. A new approach to epitaxially grow high-quality GaN films on Si substrates: the combination of MBE and PLD.

    Science.gov (United States)

    Wang, Wenliang; Wang, Haiyan; Yang, Weijia; Zhu, Yunnong; Li, Guoqiang

    2016-04-22

    High-quality GaN epitaxial films have been grown on Si substrates with Al buffer layer by the combination of molecular beam epitaxy (MBE) and pulsed laser deposition (PLD) technologies. MBE is used to grow Al buffer layer at first, and then PLD is deployed to grow GaN epitaxial films on the Al buffer layer. The surface morphology, crystalline quality, and interfacial property of as-grown GaN epitaxial films on Si substrates are studied systematically. The as-grown ~300 nm-thick GaN epitaxial films grown at 850 °C with ~30 nm-thick Al buffer layer on Si substrates show high crystalline quality with the full-width at half-maximum (FWHM) for GaN(0002) and GaN(102) X-ray rocking curves of 0.45° and 0.61°, respectively; very flat GaN surface with the root-mean-square surface roughness of 2.5 nm; as well as the sharp and abrupt GaN/AlGaN/Al/Si hetero-interfaces. Furthermore, the corresponding growth mechanism of GaN epitaxial films grown on Si substrates with Al buffer layer by the combination of MBE and PLD is hence studied in depth. This work provides a novel and simple approach for the epitaxial growth of high-quality GaN epitaxial films on Si substrates.

  15. Radiation-induced mutagenicity and lethality in Salmonella typhimurium

    International Nuclear Information System (INIS)

    Isildar, M.; Bakale, G.

    1983-01-01

    The mutagenic and lethal effects of ionizing radiation on histidine-deficient auxotrophs of Salmonella typhimurium were studied to improve the understanding of radiation damage to DNA. The auxotrophs were divided into two groups - one which is sensitive to base-pair substitutions and another sensitive to frameshifts. These groups were composed of parent-daughter pairs in which the chemical mutagenicity enhancing plasmid, pKM101, is absent in the parent strain and present in the daughter. Co-60 #betta#-radiation and 250 kV x-rays were used to irradiate the bacteria. Irradiation of the frameshift - sensitive strains which carry the pKm101 plasmid doubled the absolute number of induced revertants whereas irradiation of the base-pair substitution sensitive strain which also carries the pKm101 plasmid produced nearly no change in the number of induced revertants. A nearly negligible effect on the mutation rate was observed for all parent strains

  16. Variation of crystallinity and stoichiometry in films of gallium oxide, gallium nitride and barium zirconate prepared by means of PLD; Variation von Kristallinitaet und Stoechiometrie in mittels PLD hergestellten Schichten aus Galliumoxid, Galliumnitrid und Bariumzirkonat

    Energy Technology Data Exchange (ETDEWEB)

    Brendt, Jochen

    2011-08-05

    Pulsed Laser Deposition (PLD) is an ablation technique for thin film preparation of many materials. The film properties can be well controlled by the process parameters. Therefore, in many cases a given material can be deposited with different properties by changing one or more process parameters. In this thesis thin films of gallium oxide, gallium nitride and barium zirconate were deposited with a large variation in structure and stoichiometry by means of Pulsed Laser Deposition. The characterization of the film crystallinity, phase purity and short range structural order was completed by means of X-ray diffraction and X-ray absorption spectroscopy. The stoichiometry was investigated using electron probe microanalysis. For analyzing the correlation between the structure and stoichiometry with the optical and electrical properties, optical absorption and electrical conductivity measurements were carried out. The investigation of all three material systems showed that very unique properties can be realized when combining an amorphous structure and a non-stoichiometric composition. For example, in amorphous and oxygen deficient gallium oxide an insulator-metal-transition can be induced by partial crystallization of the as prepared phase accomplished by annealing at about 400 C in argon atmosphere (as shown in literature). Furthermore, amorphous and highly non-stoichiometric barium zirconate has the ability to split water molecules to hydrogen and oxygen at room temperature. A detailed analysis of both phenomena has been performed by means of photoemission and transmission electron microscopy in the case of gallium oxide and via X-ray absorption spectroscopy and gas chromatography in the case of barium zirconate.

  17. Localization of peroxisome proliferator-activated receptor alpha (PPARα) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) in cells expressing the Ca2+-binding proteins calbindin, calretinin, and parvalbumin in the adult rat hippocampus

    Science.gov (United States)

    Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Blanco, Eduardo; Serrano, Antonia; Pavón, Francisco J.; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2014-01-01

    The N-acylethanolamines (NAEs), oleoylethanolamide (OEA) and palmithylethanolamide (PEA) are known to be endogenous ligands of PPARα receptors, and their presence requires the activation of a specific phospholipase D (NAPE-PLD) associated with intracellular Ca2+ fluxes. Thus, the identification of a specific population of NAPE-PLD/PPARα-containing neurons that express selective Ca2+-binding proteins (CaBPs) may provide a neuroanatomical basis to better understand the PPARα system in the brain. For this purpose, we used double-label immunofluorescence and confocal laser scanning microscopy for the characterization of the co-existence of NAPE-PLD/PPARα and the CaBPs calbindin D28k, calretinin and parvalbumin in the rat hippocampus. PPARα expression was specifically localized in the cell nucleus and, occasionally, in the cytoplasm of the principal cells (dentate granular and CA pyramidal cells) and some non-principal cells of the hippocampus. PPARα was expressed in the calbindin-containing cells of the granular cell layer of the dentate gyrus (DG) and the SP of CA1. These principal PPARα+/calbindin+ cells were closely surrounded by NAPE-PLD+ fiber varicosities. No pyramidal PPARα+/calbindin+ cells were detected in CA3. Most cells containing parvalbumin expressed both NAPE-PLD and PPARα in the principal layers of the DG and CA1/3. A small number of cells containing PPARα and calretinin was found along the hippocampus. Scattered NAPE-PLD+/calretinin+ cells were specifically detected in CA3. NAPE-PLD+ puncta surrounded the calretinin+ cells localized in the principal cells of the DG and CA1. The identification of the hippocampal subpopulations of NAPE-PLD/PPARα-containing neurons that express selective CaBPs should be considered when analyzing the role of NAEs/PPARα-signaling system in the regulation of hippocampal functions. PMID:24672435

  18. Localization of peroxisome proliferator-activated receptor alpha (PPAR alpha) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) in cells expressing the Ca2+-binding proteins calbindin, calretinin, and parvalbumin in the adult rat hippocampus

    OpenAIRE

    Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Blanco, Eduardo; Serrano, Antonia; Pavon, Francisco J.; Rodriguez de Fonseca, Fernando; Suarez, Juan

    2014-01-01

    The N-acylethanolamines (NAEs), oleoylethanolamide (OEA) and palmithylethanolamide (PEA) are known to be endogenous ligands of PPARα receptors, and their presence requires the activation of a specific phospholipase D (NAPE-PLD) associated with intracellular Ca(2+) fluxes. Thus, the identification of a specific population of NAPE-PLD/PPARα-containing neurons that express selective Ca(2+)-binding proteins (CaBPs) may provide a neuroanatomical basis to better understand the PPARα system in the b...

  19. Genetics Home Reference: Amish lethal microcephaly

    Science.gov (United States)

    ... 1 in 500 newborns in the Old Order Amish population of Pennsylvania. It has not been found outside this population. Related Information What information about a genetic condition can statistics provide? Why are some genetic ... gene cause Amish lethal microcephaly . The SLC25A19 gene provides instructions for ...

  20. The evolution of lethal intergroup violence

    OpenAIRE

    Kelly, Raymond C.

    2005-01-01

    Recent findings and analyses in evolutionary biology, archaeology, and ethnology provide a favorable conjuncture for examining the evolution of lethal intergroup violence among hominids during the 2.9-million-year Paleolithic time span. Here, I seek to identify and investigate the main turning points in this evolutionary trajectory and to delineate the periodization that follows from this inquiry.

  1. The evolution of lethal intergroup violence.

    Science.gov (United States)

    Kelly, Raymond C

    2005-10-25

    Recent findings and analyses in evolutionary biology, archaeology, and ethnology provide a favorable conjuncture for examining the evolution of lethal intergroup violence among hominids during the 2.9-million-year Paleolithic time span. Here, I seek to identify and investigate the main turning points in this evolutionary trajectory and to delineate the periodization that follows from this inquiry.

  2. A new lethal sclerosing bone dysplasia

    International Nuclear Information System (INIS)

    Kingston, H.M.; Freeman, J.S.; Hall, C.M.

    1991-01-01

    A neonate is described with a lethal sclerosing bone dysplasia associated with prenatal fractures and craniofacial abnormalities including microcephaly, exophthalmos, hypoplastic nose and mid-face, small jaw and nodular hyperplasia of the gums. Parental consanguinity suggests that an autosomal recessive mutation is the likely aetiology. (orig.)

  3. Late radiation effects in animals surviving lethal irradiation

    International Nuclear Information System (INIS)

    Dimitrov, L.A.

    1974-01-01

    Animals (rats, mice, dogs) survived lethal irradiation by means of prophylactic-therapeutic treatments or previously irradiated, were studied for late radiation effects: life span, cachexia and fat growing of hypophysical type, tissue or organ hypoplasia manifested by disturbed hemopoiesis, suppressed function of adrenal gland, etc., suppressed immune reactivity of the irradiated organism, atypical biochemical changes in DNA and protein metabolism, epilation, chronic dermatitis, ulcerations, reduced reproductivity or full sterility, damage of kidneys leading to nephrosclerosis, dishormonal states, cataracts, diffuse sclerotic processes, various kinds of malignant and non-malignant tumors. In these cases hemopoiesis compensated for a definite time peripheral blood composition, but during the late period it showed features of incompleteness: shorter life survival of erythrocytes and thrombocytes manifested by a decreased binding of labelled methionine in these blood elements, anemia and relative thrombocytopenia sometimes with an increased number of polychromatic erythrocytes in peripheral blood and a decreased number of reticulocytes at the same time; lymphopenia and relative leucopenia with an increased number of hypersegmented neutrophils. Decreased reproductivity and atypical biochemical changes available in the first generation of the irradiated animals showed the probable role of mutagenic factors in the emergence of some late radiation effects. A significant part of late radiation sequences were due to neuro-endocrine desintegrations which lead to a disturbed supply of the vessels and afterwards to their sclerosis. Some of the described late radiation effects were also observed in biological controls as festures of ageing while in irradiated animals they were manifested in an earlier period. After application of optimal amounts radioprotectors (AET, cysteamine, serotonin) a more marked protective effect is demonstrated in the early reactions (time survival

  4. Variation of crystallinity and stoichiometry in films of gallium oxide, gallium nitride and barium zirconate prepared by means of PLD

    International Nuclear Information System (INIS)

    Brendt, Jochen

    2011-01-01

    Pulsed Laser Deposition (PLD) is an ablation technique for thin film preparation of many materials. The film properties can be well controlled by the process parameters. Therefore, in many cases a given material can be deposited with different properties by changing one or more process parameters. In this thesis thin films of gallium oxide, gallium nitride and barium zirconate were deposited with a large variation in structure and stoichiometry by means of Pulsed Laser Deposition. The characterization of the film crystallinity, phase purity and short range structural order was completed by means of X-ray diffraction and X-ray absorption spectroscopy. The stoichiometry was investigated using electron probe microanalysis. For analyzing the correlation between the structure and stoichiometry with the optical and electrical properties, optical absorption and electrical conductivity measurements were carried out. The investigation of all three material systems showed that very unique properties can be realized when combining an amorphous structure and a non-stoichiometric composition. For example, in amorphous and oxygen deficient gallium oxide an insulator-metal-transition can be induced by partial crystallization of the as prepared phase accomplished by annealing at about 400 C in argon atmosphere (as shown in literature). Furthermore, amorphous and highly non-stoichiometric barium zirconate has the ability to split water molecules to hydrogen and oxygen at room temperature. A detailed analysis of both phenomena has been performed by means of photoemission and transmission electron microscopy in the case of gallium oxide and via X-ray absorption spectroscopy and gas chromatography in the case of barium zirconate.

  5. Oxygen effect on mutagenic ionizing radiation damage in Bacillus subtilis spores of DNA polymerase I-proficient and -deficient strains

    International Nuclear Information System (INIS)

    Tanooka, H.

    1980-01-01

    The nature of mutagenic ionizing radiation damage modified by the presence of oxygen or water was examined by comparing mutagenic with lethal expression of the damage in Bacillus subtilis spores irradiated with 6-MeV electrons. No specific difference was recognized between oxygen-dependent and -independent damages or between polA + -dependent and -independent damages with this system. The induced mutation frequency for His + mutation per lethal hit was 4.7 x 10 -5 for all tested cases

  6. Lethal neonatal short-limbed dwarfism

    International Nuclear Information System (INIS)

    Kim, Ok Hwa; Yim, Chung Ik; Bahk, Yong Whee

    1986-01-01

    We have detailed our experiences on 6 cases of neonatal lethal short-limbed dwarfism and reviewed the articles. They include, achondrogenesis, thanatophoric dysplasia, asphyxiating thoracic dysplasia, osteogenesis imperfect a congenita, and hypophosphatasia lethals. Five babies were born alive but died soon after birth and one was a stillbirth. The main cause of failure to thrive was respiratory insufficiency. Each case was having quite characteristic radiologic findings, even if the general appearances were similar to the achondroplasts clinically. Precise diagnosis is very important for genetic counselling of the parents and alarm to them the possibility of bone dysplasias to the next offsprings. For this purpose, the radiologists play major role for the correct diagnosis. We stress that when the baby is born with short-limbed dwarfism, whole body radiogram should be taken including lateral view and postmortem radiogram is also very precious.

  7. Lethal neonatal short-limbed dwarfism

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ok Hwa; Yim, Chung Ik; Bahk, Yong Whee [Catholic Medical College, Seoul (Korea, Republic of)

    1986-02-15

    We have detailed our experiences on 6 cases of neonatal lethal short-limbed dwarfism and reviewed the articles. They include, achondrogenesis, thanatophoric dysplasia, asphyxiating thoracic dysplasia, osteogenesis imperfect a congenita, and hypophosphatasia lethals. Five babies were born alive but died soon after birth and one was a stillbirth. The main cause of failure to thrive was respiratory insufficiency. Each case was having quite characteristic radiologic findings, even if the general appearances were similar to the achondroplasts clinically. Precise diagnosis is very important for genetic counselling of the parents and alarm to them the possibility of bone dysplasias to the next offsprings. For this purpose, the radiologists play major role for the correct diagnosis. We stress that when the baby is born with short-limbed dwarfism, whole body radiogram should be taken including lateral view and postmortem radiogram is also very precious.

  8. Mining of lethal recessive genetic variation in Danish cattle

    DEFF Research Database (Denmark)

    Das, Ashutosh

    2015-01-01

    in fertility. The primary objective of this PhD projekt was to identify recessive lethal gentic variants in the main Danish dairy cattle breed. Holstein-Friesian utilzing next generation sequencing (NGS) data. This study shows a potential for the use of the NGS-based reverse genetic approach in identifying...... lethal or semi-lethal recessive gentic variation...

  9. Lethal midline granuloma syndrome: a diagnostic dilemma

    International Nuclear Information System (INIS)

    Ribeiro, Bruno Niemeyer de Freitas; Bahia, Paulo Roberto Valle; Oliveira, Ana Luiza Vianna Sobral de Magalhaes; Marchon Junior, Joao Luiz

    2012-01-01

    The rare lethal midline granuloma syndrome is difficult to diagnose because of the wide array of related diseases and lack of knowledge by the majority of physicians. In the present report, the authors describe the case of a patient with this disease, caused by squamous cell carcinoma, drawing attention to differential diagnoses and to clinical and radiological findings that may be useful to define the diagnosis. (author)

  10. Lethal Interpersonal Violence in the Middle Pleistocene

    OpenAIRE

    Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-P?rez, Ana; Pablos, Adri?n; Mart?nez, Ignacio; Quam, Rolf M.; G?mez-Olivencia, Asier; Berm?dez de Castro, Jos? Mar?a; Carbonell, Eudald

    2015-01-01

    Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force ...

  11. Lethal midline granuloma syndrome: a diagnostic dilemma

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Bruno Niemeyer de Freitas; Bahia, Paulo Roberto Valle [Radiology, Hospital Universitario Clementino Fraga Filho - Universidade Federal do Rio de Janeiro (HUCFF-UFRJ), Rio de Janeiro, RJ (Brazil); Oliveira, Ana Luiza Vianna Sobral de Magalhaes [Resident of Medical Practice, Hospital Federal da Lagoa, Rio de Janeiro, RJ (Brazil); Marchon Junior, Joao Luiz [Unit of Computed Tomography, Hospital Federal da Lagoa, Rio de Janeiro, RJ (Brazil)

    2012-11-15

    The rare lethal midline granuloma syndrome is difficult to diagnose because of the wide array of related diseases and lack of knowledge by the majority of physicians. In the present report, the authors describe the case of a patient with this disease, caused by squamous cell carcinoma, drawing attention to differential diagnoses and to clinical and radiological findings that may be useful to define the diagnosis. (author)

  12. Potentiation of radiation lethality by Topotecan, a Topoisomerase I inhibitor

    International Nuclear Information System (INIS)

    Lamond, J.P.; Kinsella, T.J.; Boothman, D.A.

    1995-01-01

    Purpose/Objective: Topotecan is a water soluble Topoisomerase I (Topo I) inhibitor that has demonstrated antineoplastic activity in phase I/II trials of solid tumors (such as non-small cell lung, small cell lung, ovarian, esophageal and head and neck primaries) and leukemias. We sought to determine (1) if Topotecan potentiated the lethal effects of ionizing radiation, and (2) the characteristics of the synergistic effect. Materials and Methods: Human radioresistant melanoma (U1-Mel) and glioma (D54) cells were grown in Dulbecco's modified Eagle's medium (DME) with 10% fetal calf serum (FCS) until confluence-arrest. Cells were x-irradiated (0-700 cGy) and exposed to various Topotecan concentrations (2-100μM), either before (for 4 hours), during, or after (for 4 hours) irradiation. Appropriate controls were also performed. Survival was determined via colony forming assays. Survival curves were normalized to correct for drug cytotoxicities and variations in initial viable cells plated. In another set of experiments, U1-Mel cells were exposed to 10 μM Topotecan either before, during or after 400 cGy, as described above. A modification of the SDS and KCl assay was used to quantify Topo I-DNA complexes via glass fiber filter binding. All experiments were performed at least 7 times in duplicate. Results: Potentiation of radiation lethality was seen in the U1-Mel and D54 cell lines. The synergistic effects were (1) dependent on drug concentration, with lethality enhancement and minimal drug lethality alone in the 2-10 μM range (2) dependent on timing, with synergy present only when the drug was present at the time of, or shortly after irradiation, and (3) irreversible, with inhibition of potential lethal damage repair (PLDR). The dose enhancement ratios (DER) for 4 μM Topotecan in the U1-Mel cells was 1.7 - 2.4, depending on the survival endpoints that were used. The DER for 2 μM Topotecan in D54 cells was 3.0 - 4.0. The U1-Mel cells that were exposed to Topotecan

  13. Nano-crystalline Ag–PbTe thermoelectric thin films by a multi-target PLD system

    Energy Technology Data Exchange (ETDEWEB)

    Cappelli, E., E-mail: emilia.cappelli@ism.cnr.it [CNR-ISM, Montelibretti, Via Salaria Km 29.3, P.O.B. 10, 00016 Rome (Italy); Bellucci, A. [CNR-ISM, Montelibretti, Via Salaria Km 29.3, P.O.B. 10, 00016 Rome (Italy); Dip. Fisica, Un. Roma Sapienza, Piazzale Aldo Moro 2, 00185 Rome (Italy); Medici, L. [CNR-IMAA, Tito Scalo, 85050 Potenza (Italy); Mezzi, A.; Kaciulis, S. [CNR-ISMN, Montelibretti, Via Salaria Km 29.3, P.O.B. 10, 00016 Rome (Italy); Fumagalli, F.; Di Fonzo, F. [Center Nano Science Technology @Polimi, I.I.T., Via Pascoli 70/3, 20133 Milano (Italy); Trucchi, D.M. [CNR-ISM, Montelibretti, Via Salaria Km 29.3, P.O.B. 10, 00016 Rome (Italy)

    2015-05-01

    Highlights: • Thermoelectric PbTe thin films, with increasing Ag percentage, were deposited by PLD. • Almost stoichiometric PbTe (Ag doped) films were grown, as verified by XPS analysis. • GI-XRD established the formation of cubic PbTe, with nano-metric structure (∼35 nm). • Surface resistivity shows an increase in conductivity, with increasing Ag doping. • From Seebeck values and XPS depth analysis, 10% Ag seems to be the solubility limit. - Abstract: It has been evaluated the ability of ArF pulsed laser ablation to grow nano-crystalline thin films of high temperature PbTe thermoelectric material, and to obtain a uniform and controlled Ag blending, through the entire thickness of the film, using a multi-target system in vacuum. The substrate used was a mirror polished technical alumina slab. The increasing atomic percentage of Ag effect on physical–chemical and electronic properties was evaluated in the range 300–575 K. The stoichiometry and the distribution of the Ag component, over the whole thickness of the samples deposited, have been studied by XPS (X-ray photoelectron spectroscopy) and corresponding depth profiles. The crystallographic structure of the film was analyzed by grazing incidence X-ray diffraction (GI-XRD) system. Scherrer analysis for crystallite size shows the presence of nano-structures, of the order of 30–35 nm. Electrical resistivity of the samples, studied by the four point probe method, as a function of increasing Ag content, shows a typical semi-conductor behavior. From conductivity values, carrier concentration and Seebeck parameter determination, the power factor of deposited films was calculated. Both XPS, Hall mobility and Seebeck analysis seem to indicate a limit value to the Ag solubility of the order of 5%, for thin films of ∼200 nm thickness, deposited at 350 °C. These data resulted to be comparable to theoretical evaluation for thin films but order of magnitude lower than the corresponding bulk materials.

  14. Lethal interpersonal violence in the Middle Pleistocene.

    Directory of Open Access Journals (Sweden)

    Nohemi Sala

    Full Text Available Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin.

  15. Lethal interpersonal violence in the Middle Pleistocene.

    Science.gov (United States)

    Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-Pérez, Ana; Pablos, Adrián; Martínez, Ignacio; Quam, Rolf M; Gómez-Olivencia, Asier; Bermúdez de Castro, José María; Carbonell, Eudald

    2015-01-01

    Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin.

  16. Association of Corynebacterium pseudotuberculosis recombinant proteins rCP09720 or rCP01850 with rPLD as immunogens in caseous lymphadenitis immunoprophylaxis.

    Science.gov (United States)

    Silva, Mara Thais de Oliveira; Bezerra, Francisco Silvestre Brilhante; de Pinho, Rodrigo Barros; Begnini, Karine Rech; Seixas, Fabiana Kommling; Collares, Tiago; Portela, Ricardo Dias; Azevedo, Vasco; Dellagostin, Odir; Borsuk, Sibele

    2018-01-02

    Caseous lymphadenitis (CLA) is a chronic disease responsible for significant economic losses in sheep and goat breeding worldwide. The treatment for this disease is not effective, and an intense vaccination schedule would be the best control strategy. In this study, we evaluated the associations of rCP09720 or rCP01850 proteins from Corynebacterium pseudotuberculosis with recombinant exotoxin phospholipase D (rPLD) as subunit vaccines in mice. Four experimental groups (10 animals each) were immunized with a sterile 0.9% saline solution (G1), rPLD (G2), rPLD + rCP09720 (G3), and rPLD + rCP01850 (G4). The mice received two doses of each vaccine at a 21-day interval and were challenged 21 days after the last immunization. The animals were evaluated daily for 40 days after the challenge, and mortality rate was recorded. The total IgG production level increased significantly in the experimental groups on day 42 after the first vaccination. Similarly, higher levels of specific IgG2a were observed in experimental groups G2, G3, and G4 compared to the IgG1 levels on day 42. G4 showed a significant (p < .05) humoral response against both antigens of the antigenic formulations. The cellular immune response induced by immunization was characterized by a significant (p < .05) production of interferon-γ compared to that in the control, while the concentrations of interleukin (IL)-4 and IL-12 were not significant in any group. A significant increase of tumor necrosis factor was observed only in G4. The survival rates after the challenge were 30% (rPLD), 40% (rPLD + rCP09720), and 50% (rPLD + rCP01850). Thus, the association of rCP01850 with rPLD resulted in the best protection against the challenge with C. pseudotuberculosis and induced a more intense type 1 T-helper cell immune response. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Aberrations of holokinetic chromosomes and associated lethality after X-irradiation of meiotic stages in Tetranychus urticae Koch (acari, tetranychidae)

    International Nuclear Information System (INIS)

    Tempelaar, M.J.

    1979-01-01

    Chromosomes of the holokinetic organization type were irradiated with X-rays in various stages of meiosis in unfertillized eggs of Tetranychus urticae Koch. Visible cytological aberrations, lethality and sterility were investigated in subsequent generations. Chromosome fragments are the most frequently occuring light-microscopically visible chromosome aberrations; bridges are not formed. Contrary to expectations, the presence of fragments appears to be positively correlated with the occurrence of lethality; loss of fragments, missegregation and the measure of damage of the broken chromosome parts are involved. In contrast with monokinetic chromosomes the earliest lethality occurs only after about 10 divisions. The ratios between different embryonic lethality types (early vs. late) differ depending on the stage irradiated: in more compact chromatin, more serious damage (i.e. more early lethality syndromes) is induced than in less compact chromatin. In the progeny of the surviving males, neither translocations nor independent fragments are found; indirect evidence indicated the occasional presence of inversions. The presumtive inversions are induced more frequently in a chromatin-compact stage (metaphase I) than in a less compact one (telophase I). (Auth.)

  18. Late radiation effects in animals surviving lethal irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Dimitrov, L A

    1974-01-01

    Animals (rats, mice, dogs) survived lethal irradiation by means of prophylactic-therapeutic treatments or previously irradiated, were studied for late radiation effects: life span, cachexia and fat growing of hypophysical type, tissue or organ hypoplasia manifested by disturbed hemopoiesis, suppressed function of adrenal gland, etc., suppressed immune reactivity of the irradiated organism, atypical biochemical changes in DNA and protein metabolism, epilation, chronic dermatitis, ulcerations, reduced reproductivity or full sterility, damage of kidneys leading to nephrosclerosis, dishormonal states, cataracts, diffuse sclerotic processes, various kinds of malignant and non-malignant tumors. In these cases hemopoiesis compensated for a definite time peripheral blood composition, but during the late period it showed features of incompleteness: shorter life survival of erythrocytes and thrombocytes manifested by a decreased binding of labelled methionine in these blood elements, anemia and relative thrombocytopenia sometimes with an increased number of polychromatic erythrocytes in peripheral blood and a decreased number of reticulocytes at the same time; lymphopenia and relative leucopenia with an increased number of hypersegmented neutrophils. Decreased reproductivity and atypical biochemical changes available in the first generation of the irradiated animals showed the probable role of mutagenic factors in the emergency of some late radiation effects. A significant part of late radiation sequences were due to neuro-endocrine disintegrations. Some of the described late radiation effects were also observed in biological controls as features of ageing. After application of radioprotectors (AET, cysteamine, serotonin) a more marked protective effect is demonstrated in the early reactions (time survival till 30th day, DNA and protein metabolism, immune reactions) of the lethally irradiated animals.

  19. Comparative studies of dose-response curves for recessive lethal mutations induced by ethylnitrosourea in spermatogonia and in spermatozoa of Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, I.; Ayaki, T.; Ohshima, K.

    1984-01-01

    Induction of recessive lethal mutation by N-ethyl-N-nitrosourea (ENU) was studied for the second chromosome of spermatogonia and spermatozoa in Drosophila melanogaster. ENU (0.03, 0.3, and 1.0 mM) was given to flies by dissolving it in feeding sucrose solution. When plotted against absorbed doses of ENU, the observed frequencies to recessive lethals showed a linear relationship for induction in spermatozoa but a sigmoidal relationship for induction in spermatogonia. These results suggest that in spermatogonia ENU-induced mutational damage is more repairable in a lower dose range of ENU. Mosaic lethal mutations were induced by ENU but not in spermatogonia.

  20. Beliefs and attitudes toward lethal management of deer in Cuyahoga Valley National Park

    Science.gov (United States)

    Fulton, D.C.; Skerl, K.; Shank, E.M.; Lime, D.W.

    2004-01-01

    We used the theory of reasoned action to help understand attitudes and beliefs about lethal management of deer (Odocoileus virginianus) in Cuyahoga Valley National Park (CVNP), Ohio. We used a mail-back survey to collect data from Ohio residents in the surrounding 9-county area. Two strata were defined: residents control of deer was acceptable (near 71%??4.7%, far 62%??5.5%) and taking no action to reduce deer populations was unacceptable (near 75%??4.5%, far 72%??5.1%). Beliefs about outcomes of lethal control and evaluation of those outcomes proved to be strong predictors of the acceptability of lethal control of deer in CVNP. Lethal control was more acceptable if it was done to prevent severe consequences for humans (e.g., spread of disease, car collisions) or the natural environment (e.g., maintain a healthy deer herd) than to prevent negative aesthetic impacts or personal property damage. Results from the study can be used to assist managers at CVNP as they make decisions regarding alternatives for deer management in the park and to inform others managing abundant deer populations of socially relevant impacts of management actions.

  1. Dominant lethal and ovarian effects of plutonium-239 in female mice

    International Nuclear Information System (INIS)

    Searle, A.G.; Beechey, C.V.; Green, D.; Howells, G.R.

    1982-01-01

    (C3H x 101)F 1 female mice were injected intravenously with 239 Pu in trisodium citrate, then mated in pairs to strain CBA males, to test for dominant lethality. In the first experiment 10μCi kg -1 and in the second 20μCi kg -1 body mass was injected. Matings were after 6 days in the first experiment (estimated ovarian absorbed dose of 0.1 Gy) and after 3,6 or 12 weeks in the second (estimated ovarian doses of 1.11, 2.45 and 5.91 Gy respectively). No evidence of dominant lethal induction was found in the first experiment, but in the second there was a significant increase over controls in pre-implantation loss in all three series. Post-implantation lethality increased significantly (by 12%) only after 12 weeks' exposure. With the 6- and 12-week exposures (especially the latter) luteal counts fell, fewer females becoming pregnant than in controls. This is attributed to oocyte killing by the α-particles. Histological and autoradiographic investigations showed a marked reduction in ovarian size and follicular numbers with fission-tracks clustered mainly over the medullary stroma. The preimplantation loss may stem from lowered fertilization of oocytes because of their damage, so that the best measure of dominant lethality is that based on post-implantation death. (author)

  2. An Immature Myeloid/Myeloid-Suppressor Cell Response Associated with Necrotizing Inflammation Mediates Lethal Pulmonary Tularemia.

    Directory of Open Access Journals (Sweden)

    Sivakumar Periasamy

    2016-03-01

    Full Text Available Inhalation of Francisella tularensis (Ft causes acute and fatal pneumonia. The lung cytokine milieu favors exponential Ft replication, but the mechanisms underlying acute pathogenesis and death remain unknown. Evaluation of the sequential and systemic host immune response in pulmonary tularemia reveals that in contrast to overwhelming bacterial burden or cytokine production, an overt innate cellular response to Ft drives tissue pathology and host mortality. Lethal infection with Ft elicits medullary and extra-medullary myelopoiesis supporting recruitment of large numbers of immature myeloid cells and MDSC to the lungs. These cells fail to mature and die, leading to subsequent necrotic lung damage, loss of pulmonary function, and host death that is partially dependent upon immature Ly6G+ cells. Acceleration of this process may account for the rapid lethality seen with Ft SchuS4. In contrast, during sub-lethal infection with Ft LVS the pulmonary cellular response is characterized by a predominance of mature neutrophils and monocytes required for protection, suggesting a required threshold for lethal bacterial infection. Further, eliciting a mature phagocyte response provides transient, but dramatic, innate protection against Ft SchuS4. This study reveals that the nature of the myeloid cell response may be the primary determinant of host mortality versus survival following Francisella infection.

  3. An Immature Myeloid/Myeloid-Suppressor Cell Response Associated with Necrotizing Inflammation Mediates Lethal Pulmonary Tularemia

    Science.gov (United States)

    Periasamy, Sivakumar; Avram, Dorina; McCabe, Amanda; MacNamara, Katherine C.; Sellati, Timothy J.; Harton, Jonathan A.

    2016-01-01

    Inhalation of Francisella tularensis (Ft) causes acute and fatal pneumonia. The lung cytokine milieu favors exponential Ft replication, but the mechanisms underlying acute pathogenesis and death remain unknown. Evaluation of the sequential and systemic host immune response in pulmonary tularemia reveals that in contrast to overwhelming bacterial burden or cytokine production, an overt innate cellular response to Ft drives tissue pathology and host mortality. Lethal infection with Ft elicits medullary and extra-medullary myelopoiesis supporting recruitment of large numbers of immature myeloid cells and MDSC to the lungs. These cells fail to mature and die, leading to subsequent necrotic lung damage, loss of pulmonary function, and host death that is partially dependent upon immature Ly6G+ cells. Acceleration of this process may account for the rapid lethality seen with Ft SchuS4. In contrast, during sub-lethal infection with Ft LVS the pulmonary cellular response is characterized by a predominance of mature neutrophils and monocytes required for protection, suggesting a required threshold for lethal bacterial infection. Further, eliciting a mature phagocyte response provides transient, but dramatic, innate protection against Ft SchuS4. This study reveals that the nature of the myeloid cell response may be the primary determinant of host mortality versus survival following Francisella infection. PMID:27015566

  4. Modification of damage following low doses

    International Nuclear Information System (INIS)

    Braby, L.A.; Nelson, J.M.; Metting, N.F.

    1988-01-01

    At very low doses the damage-interaction mechanism is responsible for very little lethal or potentially lethal damage, and repair of the latter should essentially disappear. An alternative model suggests that potentially lethal damage is either repaired with a constant half time or misrepaired at a rate which is proportional to the square of the damage concentration. In this case, as the dose decreases, the probability of misrepair decreases faster than the probability of repair, and repair becomes a more pronounced feature of the cell response. Since the consequence of unrepaired damage is an important question in determining the effects of low doses of radiation delivered at low dose rates, we have attempted to determine which of these two types of models is consistent with the response of plateau-phase CHO cells. In the earlier experiments, there was no indication of repair after a 50-rad exposure with a 24-hour split dose or plating delay; in fact, immediate plating resulted in survival slightly above control and delayed plating in survival slightly below the control value

  5. Persistent photocurrent and deep level traps in PLD-grown In-Ga-Zn-O thin films studied by thermally stimulated current spectroscopy

    Science.gov (United States)

    Wang, Buguo; Anders, Jason; Leedy, Kevin; Schuette, Michael; Look, David

    2018-02-01

    InGaZnO (IGZO) is a promising semiconductor material for thin-film transistors (TFTs) used in DC and RF switching applications, especially since it can be grown at low temperatures on a wide variety of substrates. Enhancement-mode TFTs based on IGZO thin films grown by pulsed laser deposition (PLD) have been recently fabricated and these transistors show excellent performance; however, compositional variations and defects can adversely affect film quality, especially in regard to electrical properties. In this study, we use thermally stimulated current (TSC) spectroscopy to characterize the electrical properties and the deep traps in PLD-grown IGZO thin films. It was found that the as-grown sample has a DC activation energy of 0.62 eV, and two major traps with activation energies at 0.16-0.26 eV and at 0.90 eV. However, a strong persistent photocurrent (PPC) sometimes exists in the as-grown sample, so we carry out post-growth annealing in an attempt to mitigate the effect. It was found that annealing in argon increases the conduction, produces more PPC and also makes more traps observable. Annealing in air makes the film more resistive, and removes PPC and all traps but one. This work demonstrates that current-based trap emission, such as that associated with the TSC, can effectively reveal electronic defects in highlyresistive semiconductor materials, especially those are not amenable to capacitance-based techniques, such as deeplevel transient spectroscopy (DLTS).

  6. Lethal effects of solar radiation in proficient and deficient bacteria in repair systems

    International Nuclear Information System (INIS)

    Sousa Neto, A. de.

    1980-01-01

    A study of the lethal action of solar radiation on strains of E.coli K12, proficient or deficient in repair systems, as well as the wild type strain gene products are involved in repair of damage induced by solar radiation. The inactivation of the various bacterial strains (normalized to a dose equivalent to radiation at a wavelength 254 nm) suggests that the more energetic wavelengths of the solar spectrum (290-320 nm) could be responsible for the primary damage that occurs in the DNA. The reduction in the shoulder of the survival curve in wild type strains in indicative of induction of sub-lethal damage in this region of the curve. Analysing solar inactivation curves of the bacterial strains (normalised by spore dosimetry) together with those of the same strains irradiated with UV at 254 nm, it was evident that 254 nm is not the ideal wavelength for comparison. This analysis also indicated that in addition to damage to DNA, other factors are involved in the solar radiation inactivation of wild type strains. (author)

  7. Low survival of mice following lethal gamma-irradiation after administration of inhibitors of prostaglandin synthesis

    International Nuclear Information System (INIS)

    Hofer, M.; Pospisil, M.; Tkadlecek, L.; Viklicka, S.; Pipalova, I.; Hola, J.

    1992-01-01

    An impairment was observed of the survival of mice subjected to whole-body gamma-irradiation with a lethal dose of 10 Gy and treated with a repeated postirradiation administration of the prostaglandin synthesis inhibitors (PGSIs) indomethacin or diclofenac. Morphological examination of the gastrointestinal tract and estimation of the blood loss into its lumen in animals treated with diclofenac did not show serious damage such as hemorrhages or perforation, but revealed structural injury to the intestinal mucosa indicating inflammatory processes. The lesions found are supposed to be connected with increased intestinal permeability which leads to endotoxin escape from the gut and a subsequent increased mortality rate of irradiated animals. It may be concluded that PGSIs are not suitable for the management of radiation sickness after an exposure to lethal doses of ionizing radiation. (author) 2 tabs., 4 figs., 20 refs

  8. Estimation of the contribution of ionization and excitation to the lethal effect of ionizing radiation

    International Nuclear Information System (INIS)

    Petin, V.G.; Komarov, V.P.

    1982-01-01

    A simple theoretical model is proposed for estimating the differential contribution of ionization and excitation to the lethal effect of ionizing radiation. Numerical results were obtained on the basis of published experimental data on the ability of bacterial cells Escherichia coli to undergo photoreactivation of radiation-induced damage. It was shown that inactivation by excitation may be highly significant for UV-hypersensitive cells capable of photoreactivation; inactivation by excitation increased with the energy of ionizing radiation and the volume of irradiated suspensions. The data are in qualitative agreement with the assumption of a possible contribution of the UV-component of Cerenkov radiation to the formation of excitations responsible for the lethal effect and the phenomenon of photoreactivation after ionizing radiation. Some predictions from the model are discussed. (orig.)

  9. Fluorescent-light-induced lethality and DNA repair in normal and xeroderma pigmentosum fibroblasts

    International Nuclear Information System (INIS)

    Ritter, M.A.; Williams, J.R.

    1981-01-01

    Cell survival and induction of endonuclease-sensitive sites in DNA were measured in human fibroblast cells exposed to fluorescent light or germicidal ultraviolet light. Cells from a xeroderma pigmentosum patient were hypersensitive to cell killing by fluorescent light, although less so than for germicidal ultraviolet light. Xeroderma pigmentosum cells were deficient in the removal of fluorescent light-induced endonuclease sites that are probably pyrimidine dimers, and both the xeroderma pigmentosum and normal cells removed these sites with kinetics indistinguishable from those for ultraviolet light-induced sites. A comparison of fluorescent with ultraviolet light data demonstrates that there are markedly fewer pyrimidine dimers per lethal event for fluorescent than for ultraviolet light, suggesting a major role for non-dimer damage in fluorescent lethality. (Auth.)

  10. Lethal congenital contracture syndrome (LCCS) and other lethal arthrogryposes in Finland--an epidemiological study.

    Science.gov (United States)

    Pakkasjärvi, Niklas; Ritvanen, Annukka; Herva, Riitta; Peltonen, Leena; Kestilä, Marjo; Ignatius, Jaakko

    2006-09-01

    Arthrogryposis multiplex congenita is a heterogeneous group of disorders characterized by multiple contractures with an estimated frequency of 1 in 3,000 births. With improving diagnostic methods, increasing numbers of fetuses with arthrogryposis are found. The pathogenetic mechanisms are relatively well known but the epidemiology and genetics of the prenatally lethal forms of arthrogryposis are less well known. In this study we collected all cases of a multiple contractures diagnosed in Finland during 1987-2002 including live born infants, stillbirths, and terminated pregnancies. Ninety-two cases of 214 suffered intrauterine demise (68 selective pregnancy terminations and 24 stillbirths) and 58 died in infancy. In 141 out of these cases the diagnosis could be included within lethal arthrogryposes, with a prevalence of 1 in 6,985 (1.43/10,000) births. Of these, 59 had spinal cord pathology at autopsy and thus were of neurogenic origin. Thirty-nine cases had lethal congenital contracture syndrome (LCCS) clinically characterized by total immobility of the fetus at all ultrasound examinations (12 weeks or later), multiple joint contractures in both upper and lower limbs, hydrops, and fetal death before the 32nd week of pregnancy. LCCS is noted as a unique Finnish disorder with a prevalence of 1 in 25,250 (0.40/10,000) births and is a major cause of lethal arthrogryposis in Finland.

  11. Suicide Intent and Accurate Expectations of Lethality: Predictors of Medical Lethality of Suicide Attempts

    Science.gov (United States)

    Brown, Gregory K.; Henriques, Gregg R.; Sosdjan, Daniella; Beck, Aaron T.

    2004-01-01

    The degree of intent to commit suicide and the severity of self-injury were examined in individuals (N = 180) who had recently attempted suicide. Although a minimal association was found between the degree of suicide intent and the degree of lethality of the attempt, the accuracy of expectations about the likelihood of dying was found to moderate…

  12. Lethal domestic violence in eastern North Carolina.

    Science.gov (United States)

    Gilliland, M G; Spence, P R; Spence, R L

    2000-01-01

    Strategies for preventing domestic violence can be tailored to a particular geographic or socioeconomic area if the patterns of domestic violence in the area are known. National statistics, although widely available, may not be applicable to a specific region. We reviewed homicide deaths in Eastern North Carolina between 1978 and 1999 to identify patterns in this rural area. Approximately 20% of the homicide deaths in eastern North Carolina are caused by intimate partners. Women accounted for 53% of the victims in 1976, similar to national figures but not rising to 72% as seen nationally in 1998. Latinos are an increasing presence in the area, but had only one recorded episode of lethal violence against an intimate partner. Gunshots accounted for most of the deaths (59% in men, 72% in women). Knowledge of such patterns can assist in selecting prevention strategies for this particular area. Over the last 25 years increasing attention has been devoted to domestic violence (DV), initially defined as abuse committed against a spouse, former spouse, fiancée, boy- or girlfriend, or cohabitant. As time has passed, the definition has been broadened to include other family members--elders, children, and siblings. The Centers for Disease Control and Prevention (CDC) now uses the term "intimate partner violence" for intentional emotional or physical abuse inflicted by a spouse, ex-spouse, a present or former boy- or girlfriend, or date. For the purposes of this paper, we consider DV interchangeable with intimate partner violence. There has been a national concern that abusive events are under-reported. The National Crime Victimization Survey, an anonymous household survey, indicated nearly 1 million incidents of non-lethal intimate partner violence per year between 1992 and 1996. The number decreased from 1.1 million in 1993 to 840,000 in 1996. Attempts to validate such data for a given geographic area often require subjects to violate anonymity--this may account for lower

  13. A pharmacological screen for compounds that rescue the developmental lethality of a Drosophila ATM mutant.

    Science.gov (United States)

    Rimkus, Stacey A; Wassarman, David A

    2018-01-01

    Ataxia-telangiectasia (A-T) is a neurodegenerative disease caused by mutation of the A-T mutated (ATM) gene. ATM encodes a protein kinase that is activated by DNA damage and phosphorylates many proteins, including those involved in DNA repair, cell cycle control, and apoptosis. Characteristic biological and molecular functions of ATM observed in mammals are conserved in Drosophila melanogaster. As an example, conditional loss-of-function ATM alleles in flies cause progressive neurodegeneration through activation of the innate immune response. However, unlike in mammals, null alleles of ATM in flies cause lethality during development. With the goals of understanding biological and molecular roles of ATM in a whole animal and identifying candidate therapeutics for A-T, we performed a screen of 2400 compounds, including FDA-approved drugs, natural products, and bioactive compounds, for modifiers of the developmental lethality caused by a temperature-sensitive ATM allele (ATM8) that has reduced kinase activity at non-permissive temperatures. Ten compounds reproducibly suppressed the developmental lethality of ATM8 flies, including Ronnel, which is an organophosphate. Ronnel and other suppressor compounds are known to cause mitochondrial dysfunction or to inhibit the enzyme acetylcholinesterase, which controls the levels of the neurotransmitter acetylcholine, suggesting that detrimental consequences of reduced ATM kinase activity can be rescued by inhibiting the function of mitochondria or increasing acetylcholine levels. We carried out further studies of Ronnel because, unlike the other compounds that suppressed the developmental lethality of homozygous ATM8 flies, Ronnel was toxic to the development of heterozygous ATM8 flies. Ronnel did not affect the innate immune response of ATM8 flies, and it further increased the already high levels of DNA damage in brains of ATM8 flies, but its effects were not harmful to the lifespan of rescued ATM8 flies. These results provide

  14. Imbibitional damage in conidia of the entomopathogenic fungi Beauveria bassiana, Metarhizium anisopliae, and Metarhizium acridum

    Science.gov (United States)

    When dried organisms are immersed in water, rapid imbibition may cause severe damage to plasma membranes; in unicellular organisms, such damage is usually lethal. This study investigated effects of pre-immersion moisture levels and immersion temperature on imbibitional damage in three insect pathoge...

  15. PED/PEA-15 inhibits hydrogen peroxide-induced apoptosis in Ins-1E pancreatic beta-cells via PLD-1.

    Directory of Open Access Journals (Sweden)

    Francesca Fiory

    Full Text Available The small scaffold protein PED/PEA-15 is involved in several different physiologic and pathologic processes, such as cell proliferation and survival, diabetes and cancer. PED/PEA-15 exerts an anti-apoptotic function due to its ability to interfere with both extrinsic and intrinsic apoptotic pathways in different cell types. Recent evidence shows that mice overexpressing PED/PEA-15 present larger pancreatic islets and increased beta-cells mass. In the present work we investigated PED/PEA-15 role in hydrogen peroxide-induced apoptosis in Ins-1E beta-cells. In pancreatic islets isolated from Tg(PED/PEA-15 mice hydrogen peroxide-induced DNA fragmentation was lower compared to WT islets. TUNEL analysis showed that PED/PEA-15 overexpression increases the viability of Ins-1E beta-cells and enhances their resistance to apoptosis induced by hydrogen peroxide exposure. The activity of caspase-3 and the cleavage of PARP-1 were markedly reduced in Ins-1E cells overexpressing PED/PEA-15 (Ins-1E(PED/PEA-15. In parallel, we observed a decrease of the mRNA levels of pro-apoptotic genes Bcl-xS and Bad. In contrast, the expression of the anti-apoptotic gene Bcl-xL was enhanced. Accordingly, DNA fragmentation was higher in control cells compared to Ins-1E(PED/PEA-15 cells. Interestingly, the preincubation with propranolol, an inhibitor of the pathway of PLD-1, a known interactor of PED/PEA-15, responsible for its deleterious effects on glucose tolerance, abolishes the antiapoptotic effects of PED/PEA-15 overexpression in Ins-1E beta-cells. The same results have been obtained by inhibiting PED/PEA-15 interaction with PLD-1 in Ins-1E(PED/PEA-15. These results show that PED/PEA-15 overexpression is sufficient to block hydrogen peroxide-induced apoptosis in Ins-1E cells through a PLD-1 mediated mechanism.

  16. Sub-Lethal Dose of Shiga toxin 2 from Enterohemorrhagic Escherichia coli Affects Balance and Cerebellar Cythoarquitecture.

    Directory of Open Access Journals (Sweden)

    Luciana eD’Alessio

    2016-02-01

    Full Text Available Shiga toxin producing Escherichia coli may damage the central nervous system before or concomitantly to manifested hemolytic uremic syndrome symptoms. The cerebellum is frequently damaged during this syndrome, however the deleterious effects of Shiga toxin 2 has never been integrally reported by ultrastructural, physiological and behavioral means. The aim of this study was to determine the cerebellar compromise after intravenous administration of a sub-lethal dose of Shiga toxin 2 by measuring the cerebellar blood brain barrier permeability, behavioral task of cerebellar functionality (inclined plane test, and ultrastructural analysis (transmission electron microscope. Intravenous administration of vehicle (control group, sub-lethal dose of 0.5 ηg and 1 ηg of Stx2 per mouse were tested for behavioral and ultrastructural studies. A set of three independent experiments were performed for each study (n=6. Blood–Brain Barrier resulted damaged and consequently its permeability was significantly increased. Lower scores obtained in the inclined plane task denoted poor cerebellar functionality in comparison to their controls. The most significant lower score was obtained after 5 days of 1ηg of toxin administration. Transmission electron microscope micrographs from the Stx2-treated groups showed neurons with a progressive neurodegenerative condition in a dose dependent manner. As sub-lethal intravenous Shiga toxin 2 altered the blood brain barrier permeability in the cerebellum the toxin penetrated the cerebellar parenchyma and produced cell damaged with significant functional implications in the test balance.

  17. Computed tomography of lethal medline granuloma

    International Nuclear Information System (INIS)

    Lee, Ho Suk; Kim, Tae Ho; Suh, Kyung Jin; Kim, Tae Hun; Kim, Yong Joo; Kang, Duk Sik

    1991-01-01

    In order to clarify the CT findings of lethal midline granuloma (LMG) diagnosed clinically or histopathologically, the authors retrospectively analyzed 12 patients who were seen at Kyungpook National University Hospital from February 1985 to August 1989. CT showed nasal mucosal thickening and / or soft tissue mass (9 case), spreading of the lesions along the facial subcutaneous fat plane (8 cases), invasion into the paranasal sinuses (5 cases), bone destruction (5 cases), nasopharyngeal mass lesion (2 cases), and extension of the lesion into the infratemporal fossa (1 case). In spite of the fact that CT does not make definitive diagnosis of LMG, it permits evaluation of the extent of the lesion, detection of the combined lesion, differential diagnosis, and close monitoring of its evolution under treatment

  18. Gluconeogenesis in lethally X-irradiated rats

    International Nuclear Information System (INIS)

    Paulikova, E.; Ahlers, I.; Praslicka, M.

    1983-01-01

    The in vivo incorporation of U- 14 C-alanine into blood glucose and liver glycogen was measured in rats irradiated with a single whole body lethal dose of X-rays. Changes in gluconeogenic enzyme activities were studied in the liver. Increased incorporation of 14 C-alanine into blood glucose and liver glycogen were found after irradiation. Liver phosphoenolpyruvate carboxykinase and glycogenic activity underwent almost parallel changes and were significantly elevated from the 6th to the 48th hour, with resultant accumulation of glycogen. Glucose-6-phosphatase activity was depressed and there was a negative correlation between it and liver glycogen concentration. Maximum fructose-1,6-diphosphatase activity was found at 48 hours. The results show that glycogen accumulation in the liver and the raised blood glucose level in X-irradiated rats are based on raised gluconeogenesis. (author)

  19. Gluconeogenesis in lethally X-irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Paulikova, E.; Ahlers, I.; Praslicka, M. (Univerzita P.J. Safarika, Kosice (Czechoslovakia). Katedra Vseobecnej Biologie)

    1983-02-01

    The in vivo incorporation of U-/sup 14/C-alanine into blood glucose and liver glycogen was measured in rats irradiated with a single whole body lethal dose of X-rays. Changes in gluconeogenic enzyme activities were studied in the liver. Increased incorporation of /sup 14/C-alanine into blood glucose and liver glycogen were found after irradiation. Liver phosphoenolpyruvate carboxykinase and glycogenic activity underwent almost parallel changes and were significantly elevated from the 6th to the 48th hour, with resultant accumulation of glycogen. Glucose-6-phosphatase activity was depressed and there was a negative correlation between it and liver glycogen concentration. Maximum fructose-1,6-diphosphatase activity was found at 48 hours. The results show that glycogen accumulation in the liver and the raised blood glucose level in X-irradiated rats are based on raised gluconeogenesis.

  20. Ants defend aphids against lethal disease

    Science.gov (United States)

    Nielsen, Charlotte; Agrawal, Anurag A.; Hajek, Ann E.

    2010-01-01

    Social insects defend their own colonies and some species also protect their mutualist partners. In mutualisms with aphids, ants typically feed on honeydew produced by aphids and, in turn guard and shelter aphid colonies from insect natural enemies. Here we report that Formica podzolica ants tending milkweed aphids, Aphis asclepiadis, protect aphid colonies from lethal fungal infections caused by an obligate aphid pathogen, Pandora neoaphidis. In field experiments, bodies of fungal-killed aphids were quickly removed from ant-tended aphid colonies. Ant workers were also able to detect infective conidia on the cuticle of living aphids and responded by either removing or grooming these aphids. Our results extend the long-standing view of ants as mutualists and protectors of aphids by demonstrating focused sanitizing and quarantining behaviour that may lead to reduced disease transmission in aphid colonies. PMID:19923138

  1. Lethal photosensitization of biofilm-grown bacteria

    Science.gov (United States)

    Wilson, Michael

    1997-12-01

    Antibacterial agents are increasingly being used for the prophylaxis and treatment of oral diseases. As these agents can be rendered ineffective by resistance development in the target organisms there is a need to develop alternative antimicrobial approaches. Light-activated antimicrobial agents release singlet oxygen and free radicals which can kill adjacent bacteria and a wide range of cariogenic and periodontopathogenic bacteria has been shown to be susceptible to such agents. In the oral cavity these organisms are present as biofilms (dental plaques) which are less susceptible to traditional antimicrobial agents than bacterial suspensions. The results of these studies have shown that biofilm-grown oral bacteria are also susceptible to lethal photosensitization although the light energy doses required are grater than those needed to kill the organisms when they are grown as aqueous suspensions.

  2. Tityus serrulatus venom--A lethal cocktail.

    Science.gov (United States)

    Pucca, Manuela Berto; Cerni, Felipe Augusto; Pinheiro Junior, Ernesto Lopes; Bordon, Karla de Castro Figueiredo; Amorim, Fernanda Gobbi; Cordeiro, Francielle Almeida; Longhim, Heloisa Tavoni; Cremonez, Caroline Marroni; Oliveira, Guilherme Honda; Arantes, Eliane Candiani

    2015-12-15

    Tityus serrulatus (Ts) is the main scorpion species of medical importance in Brazil. Ts venom is composed of several compounds such as mucus, inorganic salts, lipids, amines, nucleotides, enzymes, kallikrein inhibitor, natriuretic peptide, proteins with high molecular mass, peptides, free amino acids and neurotoxins. Neurotoxins are considered the most responsible for the envenoming syndrome due to their pharmacological action on ion channels such as voltage-gated sodium (Nav) and potassium (Kv) channels. The major goal of this review is to present important advances in Ts envenoming research, correlating both the crude Ts venom and isolated toxins with alterations observed in all human systems. The most remarkable event lies in the Ts induced massive releasing of neurotransmitters influencing, directly or indirectly, the entire body. Ts venom proved to extremely affect nervous and muscular systems, to modulate the immune system, to induce cardiac disorders, to cause pulmonary edema, to decrease urinary flow and to alter endocrine, exocrine, reproductive, integumentary, skeletal and digestive functions. Therefore, Ts venom possesses toxins affecting all anatomic systems, making it a lethal cocktail. However, its low lethality may be due to the low venom mass injected, to the different venom compositions, the body characteristics and health conditions of the victim and the local of Ts sting. Furthermore, we also described the different treatments employed during envenoming cases. In particular, throughout the review, an effort will be made to provide information from an extensive documented studies concerning Ts venom in vitro, in animals and in humans (a total of 151 references). Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Reduction in L10 phase transition temperature of PLD grown FePt thin by pre-annealing pulse laser exposure

    International Nuclear Information System (INIS)

    Wang, Y.; Rawat, R.S.; Bisht, A.

    2013-01-01

    A pre-annealing atmospheric pulsed laser exposure was applied to decrease the phase transition (from chemically disordered A1 phase to chemically ordered L1 0 phase) temperature of FePt nano-particles on a Si (100) substrate. Different pre-annealing laser energy densities of 0.024 and 0.079 J/cm2 were utilized to expose the pulsed laser deposition (PLD) FePt thin film samples under atmospheric conditions. Subsequently, FePt thin film samples were annealed at different temperatures of 300 and 400 ºC to observe the influence of laser exposure on the phase transition temperature. The phase transition temperature was decreased from conventional 600 ºC to 400 ºC by one shot pre-annealing atmospheric pulsed laser exposure. (author)

  4. Structural and dielectric properties of Ba{sub 0.7}Sr{sub 0.3}TiO{sub 3} thin films grown by PLD

    Energy Technology Data Exchange (ETDEWEB)

    James, K. K.; Satish, B.; Jayaraj, M. K. [Nanophotonic and Optoelectronic Devices Laboratory, Department of Physics, Cochin University of Science and Technology, Kerala (India)

    2014-01-28

    Ferroelectric thin films of Ba{sub 0.7}Sr{sub 0.3}TiO{sub 3} (BST) were deposited on Si/SiO{sub 2}/TiO{sub 2}/Pt (PtSi) substrate by pulsed laser deposition (PLD). Crystalline films with perovskite structure were obtained without post-deposition annealing. Phase purity of the deposited films was confirmed by x-ray diffraction. The lowest value of FWHM obtained for the film deposited at oxygen pressure 5.4×10{sup −4} mbar and substrate temperature 600°C, indicates the high crystallinity of the film. The room temperature dielectric constant at 100 kHz was 85. Butterfly loop, which is the characteristic of ferroelectric materials, was obtained in the regime of −4 to +4V. The leakage current density was nearly 9×10{sup −13} Acm{sup −2}.

  5. The protective effect of hypoxia and dithiothreitol on X-ray-induced genetic damage in Arabidopsis

    International Nuclear Information System (INIS)

    Sree Ramulu, K.; Veen, J.H. van der

    1987-01-01

    A study was made on the protective effect of hypoxia and dithiothreitol (DTT) on X-ray-induced ovule sterility and embryonic lethality in Arabidopsis. Both hypoxia and DTT gave a pronounced and additive reduction of radiation-induced genetic damage. The reduction was significantly higher for ovule sterility than for embryonic lethals. It is suggested that non-fertilized ovules contain a higher ratio of strand breaks/other damage than embryonic lethals do, for hypoxia and DTT are known specifically to give a reduction of strand breaks. (Auth.)

  6. Activity in SRL Nagoya Coated Conductor Center for YBCO Coated Conductor by IBAD+ PLD Method -Long, high Ic conductor and a new bamboo-like nanostructure for efficient pinning

    International Nuclear Information System (INIS)

    Yamada, Yutaka; Ibi, Akira; Fukushima, Hiroyuki; Kuriki, Reiji; Takahashi, Kazuhiro; Kobayashi, Hiroyoshi; Ishida, Satoru; Konishi, Masaya; Miyata, Seiki; Watanabe, Tomonori; Kato, Takeharu; Hirayama, Tsukasa; Shiohara, Yuh

    2006-01-01

    In SRL-Nagoya Coated Conductor Center (NCCC), long buffered substrate tapes and YBCO coated conductors have been successfully fabricated by using ion-beam assisted deposition (IBAD) and pulsed laser deposition (PLD) methods. For the buffered tape, the PLD-CeO2 method, what we call the 'Self-Epitaxial' method, realized the high degree of in-plane texturing around 4 degrees along the length of 220 m. For YBCO deposition, we have recently introduced new reel-to-reel PLD equipment with a multi-plume and multi-turn deposition system (MPMT PLD). This system succeeded in fabricating a long coated conductor with a high critical current, Ic, of 245 A and length of 212 m. Ic xL (length) reached the world record of 51940 Am. Furthermore, the introduction of artificial pinning center and RE 123 materials were also studied for improving flux pinning and enhancing Ic. A new columnar structure of the 'bamboo structure' (BaZrO3/Y123 layer-stacked structure) was found in Y123+YSZ sample. This columnar structure and the stacking faults in Gd123 were found to be effective for enhancing pinning properties. Using these techniques, we have succeeded in increasing Ic at 0 T to 480 A/cm and also enhancing Ic in a magnetic field

  7. Phleomycin-induced lethality and DNA degradation in Escherichia coli K12

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, H

    1975-01-01

    The cell lethality and DNA fragmentation caused by phleomycin (PM) were studied in E. coli K12 strains with special reference to the effects of repair or recombination deficiencies and metabolic inhibitors. Unlike excision-defective derivatives of E. coli B, uvrA, uvrB, and uvrC mutants of strain K12 showed no peculiarities compared with wild type in regard to cell survival. Likewise, mutant alleles at uvrD and polA loci had no effect. In contrast, rec mutants were more sensitive to PM-killing than were rec/sup +/ strains. PM-induced strand breakage in DNA was observed in all strains tested including the above-mentioned mutants. There was no significant distinction between the uvr mutants and the wild type strain, indicating that the uvr-endonuclease was not responsible for the strand breaks. Involvement of endonuclease I was also ruled out. At least some of the PM-induced strand breaks were repairable. PM-induced lethality and strand breakage were totally dependent on energy supply. Inhibition of protein synthesis resulted in a partial and parallel suppression of the two effects. Our results suggest that the lethality is due to DNA strand breakage and the repair of such damage is postulated to be controlled by rec genes.

  8. Genetic doping and health damages.

    Science.gov (United States)

    Fallahi, Aa; Ravasi, Aa; Farhud, Dd

    2011-01-01

    Use of genetic doping or gene transfer technology will be the newest and the lethal method of doping in future and have some unpleasant consequences for sports, athletes, and outcomes of competitions. The World Anti-Doping Agency (WADA) defines genetic doping as "the non-therapeutic use of genes, genetic elements, and/or cells that have the capacity to enhance athletic performance ". The purpose of this review is to consider genetic doping, health damages and risks of new genes if delivered in athletes. This review, which is carried out by reviewing relevant publications, is primarily based on the journals available in GOOGLE, ELSEVIER, PUBMED in fields of genetic technology, and health using a combination of keywords (e.g., genetic doping, genes, exercise, performance, athletes) until July 2010. There are several genes related to sport performance and if they are used, they will have health risks and sever damages such as cancer, autoimmunization, and heart attack.

  9. Lethal and sub-lethal effects of five pesticides used in rice farming on the earthworm Eisenia fetida

    NARCIS (Netherlands)

    Rico, Andreu; Sabater, Consuelo; Castillo, María Ángeles

    2016-01-01

    The toxicity of five pesticides typically used in rice farming (trichlorfon, dimethoate, carbendazim, tebuconazole and prochloraz) was evaluated on different lethal and sub-lethal endpoints of the earthworm Eisenia fetida. The evaluated endpoints included: avoidance behaviour after an exposure

  10. ATM inhibition induces synthetic lethality and enhances sensitivity of PTEN-deficient breast cancer cells to cisplatin.

    Science.gov (United States)

    Li, Ke; Yan, Huaying; Guo, Wenhao; Tang, Mei; Zhao, Xinyu; Tong, Aiping; Peng, Yong; Li, Qintong; Yuan, Zhu

    2018-05-01

    PTEN deficiency often causes defects in DNA damage repair. Currently, effective therapies for breast cancer are lacking. ATM is an attractive target for cancer treatment. Previous studies suggested a synthetic lethality between PTEN and PARP. However, the synthetically lethal interaction between PTEN and ATM in breast cancer has not been reported. Moreover, the mechanism remains elusive. Here, using KU-60019, an ATM kinase inhibitor, we investigated ATM inhibition as a synthetically lethal strategy to target breast cancer cells with PTEN defects. We found that KU-60019 preferentially sensitizes PTEN-deficient MDA-MB-468 breast cancer cells to cisplatin, though it also slightly enhances sensitivity of PTEN wild-type breast cancer cells. The increased cytotoxic sensitivity is associated with apoptosis, as evidenced by flow cytometry and PARP cleavage. Additionally, the increase of DNA damage accumulation due to the decreased capability of DNA repair, as indicated by γ-H2AX and Rad51 foci, also contributed to this selective cytotoxicity. Mechanistically, compared with PTEN wild-type MDA-MB-231 cells, PTEN-deficient MDA-MB-468 cells have lower level of Rad51, higher ATM kinase activity, and display the elevated level of DNA damage. Moreover, these differences could be further enlarged by cisplatin. Our findings suggest that ATM is a promising target for PTEN-defective breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Lethal endomyocarditis caused by chronic "Krokodil" intoxication.

    Science.gov (United States)

    Sorrentino, Antonella; Trotta, Silvia; Colucci, Anna Pia; Aventaggiato, Lucia; Marzullo, Andrea; Solarino, Biagio

    2018-03-19

    "Krokodil" is a home-made opioid drug obtained by synthesizing desomorphine from codeine and combining it with other low-cost additives. Initially introduced in the former Soviet countries, it was then imported to Western Europe as a heroin substitute. To our knowledge, this is the first report of an Italian case of lethal krokodil abuse, that occurred in a 39-year-old man, who died suddenly after transportation to the Emergency Department (ED) for hyperthermia associated with sweating, dyspnoea and tachycardia. Post-mortem examination revealed extensive necrotic ulcerative lesions on the forearms, and autopsy showed a hypertrophic heart with ample endocardial vegetation on the aortic valve and patency of the foramen ovale. Histopathological examination of the heart showed ulcero-vegetative lesions of the aortic valve with an abscess on the annulus and extension to the periaortic adipose tissue, as well as diffuse myocardial interstitial inflammatory neutrophilic infiltrates. Toxicological analysis demonstrated a desomorphine metabolite in urine. On the basis of all these findings the cause of death was ruled to be congestive heart failure caused by endocarditis and myocarditis, correlated with chronic abuse of krokodil.

  12. Tumor clone dynamics in lethal prostate cancer.

    Science.gov (United States)

    Carreira, Suzanne; Romanel, Alessandro; Goodall, Jane; Grist, Emily; Ferraldeschi, Roberta; Miranda, Susana; Prandi, Davide; Lorente, David; Frenel, Jean-Sebastien; Pezaro, Carmel; Omlin, Aurelius; Rodrigues, Daniel Nava; Flohr, Penelope; Tunariu, Nina; S de Bono, Johann; Demichelis, Francesca; Attard, Gerhardt

    2014-09-17

    It is unclear whether a single clone metastasizes and remains dominant over the course of lethal prostate cancer. We describe the clonal architectural heterogeneity at different stages of disease progression by sequencing serial plasma and tumor samples from 16 ERG-positive patients. By characterizing the clonality of commonly occurring deletions at 21q22, 8p21, and 10q23, we identified multiple independent clones in metastatic disease that are differentially represented in tissue and circulation. To exemplify the clinical utility of our studies, we then showed a temporal association between clinical progression and emergence of androgen receptor (AR) mutations activated by glucocorticoids in about 20% of patients progressing on abiraterone and prednisolone or dexamethasone. Resistant clones showed a complex dynamic with temporal and spatial heterogeneity, suggesting distinct mechanisms of resistance at different sites that emerged and regressed depending on treatment selection pressure. This introduces a management paradigm requiring sequential monitoring of advanced prostate cancer patients with plasma and tumor biopsies to ensure early discontinuation of agents when they become potential disease drivers. Copyright © 2014, American Association for the Advancement of Science.

  13. Human cooperation by lethal group competition.

    Science.gov (United States)

    Egas, Martijn; Kats, Ralph; van der Sar, Xander; Reuben, Ernesto; Sabelis, Maurice W

    2013-01-01

    Why humans are prone to cooperate puzzles biologists, psychologists and economists alike. Between-group conflict has been hypothesized to drive within-group cooperation. However, such conflicts did not have lasting effects in laboratory experiments, because they were about luxury goods, not needed for survival ("looting"). Here, we find within-group cooperation to last when between-group conflict is implemented as "all-out war" (eliminating the weakest groups). Human subjects invested in helping group members to avoid having the lowest collective pay-off, whereas they failed to cooperate in control treatments with random group elimination or with no subdivision in groups. When the game was repeated, experience was found to promote helping. Thus, not within-group interactions alone, not random group elimination, but pay-off-dependent group elimination was found to drive within-group cooperation in our experiment. We suggest that some forms of human cooperation are maintained by multi-level selection: reciprocity within groups and lethal competition among groups acting together.

  14. Enhanced lethal effect of combined ACNU with x-ray on cultured HeLaS3 cells

    International Nuclear Information System (INIS)

    Kanazawa, Haruyuki; Miyamoto, Tadaaki

    1983-01-01

    The combined effects of ACNU and X-irradiation on cultured HeLaS 3 cells were investigated. Pretreatment with either ACNU or X-ray induced a substantial reduction in shoulder width the D 0 value of the dose-response curve for the other agent, given later was unchanged. ACNU did not inhibit the recovery of sublethal damage (SLD) induced by X-ray when this treatment preceded the spilit-dose experiment. Our results indicate that some cell damage induced by each agent is transmissible to the progeny of the surviving cells and that the interaction of ACNU and X-irradiation was lethal to the cells. (author)

  15. Evaluation of the performance of three elastomers for non-lethal projectile applications

    Science.gov (United States)

    Thota, N.; Epaarachchi, J.; Lau, K. T.

    2015-09-01

    Less lethal kinetic ammunitions with soft noses such as eXact iMpact 1006, National Sports Spartan and B&T have been commonly used by military and law enforcement officers in the situations where lethal force is not warranted. In order to explore new materials to be used as nose in such ammunitions, a scholastic study using finite element simulations has been carried out to evaluate the effectiveness of two rubber like elastomers and a polyolefinic foam (low density, highly compressible, stiff and closed cell type of thermos plastic elastomer). State-of-the art thorax surrogate MTHOTA has been employed for the evaluation of blunt thoracic trauma. Force-rigid wall method was employed for the evaluation of head damage curves for each material. XM 1006 has been used as the benchmark projectile for the purpose of comparison. Both blunt thoracic trauma and head damage criterion point of view, both rubbers (R1 and R2) have yielded high values of VCmax and peak impact force. Polyolefinic foam (F1) considered in the study has yielded very promising VCmax values and very less peak impact force when compared with those of bench mark projectile XM 1006.

  16. High LET radiation and mechanism of DNA damage repair

    International Nuclear Information System (INIS)

    Furusawa, Yoshiya

    2004-01-01

    Clarifying the mechanism of repair from radiation damage gives most important information on radiation effects on cells. Approximately 10% of biological experiments groups in Heavy Ion Medical Accelerator in Chiba (HIMAC) cooperative research group has performed the subject. They gave a lot of new findings on the mechanism, and solved some open questions. The reason to show the peak of relative biological effectiveness RBE at around 100-200 keV/μm causes miss-repair of DNA damage. Sub-lethal damage generated by high linear energy transfer (LET) radiation can be repaired fully. Potentially lethal damages by high-LET radiation also repaired, but the efficiency decreased with the LET, and so on. (author)

  17. Radiation damage

    CERN Document Server

    Heijne, Erik H M; CERN. Geneva

    1998-01-01

    a) Radiation damage in organic materials. This series of lectures will give an overview of radiation effects on materials and components frequently used in accelerator engineering and experiments. Basic degradation phenomena will be presented for organic materials with comprehensive damage threshold doses for commonly used rubbers, thermoplastics, thermosets and composite materials. Some indications will be given for glass, scintillators and optical fibres. b) Radiation effects in semiconductor materials and devices. The major part of the time will be devoted to treat radiation effects in semiconductor sensors and the associated electronics, in particular displacement damage, interface and single event phenomena. Evaluation methods and practical aspects will be shown. Strategies will be developed for the survival of the materials under the expected environmental conditions of the LHC machine and detectors. I will describe profound revolution in our understanding of black holes and their relation to quantum me...

  18. Early models of DNA damage formation

    International Nuclear Information System (INIS)

    Śmiałek, Małgorzata A

    2012-01-01

    Quantification of DNA damage, induced by various types of incident radiation as well as chemical agents, has been the subject of many theoretical and experimental studies, supporting the development of modern cancer therapy. The primary observations showed that many factors can lead to damage of DNA molecules. It became clear that the development of experimental techniques for exploring this phenomenon is required. Another problem was simultaneously dealt with, anticipating on how the damage is distributed within the double helix of the DNA molecule and how the single strand break formation and accumulation can influence the lethal double strand break formation. In this work the most important probabilistic models for DNA strand breakage and damage propagation are summarized and compared.

  19. Dominant lethal effect of gamma radiation of 60Co in Biomphalaria glabrata (SAY, 1818)

    International Nuclear Information System (INIS)

    Tallarico, Lenita de Freitas

    2003-01-01

    Germ cell mutations are used in ecotoxicological studies as biomarkers of population effects and indicators of ecological changes. Biomphalaria glabrata, a freshwater mollusk, is a good experimental model for biomonitoring studies due to its biological characteristics and the ecological importance of this invertebrate group. The dominant lethal test was established in B. glabrata for the detection of germ cell mutations. Results with chemical mutagens showed that this system is efficient, specific and sensitive in the evaluation of germ cell mutations induced by reference mutagens. In this work, the dominant lethal effects of gamma radiation of 60 Co were studied. A preliminary experiment was done to establish the dose range and to estimate the chronology of spermatogenesis in B. glabrata. This estimate is possible because of the uniformity in response to ionizing radiation between germ cells at homologous stages of spermatogenesis in widely different species. In general, pre-meiotic germ cells are less sensitive to the induction of lethal dominant mutations than post-meiotic cells. This effect can be attributed to: young gametogenic cells - mitotically active - have greater repair ability from sub-lethal DNA damage and there is a selective elimination of the damaged cells. In our system: induction of lethal dominant mutations causes an increase in the frequency of malformations and, cytotoxic effect is displayed as a reduction in the crossing rates. Total duration of spermatogenesis was estimated in approximately 36 days, with the following distribution of stages: 1 to 13 days - spermatogonia, 14 to 20 days - spermatocytes, 21 to 36 days - spermatids and spermatozoa. Based on this chronology, irradiated wild-type snails with 2,5; 10 and 20Gy and crossed with non-irradiated albino snails after 7, 17, 23, 30 and 36 days. The frequencies of malformations in the heterozygous wild-type offspring of the nonirradiated albino snails were used as indicator of germ cell

  20. A new type of lethal short-limbed dwarfism

    International Nuclear Information System (INIS)

    Nairn, E.R.; Chapman, S.

    1989-01-01

    Details are presented of a most unusual osteo-chondrodysplasia which presents with lethal neonatal short-limbed dwarfism, defective ossification and nodular calcification with cartilage. The features resemble one case previously described in the literature. (orig.)

  1. Back to the future: revisiting HIV-1 lethal mutagenesis

    Science.gov (United States)

    Dapp, Michael J.; Patterson, Steven E.; Mansky, Louis M.

    2012-01-01

    The concept of eliminating HIV-1 infectivity by elevating the viral mutation rate was first proposed over a decade ago, even though the general concept had been conceived earlier for RNA viruses. Lethal mutagenesis was originally viewed as a novel chemotherapeutic approach for treating HIV-1 infection in which use of a viral mutagen would over multiple rounds of replication lead to the lethal accumulation of mutations, rendering the virus population non infectious – known as the slow mutation accumulation model. There have been limitations in obtaining good efficacy data with drug leads, leaving some doubt into clinical translation. More recent studies of the APOBEC3 proteins as well as new progress in the use of nucleoside analogs for inducing lethal mutagenesis have helped to refocus attention on rapid induction of HIV-1 lethal mutagenesis in a single or limited number of replication cycles leading to a rapid mutation accumulation model. PMID:23195922

  2. New type of lethal short-limbed dwarfism

    Energy Technology Data Exchange (ETDEWEB)

    Nairn, E.R.; Chapman, S.

    1989-05-01

    Details are presented of a most unusual osteo-chondrodysplasia which presents with lethal neonatal short-limbed dwarfism, defective ossification and nodular calcification with cartilage. The features resemble one case previously described in the literature.

  3. Perinatal-lethal Gaucher disease presenting as hydrops fetalis.

    Science.gov (United States)

    BenHamida, Emira; Ayadi, Imene; Ouertani, Ines; Chammem, Maroua; Bezzine, Ahlem; BenTmime, Riadh; Attia, Leila; Mrad, Ridha; Marrakchi, Zahra

    2015-01-01

    Perinatal-lethal Gaucher disease is very rare and is considered a variant of type 2 Gaucher disease that occurs in the neonatal period. The most distinct features of perinatal-lethal Gaucher disease are non-immune hydrops fetalis. Less common signs of the disease are hepatosplenomegaly, ichthyosis and arthrogryposis. We report a case of Gaucher's disease (type 2) diagnosed in a newborn who presented with Hydrops Fetalis.

  4. Conflict Without Casualties: Non-Lethal Weapons in Irregular Warfare

    Science.gov (United States)

    2007-09-01

    the body,” and the Geneva Protocol of 1925, bans the use of chemical and biological weapons .11 On 8 April 1975, President Ford issued Executive...E Funding – PE 63851M) (accessed 15 December 2006). The American Journal of Bioethics . “Medical Ethics and Non-Lethal Weapons .” Bioethics.net...CASUALTIES: NON-LETHAL WEAPONS IN IRREGULAR WARFARE by Richard L. Scott September 2007 Thesis Advisor: Robert McNab Second Reader

  5. Non-Lethal Weapons: Opportunities for R&D

    Science.gov (United States)

    2004-12-01

    during the Vietnam War. US; emulsifying agents are used in food processing, drilling fluids, cosmetics , pharmaceuticals, heavy- duty cleaners, textile...conducted in a professional manner, with no threat to public safety or the environment. 11 References [1] Fenton , G., (2001). NLW Technology Taxonomy...W.A., Mason, R.L., Collins, K.R., (2000). Non-Lethal Applicants of Slippery Substances. NDIA Non-Lethal Defense IV. [24] Fenton , G., (2000). Overview

  6. Lethal synergy involving bicyclomycin: an approach for reviving old antibiotics.

    Science.gov (United States)

    Malik, Muhammad; Li, Liping; Zhao, Xilin; Kerns, Robert J; Berger, James M; Drlica, Karl

    2014-12-01

    One way to address the growing problem of antimicrobial resistance is to revive old compounds that may have intrinsic lethal activity that is obscured by protective factors. Bicyclomycin is an old inhibitor of the Rho transcription terminator that by itself shows little rapid lethal activity. However, bicyclomycin participates in bacteriostatic synergy, which raises the possibility that conditions for lethal synergy may exist, perhaps through a suppression of protective factors. Bicyclomycin was combined with bacteriostatic inhibitors of gene expression, and bactericidal activity was measured with several cultured Gram-negative pathogens. When used alone, bicyclomycin failed to rapidly kill growing cultures of Escherichia coli; however, the additional presence of bacteriostatic concentrations of tetracycline, chloramphenicol or rifampicin led to rapid killing. Four other pathogen species, Acinetobacter baumannii, Klebsiella pneumoniae, Salmonella enterica serotype Typhimurium and Shigella dysenteriae, also exhibited enhanced killing when bicyclomycin was combined with tetracycline or rifampicin. This lethal synergy was achieved at low concentrations (slightly above the MIC) for all agents tested in combinations. Follow-up work with E. coli indicated that lethal synergy arose from a blockage of transcription elongation. Moreover, lethal synergy was reduced when bicyclomycin was added 60 min before tetracycline, suggesting that bicyclomycin induces a protective factor. The action of bicyclomycin illustrates the potential present in a largely abandoned antibacterial agent; it exhibits lethal synergy when coadministered with known, bacteriostatic inhibitors of gene expression. The identification of protective factors, which are currently uncharacterized, may reveal new ways to promote the lethal action of some old antibiotics. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved

  7. Sonographic features of lethal multiple pterygium syndrome at 14 weeks.

    Science.gov (United States)

    Chen, Min; Chan, Gavin Shueng Wai; Lee, Chin Peng; Tang, Mary Hoi Yin

    2005-06-01

    Lethal multiple pterygium syndrome is a rare inherited disorder. Previous reports suggest that the diagnosis may be based on prenatal sonographic demonstration of severe limb flexion, absence of fetal motion, and a large cystic hygroma in the second and third trimesters. We present the sonographic features and postmortem features of a fetus with lethal multiple pterygium syndrome at 13 weeks of gestation, which shows that the condition can possibly be diagnosed in the first trimester of pregnancy.

  8. Tort Damages

    NARCIS (Netherlands)

    L.T. Visscher (Louis)

    2008-01-01

    textabstractAbstract: In this Chapter, I provide an overview of Law and Economics literature regarding tort damages. Where necessary, attention is also spent to rules of tort liability. Both types of rules provide behavioral incentives to both injurers and victims, with respect to their level of

  9. Dependence of critical current properties on growth temperature and doping level of nanorods in PLD-YBa2Cu3Oy films

    International Nuclear Information System (INIS)

    Fujita, N.; Haruta, M.; Ichinose, A.; Maeda, T.; Horii, S.

    2013-01-01

    Highlights: •We fabricated Y123 films with Ba–Nb–O nanorods at various growth temperatures. •Irreversibility lines depended on growth temperature and doping level of Ba–Nb–O. •Nanorod morphology was drastically changed by growth temperature (T s ). •Its T s dependence of the matching field was different from that for Er123 + Ba–Nb–O. -- Abstract: The vortex-Bose-glass-like irreversibility lines (ILs) emerged for 2.5 and 5.0 at.% Ba–Nb–O (BNO)-doped YBa 2 Cu 3 O y films deposited by PLD using Nd:YAG-laser. The ILs strongly depended on growth temperature (T s ) in addition to the doping level of BNO. The vortex glass region was expanded with increasing T s or doping level of BNO. Drastic change of the nanorod morphology from short and bended nanorods to long and linear nanorods with increasing T s was clarified. Moreover, it was found that T s -dependent ILs were quite different from our previous results in BNO-doped ErBa 2 Cu 3 O y films

  10. Are Trp53 rescue of Brca1 embryonic lethality and Trp53/Brca1 breast cancer association related?

    International Nuclear Information System (INIS)

    McAllister, Kimberly A; Wiseman, Roger W

    2002-01-01

    Brca1 is involved in multiple biological pathways including DNA damage repair, transcriptional regulation, and cell-cycle progression. A complex pattern of interactions of Brca1 with Trp53 has also emerged. Xu and coworkers found that haploid loss of Trp53 significantly reduces the embryonic lethality observed in mice with a homozygous in-frame deletion of Brca1 exon 11. They report that widespread apoptosis correlates with the embryonic lethality resulting from this homozygous Δ11 Brca1 mutation. A mechanism responsible for Brca1-associated carcinogenesis is proposed. These experiments extend our knowledge of a complex Brca1/Trp53 relationship. However, the precise mechanisms through which Brca1 interacts with Trp53 to suppress mammary tumor formation have yet to be elucidated

  11. Deformation-driven, lethal damage to cancer cells. Its contribution to metastatic inefficiency.

    Science.gov (United States)

    Weiss, L

    1991-04-01

    Direct and indirect, in vivo and in vitro observations are in accord with the hypothesis that as a consequence of their deformation within capillaries, cancer cells undergo sphere-to-cylinder shape-transformations that create a demand for increased surface area. When this demand cannot be met by apparent increases in surface area accomplished by nonlethal, surface "unfolding," the cell surface membrane is stretched; if expansion results in more than a 4% increase in true surface area, the membrane ruptures, resulting in cancer cell death. It is suggested that this deformation-driven process is an important factor in accounting for the rapid death of circulating cancer cells that have been trapped in the microvasculature. Therefore, this mechanism is thought to make a significant contribution to metastatic inefficiency by acting as a potent rate-regulator for hematogenous metastasis.

  12. Heritable non-lethal damage to cultured human cells irradiated with heavy ions

    International Nuclear Information System (INIS)

    Walker, J.T.; Walker, O.A.

    2002-01-01

    During interplanetary flights the nuclei of all of a crew member's cells could be traversed by at least one high-LET (linear energy transfer) cosmic-ray particle. In mammalian cells irradiated in vitro about 1 in 10,000 of the surviving cells traversed by heavy particles is transformed to malignancy or mutated. What, if anything, happens to the remaining >99% of surviving cells? A retrospective analysis of archived data and samples from heavy-ion irradiation experiments with cultured human cells in vitro indicated that heavy ions caused a dose- and LET-dependent reduction in growth rates of progeny of irradiated cells, based on colony-size distributions. The maximum action cross section for this effect is between 100 and 300 μm 2 , at least as large as the cell nuclear area and up to 3 times the cross section for cell killing. Thus, heritable slow growth is the most prevalent effect of high-LET radiations on cultured animal cells, which may have implications for crew health during deep space travel. (author)

  13. Empirical complexities in the genetic foundations of lethal mutagenesis.

    Science.gov (United States)

    Bull, James J; Joyce, Paul; Gladstone, Eric; Molineux, Ian J

    2013-10-01

    From population genetics theory, elevating the mutation rate of a large population should progressively reduce average fitness. If the fitness decline is large enough, the population will go extinct in a process known as lethal mutagenesis. Lethal mutagenesis has been endorsed in the virology literature as a promising approach to viral treatment, and several in vitro studies have forced viral extinction with high doses of mutagenic drugs. Yet only one empirical study has tested the genetic models underlying lethal mutagenesis, and the theory failed on even a qualitative level. Here we provide a new level of analysis of lethal mutagenesis by developing and evaluating models specifically tailored to empirical systems that may be used to test the theory. We first quantify a bias in the estimation of a critical parameter and consider whether that bias underlies the previously observed lack of concordance between theory and experiment. We then consider a seemingly ideal protocol that avoids this bias-mutagenesis of virions-but find that it is hampered by other problems. Finally, results that reveal difficulties in the mere interpretation of mutations assayed from double-strand genomes are derived. Our analyses expose unanticipated complexities in testing the theory. Nevertheless, the previous failure of the theory to predict experimental outcomes appears to reside in evolutionary mechanisms neglected by the theory (e.g., beneficial mutations) rather than from a mismatch between the empirical setup and model assumptions. This interpretation raises the specter that naive attempts at lethal mutagenesis may augment adaptation rather than retard it.

  14. A multivariate model of stakeholder preference for lethal cat management.

    Science.gov (United States)

    Wald, Dara M; Jacobson, Susan K

    2014-01-01

    Identifying stakeholder beliefs and attitudes is critical for resolving management conflicts. Debate over outdoor cat management is often described as a conflict between two groups, environmental advocates and animal welfare advocates, but little is known about the variables predicting differences among these critical stakeholder groups. We administered a mail survey to randomly selected stakeholders representing both of these groups (n=1,596) in Florida, where contention over the management of outdoor cats has been widespread. We used a structural equation model to evaluate stakeholder intention to support non-lethal management. The cognitive hierarchy model predicted that values influenced beliefs, which predicted general and specific attitudes, which in turn, influenced behavioral intentions. We posited that specific attitudes would mediate the effect of general attitudes, beliefs, and values on management support. Model fit statistics suggested that the final model fit the data well (CFI=0.94, RMSEA=0.062). The final model explained 74% of the variance in management support, and positive attitudes toward lethal management (humaneness) had the largest direct effect on management support. Specific attitudes toward lethal management and general attitudes toward outdoor cats mediated the relationship between positive (pstakeholder intention to support non-lethal cat management. Our findings suggest that stakeholders can simultaneously perceive both positive and negative beliefs about outdoor cats, which influence attitudes toward and support for non-lethal management.

  15. Role of DNA damage in ultraviolet (313 nm) inactivation of yeasts Saccharomyces cerevisial

    International Nuclear Information System (INIS)

    Pospelov, M.E.; Ivanova, Eh.V.; Frajkin, G.Ya.

    1984-01-01

    Relative contribution of photoinhibition of cell respiration and DNA damage to lethal effect, caused by ultraviolet (UV) radiation of 313 m in certain yeast strains Saccharomyces cerevisiae, has been studied. It is shown that cell inactivation is mainly conditioned by DNA photodamage. When studying photoreactivation it has been established, that dimers of pyrimidine bases are the main lethal photoproducts, formed in DNA Under the effect of UV-radiation of 313 nm

  16. Inhibitory action of chlorophyllin of autosome recessive lethals induced by irradiation; Accion inhibidora de la clorofilina de letales recesivos autosonicos inducidos por irradiacion

    Energy Technology Data Exchange (ETDEWEB)

    Salceda, V M; Pimentel, P A.E.; Cruces, M P [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2006-07-01

    The chlorolin is a sodium salt of the chlorophyll that has a strong protective action of the damage induced by different agents so much physical as chemical. In Drosophila there is reported this effect in somatic cells. In contrast, in germinal cells using tests with the sexual chromosomes has not been found such inhibitory action. For this reason, in this occasion we will refer to the effect of the lethality induced in autosome chromosomes, in particular to the chromosome II of this species. For such effect groups of males of the line Canton-S its were pre-treated for 24h with or without 69 mm of CCS and later on treaties with or without 40 Gy of gamma irradiation. The males were then subjected to the technical Cy L / Pm for the detection of recessive lethals. In the third generation the respective counts of the descendant of each one of them to determine the corresponding categories for each extracted chromosome were made. To be mendelian crosses it is expected for a normal chromosome a proportion 2:1 of individuals with genotype Cy L / +: +/+. The absence of individuals +/+ it is indicative of a lethal gene, until 10% of these individuals of each male's total descendant, it is considered that is carrying of a semi lethal gene. The sum of lethal and semi lethals constitutes the category detrimental. The obtained results indicated that the pre-treatment with CCS reduces in a significant way the frequency of induced lethals by 40 Gy of gamma rays. The fact that an effect inhibitor has not been observed in the test of recessive lethal bound to the sex obtained previously, it contrasts with the effect observed in the chromosome II, results of this study and with the one observed in the chromosome III in somatic cells. The above-mentioned shows a differential action of the CCS between sexual chromosomes and autosomal before the effect of the gamma radiation. At the moment we don't have an explanation to these evidences. To evaluate the action of the chlorophyllin on

  17. Inhibitory action of chlorophyllin of autosome recessive lethals induced by irradiation; Accion inhibidora de la clorofilina de letales recesivos autosonicos inducidos por irradiacion

    Energy Technology Data Exchange (ETDEWEB)

    Salceda, V.M.; Pimentel, P.A.E.; Cruces, M.P. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)]. e-mail: vmss@nuclear.inin.mx

    2006-07-01

    The chlorolin is a sodium salt of the chlorophyll that has a strong protective action of the damage induced by different agents so much physical as chemical. In Drosophila there is reported this effect in somatic cells. In contrast, in germinal cells using tests with the sexual chromosomes has not been found such inhibitory action. For this reason, in this occasion we will refer to the effect of the lethality induced in autosome chromosomes, in particular to the chromosome II of this species. For such effect groups of males of the line Canton-S its were pre-treated for 24h with or without 69 mm of CCS and later on treaties with or without 40 Gy of gamma irradiation. The males were then subjected to the technical Cy L / Pm for the detection of recessive lethals. In the third generation the respective counts of the descendant of each one of them to determine the corresponding categories for each extracted chromosome were made. To be mendelian crosses it is expected for a normal chromosome a proportion 2:1 of individuals with genotype Cy L / +: +/+. The absence of individuals +/+ it is indicative of a lethal gene, until 10% of these individuals of each male's total descendant, it is considered that is carrying of a semi lethal gene. The sum of lethal and semi lethals constitutes the category detrimental. The obtained results indicated that the pre-treatment with CCS reduces in a significant way the frequency of induced lethals by 40 Gy of gamma rays. The fact that an effect inhibitor has not been observed in the test of recessive lethal bound to the sex obtained previously, it contrasts with the effect observed in the chromosome II, results of this study and with the one observed in the chromosome III in somatic cells. The above-mentioned shows a differential action of the CCS between sexual chromosomes and autosomal before the effect of the gamma radiation. At the moment we don't have an explanation to these evidences. To evaluate the action of the

  18. Preparation of CuIn(S,Se){sub 2} films by PLD of precursor layers and post-annealing and their application to solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Kawabe, Toshiyuki; Maeda, Tsuyoshi; Wada, Takahiro [Department of Materials Chemistry, Ryukoku University, Seta, Otsu (Japan)

    2017-06-15

    Cu-In-S precursor films were deposited at various substrate temperatures by pulsed laser deposition (PLD). CuIn(S,Se){sub 2} films were prepared by post-annealing the Cu-In-S precursor films in H{sub 2}S and Se atmosphere. CuIn(S,Se){sub 2} solar cells with a device structure of Au/ITO/i-ZnO/CdS/CuIn(S,Se){sub 2}/Mo/soda-lime (SLG) glass were fabricated and characterized. Higher conversion efficiency was obtained for the CuIn(S,Se){sub 2} solar cell with the precursor film deposited at room temperature. The phase and microstructure of the Cu-In-S precursor and the annealed CuIn(S,Se){sub 2} films were examined by X-ray diffraction (XRD) and scanning electron microscopy (SEM). We found that the quality of the CuIn(S,Se){sub 2} films was strongly affected by the deposition temperature of Cu-In-S precursor films. We discuss the grain growth and sintering in CuIn(S,Se){sub 2} films on the basis of the results of XRD and SEM. The highest conversion efficiency of 6.38% (V{sub oc}= 521 mV, J{sub sc}= 22.6 mA cm{sup -2}, FF = 0.541) was obtained for the CuIn(S,Se){sub 2} solar cell with the precursor film deposited at room temperature and post-annealed at 620 C. The solar cell was analyzed by secondary ion mass spectroscopy (SIMS) and transmission electron microscopy (TEM). (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  19. Effects of lethal and non-lethal malaria on the mononuclear phagocyte system

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Tosta

    1983-03-01

    Full Text Available The effects ofone non-lethal species ofmalarialparasite, Plasmodium yoelii, and one lethal species, P. berghei, on the mononuclear phagocyte system (MPS of BALB/c mice were studied. P. yoelii caused a greater and more sustained expansion and activation of the MPS, and the two major populations of spleen phagocytic cells-red pulp and marginal zone macrophages - exhibited a greater increase in numbers in this infection. During the course of P. berghei mataria, the spleen was progressively occupied by haematopoietic tissue and, at the terminal stage of infection, an extensive depletion of lymphocytes and macrophages was apparent. The possibility was suggested that the outcome of mataria may be inftuenced by the particular way the parasite interacts with the MPS.Estudou-se o efeito da infecção causada por espécie letal (Plasmodium berghei e não- letal (P. yoelii de plasmódio sobre o sistema de fagócitos mononucleares de camundongo BALB/c. O P. yoelii causou maior e mais prolongada expansão e ativação do sistema de macrófagos. As duas mais importantes populações de fagócitos esplênicos - macrófagos de polpa vermelha e da zona marginal - exibiam maior aumento do número de células nesta infecção. Durante a evolução da malária por P. berghei, o baço foi progressivamente ocupado por tecido hematopoiético e, na fase terminal da infecção, observou-se significativa depleção dos linfócitos e macrófagos esplênicos. Os dados apresentados indicam que a evolução da malária depende do tipo de interação entre o plasmódio e o sistema de fagócitos mononucleares.

  20. Analysis of time of death of prenatally lethal Steeloid mutations

    International Nuclear Information System (INIS)

    Rinchik, E.M.; Cummings, C.C.; Bangham, J.W.; Hunsicker, P.R.; Phipps, E.L.; Stelzner, K.F.

    1987-01-01

    Deletion mutations have been extremely useful in initiating the functional and molecular dissections of regions of the mouse genome. For the d-se and c regions, for example, it was observed that radiation mutations carrying lethal factors separable, by complementation analysis, from the primary d, se, or c mutation itself, could often be associated at both the genetic and molecular levels with multilocus chromosomal deletions. Since many of the Oak Ridge Sld mutations arose in radiation mutagenesis experiments, a substantial number may carry chromosomal deletions that involve the Sl locus in chromosome 10. Because of the great value of deletion mutations for the genetic and molecular analysis of chromosomal regions and complex genetic loci, they have initiated a series of experiments designed to test whether radiation-induced Sld mutations carry other lethal factors, in addition to the lethality caused by severe alleles of the Sl locus itself, as one prescreen for identifying Sld's that are caused by deletions

  1. The Effects of Anthrax Lethal Toxin on Host Barrier Function

    Directory of Open Access Journals (Sweden)

    David M. Frucht

    2011-06-01

    Full Text Available The pathological actions of anthrax toxin require the activities of its edema factor (EF and lethal factor (LF enzyme components, which gain intracellular access via its receptor-binding component, protective antigen (PA. LF is a metalloproteinase with specificity for selected mitogen-activated protein kinase kinases (MKKs, but its activity is not directly lethal to many types of primary and transformed cells in vitro. Nevertheless, in vivo treatment of several animal species with the combination of LF and PA (termed lethal toxin or LT leads to morbidity and mortality, suggesting that LT-dependent toxicity is mediated by cellular interactions between host cells. Decades of research have revealed that a central hallmark of this toxicity is the disruption of key cellular barriers required to maintain homeostasis. This review will focus on the current understanding of the effects of LT on barrier function, highlighting recent progress in establishing the molecular mechanisms underlying these effects.

  2. Caffeine protects mice against whole-body lethal dose of {gamma}-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    George, K.C.; Hebbar, S.A.; Kale, S.P.; Kesavan, P.C. [Biosciences Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

    1999-06-01

    Administration of caffeine (1,3,7-trimethylxanthine), a major component of coffee, to Swiss mice at doses of 80 or 100 mg/kg body weight 60 min prior to whole-body lethal dose of {gamma}-irradiation (7.5 Gy) resulted in the survival of 70 and 63% of animals, respectively, at the above doses in contrast to absolutely no survivors (LD-100/25 days) in the group exposed to radiation alone. Pre-treatment with a lower concentration of caffeine (50 mg/kg) did not confer any radioprotection. The protection exerted by caffeine (80 mg/kg), however, was reduced from 70 to 50% if administered 30 min prior to irradiation. The trend statistics reveal that a dose of 80 mg/kg administered 60 min before whole-body exposure to 7.5 Gy is optimal for maximal radioprotection. However, caffeine (80 mg/kg) administered within 3 min after irradiation offered no protection. While there is documentation in the literature that caffeine is an antioxidant and radioprotector against the toxic pathway of radiation damage in a wide range of cells and organisms, this is the first report demonstrating unequivocally its potent radioprotective action in terms of survival of lethally whole-body irradiated mice. (author)

  3. Repair in schizosaccharomyces pombe as measured by recovery from caffeine enhancement of radiation-induced lethality

    International Nuclear Information System (INIS)

    Gentner, N.E.; Werner, M.M.

    1975-01-01

    Inhibition of DNA repair by caffeine is manifested in Schizosaccharomyces pombe wild-type cells as an enhancement of UV- or γ-irradiation-induced lethality. The progress of DNA repair processes involving one or more caffeine-sensitive steps may be conveniently followed by measuring the concomitant decrease of this lethal enhancement effect. By measuring, during post-irradiation incubation, the ability of cells to overcome susceptibility to repair inhibition by caffeine, we have determined the time course and requirements for repair in S. pombe. Recovery began immediately and took 150-200 min after γ-irradiation and more than 500 min after UV-irradiation, for exposures which gave about 10% survival in the absence of caffeine. An incubation medium capable of supporting growth was required for caffeine-sensitive repair; no recovery occurred under liquid holding conditions. Survival curves after various recovery times indicated that a logarithmic phase cell population was homogeneous with respect to caffeine-sensitive repair of both UV- and γ-ray-induced damage. Recovery from caffeine inhibition was compared for cells of different physiological states (logarithmic and stationary phase); although the importance of the physiological state was not the same for the two types of radiation, recovery was found to occur more rapidly in the more radiation-resistant state, in each case. (orig.) [de

  4. Oxygen-dependent radiosensitivity of Escherichia coli and mitigation in lethality by superoxide dismutase

    International Nuclear Information System (INIS)

    Niwa, Taeko; Yamaguchi, Hikoyuki; Yano, Keiji

    1978-01-01

    Oxygen-dependent radiosensitivity of Escherichia coli W3623 his - was confirmed. Regarding cellular superoxide dismutase (SOD), cells grown oxically gained higher activity than those anoxically, however, the reinforced enzyme level could not compensate the oxygen effect, i.e., the enhanced lethal effect of oxic γ-irradiation. Rather, the enhancement of oxygen effect was found in cells grown oxically compared with those anoxically. Oxygen enhanced lethality was mitigated to the extent by the amount of added SOD into the cell suspension to be irradiated. The results supported a proposal that superoxide anion, O 2 - , is involved in the oxygen effect, with the most likely site of the damage in the outer structure of cell but not in the cell matrix. Reverse oxygen effect could be found with lambda phage DNA in transfecting ability. Added SOD protected phage DNA somewhat in oxic irradiation. While considerable protections were found in anoxic one with the added SOD even autoclaved but their function was still unknown. (auth.)

  5. Impact of acute alcohol consumption on lethality of suicide methods.

    Science.gov (United States)

    Park, C Hyung Keun; Yoo, Seong Ho; Lee, Jaewon; Cho, Sung Joon; Shin, Min-Sup; Kim, Eun Young; Kim, Se Hyun; Ham, Keunsoo; Ahn, Yong Min

    2017-05-01

    The influence of acute alcohol consumption on the factors related to suicide remains understudied. Thus, the present study investigated the relationship between blood alcohol content (BAC) and the lethality of suicide methods. Autopsy data on 315 South Korean suicide completers with a positive BAC were collected from a nationwide pool between May 2015 and November 2015, and the methods were dichotomised as suicide methods of low lethality (SMLL; drug/chemical overdose and sharp objects, n=67) and suicide methods of high lethality (SMHL; everything else, n=243). BAC at the time of autopsy and various suicide-related factors of these two groups were compared with logistic regression analyses. Compared to suicide completers with a BAC in the lowest range of 0.011-0.049%, suicide completers with a BAC in the range of 0.150-0.199% were more likely to use SMHL (odds ratio [OR]: 3.644, 95% confidence interval [CI]: 1.221-10.874). Additionally, the adoption of SMHL was significantly associated with the absence of a psychiatric illness (OR: 0.433, 95% CI: 0.222-0.843) and a younger age; the OR for high BAC among subjects in their 40s was 0.266 (95% CI: 0.083-0.856); in their 50s, 0.183 (95% CI: 0.055-0.615); and in their 60s, 0.057 (95% CI: 0.015-0.216). The relationship between BAC and suicide method lethality was represented by a bell-shaped pattern in which suicide methods of high lethality were more likely to be used by suicide completers with mid-range BAC levels. The increased impulsivity and impairments in particular executive functions, including planning and organization, associated with acute alcohol use may influence the selection of a particular suicide method based on its lethality. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. DNA damage in synchronized hela cells irradiated with ultraviolet

    International Nuclear Information System (INIS)

    Downes, C.S.; Collins, A.R.S.; Johnson, R.T.

    1979-01-01

    The lethal effect of uv radiation on HeLa cells is least in mitosis and greatest in late G 1 -early S. Photochemical damage to HeLa DNA, as measured by thymine-containing dimer formation and by alkaline sucrose sedimentation, also increases from mitosis towards early S phase. Computer simulations of uv absorption by an idealized HeLa cell at different stages of the cell cycle indicate that changes in damage could be due solely to changes in chromatin geometry. But survival is not exclusively a function of damage

  7. Lethals induced by γ-radiation in drosophila somatic cells

    International Nuclear Information System (INIS)

    Ivanov, A.I.

    1989-01-01

    Exposure of 3-hour drosophila male embryos to γ-radiation during the topographic segregation of the germ anlage nuclei caused recessive sex-linked lethals in somatic cells only. The selectivity of the screening was determined by the ratio of mutation frequencies induced in embryos and adult males. Analysis of lethal mutations shows that a minimal rate of the divergence between germinal and somatic patterns of the cell development is observed in the embryogenesis, the 3d instar larva and prepupa, and maximal in the 1st and 2nd larva and pupa

  8. Effective lethal mutagenesis of influenza virus by three nucleoside analogs.

    Science.gov (United States)

    Pauly, Matthew D; Lauring, Adam S

    2015-04-01

    Lethal mutagenesis is a broad-spectrum antiviral strategy that exploits the high mutation rate and low mutational tolerance of many RNA viruses. This approach uses mutagenic drugs to increase viral mutation rates and burden viral populations with mutations that reduce the number of infectious progeny. We investigated the effectiveness of lethal mutagenesis as a strategy against influenza virus using three nucleoside analogs, ribavirin, 5-azacytidine, and 5-fluorouracil. All three drugs were active against a panel of seasonal H3N2 and laboratory-adapted H1N1 strains. We found that each drug increased the frequency of mutations in influenza virus populations and decreased the virus' specific infectivity, indicating a mutagenic mode of action. We were able to drive viral populations to extinction by passaging influenza virus in the presence of each drug, indicating that complete lethal mutagenesis of influenza virus populations can be achieved when a sufficient mutational burden is applied. Population-wide resistance to these mutagenic agents did not arise after serial passage of influenza virus populations in sublethal concentrations of drug. Sequencing of these drug-passaged viral populations revealed genome-wide accumulation of mutations at low frequency. The replicative capacity of drug-passaged populations was reduced at higher multiplicities of infection, suggesting the presence of defective interfering particles and a possible barrier to the evolution of resistance. Together, our data suggest that lethal mutagenesis may be a particularly effective therapeutic approach with a high genetic barrier to resistance for influenza virus. Influenza virus is an RNA virus that causes significant morbidity and mortality during annual epidemics. Novel therapies for RNA viruses are needed due to the ease with which these viruses evolve resistance to existing therapeutics. Lethal mutagenesis is a broad-spectrum strategy that exploits the high mutation rate and the low

  9. Irradiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Howe, L.M

    2000-07-01

    There is considerable interest in irradiation effects in intermetallic compounds from both the applied and fundamental aspects. Initially, this interest was associated mainly with nuclear reactor programs but it now extends to the fields of ion-beam modification of metals, behaviour of amorphous materials, ion-beam processing of electronic materials, and ion-beam simulations of various kinds. The field of irradiation damage in intermetallic compounds is rapidly expanding, and no attempt will be made in this chapter to cover all of the various aspects. Instead, attention will be focused on some specific areas and, hopefully, through these, some insight will be given into the physical processes involved, the present state of our knowledge, and the challenge of obtaining more comprehensive understanding in the future. The specific areas that will be covered are: point defects in intermetallic compounds; irradiation-enhanced ordering and irradiation-induced disordering of ordered alloys; irradiation-induced amorphization.

  10. Irradiation damage

    International Nuclear Information System (INIS)

    Howe, L.M.

    2000-01-01

    There is considerable interest in irradiation effects in intermetallic compounds from both the applied and fundamental aspects. Initially, this interest was associated mainly with nuclear reactor programs but it now extends to the fields of ion-beam modification of metals, behaviour of amorphous materials, ion-beam processing of electronic materials, and ion-beam simulations of various kinds. The field of irradiation damage in intermetallic compounds is rapidly expanding, and no attempt will be made in this chapter to cover all of the various aspects. Instead, attention will be focused on some specific areas and, hopefully, through these, some insight will be given into the physical processes involved, the present state of our knowledge, and the challenge of obtaining more comprehensive understanding in the future. The specific areas that will be covered are: point defects in intermetallic compounds; irradiation-enhanced ordering and irradiation-induced disordering of ordered alloys; irradiation-induced amorphization

  11. Perforated appendicitis presenting as a thigh abscess: A lethal ...

    African Journals Online (AJOL)

    Typical cases of acute appendicitis have excellent treatment outcomes, if managed appropriately.1 We discuss an unusual case of perforated retrocaecal appendicitis that presented as a right thigh abscess without prominent abdominal symptoms, which highlights the lethal nature of advanced appendicitis even when ...

  12. The "Lethal Chamber": Further Evidence of the Euthanasia Option.

    Science.gov (United States)

    Elks, Martin A.

    1993-01-01

    Historical discussions of the euthanasia or "lethal chamber" option in relation to people with mental retardation are presented. The paper concludes that eugenic beliefs in the primacy of heredity over environment and the positive role of natural selection may have condoned the poor conditions characteristic of large, segregated institutions and…

  13. Papaya Lethal Yellowing Virus (PLYV) Infects Vasconcellea cauliflora

    NARCIS (Netherlands)

    Amaral, P.P.R.; Resende, de R.O.; Souza, M.T.

    2006-01-01

    Papaya lethal yellowing virus (PLYV) é um dos três vírus descritos infectando mamoeiros (Carica papaya L.) no Brasil. Vasconcellea cauliflora (Jacq.) A. DC., antes denominada de Carica cauliflora (Jacq.), é uma reconhecida fonte de resistência natural ao Papaya ringspot virus (PRSV), causador da

  14. Fighting Lethal Yellowing Disease for Coconut Farmers (CIFSRF ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Copra is the dried kernel of the coconut, which is used to extract coconut oil. Coconut is the main income source for the coastal region's poor farmers. Over the past 10 years, Côte d'Ivoire lethal yellowing disease has destroyed more than 350 hectares of coconut and caused losses of 12,000 tons of copra per year.

  15. Why the United States Must Adopt Lethal Autonomous Weapon Systems

    Science.gov (United States)

    2017-05-25

    intelligence , Lethal Autonomous Weapon Systems, energy production, energy storage, three-dimensional printing , bandwidth improvements, computer...views on the morality of artificial intelligence (AI) and robotics technology. Eastern culture sees artificial intelligence as an economic savior...capable of improving their society. In contrast, Western culture regards artificial intelligence with paranoia, anxiety, and skepticism. As Eastern

  16. Influence of temperature and pressure on the lethality of ultrasound

    International Nuclear Information System (INIS)

    Raso, J.; Pagan, R.; Condon, S.; Sala, F.J.

    1998-01-01

    A specially designed resistometer was constructed, and the lethal effect on Yersinia enterocolitica of ultrasonic waves (UW) at different static pressures (manosonication [MS]) and of combined heat-UW under pressure treatments (manothermosonication [MTS]) was investigated. During MS treatments at 30 degrees C and 200 kPa, the increase in the amplitude of UW of 20 kHz from 21 to 150 micrometers exponentially decreased decimal reduction time values (D(MS)) from 4 to 0.37 min. When pressure was increased from 0 to 600 kPa at a constant amplitude (150 micrometers) and temperature (30 degrees C), D(MS) values decreased from 1.52 to 0.20 min. The magnitude of this decrease in D(MS) declined progressively as pressure was increased. The influence of pressure on D(MS) values was greater with increased amplitude of UW. Pressure alone of as much as 600 kPa did not influence the heat resistance of Y. enterocolitica (D60 = 0.094; zeta = 5.65). At temperatures of as much as 58 degrees C, the lethality of UW under pressure was greater than that of heat treatment alone at the same temperature. At higher temperatures, this difference disappeared. Heat and UW under pressure seemed to act independently. The lethality of MTS treatments appeared to result from the added effects of UW under pressure and the lethal effect of heat. The individual contributions of heat and of UW under pressure to the total lethal effect of MTS depended on temperature. The inactivating effect of UW was not due to titanium particles eroded from the sonication horn. The addition to the MS media of cysteamine did not increase the resistance of Y. enterocolitica to MS treatment. MS treatment caused cell disruption

  17. Annotating novel genes by integrating synthetic lethals and genomic information

    Directory of Open Access Journals (Sweden)

    Faty Mahamadou

    2008-01-01

    Full Text Available Abstract Background Large scale screening for synthetic lethality serves as a common tool in yeast genetics to systematically search for genes that play a role in specific biological processes. Often the amounts of data resulting from a single large scale screen far exceed the capacities of experimental characterization of every identified target. Thus, there is need for computational tools that select promising candidate genes in order to reduce the number of follow-up experiments to a manageable size. Results We analyze synthetic lethality data for arp1 and jnm1, two spindle migration genes, in order to identify novel members in this process. To this end, we use an unsupervised statistical method that integrates additional information from biological data sources, such as gene expression, phenotypic profiling, RNA degradation and sequence similarity. Different from existing methods that require large amounts of synthetic lethal data, our method merely relies on synthetic lethality information from two single screens. Using a Multivariate Gaussian Mixture Model, we determine the best subset of features that assign the target genes to two groups. The approach identifies a small group of genes as candidates involved in spindle migration. Experimental testing confirms the majority of our candidates and we present she1 (YBL031W as a novel gene involved in spindle migration. We applied the statistical methodology also to TOR2 signaling as another example. Conclusion We demonstrate the general use of Multivariate Gaussian Mixture Modeling for selecting candidate genes for experimental characterization from synthetic lethality data sets. For the given example, integration of different data sources contributes to the identification of genetic interaction partners of arp1 and jnm1 that play a role in the same biological process.

  18. Damaged Skylab

    Science.gov (United States)

    1973-01-01

    The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into the flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop protecting it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Internal temperatures soared, rendering the station uninhabitable, threatening foods, medicines, films, and experiments. This image, taken during a fly-around inspection by the Skylab-2 crew, shows a crippled Skylab in orbit. The crew found their home in space to be in serious shape; the heat shield gone, one solar wing gone, and the other jammed. The Marshall Space Flight Center (MSFC) developed, tested, rehearsed, and approved three repair options. These options included a parasol sunshade and a twin-pole sunshade to restore the temperature inside the workshop, and a set of metal cutting tools to free the jammed solar panel.

  19. Structural damage

    International Nuclear Information System (INIS)

    Gray, R.E.; Bruhn, R.W.

    1992-01-01

    Virtually all structures show some signs of distress due to deterioration of the building components, to changed loads, or to changed support conditions. Changed support conditions result from ground movements. In mining regions many cases of structural distress are attributed to mining without considering alternative causes. This is particularly true of coal mining since it occurs under extensive areas. Coal mining is estimated to have already undermined more than eight million acres and may eventually undermine 40 million acres in the United States. Other nonmetal and metal underground mines impact much smaller areas. Although it is sometimes difficult, even with careful study, to identify the actual cause of damage, persons responsible for underground coal mining should at least be aware of possible causes of building stress other than mine subsidence. This paper presents information on distress to structures and briefly reviews a number of causes of ground movements other than subsidence: Mass movements, dissolution, erosion, frost action, shrinking and swelling, yield into excavations and compressibility

  20. Radiation damage prediction system using damage function

    International Nuclear Information System (INIS)

    Tanaka, Yoshihisa; Mori, Seiji

    1979-01-01

    The irradiation damage analysis system using a damage function was investigated. This irradiation damage analysis system consists of the following three processes, the unfolding of a damage function, the calculation of the neutron flux spectrum of the object of damage analysis and the estimation of irradiation effect of the object of damage analysis. The damage function is calculated by applying the SAND-2 code. The ANISN and DOT3, 5 codes are used to calculate neutron flux. The neutron radiation and the allowable time of reactor operation can be estimated based on these calculations of the damage function and neutron flux. The flow diagram of the process of analyzing irradiation damage by a damage function and the flow diagram of SAND-2 code are presented, and the analytical code for estimating damage, which is determined with a damage function and a neutron spectrum, is explained. The application of the irradiation damage analysis system using a damage function was carried out to the core support structure of a fast breeder reactor for the damage estimation and the uncertainty evaluation. The fundamental analytical conditions and the analytical model for this work are presented, then the irradiation data for SUS304, the initial estimated values of a damage function, the error analysis for a damage function and the analytical results are explained concerning the computation of a damage function for 10% total elongation. Concerning the damage estimation of FBR core support structure, the standard and lower limiting values of damage, the permissible neutron flux and the allowable years of reactor operation are presented and were evaluated. (Nakai, Y.)

  1. Why is intracellular ice lethal? A microscopical study showing evidence of programmed cell death in cryo-exposed embryonic axes of recalcitrant seeds of Acer saccharinum

    CSIR Research Space (South Africa)

    Wesley-Smith, J

    2015-10-01

    Full Text Available Walters3,*, N. W. Pammenter1 and Patricia Berjak1,‡ 1Plant Germplasm Conservation Research, School of Life Sciences, University of KwaZulu-Natal (Westville Campus), Durban, 4001 South Africa, 2National Centre for Nanostructured Materials, Council.... In roots, regrowth occurred from the ground meristem and procambium, not the distal meristem, which became lethally damaged. Regrowth of shoots occurred from isolated pockets of surviving cells of peripheral and pith meristems. The size of these pockets...

  2. Study of puromycin and acridic orange strain effect on photoprotection of yeasts Candida guillermondii from the lethal action of short-wave ultraviolet

    International Nuclear Information System (INIS)

    Fraikin, G.Ya.; Strakhovskaya, M.G.; Rubvin, L.B.

    1980-01-01

    The synthesis inhibitor of puromycin albumen has been used to establish that photoprotection formation in yeasts of a hypothetic compound which protects DNA from lethal damages, is not connected with macromolecular synthesis. The combined effect of photoprotective light and acridic orange strain on cells has been studied. It is shown that the mechanism in the base of the protector action is analogous to the mechanism of DNA protection with acridic orange

  3. FY 1997 report on the study on cryogenic aggregate target PLD process by multi-laser excitation for using gaseous materials; 1997 nendo chosa hokokusho (kitai genryo riyo no tame no taju laser reiki ni yoru gokuteion gyoshutai target PLD process ni kansuru kenkyu)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-03-01

    This paper reports the result in fiscal 1995 of the study on PLD (pulse laser deposition) thin film formation process having been made since 1993. In fiscal 1995, the effect of irradiation of excimer laser and YGA(SHG) on ablation of aggregates of N2, CH4, Ar, Kr and Xe, and the effect of time-delayed irradiation of YGA(SHG) and KrF excimer laser on ablation of N2 aggregate were studied aiming at exciting ablation by cryogenic aggregate alone. Experimental results by a newly developed multi-laser excitation experiment equipment are as follows. Ablation was not caused by KrF excimer laser irradiation, while caused by YGA(SHG) irradiation. Ablation was caused by 1mm thick N2 or CH4 aggregate alone. Kr target was the most promising among rare gas solid targets expected as seed of ablation occurrence. Multi-irradiation showed a different ablation behavior as compared with single YGA(SHG) irradiation, and in some cases, multi-irradiation not increased scattering of particles. Time-delayed multi- irradiation (YGA(SHG) excitation after excimer excitation) was effective. 23 figs., 4 tabs.

  4. On Theft with Lethal Weapons in Criminal Law%论刑法中的携带凶器盗窃

    Institute of Scientific and Technical Information of China (English)

    安军

    2012-01-01

    我国刑法中携带凶器型盗窃的立法意图及模式为具体理解与适用提供了基准。作为规范构成要件要素的凶器,除了需要考察凶器的客观因素外,还必须考虑行为人的主观因素,即在具体的案件中应以客观的及主观的要素为根据综合判断。携带凶器的时间段应包括着手实行盗窃行为至盗窃罪构成要件完成(既遂)的全过程。在这一过程中,行为人认识到自己携带了凶器,认识到自己在盗窃他人财物,希望通过携带的凶器排除或阻止他人的反抗,以便非法占有他人财物。与普通盗窃相比,携带凶器型盗窃除了属于行为犯外,更具有抽象危险犯的特征,二者并行不悖。%In Chinese criminal law,the legislative intent and model of theft with lethal weapons provides a benchmark for specific understanding and application.As normative elements of constitutive requirements of lethal weapons,the behavior of subjective factors should also be considered in addition to the objective factors of the weapon;in other words,the judgment should be based on objective and subjective elements in specific cases.The period of carrying lethal weapons should be from the start of acting to execute theft to complete offense of theft.The subject recognized carrying lethal weapons and his stealing behaviors,wished to exclude or block resistance and occupy property of others by carrying lethal weapons in this process.Compared with ordinary theft,theft with lethal weapons has more features of abstract potential damage offense in addition to belonging to behavioral offense,two of which are not contradictary to each other.

  5. Induction of the early response protein EGR-1 in human tumour cells after ionizing radiation is correlated with a reduction of repair of lethal lesions and an increase of repair of sublethal lesions

    NARCIS (Netherlands)

    Franken, Nicolaas A. P.; ten Cate, Rosemarie; van Bree, Chris; Haveman, Jaap

    2004-01-01

    The role of EGR-1 in potentially lethal damage repair (PLDR) was studied. Induction of the early response protein EGR-1 and survival after ionizing radiation of two human tumour cell lines after culturing for 48 h in serum-deprived medium was investigated. The glioblastoma cell line (Gli-6) and a

  6. Humanitarian Algorithms : A Codified Key Safety Switch Protocol for Lethal Autonomy

    OpenAIRE

    Nyagudi, Nyagudi Musandu

    2014-01-01

    With the deployment of lethal autonomous weapons, there is the requirement that any such platform complies with the precepts of International Humanitarian Law. Humanitarian Algorithms[9: p. 9] ensure that lethal autonomous weapon systems perform military/security operations, within the confines of International Humanitarian Law. Unlike other existing techniques of regulating lethal autonomy this scheme advocates for an approach that enables Machine Learning. Lethal autonomous weapons must be ...

  7. Multi-scale approach to radiation damage induced by ion beams: complex DNA damage and effects of thermal spikes

    International Nuclear Information System (INIS)

    Surdutovich, E.; Yakubovich, A.V.; Solov'yov, A.V.; Surdutovich, E.; Yakubovich, A.V.; Solov'yov, A.V.

    2010-01-01

    We present the latest advances of the multi-scale approach to radiation damage caused by irradiation of a tissue with energetic ions and report the calculations of complex DNA damage and the effects of thermal spikes on biomolecules. The multi-scale approach aims to quantify the most important physical, chemical, and biological phenomena taking place during and following irradiation with ions and provide a better means for clinically-necessary calculations with adequate accuracy. We suggest a way of quantifying the complex clustered damage, one of the most important features of the radiation damage caused by ions. This quantification allows the studying of how the clusterization of DNA lesions affects the lethality of damage. We discuss the first results of molecular dynamics simulations of ubiquitin in the environment of thermal spikes, predicted to occur in tissue for a short time after an ion's passage in the vicinity of the ions' tracks. (authors)

  8. Pacman dysplasia: a lethal skeletal dysplasia with variable radiographic features

    Energy Technology Data Exchange (ETDEWEB)

    Miller, S.F. [Dept. of Radiology, Children' s Hospital of the King' s Daughters, Norfolk (United States); Proud, V.K. [Dept. of Genetics, Children' s Hospital of the King' s Daughters, Norfolk (United States); Werner, A.L. [Dept. of Pathology, Children' s Hospital of the King' s Daughters, Norfolk (United States); Field, F.M.; Wilcox, W.F.; Lachman, R.S.; Rimoin, D.L. [International Skeletal Dysplasia Registry, Cedars-Sinai Medical Center, Los Angeles (United States)

    2003-04-01

    Background: Punctate or stippled cartilaginous calcifications are associated with many conditions, including chromosomal, infectious, endocrine, and teratogenic etiologies. Some of these conditions are clinically mild, while others are lethal. Accurate diagnosis can prove instrumental in clinical management and in genetic counseling. Objective: To describe the diagnostic radiographic features seen in Pacman dysplasia, a distinct autosomal recessive, lethal skeletal dysplasia. Materials and methods: We present the fourth reported case of Pacman dysplasia and compare the findings seen in our patient with the three previously described patients. Results: Invariable and variable radiographic findings were seen in all four cases of histologically proven Pacman dysplasia. Conclusion: Pacman dysplasia presents both constant and variable diagnostic radiographic features. (orig.)

  9. Neonatal lethal dwarfism with distinct skeletal malformations - a separate entity?

    Energy Technology Data Exchange (ETDEWEB)

    Rosendahl, K.; Maurseth, K.; Olsen, Oe.E. [Dept. of Paediatric Radiology, Haukeland University Hospital, Bergen (Norway); Halvorsen, O.J. [Dept. of Pathology, Haukeland University Hospital, Bergen (Norway); Gjelland, K. [Dept. of Gynaecology, Haukeland University Hospital, Bergen (Norway); Engebretsen, L. [Dept. of Genetics, Haukeland University Hospital, Bergen (Norway)

    2001-09-01

    We describe a case of neonatal lethal dwarfism characterised by short trunk, short, stick-like tubular bones, deficient ossification of the axial skeleton and broad, sclerotic horizontal ribs. Two similar cases have previously been reported as examples of the Neu-Laxova syndrome. However, the radiological findings of the Neu-Laxova syndrome, as reported in 16 out of 40 documented cases, show a heterogeneous pattern of minor features, which differ distinctively from those found in the previous two cases and by us. A literature research did not reveal similar cases, and we therefore suggest that our case, together with the two previous cases, may represent a new distinctive form of neonatal lethal dwarfism. (orig.)

  10. Neonatal lethal dwarfism with distinct skeletal malformations - a separate entity?

    International Nuclear Information System (INIS)

    Rosendahl, K.; Maurseth, K.; Olsen, Oe.E.; Halvorsen, O.J.; Gjelland, K.; Engebretsen, L.

    2001-01-01

    We describe a case of neonatal lethal dwarfism characterised by short trunk, short, stick-like tubular bones, deficient ossification of the axial skeleton and broad, sclerotic horizontal ribs. Two similar cases have previously been reported as examples of the Neu-Laxova syndrome. However, the radiological findings of the Neu-Laxova syndrome, as reported in 16 out of 40 documented cases, show a heterogeneous pattern of minor features, which differ distinctively from those found in the previous two cases and by us. A literature research did not reveal similar cases, and we therefore suggest that our case, together with the two previous cases, may represent a new distinctive form of neonatal lethal dwarfism. (orig.)

  11. Hematologic syndrome in man modeled from mammalian lethality

    International Nuclear Information System (INIS)

    Jones, T.D.

    1981-01-01

    Data on acute radiation lethality due to failure of the hematologic system in rats, mice, dogs, swine, monkeys and man are analyzed. Based on the available data, the mortality incidences for 1-100% levels can be computed directly if one has only an estimate of the dose lethal to 50% of the population (LD 50 ) for the mammalian strain and radiation environment of interest. The sole restriction is that the dose profile to the marrow be moderately uniform. If an LD 50 for any exposure situation has been measured, then one can readily scale to any desired situation through implicit-biological and empirical-physical relationships. The LD 50 for man, exposed to an isotropic cloud of photons, and knowledge of the bone-marrow dose profiles readily permit evaluation of the model for other levels of human mortality from different irradiating particles, partial body irradiation and spatially dependent and/or mixed radiation environments. (author)

  12. Chemical and radiation induced late dominant lethal effects in mice

    International Nuclear Information System (INIS)

    Favor, J.; Crenshaw, J.W. Jr.; Soares, E.R.

    1978-01-01

    Although theoretically expected, experimental data to date have not shown dominant lethal expression to occur throughout the developmental period. Specifically, late post-implantation effects have not been demonstrated. The authors routinely use an experimental technique in which parental females mated to mutagenically treated males are allowed to give birth and wean their litter, and their uterine horns are then inspected for uterine scars indicative of live and dead embryos. In a number of experiments in which males were mutagenically treated with either chemicals or X-irradiation, a discrepancy was observed between the number of live embryos as determined by the scar technique and the number of live observed at birth, suggesting the possibility of embryonic losses at a late stage in development. Initial analyses showed that mutagenic treatment increased the percentage of these late losses. These differences were statistically significant in 2 of 3 analyses. Factors affecting statistical significance and an understanding of dominant lethal mutations are discussed. (Auth.)

  13. An improved brine shrimp larvae lethality microwell test method.

    Science.gov (United States)

    Zhang, Yi; Mu, Jun; Han, Jinyuan; Gu, Xiaojie

    2012-01-01

    This article described an improved brine shrimp larvae lethality microwell test method. A simply designed connecting vessel with alternative photoperiod was used to culture and collect high yield of active Artemia parthenogenetica nauplii for brine shrimp larvae lethality microwell test. Using this method, pure A. parthenogenetica nauplii suspension was easily cultured and harvested with high density about 100-150 larvae per milliliter and the natural mortality was reduced to near zero by elimination of unnecessary artificial disturbance. And its sensitivity was validated by determination of LC(50)-24 h of different reference toxicants including five antitumor agents, two pesticides, three organic pollutants, and four heavy metals salts, most of which exhibited LC(50)-24 h between 0.07 and 58.43 mg/L except for bleomycin and mitomycin C with LC(50)-24 h over 300 mg/L.

  14. Radiation-induced mutagenicity and lethality in Ames tester strains of Salmonella

    International Nuclear Information System (INIS)

    Isildar, M.; Bakale, G.

    1984-01-01

    Mutation and killing induced by X radiation and 60 Co γ radiation were studied in six different histidine-requiring auxotrophs of Salmonella typhimurium. Strain TA100, which is sensitive to base-pair substitutions, and strains TA2637 and TA98, which are sensitive to frameshifts, carry the pKM101 plasmid and exhibit significantly higher radiation-induced mutations compared to their plasmidless parent strains TA1535, TA1537, and TA1538, respectively. Among the plasmid-containing strains, TA98 and TA2637 are much more sensitive to the mutagenic action of radiation than is TA100 based on a comparison with their respective spontaneous mutation rates; however, no uniformity was observed in the responses of the strains to the lethal action of ionizing radiation. The following conclusions are consistent with these observations: (1) the standard Ames Salmonella assay correctly identifies ionizing radiation as a mutagenic agent; (2) frameshift-sensitive parent strains are more sensitive to the mutagenic effects of ionizing radiation than is the only strain studied that is sensitive to base-pair substitutions; and (3) enhancement of mutagenesis and survival is related to plasmid-mediated repair of DNA damage induced by ionizing radiation and does not involve damage induced by Cerenkov-generated uv radiation which is negligible for our irradiation conditions

  15. Local inflammation, lethality and cytokine release in mice injected with Bothrops atrox venom

    Directory of Open Access Journals (Sweden)

    S. F. Barros

    1998-01-01

    Full Text Available We have provided evidence that: (a lethality of mice to crude Bothrops venom varies according the isogenic strain (A/J > C57Bl/6 > A/Sn > BALB/c > C3H/ HePas > DBA/2 > C3H/He; (bBALB/c mice (LD50=100.0 μg were injected i.p. with 50 μg of venom produced IL-6, IL-10, INF-γ, TNF-α and NO in the serum. In vitro the cells from the mice injected and challenged with the venom only released IL-10 while peritoneal macrophages released IL-10, INF-γ and less amounts of IL-6; (c establishment of local inflammation and necrosis induced by the venom, coincides with the peaks of TNF-α, IFN-γ and NO and the damage was neutralized when the venom was incubated with a monoclonal antibody against a 60 kDa haemorrhagic factor. These results suggest that susceptibility to Bothrops a trox venom is genetically dependent but MHC independent; that IL-6, IL10, TNF-α, IFN-γ and NO can be involved in the mediation of tissue damage; and that the major venom component inducers of the lesions are haemorrhagins.

  16. Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation

    International Nuclear Information System (INIS)

    Yamamoto, Tetsuo; Kinoshita, Manabu; Shinomiya, Nariyoshi; Hiroi, Sadayuki; Sugasawa, Hidekazu; Majima, Takashi; Seki, Shuhji; Matsushita, Yoshitaro; Saitoh, Daizoh

    2010-01-01

    While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome. (author)

  17. Non-Lethal Weaponry: A Framework for Future Integration

    Science.gov (United States)

    1998-04-01

    community, but was widely popularized by John Naisbitt in his 1982 work, Megatrends . In short, it asserts that much may be learned about a dynamic, but...Notes 1 John Naisbitt, Megatrends : Ten New Directions Transforming Our Lives (New York, NY: Warner Books, Inc., 1982), 3-5. 2 Robert J. Bunker...lethals by opponents of biological and chemical weapons. The use of chemical agents…is seen as a Trojan Horse to circumvent the Chemical Weapons

  18. Genome Replikin Count Predicts Increased Infectivity/Lethality of Viruses

    OpenAIRE

    Samuel Bogoch; Elenore S. Bogoch

    2012-01-01

    The genomes of all groups of viruses whose sequences are listed on Pubmed, specimens since 1918, analyzed by a software from Bioradar UK Ltd., contain Replikins which range in concentration from a Replikin Count (number of Replikins per 100 amino acids) of less than 1 to 30 (see accompanying communications for higher Counts in tuberculosis, malaria, and cancer, associated with higher lethality). Counts of less than 4.0 were found in ‘resting’ virus states; Counts greater than 4....

  19. Spondyloepiphyseal dysplasia congenita. A cause of lethal neonatal dwarfism

    Energy Technology Data Exchange (ETDEWEB)

    Macpherson, R.I.; Wood, B.P.

    1980-07-01

    Spondyloepiphyseal dysplasia congenita is a form of primarily short trunk dwarfism, that is manifest at birth but generally has not been regarded as a cause of lethal neonatal dwarfism. Seven neonates with severe dwarfism are presented. The first survived the newborn period, but the other six were early neonatal deaths. All displayed the clinical and radiologic features of spondyloepiphyseal dysplasia congenita. The striking similarities between spondyloepiphyseal dysplasia congenita and achondrogenesis type 2 are discussed.

  20. Torrance type of lethal neonatal short-limbed platyspondylic dwarfism

    International Nuclear Information System (INIS)

    Kaibara, N.; Yokoyama, K.; Nakano, H.

    1983-01-01

    A rare case of lethal neonatal short-limbed platyspondylic dwarfism is described. Roentgenographic features of this case, distinctly different from those of the classical thanatophoric dysplasia, are indistinguishable from the other three types of short-limbed platyspondylic dwarfism. Histologic features of the cartilage in this case are not very different from those of the Torrance type, but the presence of focal disruption of column formation in this case suggests a wider spectrum for this entity. (orig.)

  1. Torrance type of lethal neonatal short-limbed platyspondylic dwarfism

    Energy Technology Data Exchange (ETDEWEB)

    Kaibara, N.; Yokoyama, K.; Nakano, H.

    1983-06-01

    A rare case of lethal neonatal short-limbed platyspondylic dwarfism is described. Roentgenographic features of this case, distinctly different from those of the classical thanatophoric dysplasia, are indistinguishable from the other three types of short-limbed platyspondylic dwarfism. Histologic features of the cartilage in this case are not very different from those of the Torrance type, but the presence of focal disruption of column formation in this case suggests a wider spectrum for this entity.

  2. First diagnosed lethal case of lyssavirus infection in Primorsky krai

    OpenAIRE

    Leonova, G.; Chentsova, I.; Petukhova, S.; Somova, L.; Belikov, S.; Kondratov, I.; Kryilova, N.; Plekhova, N.; Pavlenko, E.; Romanova, E.; Matsak, V.; Smirnov, G.; Novikov, D.

    2010-01-01

    The paper provides data of comprehensive study of lethal case of lyssavirus infection first diagnosed in Yakovlevsky municipal district in Primorsky Krai. The data of epidemiologic analysis (contact with a rattle mouse), clinical picture and results of virologic, morphological and molecular genetic tests allow attributing this case to lyssavirus infection. This is the first diagnosed case of lyssavirus infection in the Siberia and Far East.

  3. Transplantation of bone marrow cells into lethally irradiated mice

    International Nuclear Information System (INIS)

    Viktora, L.; Hermanova, E.

    1978-01-01

    Morphological changes were studied of megakaryocytes in the bone marrow and spleen of lethally irradiated mice (0.2 C/kg) after transplantation of living bone marrow cells. It was observed that functional trombopoietic megakaryocytes occur from day 15 after transplantation and that functional active megakaryocytes predominate in bone marrow and spleen from day 20. In addition, other types of cells, primarily granulocytes, were detected in some megakaryocytes. (author)

  4. Disruption of murine mp29/Syf2/Ntc31 gene results in embryonic lethality with aberrant checkpoint response.

    Directory of Open Access Journals (Sweden)

    Chia-Hsin Chen

    Full Text Available Human p29 is a putative component of spliceosomes, but its role in pre-mRNA is elusive. By siRNA knockdown and stable overexpression, we demonstrated that human p29 is involved in DNA damage response and Fanconi anemia pathway in cultured cells. In this study, we generated p29 knockout mice (mp29(GT/GT using the mp29 gene trap embryonic stem cells to study the role of mp29 in DNA damage response in vivo. Interruption of mp29 at both alleles resulted in embryonic lethality. Embryonic abnormality occurred as early as E6.5 in mp29(GT/GT mice accompanied with decreased mRNA levels of α-tubulin and Chk1. The reduction of α-tubulin and Chk1 mRNAs is likely due to an impaired post-transcriptional event. An aberrant G2/M checkpoint was found in mp29 gene trap embryos when exposed to aphidicolin and UV light. This embryonic lethality was rescued by crossing with mp29 transgenic mice. Additionally, the knockdown of zfp29 in zebrafish resulted in embryonic death at 72 hours of development postfertilization (hpf. A lower level of acetylated α-tubulin was also observed in zfp29 morphants. Together, these results illustrate an indispensable role of mp29 in DNA checkpoint response during embryonic development.

  5. Lethal mutagenesis: targeting the mutator phenotype in cancer.

    Science.gov (United States)

    Fox, Edward J; Loeb, Lawrence A

    2010-10-01

    The evolution of cancer and RNA viruses share many similarities. Both exploit high levels of genotypic diversity to enable extensive phenotypic plasticity and thereby facilitate rapid adaptation. In order to accumulate large numbers of mutations, we have proposed that cancers express a mutator phenotype. Similar to cancer cells, many viral populations, by replicating their genomes with low fidelity, carry a substantial mutational load. As high levels of mutation are potentially deleterious, the viral mutation frequency is thresholded at a level below which viral populations equilibrate in a traditional mutation-selection balance, and above which the population is no longer viable, i.e., the population undergoes an error catastrophe. Because their mutation frequencies are fine-tuned just below this error threshold, viral populations are susceptible to further increases in mutational load and, recently this phenomenon has been exploited therapeutically by a concept that has been termed lethal mutagenesis. Here we review the application of lethal mutagenesis to the treatment of HIV and discuss how lethal mutagenesis may represent a novel therapeutic approach for the treatment of solid cancers. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Residual γH2AX foci as an indication of lethal DNA lesions

    Directory of Open Access Journals (Sweden)

    Banuelos C Adriana

    2010-01-01

    Full Text Available Abstract Background Evidence suggests that tumor cells exposed to some DNA damaging agents are more likely to die if they retain microscopically visible γH2AX foci that are known to mark sites of double-strand breaks. This appears to be true even after exposure to the alkylating agent MNNG that does not cause direct double-strand breaks but does produce γH2AX foci when damaged DNA undergoes replication. Methods To examine this predictive ability further, SiHa human cervical carcinoma cells were exposed to 8 DNA damaging drugs (camptothecin, cisplatin, doxorubicin, etoposide, hydrogen peroxide, MNNG, temozolomide, and tirapazamine and the fraction of cells that retained γH2AX foci 24 hours after a 30 or 60 min treatment was compared with the fraction of cells that lost clonogenicity. To determine if cells with residual repair foci are the cells that die, SiHa cervical cancer cells were stably transfected with a RAD51-GFP construct and live cell analysis was used to follow the fate of irradiated cells with RAD51-GFP foci. Results For all drugs regardless of their mechanism of interaction with DNA, close to a 1:1 correlation was observed between clonogenic surviving fraction and the fraction of cells that retained γH2AX foci 24 hours after treatment. Initial studies established that the fraction of cells that retained RAD51 foci after irradiation was similar to the fraction of cells that retained γH2AX foci and subsequently lost clonogenicity. Tracking individual irradiated live cells confirmed that SiHa cells with RAD51-GFP foci 24 hours after irradiation were more likely to die. Conclusion Retention of DNA damage-induced γH2AX foci appears to be indicative of lethal DNA damage so that it may be possible to predict tumor cell killing by a wide variety of DNA damaging agents simply by scoring the fraction of cells that retain γH2AX foci.

  7. Residual γH2AX foci as an indication of lethal DNA lesions

    International Nuclear Information System (INIS)

    Banáth, Judit P; Klokov, Dmitry; MacPhail, Susan H; Banuelos, C Adriana; Olive, Peggy L

    2010-01-01

    Evidence suggests that tumor cells exposed to some DNA damaging agents are more likely to die if they retain microscopically visible γH2AX foci that are known to mark sites of double-strand breaks. This appears to be true even after exposure to the alkylating agent MNNG that does not cause direct double-strand breaks but does produce γH2AX foci when damaged DNA undergoes replication. To examine this predictive ability further, SiHa human cervical carcinoma cells were exposed to 8 DNA damaging drugs (camptothecin, cisplatin, doxorubicin, etoposide, hydrogen peroxide, MNNG, temozolomide, and tirapazamine) and the fraction of cells that retained γH2AX foci 24 hours after a 30 or 60 min treatment was compared with the fraction of cells that lost clonogenicity. To determine if cells with residual repair foci are the cells that die, SiHa cervical cancer cells were stably transfected with a RAD51-GFP construct and live cell analysis was used to follow the fate of irradiated cells with RAD51-GFP foci. For all drugs regardless of their mechanism of interaction with DNA, close to a 1:1 correlation was observed between clonogenic surviving fraction and the fraction of cells that retained γH2AX foci 24 hours after treatment. Initial studies established that the fraction of cells that retained RAD51 foci after irradiation was similar to the fraction of cells that retained γH2AX foci and subsequently lost clonogenicity. Tracking individual irradiated live cells confirmed that SiHa cells with RAD51-GFP foci 24 hours after irradiation were more likely to die. Retention of DNA damage-induced γH2AX foci appears to be indicative of lethal DNA damage so that it may be possible to predict tumor cell killing by a wide variety of DNA damaging agents simply by scoring the fraction of cells that retain γH2AX foci

  8. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    International Nuclear Information System (INIS)

    Kim, Yoo-Shin; Lee, Tae Hoon; O'Neill, Brian E.

    2015-01-01

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy

  9. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo-Shin; Lee, Tae Hoon; O' Neill, Brian E., E-mail: BEOneill@houstonmethodist.org

    2015-08-14

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.

  10. Lethal and Sub-lethal Effects of Four Insecticides on the Aphidophagous Coccinellid Adalia bipunctata (Coleoptera: Coccinellidae).

    Science.gov (United States)

    Depalo, Laura; Lanzoni, Alberto; Masetti, Antonio; Pasqualini, Edison; Burgio, Giovanni

    2017-12-05

    Conventional insecticide assays, which measure the effects of insecticide exposure on short-term mortality, overlook important traits, including persistence of toxicity or sub-lethal effects. Therefore, such approaches are especially inadequate for prediction of the overall impact of insecticides on beneficial arthropods. In this study, the side effects of four modern insecticides (chlorantraniliprole, emamectin benzoate, spinosad, and spirotetramat) on Adalia bipunctata (L.) (Coleoptera: Coccinellidae) were evaluated under laboratory conditions by exposition on treated potted plants. In addition to investigation of acute toxicity and persistence of harmful activity in both larvae and adults of A. bipunctata, demographic parameters were evaluated, to provide a comprehensive picture of the nontarget effects of these products. Field doses of the four insecticides caused detrimental effects to A. bipunctata; but in different ways. Overall, spinosad showed the best toxicological profile among the products tested. Emamectin benzoate could be considered a low-risk insecticide, but had high persistence. Chlorantraniliprole exhibited lethal effects on early instar larvae and adults, along with a long-lasting activity, instead spirotetramat showed a low impact on larval and adult mortality and can be considered a short-lived insecticide. However, demographic analysis demonstrated that chlorantraniliprole and spirotetramat caused sub-lethal effects. Our findings highlight that sole assessment of mortality can lead to underestimation of the full impact of pesticides on nontarget insects. Demographic analysis was demonstrated to be a sensitive method for detection of the sub-lethal effects of insecticides on A. bipunctata, and this approach should be considered for evaluation of insecticide selectivity. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. [Bladder tumor lethality. Results in the autonomous community of Rioja between 1975-1991].

    Science.gov (United States)

    Fernández Fernández, A; Gil Fabra, J; Fernández Ruíz, M; Angulo Castellanos, M G; Blanco Martín, E; Otero Mauricio, G

    1998-01-01

    Between 1975-1991, a total of 557 cases of bladder carcinoma were identified in the Autonomous Community of La Rioja (CAR) which were followed up to December 1994. The overall lethality was 21.9%. 492 cases with 22.35% lethality were identified in males. In females, however, there was 65 cases with 18.46% lethality. The comparison of males and females lethality resulted in p = 0.525. Lethality between cases diagnosed within each 5-year period analyzed is: 1975-1981: 177 cases, lethality 23.72%. 1982-1986: 168 cases, lethality 30.95%. 1987-1991: 212 cases, lethality 13.20%. Between the first and the second 5-year periods, p = 0.132; between the first and third 5-year periods p = 0.007 and between the second and third 5-year periods p CAR for a 22.35% lethality. Lethality is higher in males that in females but the difference is not statistically significant. In the last 5-year period assessed, 1987-1991, a reduction of lethality from bladder neoplasms has been documented.

  12. Chromatin modifications and the DNA damage response to ionizing radiation

    International Nuclear Information System (INIS)

    Kumar, Rakesh; Horikoshi, Nobuo; Singh, Mayank; Gupta, Arun; Misra, Hari S.; Albuquerque, Kevin; Hunt, Clayton R.; Pandita, Tej K.

    2013-01-01

    In order to survive, cells have evolved highly effective repair mechanisms to deal with the potentially lethal DNA damage produced by exposure to endogenous as well as exogenous agents. Ionizing radiation exposure induces highly lethal DNA damage, especially DNA double-strand breaks (DSBs), that is sensed by the cellular machinery and then subsequently repaired by either of two different DSB repair mechanisms: (1) non-homologous end joining, which re-ligates the broken ends of the DNA and (2) homologous recombination, that employs an undamaged identical DNA sequence as a template, to maintain the fidelity of DNA repair. Repair of DSBs must occur within the natural context of the cellular DNA which, along with specific proteins, is organized to form chromatin, the overall structure of which can impede DNA damage site access by repair proteins. The chromatin complex is a dynamic structure and is known to change as required for ongoing cellular processes such as gene transcription or DNA replication. Similarly, during the process of DNA damage sensing and repair, chromatin needs to undergo several changes in order to facilitate accessibility of the repair machinery. Cells utilize several factors to modify the chromatin in order to locally open up the structure to reveal the underlying DNA sequence but post-translational modification of the histone components is one of the primary mechanisms. In this review, we will summarize chromatin modifications by the respective chromatin modifying factors that occur during the DNA damage response.

  13. [Damage control in trauma patients with hemodynamic instability].

    Science.gov (United States)

    Müller, Thorben; Doll, Dietrich; Kliebe, Frank; Ruchholtz, Steffen; Kühne, Christian

    2010-10-01

    The term "Damage-control" is borrowed from naval terminology. It means the initial control of a damaged ship. Because of the lethal triad in multiple injured patients the classical concept of definitive surgically therapy in the acute phase of the injury has a high rate of complications such as exsanguination, sepsis, heart failure and multiple organ failure. The core idea of the damage control concept was to minimize the additional trauma by surgical operations in these critical patients in the first phase. This means temporary control of a hemorrhage and measures for stopping abdominal contamination. After 24 - 48 hours in the intensive care unit and correction of physiological disturbances further interventions are performed for definitively treatment of the injuries. Summarized, the damage control strategy comprises an abbreviated operation, intensive care unit resuscitation, and a return to the operating room for the definitive operation after hemodynamic stabilisation of the patient. © Georg Thieme Verlag Stuttgart · New York.

  14. Electrolytic reduction of nitroheterocyclic drugs leads to biologically important damage in DNA

    International Nuclear Information System (INIS)

    Lafleur, M.V.M.; Pluijmackers-Westmijze, E.J.; Loman, H.

    1985-01-01

    The effects of electrolytic reduction of nitroimidazole drugs on biologically active DNA was studied. The results show that reduction of the drugs in the presence of DNA affects inactivation for both double-stranded (RF) and single-stranded phiX174 DNA. However, stable reduction products did not make a significant contribution to the lethal damage in DNA. This suggests that probably a short-lived intermediate of reduction of nitro-compounds is responsible for damage to DNA. (author)

  15. Left ventricular function during lethal and sublethal endotoxemia in swine

    International Nuclear Information System (INIS)

    Goldfarb, R.D.; Nightingale, L.M.; Kish, P.; Weber, P.B.; Loegering, D.J.

    1986-01-01

    Previous studies suggested that after a median lethal dose (LD 50 ) of endotoxin, cardiac contractility was depressed in nonsurviving dogs. The canine cardiovascular system is unlike humans in that dogs have a hepatic vein sphincter that is susceptible to adrenergic stimulation capable of raising hepatic and splanchnic venous pressures. The authors retested the hypothesis that lethality after endotoxin administration is associated with cardiac contractile depression in pigs, because of the hepatic circulation in this species is similar to that of humans. They compared cardiac mechanical function of pigs administered a high dose (250 μg/kg) or a low dose (100 μg/kg) endotoxin by use of the slope of the end-systolic pressure-diameter relationship (ESPDR) as well as other measurements of cardiac performance. In all the pigs administered a high dose, ESPDR demonstrated a marked, time-dependent depression whereas we observed no significant ESPDR changes after low endotoxin doses. The other cardiodynamic variables were uninterpretable, due to the significant changes in heart rate, end-diastolic diameter (preload), and aortic diastolic pressure (afterload). Plasma myocardia depressant factor activity accumulated in all endotoxin-administered animals, tending to be greater in the high-dose group. In this group, both subendocardial blood flow and global function were depressed, whereas pigs administered the low dose endotoxin demonstrated slight, but nonsignificant, increases in flow and function. These observations indicate that myocardial contractile depression is associated with a lethal outcome to high doses of endotoxin. Myocardial perfusion was measured using radiolabeled microspheres infused into the left atria

  16. Rifaximin diminishes neutropenia following potentially lethal whole-body radiation.

    Science.gov (United States)

    Jahraus, Christopher D; Schemera, Bettina; Rynders, Patricia; Ramos, Melissa; Powell, Charles; Faircloth, John; Brawner, William R

    2010-07-01

    Terrorist attacks involving radiological or nuclear weapons are a substantial geopolitical concern, given that large populations could be exposed to potentially lethal doses of radiation. Because of this, evaluating potential countermeasures against radiation-induced mortality is critical. Gut microflora are the most common source of systemic infection following exposure to lethal doses of whole-body radiation, suggesting that prophylactic antibiotic therapy may reduce mortality after radiation exposure. The chemical stability, easy administration and favorable tolerability profile of the non-systemic antibiotic, rifaximin, make it an ideal potential candidate for use as a countermeasure. This study evaluated the use of rifaximin as a countermeasure against low-to-intermediate-dose whole-body radiation in rodents. Female Wistar rats (8 weeks old) were irradiated with 550 cGy to the whole body and were evaluated for 30 d. Animals received methylcellulose, neomycin (179 mg/kg/d) or variably dosed rifaximin (150-2000 mg/kg/d) one hour after irradiation and daily throughout the study period. Clinical assessments (e.g. body weight) were made daily. On postirradiation day 30, blood samples were collected and a complete blood cell count was performed. Animals receiving high doses of rifaximin (i.e. 1000 or 2000 mg/kg/d) had a greater increase in weight from the day of irradiation to postirradiation day 30 compared with animals that received placebo or neomycin. For animals with an increase in average body weight from irradiation day within 80-110% of the group average, methylcellulose rendered an absolute neutrophil count (ANC) of 211, neomycin rendered an ANC of 334, rifaximin 300 mg/kg/d rendered an ANC of 582 and rifaximin 1000 mg/kg/d rendered an ANC of 854 (P = 0.05 for group comparison). Exposure to rifaximin after near-lethal whole-body radiation resulted in diminished levels of neutropenia.

  17. Metformin is synthetically lethal with glucose withdrawal in cancer cells.

    Science.gov (United States)

    Menendez, Javier A; Oliveras-Ferraros, Cristina; Cufí, Sílvia; Corominas-Faja, Bruna; Joven, Jorge; Martin-Castillo, Begoña; Vazquez-Martin, Alejandro

    2012-08-01

    Glucose deprivation is a distinctive feature of the tumor microecosystem caused by the imbalance between poor supply and an extraordinarily high consumption rate. The metabolic reprogramming from mitochondrial respiration to aerobic glycolysis in cancer cells (the "Warburg effect") is linked to oncogenic transformation in a manner that frequently implies the inactivation of metabolic checkpoints such as the energy rheostat AMP-activated protein kinase (AMPK). Because the concept of synthetic lethality in oncology can be applied not only to genetic and epigenetic intrinsic differences between normal and cancer cells but also to extrinsic ones such as altered microenvironment, we recently hypothesized that stress-energy mimickers such as the AMPK agonist metformin should produce metabolic synthetic lethality in a glucose-starved cell culture milieu imitating the adverse tumor growth conditions in vivo. Under standard high-glucose conditions, metformin supplementation mostly caused cell cycle arrest without signs of apoptotic cell death. Under glucose withdrawal stress, metformin supplementation circumvented the ability of oncogenes (e.g., HER2) to protect breast cancer cells from glucose-deprivation apoptosis. Significantly, representative cell models of breast cancer heterogeneity underwent massive apoptosis (by >90% in some cases) when glucose-starved cell cultures were supplemented with metformin. Our current findings may uncover crucial issues regarding the cell-autonomous metformin's anti-cancer actions: (1) The offently claimed clinically irrelevant, non-physiological concentrations needed to observe the metformin's anti-cancer effects in vitro merely underlie the artifactual interference of erroneous glucose-rich experimental conditions that poorly reflect glucose-starved in vivo conditions; (2) the preferential killing of cancer stem cells (CSC) by metformin may simply expose the best-case scenario for its synthetically lethal activity because an increased

  18. Genotoxicity test of irradiated spice mixture by dominant lethal test

    Energy Technology Data Exchange (ETDEWEB)

    Barna, J

    1986-03-01

    Dominant lethal test (DLT) was performed in Sprague Dawley male rats prefed with 25% irradiated spice mixture which was composed of 55% non-pungent ground paprika, 14% black pepper, 9% allspice, 9% coriander, 7% marjoram, 4% cumin, 2% nutmeg. Microbial count of the spice mixture was reduced with 15 kGy from a sup(60)Co source. Control groups received spice-free or untreated spice diet or were administered to cyclophosphamide i.p., respectively. DTL parameters altered significantly in the latter group but neither untreated nor irradiated spice mixture proved to be germ cell mutagens. 24 refs.; 8 figs.

  19. Lethal subarachnoid bleeding under immunosuppressive therapy due to mycotic arteritis

    International Nuclear Information System (INIS)

    Weigel, S.; Kloska, S.; Freund, M.; Kehl, H.G.

    2003-01-01

    A subarachnoid haemorrhage (SAH) occurred 67 days after cardiac transplantation in 10-year-old girl with consecutive immunocompromising therapy. Neither digital subtraction angiography (DSA) nor computed tomographic angiography showed signs of intracranial vascular malformations. One month before the lethal SAH occurred, she had developed arterial hypertension and attacks of severe headache with cerebrospinal fluid (CSF) pleocytosis while CT scans showed an infarct of the left thalamus. Pathologic findings established the rare diagnosis of SAH due to aspergillosis-related mycotic arteritis. Imaging characteristics are presented. (orig.)

  20. Lethal and sub-lethal chronic effects of the herbicide diuron on seagrass.

    Science.gov (United States)

    Negri, Andrew P; Flores, Florita; Mercurio, Phil; Mueller, Jochen F; Collier, Catherine J

    2015-08-01

    Photosystem II herbicides from agricultural sources have been detected throughout nearshore tropical habitats including seagrass meadows. While PSII herbicides have been shown to inhibit growth in microalgae at low concentrations, the potential impacts of chronic low concentration exposures to seagrass health and growth have not been investigated. Here we exposed two tropical seagrass species Halodule uninervis and Zostera muelleri to elevated diuron concentrations (from 0.3 to 7.2μgl(-1)) over a 79-day period followed by a 2-week recovery period in uncontaminated seawater. PAM fluorometry demonstrated rapid effect of diuron on photosystem II (PSII) in both seagrass species at 0.3μgl(-1). This effect included significant inhibition of photosynthetic efficiency (ΔF/Fm') and inactivation of PSII (Fv/Fm) over the 11 week exposure period. Significant mortality and reductions in growth was only observed at the highest exposure concentration of 7.2μgl(-1) diuron. However, biochemical indicators demonstrated that the health of seagrass after this prolonged exposure was significantly compromised at lower concentrations. For example, the drop in C:N ratios (0.6μgl(-1)) and reduced δ(13)C (1.7μgl(-1)) in seagrass leaves indicated reduced C-assimilation from photosynthesis. Critically, the energetic reserves of the plants (as measured by starch content in the root-rhizome complex) were approximately halved following diuron exposure at and above 1.7μgl(-1). During the 2-week recovery period, the photosynthetic capacity of the seagrass improved with only plants from the highest diuron treatment still exhibiting chronic damage to PSII. This study shows that, although seagrass may survive prolonged herbicide exposures, concentrations ≥0.6μgl(-1) diuron equivalents cause measureable impacts on energetic status that may leave the plants vulnerable to other simultaneous stressors. For example, tropical seagrasses have been heavily impacted by reduced light from coastal

  1. Damage analysis: damage function development and application

    International Nuclear Information System (INIS)

    Simons, R.L.; Odette, G.R.

    1975-01-01

    The derivation and application of damage functions, including recent developments for the U.S. LMFBR and CTR programs, is reviewed. A primary application of damage functions is in predicting component life expectancies; i.e., the fluence required in a service spectrum to attain a specified design property change. An important part of the analysis is the estimation of the uncertainty in such fluence limit predictions. The status of standardizing the procedures for the derivation and application of damage functions is discussed. Improvements in several areas of damage function development are needed before standardization can be completed. These include increasing the quantity and quality of the data used in the analysis, determining the limitations of the analysis due to the presence of multiple damage mechanisms, and finally, testing of damage function predictions against data obtained from material surveillance programs in operating thermal and fast reactors. 23 references. (auth)

  2. Lethal effects of solar radiation in proficient and deficient bacteria in repair systems; Efeitos letais da luz solar em bacterias proficientes e deficientes em reparos: acoes e interacoes

    Energy Technology Data Exchange (ETDEWEB)

    Sousa Neto, A de

    1981-12-31

    A study of the lethal action of solar radiation on strains of E.coli K12, proficient or deficient in repair systems, as well as the wild type strain gene products are involved in repair of damage induced by solar radiation. The inactivation of the various bacterial strains (normalized to a dose equivalent to radiation at a wavelength 254 nm) suggests that the more energetic wavelengths of the solar spectrum (290-320 nm) could be responsible for the primary damage that occurs in the DNA. The reduction in the shoulder of the survival curve in wild type strains in indicative of induction of sub-lethal damage in this region of the curve. Analysing solar inactivation curves of the bacterial strains (normalised by spore dosimetry) together with those of the same strains irradiated with UV at 254 nm, it was evident that 254 nm is not the ideal wavelength for comparison. This analysis also indicated that in addition to damage to DNA, other factors are involved in the solar radiation inactivation of wild type strains. (author).

  3. Lethal and sub-lethal chronic effects of the herbicide diuron on seagrass

    Energy Technology Data Exchange (ETDEWEB)

    Negri, Andrew P., E-mail: a.negri@aims.gov.au [Australian Institute of Marine Science, Townsville, Queensland 4810 (Australia); Flores, Florita [Australian Institute of Marine Science, Townsville, Queensland 4810 (Australia); Mercurio, Phil [Australian Institute of Marine Science, Townsville, Queensland 4810 (Australia); University of Queensland and National Research Centre for Environmental Toxicology, Coopers Plains, Queensland 4108 (Australia); Mueller, Jochen F. [University of Queensland and National Research Centre for Environmental Toxicology, Coopers Plains, Queensland 4108 (Australia); Collier, Catherine J. [Centre for Tropical Water & Aquatic Ecosystem Research (TropWATER), James Cook University, Cairns, Queensland 4870 (Australia)

    2015-08-15

    approximately halved following diuron exposure at and above 1.7 μg l{sup −1}. During the 2-week recovery period, the photosynthetic capacity of the seagrass improved with only plants from the highest diuron treatment still exhibiting chronic damage to PSII. This study shows that, although seagrass may survive prolonged herbicide exposures, concentrations ≥0.6 μg l{sup −1} diuron equivalents cause measureable impacts on energetic status that may leave the plants vulnerable to other simultaneous stressors. For example, tropical seagrasses have been heavily impacted by reduced light from coastal flood plumes and the effects on plant energetics from light limitation and diuron exposure (highest in flood plumes) are very similar, potentially leading to cumulative negative effects.

  4. Lethal and sub-lethal chronic effects of the herbicide diuron on seagrass

    International Nuclear Information System (INIS)

    Negri, Andrew P.; Flores, Florita; Mercurio, Phil; Mueller, Jochen F.; Collier, Catherine J.

    2015-01-01

    1.7 μg l −1 . During the 2-week recovery period, the photosynthetic capacity of the seagrass improved with only plants from the highest diuron treatment still exhibiting chronic damage to PSII. This study shows that, although seagrass may survive prolonged herbicide exposures, concentrations ≥0.6 μg l −1 diuron equivalents cause measureable impacts on energetic status that may leave the plants vulnerable to other simultaneous stressors. For example, tropical seagrasses have been heavily impacted by reduced light from coastal flood plumes and the effects on plant energetics from light limitation and diuron exposure (highest in flood plumes) are very similar, potentially leading to cumulative negative effects

  5. Chromosome condensation may enhance X-ray-related cell lethality in a temperature-sensitive mutant (tsBN2) of baby hamster kidney cells (BHK21)

    International Nuclear Information System (INIS)

    Sasaki, H.; Nishimoto, T.

    1987-01-01

    In the tsBN2 cell line, which has a temperature-sensitive defect in the regulatory mechanism for chromosome condensation, the lethal effect of X rays was enhanced by incubating the cells at a nonpermissive temperature (40 degrees C) following X irradiation. This enhancement was suppressed in the presence of cycloheximide, which inhibits induction of premature chromosome condensation. The findings obtained in the case of delayed incubation at 40 degrees C and in synchronized cells indicate that X-ray-related potentially lethal damage, which can be expressed by chromosome condensation, is produced in the cells at any stage of the cell cycle, but it is repairable for all cells except those at around the late G2-M phase, where chromosome condensation occurs at a permissive temperature (33.5 degrees C). These observations suggest that the high sensitivity of late G2-M cells to X rays is caused by the events associated with chromosome condensation

  6. Experimental evaluation of the relationship between lethal or non-lethal virulence and transmission success in malaria parasite infections

    Directory of Open Access Journals (Sweden)

    Nithiuthai S

    2004-09-01

    Full Text Available Abstract Background Evolutionary theory suggests that the selection pressure on parasites to maximize their transmission determines their optimal host exploitation strategies and thus their virulence. Establishing the adaptive basis to parasite life history traits has important consequences for predicting parasite responses to public health interventions. In this study we examine the extent to which malaria parasites conform to the predicted adaptive trade-off between transmission and virulence, as defined by mortality. The majority of natural infections, however, result in sub-lethal virulent effects (e.g. anaemia and are often composed of many strains. Both sub-lethal effects and pathogen population structure have been theoretically shown to have important consequences for virulence evolution. Thus, we additionally examine the relationship between anaemia and transmission in single and mixed clone infections. Results Whereas there was a trade-off between transmission success and virulence as defined by host mortality, contradictory clone-specific patterns occurred when defining virulence by anaemia. A negative relationship between anaemia and transmission success was found for one of the parasite clones, whereas there was no relationship for the other. Notably the two parasite clones also differed in a transmission phenotype (gametocyte sex ratio that has previously been shown to respond adaptively to a changing blood environment. In addition, as predicted by evolutionary theory, mixed infections resulted in increased anaemia. The increased anaemia was, however, not correlated with any discernable parasite trait (e.g. parasite density or with increased transmission. Conclusions We found some evidence supporting the hypothesis that there is an adaptive basis correlating virulence (as defined by host mortality and transmission success in malaria parasites. This confirms the validity of applying evolutionary virulence theory to biomedical

  7. Lethal Nipah virus infection induces rapid overexpression of CXCL10.

    Directory of Open Access Journals (Sweden)

    Cyrille Mathieu

    Full Text Available Nipah virus (NiV is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10, an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication. Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections. This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis.

  8. Parental response to severe or lethal prenatal diagnosis

    DEFF Research Database (Denmark)

    Lou, Stina; Jensen, Lotte Groth; Petersen, Olav Bjørn

    2017-01-01

    Objective A severe or lethal prenatal diagnosis places great demands on prospective parents, who face choices of far-reaching consequences, such as continuing or terminating the pregnancy. How best to support these parents is a clinical challenge. This systematic review aimed to identify and synt......Objective A severe or lethal prenatal diagnosis places great demands on prospective parents, who face choices of far-reaching consequences, such as continuing or terminating the pregnancy. How best to support these parents is a clinical challenge. This systematic review aimed to identify...... and synthesize the qualitative evidence regarding prospective parents’ responses to such prenatal diagnoses. Methods Following PRISMA guidelines, four databases were systematically searched and 28 studies met the inclusion criteria. Thematic analysis guided data extraction and synthesis of findings. The CERQual....... Prospective parents who continued the pregnancy wished to be acknowledged as parents, and engaged in planning to obtain a sense of meaning and control. Selective disclosure and concerns about negative responses were issues both for the parents who terminated and those who continued a pregnancy. Conclusion...

  9. Lethal mutation of internal irradiation brown planthopper (Nilaparvita lugens Stal)

    International Nuclear Information System (INIS)

    Wahid, R.A.

    1988-01-01

    The moulting IVth of BPH nympha were irradiated internally with radiophosphorous 32-P 1 uCi/ml, 10 uCi/ml, 50 uCi/ml, 100 uCi/ml, and 500 uCi/ml concentrations respectivelly. An observation was carried out to determines heredity of hopper sterilities from the mating groups of R male x N female, R male x R female, and N male x R female. The 32-P concentration below of 50 uCi/ml seemed to be the substerile dose, however, the dominant lethal mutation has been visually shown by R male x R female F1 mating group. The hereditary lines of F1, F2, F3, and F4 of the hopper sterilities wich were indicated by the nympha hatch ability have some significant correlations (r1= -0.77, r2= -0.92, r3= -0.93 and r4= -0.85). Thus, the resesif lethal mutations visually showed by F3 and F4 from all of the 100 uCi/ml and 50 uCi/ml treated groups. (author). 10 refs, 2 figs, 2 tabs

  10. Manifestations of damage from ionizing radiation in mammalian cells in the postirradiation generations

    International Nuclear Information System (INIS)

    Hopwood, L.E.; Tolmach, L.J.

    1979-01-01

    The lethally irradiated cell does not immediately cease metabolism. It may undergo one or many divisions before physiological death and disintegration ensue. Attention has been focused mainly on cell behavior during the generation in which the radiation is delivered, and cell behavior is in several respects very different in the irradiated generation from what it is in the succeeding generations. In particular, some of the responses in the irradiated generation are transient, and certain responses seem unrelated to lethal damage. The behavior of lethally irradiated cells during the postirradiation generations before they die is intrinsically of interest, and should provide information concerning the nature of the lethal damage they harbor. Accordingly, in reviewing the behavior of irradiated cells, the discussion is confined for the most part, though not entirely, to the postirradiations, even though distinction between the irradiated and the postirradiation generations is in several respects arbitrary. Effects at the cellular level are considered first; the final part of this section is devoted to a discussion of in vivo measurements of cellular effects, and includes responses that are properly classified as effects at the tissue level. The effects at the subcellular level are considered; the discussion is restricted to chromosomal effects. Biochemical effects are then considered; these are concerned entirely with macromolecular synthesis. In the final section possible interpretations of the experimental findings in terms of cell lethality are discussed but not loss of colony-forming ability (''clonogenicity'') directly

  11. Radiation-induced DNA damage in halogenated pyrimidine incorporated cells and its correlation with radiosensitivity

    International Nuclear Information System (INIS)

    Watanabe, R.; Nikjoo, H.

    2003-01-01

    Cells with DNA containing 5-halogenated pyrimidines in place of thymidine show significant reductions of slope (Do) and shoulder (Dq) of their radiation survival curves. Similar radiosensitization has also been observed in the yield of DNA strand breaks. The purpose of this study is to obtain an insight into the mechanism of cell lethality by examining the relationship between the spectrum of DNA damage and the cell survival. In this study we estimated the enhancement of strand breaks due to incorporation of halogenated pyrimidine, the complexity of DNA damage and the probability of the initial DNA damage leading to cell inactivation. Monte Carlo track structure methods were used to model and simulate the induction of strand breakage by X-rays. The increase of DNA strand break was estimated by assuming the excess strand break was caused by the highly reactive uracil radicals at the halouracil substituted sites. The assumption of the enhancement mechanism of strand breaks was examined and verified by comparison with experimental data for induction of SSB and DSB. The calculated DNA damage spectrum shows the increase in complexity of strand breaks is due to incorporation of halogenated pyrimidines. The increase in the yield of DSB and cell lethality show similar trend at various degrees of halogenated pyrimidine substitution. We asked the question whether this agreement supports the hypothesis that DSB is responsible for cell lethality? The estimated number of lethal damage from the cell survival using a linear-quadratic model is much less than the initial yield of DSB. This work examines the correlation of cell lethality as a function of frequencies of complex form of double strand breaks

  12. Deoxyribonucleoprotein structure and radiation injury - Cellular radiosensitivity is determined by LET-infinity-dependent DNA damage in hydrated deoxyribonucleoproteins and the extent of its repair

    Science.gov (United States)

    Lett, J. T.; Peters, E. L.

    1992-01-01

    Until recently, OH radicals formed in bulk nuclear water were believed to be the major causes of DNA damage that results in cell death, especially for sparsely ionizing radiations. That hypothesis has now been challenged, if not refuted. Lethal genomic DNA damage is determined mainly by energy deposition in deoxyribonucleoproteins, and their hydration shells, and charge (energy) transfer processes within those structures.

  13. Forecasting of the lethality in cases of nonuniform accidental irradiation (experimental studies at external gamma irradiation of rats)

    International Nuclear Information System (INIS)

    Ingilizova, K.

    1983-01-01

    A model is suggested that enables the prediction of death probability for the body (L) within the whole lethality dose range (DL 0 -DL 100 ), on the basis of predetermined physical characteristics: in cases of uneven external wholebody irradiation. Some biological effects of 4 variants of uneven irradiation have been studied, i.e. ventro-dorsal (V-D), dorso-ventral (D-V), cranio-caudal (Cr-Ca) and caudo-cranial (Ca-Cr). The following basic conclusions have been drawn: 1. The study of the biological effects of uneven irradiation, when estimated by the lethality factor, points out the lower efficiency of the former, if compared to even irradiation. 2. The even irradiation lethality in the conducted experiments, according to the ALE data and the postradiation mortality dynamics, is determined basically by the damage of the bloodforming tissue and the animals die of bone marrow syndrome. 3. The uneven irradiation, estimated by the total weight factor, is of lower efficiency than the even one. 4. The radiation-induced hypoplasia of the studied organs is exponential in character. 5. An original model for predicting radiation mortality in cases of uneven irradiation has been constructed. The model gives the possibility of relating the alterations in the index of biological efficiency reduction to the wholebody irradiation factor, as well as to the two systems with highest radiosensitivity: red bone marrow and the small intestine. The model helps determining the numerical value of death probability, depending on the average body irradiation doses and the integral unevenness factors for RBM. (author)

  14. Repair of radiation damage caused by cyclotron-produced neutrons

    International Nuclear Information System (INIS)

    Martins, B.I.

    1979-01-01

    Hall et al. present experimental data on repair of sublethal damage in cultured mammalian cells exposed to 35 MeV neutrons and 60 Co γ rays. Hall and Kraljevic present experimental data on repair of potentially lethal damage in cultured mammalian cells exposed to 35 MeV neutrons and 210 kVp x rays. These results of Hall et al. are very difficult to explain from basic concepts in radiobiology. Contrary to Rossi, these data do not support his thesis that repair of radiation damage is dose-dependent and linear energy transfer independent. Nor do these results meet the expectations of multitarget-single hit theory which would require dose-independent repair equal to n. The observation of the same extrapolation number for neutrons and for x rays is also surprising. From the point of view of radiotherapy, the doses of interest are about 140 rad for neutrons and about 300 rad for x rays. There are no data for repair of potentially lethal damage below 800 rad for x rays and 400 rad for neutrons. The difference in survival between single and split dose is negligible up to a total of about 600 rad of x rays or of neutrons. These data of Hall et al. therefore have little significance to radiotherapists and are an enigma to radiobiologists

  15. Toxicity assessment of sodium fluoride in Drosophila melanogaster after chronic sub-lethal exposure.

    Science.gov (United States)

    Dutta, Moumita; Rajak, Prem; Khatun, Salma; Roy, Sumedha

    2017-01-01

    Sodium fluoride (NaF), one of the most frequently used fluoride compound is composed of Na + and F - . Apart from its use in water fluoridation, NaF also acts as a major component for different dental products like toothpastes, gels and mouth rinses etc. The present study was carried out to explore the toxic impact of chronic NaF exposure on a non-target organism, Drosophila melanogaster. The larvae exposed to different concentrations of NaF through food showed a significant increase in HSP70 expression both qualitatively and quantitatively. The altered tail length and tail intensity in Comet assay validate the increased DNA damage in treated larvae. The activity of AChE, oxidative stress marker enzymes, phase I and phase II detoxifying enzymes were found to be significantly inhibited in the treated larvae when compared to control though there was no evidence of dose dependent change in each case. The alterations in the mentioned parameters can be due to increased body Fluoride ion (F - ) concentration since the analysis with ion electrode analyzer revealed that F - concentration increased significantly with NaF treatment. Hence, the results suggest that D. melanogaster manifest prominent toxic response when subjected to chronic exposure to sub-lethal NaF concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Structural specificity in the lethal and mutagenic activity of furocoumarins in yeast cells

    International Nuclear Information System (INIS)

    Averbeck, D.; Chandra, P.; Biswas, R.K.; Gesellschaft fuer Strahlen- und Umweltforschung m.b.H., Frankfurt am Main

    1975-01-01

    Using monofunctional (Angelicin) and bifunctional furocoumarins (Psoralen and 8 Methoxypsoralen) plus 365 nm light it is shown that both kinds of damage, the induced monoadducts and/or crosslinks in DNA, provoke lethal and mutagenic effects in haploid and diploid cells of Saccharomyces cerevisiae. Bifunctional furocoumarins are about 20 times more effective in cell killing than Angelicin. Diploid cells are always more resistant than haploid cells. Dark repair (agar holding) increases survival. This effect can be at least in part correlated to the release of bound material from DNA in dark repair conditions. Bifunctional psoralens (10 μg/ml) are at least 10-fold more effective in inducing nuclear gene back mutations (his - to HIS + ) than Angelicin (10 μg/ml) plus 365 nm light or 254 nm ultraviolet light. In contrast cytoplasmic 'petite' (rho-) mutations are about as frequently induced by Angelicin plus 365 nm light as by 254 nm UV light. Bifunctional furocoumarins are less effective. The frequency of cytoplasmic 'petite' mutations per survivors decreases during dark repair conditions more efficiently after Angelicin than after Psoralen plus 365 nm light treatment. (orig.) [de

  17. Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge

    Directory of Open Access Journals (Sweden)

    T. Scott Devera

    2015-06-01

    Full Text Available Protective immunity against anthrax is inferred from measurement of vaccine antigen-specific neutralizing antibody titers in serum samples. In animal models, in vivo challenges with toxin and/or spores can also be performed. However, neither of these approaches considers toxin-induced damage to specific organ systems. It is therefore important to determine to what extent anthrax vaccines and existing or candidate adjuvants can provide organ-specific protection against intoxication. We therefore compared the ability of Alum, CpG DNA and the CD1d ligand α-galactosylceramide (αGC to enhance protective antigen-specific antibody titers, to protect mice against challenge with lethal toxin, and to block cardiotoxicity and hepatotoxicity. By measurement of serum cardiac Troponin I (cTnI, and hepatic alanine aminotransferase (ALT, and aspartate aminotransferase (AST, it was apparent that neither vaccine modality prevented hepatic intoxication, despite high Ab titers and ultimate survival of the subject. In contrast, cardiotoxicity was greatly diminished by prior immunization. This shows that a vaccine that confers survival following toxin exposure may still have an associated morbidity. We propose that organ-specific intoxication should be monitored routinely during research into new vaccine modalities.

  18. Loss of ATM kinase activity leads to embryonic lethality in mice.

    Science.gov (United States)

    Daniel, Jeremy A; Pellegrini, Manuela; Lee, Baeck-Seung; Guo, Zhi; Filsuf, Darius; Belkina, Natalya V; You, Zhongsheng; Paull, Tanya T; Sleckman, Barry P; Feigenbaum, Lionel; Nussenzweig, André

    2012-08-06

    Ataxia telangiectasia (A-T) mutated (ATM) is a key deoxyribonucleic acid (DNA) damage signaling kinase that regulates DNA repair, cell cycle checkpoints, and apoptosis. The majority of patients with A-T, a cancer-prone neurodegenerative disease, present with null mutations in Atm. To determine whether the functions of ATM are mediated solely by its kinase activity, we generated two mouse models containing single, catalytically inactivating point mutations in Atm. In this paper, we show that, in contrast to Atm-null mice, both D2899A and Q2740P mutations cause early embryonic lethality in mice, without displaying dominant-negative interfering activity. Using conditional deletion, we find that the D2899A mutation in adult mice behaves largely similar to Atm-null cells but shows greater deficiency in homologous recombination (HR) as measured by hypersensitivity to poly (adenosine diphosphate-ribose) polymerase inhibition and increased genomic instability. These results may explain why missense mutations with no detectable kinase activity are rarely found in patients with classical A-T. We propose that ATM kinase-inactive missense mutations, unless otherwise compensated for, interfere with HR during embryogenesis.

  19. Radiation damage of nonmetallic solids

    International Nuclear Information System (INIS)

    Goland, A.N.

    1975-01-01

    A review of data and information on radiation damage in nonmetallic solids is presented. Discussions are included on defects in nonmetals, radiation damage processes in nonmetals, electronic damage processes, physical damage processes, atomic displacement, photochemical damage processes, and ion implantation

  20. Hypoxial death inferred from thermally induced injuries at upper lethal temperatures, in the banded killifish, Fundulus diaphanus (LeSueur)

    Energy Technology Data Exchange (ETDEWEB)

    Rombough, P J; Garside, E T

    1977-10-01

    Banded killifish, Fundulus diaphanus (LeSueur), acclimated to 25/sup 0/C were subjected to upper lethal temperatures using a 10,000 min bioassay procedure. The incipient upper lethal temperature (LT/sub 50/) was about 34.5/sup 0/C. Histologic examination of heat-treated fish revealed no obvious injury to the heart, spleen, trunk musculature, eye, naris, integument, or digestive tract. Thermal stress induced progressive injury to the gills characterized by subepithelial edema, congestion of lamellar capillaries, and delamination of the respiratory epithelium from the pillar cell system. Areas of necrosis were observed in the lobus inferior of the hypothalamus and in the medulla oblongata. The pseudobranch epithelium was necrotic. Fatty change occurred in the liver. Acinar cells of the pancreas appeared autolytic and adjacent blood vessels damaged. Degenerative tubular changes and contracted glomerular tufts were noted in the kidney. The ovary was extremely temperature sensitive and displayed severe injury to oocytes and follicular cells after relatively short exposure to temperatures near the LT/sub 50/. It is proposed that primary thermally induced injury is to the gills. This results in abnormal gas exchange and osmoregulation and leads to pathologic changes in other tissues. Hypoxia of the central nervous system appears to be the ultimate cause of death.

  1. Impulsivity, aggression and brain structure in high and low lethality suicide attempters with borderline personality disorder.

    Science.gov (United States)

    Soloff, Paul; White, Richard; Diwadkar, Vaibhav A

    2014-06-30

    Impulsivity and aggressiveness are trait dispositions associated with the vulnerability to suicidal behavior across diagnoses. They are associated with structural and functional abnormalities in brain networks involved in regulation of mood, impulse and behavior. They are also core characteristics of borderline personality disorder (BPD), a disorder defined, in part, by recurrent suicidal behavior. We assessed the relationships between personality traits, brain structure and lethality of suicide attempts in 51 BPD attempters using multiple regression analyses on structural MRI data. BPD was diagnosed by the Diagnostic Interview for Borderline Patients-revised, impulsivity by the Barratt Impulsiveness Scale (BIS), aggression by the Brown-Goodwin Lifetime History of Aggression (LHA), and high lethality by a score of 4 or more on the Lethality Rating Scale (LRS). Sixteen High Lethality attempters were compared to 35 Low Lethality attempters, with no significant differences noted in gender, co-morbidity, childhood abuse, BIS or LHA scores. Degree of medical lethality (LRS) was negatively related to gray matter volumes across multiple fronto-temporal-limbic regions. Effects of impulsivity and aggression on gray matter volumes discriminated High from Low Lethality attempters and differed markedly within lethality groups. Lethality of suicide attempts in BPD may be related to the mediation of these personality traits by specific neural networks. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Heterochromatin position effects on circularized sex chromosomes cause filicidal embryonic lethality in Drosophila melanogaster.

    Science.gov (United States)

    Ferree, Patrick M; Gomez, Karina; Rominger, Peter; Howard, Dagnie; Kornfeld, Hannah; Barbash, Daniel A

    2014-04-01

    Some circularized X-Y chromosomes in Drosophila melanogaster are mitotically unstable and induce early embryonic lethality, but the genetic basis is unknown. Our experiments suggest that a large region of X-linked satellite DNA causes anaphase bridges and lethality when placed into a new heterochromatic environment within certain circularized X-Y chromosomes. These results reveal that repetitive sequences can be incompatible with one another in cis. The lethal phenotype also bears a remarkable resemblance to a case of interspecific hybrid lethality.

  3. Femoral nerve damage (image)

    Science.gov (United States)

    The femoral nerve is located in the leg and supplies the muscles that assist help straighten the leg. It supplies sensation ... leg. One risk of damage to the femoral nerve is pelvic fracture. Symptoms of femoral nerve damage ...

  4. Gastrointestinal decontamination in healthy and lethally irradiated monkeys

    International Nuclear Information System (INIS)

    Hendriks, W.D.H.

    1980-01-01

    In periods of extreme immunosuppression, infections which are often life-threatening, frequently occur. In an attempt to prevent such infections in lethally irradiated rhesus monkeys, the animals were subjected to strict reverse isolation prior to irradiation and administrated orally with nonabsorbable antibiotics in order to eliminate their microflora. The antibiotic combination was selected on the basis of a sensitivity test and was added to the liquid food supply. To rapidly achieve a high bactericidal concentration in the intestine, the same antibiotics were additionally given orally for 5 days. The microflora was reduced rapidly; within a few days sterile cultures were obtained. Particularly after discontinuation of the administration of the additional antibiotics were colonizations found. In contrast to colonizations persisting from the first day of treatment on, the first were rather easy to suppress. (Auth.)

  5. In vitro cell culture lethal dose submitted to gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Moreno, Carolina S.; Rogero, Sizue O.; Rogero, Jose Roberto [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], e-mail: carolina_sm@hotmail.com; Ikeda, Tamiko I.; Cruz, Aurea S. [Instituto Adolfo Lutz, Sao Paulo, SP (Brazil)

    2009-07-01

    The present study was designed to evaluate the in vitro effect of gamma radiation in cell culture of mouse connective tissue exposed to different doses of gamma radiation and under several conditions. The cell viability was analyzed by neutral red uptake methodology. This assay was developed for establish a methodology to be used in the future in the study of resveratrol radioprotection. Resveratrol (3,4',5- trihydroxystilbene), a phenolic phytoalexin that occurs naturally in some spermatophytes, such as grapevines, in response to injury as fungal infections and exposure to ultraviolet light. In the wines this compound is found at high levels and is considered one of the highest antioxidant constituents. The intense antioxidant potential of resveratrol provides many pharmacological activities including cardioprotection, chemoprevention and anti-tumor effects. Our results demonstrated that {sup 60}Co gamma radiation lethal dose (LD50) on NCTC clone 929 cells was about 340Gy. (author)

  6. In vitro cell culture lethal dose submitted to gamma radiation

    International Nuclear Information System (INIS)

    Moreno, Carolina S.; Rogero, Sizue O.; Rogero, Jose Roberto; Ikeda, Tamiko I.; Cruz, Aurea S.

    2009-01-01

    The present study was designed to evaluate the in vitro effect of gamma radiation in cell culture of mouse connective tissue exposed to different doses of gamma radiation and under several conditions. The cell viability was analyzed by neutral red uptake methodology. This assay was developed for establish a methodology to be used in the future in the study of resveratrol radioprotection. Resveratrol (3,4',5- trihydroxystilbene), a phenolic phytoalexin that occurs naturally in some spermatophytes, such as grapevines, in response to injury as fungal infections and exposure to ultraviolet light. In the wines this compound is found at high levels and is considered one of the highest antioxidant constituents. The intense antioxidant potential of resveratrol provides many pharmacological activities including cardioprotection, chemoprevention and anti-tumor effects. Our results demonstrated that 60 Co gamma radiation lethal dose (LD50) on NCTC clone 929 cells was about 340Gy. (author)

  7. Perinatally lethal short rib-polydactyly syndromes. Pt. 1

    International Nuclear Information System (INIS)

    Sillence, D.; Kozlowski, K.; Bar-ziv, J.; Fuhrmann-Rieger, A.; Fuhrmann, W.; Pascu, F.

    1987-01-01

    Thirteen newborns with lethal short rib-polydactyly (SRP) have been reviewed, 11 with SRP type 3 (Verma-Naumoff) and 2 with SRP tye 2 (Majewski). In the former group there were three sets of siblings. The excess of males with SRP type III (Verma-Naumoff) is confirmed in this present study. A high frequency of phenotypic females including sex-reversed constitutional males with SRP type 1 (Saldino-Noonan) is in marked contrast to these findings in SRP type 3. Possible hypotheses include variable expressivity in non-Majewski short rib-polydactyly syndromes with sex-reversed and constitutional female cases tending to show more severe phenotypic expression both in terms of major anomalies and skeletal dysplastic effects. (orig.)

  8. Lethal carbon monoxide toxicity in a concrete shower unit.

    Science.gov (United States)

    Heath, Karen; Byard, Roger W

    2018-05-23

    A 47-year-old previously-well woman was found dead on the floor of a shower cubicle on a property in rural South Australia. The impression of the attending doctor and police was of collapse due to natural disease. Although there was significant stenosing coronary artery atherosclerosis found at autopsy, cherry pink discoloration of tissues prompted measurement of the blood carboxyhemoglobin level which was found to be 55%. The source of the gas was a poorly-maintained hot water heater that was mounted on the inside wall of the shower. Construction of the shower using an impermeable concrete rain water tank had caused gas accumulation when the water heater malfunctioned. Had lethal carbon monoxide exposure not been identified others using the same shower unit would also have been at risk.

  9. Analysis of Lethality and Malformations During Zebrafish (Danio rerio) Development.

    Science.gov (United States)

    Raghunath, Azhwar; Perumal, Ekambaram

    2018-01-01

    The versatility offered by zebrafish (Danio rerio) makes it a powerful and an attractive vertebrate model in developmental toxicity and teratogenicity assays. Apart from the newly introduced chemicals as drugs, xenobiotics also induce abnormal developmental abnormalities and congenital malformations in living organisms. Over the recent decades, zebrafish embryo/larva has emerged as a potential tool to test teratogenicity potential of these chemicals. Zebrafish responds to compounds as mammals do as they share similarities in their development, metabolism, physiology, and signaling pathways with that of mammals. The methodology used by the different scientists varies enormously in the zebrafish embryotoxicity test. In this chapter, we present methods to assess lethality and malformations during zebrafish development. We propose two major malformations scoring systems: binomial and relative morphological scoring systems to assess the malformations in zebrafish embryos/larvae. Based on the scoring of the malformations, the test compound can be classified as a teratogen or a nonteratogen and its teratogenic potential is evaluated.

  10. BRINE SHRIMP LETHALITY BIOASSAY OF GLAUCIUM GRANDIFLORUM VAR. GRANDIFLORUM

    OpenAIRE

    A. SARI, Ç. ÜNSAL, İ. SARIOĞLU, A. SARI, Ç. ÜNSAL, İ. SARIOĞLU

    2013-01-01

    Türkiye'nin 3 farklı bölgesinden toplanan Glaucium grandiflorum Boiss. et Huet var. grandiflorum örneklerinin toprak üstü kısımlarından elde edilen alkaloit ekstreleri ve bu ekstrelerden elde edilen majör alkaloitler allokriptopin, protopİn, (+)-izokoridin, (+)-korİdin üzerinde brİne shrimp lethality testi yapılarak sitotoksisiteleri İncelenmiştir. Glaucium grandiflorum var. grandiflorum türünün 3 örneği de önemli oranda sitotoksik aktİvite göstermiştir. Allokriptopin, protopin, (+)-izok...

  11. Mechanisms of Lethal Cerebrovascular Accidents in Turner Syndrome.

    Science.gov (United States)

    Byard, Roger W

    2016-05-01

    A case of intracerebral hemorrhage in Turner syndrome is reported with an analysis of possible causes of cerebrovascular accidents in this condition. A 42-year-old woman with known Turner syndrome died soon after hospital admission having been found unconscious at her home address. At autopsy, she showed typical features of Turner syndrome with short stature, webbing of the neck, underdeveloped breasts, and an increased carrying angle of the arm. Death was due to a large left-sided intracerebral hemorrhage extending from the left basal ganglia into the white matter of the frontal lobe and lateral ventricle. Cases of unexpected death in Turner syndrome may arise from occult cerebrovascular accidents which may be hemorrhagic or nonhemorrhagic. Associated features include hypertension, vascular malformations, accelerated atherogenesis, cystic medial necrosis, and moyamoya syndrome. The possibility of Turner syndrome should be considered in cases where there has been a lethal cerebrovascular event in a younger woman. © 2016 American Academy of Forensic Sciences.

  12. Preliminary results on epidemiology of Coconut Lethal Yellowing in Ghana

    Directory of Open Access Journals (Sweden)

    Bonnot François

    2009-03-01

    Full Text Available Epidemiological studies are of major importance in understanding the determinants of plant diseases in order to control the risks of their spreading. A research programme on the epidemiology of coconut lethal yellowing, or Cape Saint Paul Wilt Disease (CSPWD, in Ghana was launched in March 2007. The objective was to characterize the distribution and spread of the disease in space and time at various scales, and their relation with the environment. This article presents the general strategy used to evaluate the incidence of CSPWD along with the environmental, ecological and agronomical variables at regional level. A survey was undertaken on 1,166 plots of Coconut Sector Development Project (CSDP planted with Malayan Yellow Dwarf (MYD × Vanuatu Tall (VTT hybrids in Western Region and Central Region. Preliminary results on the distribution of CSPWD and outside variables at regional scale, along with their relations, are given.

  13. Thyroid and pancreatic hormones in lethally irradiated rats

    International Nuclear Information System (INIS)

    Ahlersova, E.; Ahlers, I.; Praslicka, M.

    1985-01-01

    The concentrations of thyroxine, triiodothyronine and reverse triiodothyronine, glucagon and insulin in the serum or plasma were determined by radioimmunoassay in male rats of the Wistar strain 1, 6, 24, 48 and 72 hours after irradiation with 14.35 Gy (1500R) of X-rays. The irradiated and sham-irradiated rats were starved till examination. The concentrations of thyroxine and triiodothyronine dropped 6 hours after irradiation as compared with controls, the concentration of thyroxine also dropped after 72 hours. The level of reverse triiodothyronine in irradiated rats increased in the terminal period. The level of insulin dropped 24 hours after irradiation, at 72 hours it was higher than that in controls. The concentration of glucagon in irradiated rats increased in the terminal phase of radiation disease. The results document the diverse reaction of hormones in lethally irradiated rats and contribute to a deeper recognition of metabolic imbalance in the course of radiation disease. (author)

  14. Lethal midline granuloma histologically. Management with radiation therapy

    International Nuclear Information System (INIS)

    Barriga T, L.; Misad, O.; Moscol, A.; Pinillos G, L.; Barriga T, O.; Heredia, A.; Pinillos A, L.; Mayer Z, T.

    1995-01-01

    From 1973 through 1990, 24 patients with lethal midline granuloma histologically demonstrated were treated with radiation therapy at the Radiation Oncology Department of the National Institute of Neoplasmic Diseases from Peru. The authors reports the results of their experience, reviewed the literature and present a clinic and pathologic discussion of this rare entity. All the patients received radiotherapy as the main treatment and 12 of them received chemotherapy. The male to female ratio was 5:3 with a mean age of 29.33 years (range 6 to 84 years old). Symptoms of nasal obstruction were presented 45.83%, nasal enlargement in 33.33%, nasal discharge in 29.16% and fever in 29.16%, principally. We believe that radiotherapy is the treatment of choice in this report we can not demonstrate it because of the small number of patients. (authors). 28 refs., 10 tabs

  15. Evaluation of Lethal Giant Larvae as a Schistosomiasis Vaccine Candidate

    Directory of Open Access Journals (Sweden)

    Yufan Cao

    2016-01-01

    Full Text Available Schistosomiasis is a neglected tropical disease of humans, and it is considered to be the second most devastating parasitic disease after malaria. Eggs produced by normally developed female worms are important in the transmission of the parasite, and they responsible for the pathogenesis of schistosomiasis. The tumor suppressor gene lethal giant larvae (lgl has an essential function in establishing apical-basal cell polarity, cell proliferation, differentiation, and tissue organization. In our earlier study, downregulation of the lgl gene induced a significant reduction in the egg hatching rate of Schistosoma japonicum (Sj eggs. In this study, the Sjlgl gene was used as a vaccine candidate against schistosomiasis, and vaccination achieved and maintained a stable reduction of the egg hatching rate, which is consistent with previous studies, in addition to reducing the worm burden and liver egg burden in some trials.

  16. Evaluating the lethal and pre-lethal effects of a range of fungi against adult Anopheles stephensi mosquitoes

    Directory of Open Access Journals (Sweden)

    Blanford Simon

    2012-11-01

    Full Text Available Abstract Background Insecticide resistance is seriously undermining efforts to eliminate malaria. In response, research on alternatives to the use of chemical insecticides against adult mosquito vectors has been increasing. Fungal entomopathogens formulated as biopesticides have received much attention and have shown considerable potential. This research has necessarily focused on relatively few fungal isolates in order to ‘prove concept’. Further, most attention has been paid to examining fungal virulence (lethality and not the other properties of fungal infection that might also contribute to reducing transmission potential. Here, a range of fungal isolates were screened to examine variation in virulence and how this relates to additional pre-lethal reductions in feeding propensity. Methods The Asian malaria vector, Anopheles stephensi was exposed to 17 different isolates of entomopathogenic fungi belonging to species of Beauveria bassiana, Metarhizium anisopliae, Metarhizium acridum and Isaria farinosus. Each isolate was applied to a test substrate at a standard dose rate of 1×109 spores ml-1 and the mosquitoes exposed for six hours. Subsequently the insects were removed to mesh cages where survival was monitored over the next 14 days. During this incubation period the mosquitoes’ propensity to feed was assayed for each isolate by offering a feeding stimulant at the side of the cage and recording the number probing. Results and conclusions Fungal isolates showed a range of virulence to A. stephensi with some causing >80% mortality within 7 days, while others caused little increase in mortality relative to controls over the study period. Similarly, some isolates had a large impact on feeding propensity, causing >50% pre-lethal reductions in feeding rate, whereas other isolates had very little impact. There was clear correlation between fungal virulence and feeding reduction with virulence explaining nearly 70% of the variation in

  17. Evidence of heritable lethal mutations in progeny of X-irradiated CHO cells by micronucleus count in clon-cells

    International Nuclear Information System (INIS)

    Hagemann, G.; Kreczik, A.; Treichel, M.

    1996-01-01

    Low doses of ionizing radiation reduce the growth rates of clones following irradiation of the progenitor cells. Such reductions of clone growth have been proven by means of measurements of clone size distributions. The medians of such distributions can be used to quantify the radiation damage. Prolongations of generation times and cell death as result of heritable lethal mutations have been discussed as causes for the reduction of clone growth. The cell number of a clone of hypotetraploid CHO-cells was compared to the frequency of micronucleated binucleated cells in the same clone using the cytokinesis-block-micronucleus method. The dose dependent reduction of clone sizes is measured by the difference of the medians (after log transformation) of the clone size distributions. At cytochalasin-B concentrations of 1 μg/ml and after an incubation time of 16 h a yield of binucleated cells of about 50% was obtained. Median clone size differences as a measure of clonal radiation damage increased linearly with incubation times of 76, 100, 124, and 240 h following irradiation with 3, 5, 7, and 12 Gy. The frequency of binucleated clone cells with micronuclei strongly increased with decreasing clone size by a factor up to 20 following irradiation with 3, 5, and 7 Gy. The frequency of micronucleated binucleated clone cells was found to be independent of incubation time after irradiation. Radiation induced clone size reductions result from cell losses caused by intraclonal expression of micronuclei which have its origin in heritable lethal mutations. Measurements of clone size distributions can be done automatically. They can serve as predictive test for determination of median cell loss rates of surviving cell clones. (orig./MG) [de

  18. Expression of assayable residual stem cell damage in erythroid differentiation

    International Nuclear Information System (INIS)

    Huebner, G.E.; Miller, M.E.; Cronkite, E.P.

    1985-01-01

    In rodents, residual damage is inducible in hematopoietic stem cells by exposure to ionizing radiation or alkylating agents. This damage can b e assayed in mice by transferring bone marrow into lethally irradiated syngeneic recipients and subsequently measuring the incremental increase of-( 125 I)iodo-2'-deoxyuridine incorporation in spleens. In this study, bone marrow from mice treated 3 weeks previously with Methylnitrosourea (50 mg/kg) or 450 rad was injected into recipients in order to determine possible residual effects of treatment of erythroid cell differentiation following stem cell seeding. Such effects were detected by a reduced amount of 59 Fe incorporation into spleens, thus indicatin g transfer of residual stem cell damage to differentiating cells. (orig.)

  19. The lethal interaction of x ray and penicillin induced lesions following x-irradiation of Escherichia coli B/r in the presence of hypoxic cell sensitizers

    International Nuclear Information System (INIS)

    Gillies, N.E.; Obioha, F.I.

    1982-01-01

    When Escherichia coli B/r were x-irradiated under anoxia in the presence of different electron-affinic sensitizers and then incubated in broth containing penicillin (at a concentration that did not kill unirradiated cells) additional killing of the bacteria occurred provided the sensitizers were of relatively high lipophilicity. The overall effect was to increase the efficiency of these sensitizers. It is concluded that sensitizer-dependent latent radiation lesions(s) are produced in membrane components of the cell envelope that interact with damage caused by penicillin in the peptidoglycan layer and this causes the additional lethality

  20. 77 FR 6548 - Notice of Availability of Ballistic Survivability, Lethality and Vulnerability Analyses

    Science.gov (United States)

    2012-02-08

    ... DEPARTMENT OF DEFENSE Department of the Army Notice of Availability of Ballistic Survivability, Lethality and Vulnerability Analyses AGENCY: Department of the Army, DoD. ACTION: Notice of availability. SUMMARY: The US Army Research Laboratory's (ARL's), Survivability, Lethality Analysis Directorate (SLAD...

  1. Acute and sub-lethal response to mercury in Arctic and boreal calanoid copepods.

    Science.gov (United States)

    Overjordet, Ida Beathe; Altin, Dag; Berg, Torunn; Jenssen, Bjørn Munro; Gabrielsen, Geir Wing; Hansen, Bjørn Henrik

    2014-10-01

    Acute lethal toxicity, expressed as LC50 values, is a widely used parameter in risk assessment of chemicals, and has been proposed as a tool to assess differences in species sensitivities to chemicals between climatic regions. Arctic Calanus glacialis and boreal Calanus finmarchicus were exposed to mercury (Hg(2+)) under natural environmental conditions including sea temperatures of 2° and 10°C, respectively. Acute lethal toxicity (96 h LC50) and sub-lethal molecular response (GST expression; in this article gene expression is used as a synonym of gene transcription, although it is acknowledged that gene expression is also regulated, e.g., at translation and protein stability level) were studied. The acute lethal toxicity was monitored for 96 h using seven different Hg concentrations. The sub-lethal experiment was set up on the basis of nominal LC50 values for each species using concentrations equivalent to 50, 5 and 0.5% of their 96 h LC50 value. No significant differences were found in acute lethal toxicity between the two species. The sub-lethal molecular response revealed large differences both in response time and the fold induction of GST, where the Arctic species responded both faster and with higher mRNA levels of GST after 48 h exposure. Under the natural exposure conditions applied in the present study, the Arctic species C. glacialis may potentially be more susceptible to mercury exposure on the sub-lethal level. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Indirect effects of non-lethal predation on bivalve activity and sediment reworking

    NARCIS (Netherlands)

    Maire, O.; Merchant, J.N.; Bulling, M.; Teal, L.R.; Gremare, A.; Duchene, J.C.; Solan, M.

    2010-01-01

    Deposit-feeders are the dominant bioturbators of aquatic sediments, where they profoundly impact biogeochemical processes, but they are also vulnerable to both lethal and non-lethal predation by a large variety of predators. In this study, we performed a series of experiments to test the effects of

  3. Evaluating the Predictive Validity of Suicidal Intent and Medical Lethality in Youth

    Science.gov (United States)

    Sapyta, Jeffrey; Goldston, David B.; Erkanli, Alaattin; Daniel, Stephanie S.; Heilbron, Nicole; Mayfield, Andrew; Treadway, S. Lyn

    2012-01-01

    Objectives: To examine whether suicidal intent and medical lethality of past suicide attempts are predictive of future attempts, the association between intent and lethality, and the consistency of these characteristics across repeated attempts among youth. Method: Suicide attempts in a 15-year prospective study of 180 formerly psychiatrically…

  4. Effect of lethality on the extinction and on the error threshold of quasispecies.

    Science.gov (United States)

    Tejero, Hector; Marín, Arturo; Montero, Francisco

    2010-02-21

    In this paper the effect of lethality on error threshold and extinction has been studied in a population of error-prone self-replicating molecules. For given lethality and a simple fitness landscape, three dynamic regimes can be obtained: quasispecies, error catastrophe, and extinction. Using a simple model in which molecules are classified as master, lethal and non-lethal mutants, it is possible to obtain the mutation rates of the transitions between the three regimes analytically. The numerical resolution of the extended model, in which molecules are classified depending on their Hamming distance to the master sequence, confirms the results obtained in the simple model and shows how an error catastrophe regime changes when lethality is taken in account. (c) 2009 Elsevier Ltd. All rights reserved.

  5. Influence Analysis of Shell Material and Charge on Shrapnel Lethal Power

    Directory of Open Access Journals (Sweden)

    Wang Lin

    2015-01-01

    Full Text Available To compare the shrapnel lethal power with different shell material and charge, LS-DYNA was used to numerically simulate four kinds of shrapnel lethal power. The shell material was 58SiMn, 50SiMnVB or 40Cr, whereas the charge was RL-F. And the shell material was 58SiMn, whereas the charge was TNT. The shell rupture process and lethal power test were analyzed. The results show that, the lethal power of RL-F charge increase by 25%, 45%, 14% compared with the TNT charge, whereas the shell material was 58SiMn, 50SiMnVB, 40Cr. And then the guarantee range and lethal power can be improved by using the high explosive and changing shell material, whereas the projectile shape coefficient is invariable.

  6. MASM, a Matrine Derivative, Offers Radioprotection by Modulating Lethal Total-Body Irradiation-Induced Multiple Signaling Pathways in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Jianzhong Li

    2016-05-01

    Full Text Available Matrine is an alkaloid extracted from Sophora flavescens Ait and has many biological activities, such as anti-inflammatory, antitumor, anti-fibrosis, and immunosuppressive properties. In our previous studies, the matrine derivative MASM was synthesized and exhibited potent inhibitory activity against liver fibrosis. In this study, we mainly investigated its protection against lethal total-body irradiation (TBI in rats. Administration of MASM reduced the radiation sickness characteristics and increased the 30-day survival of rats before or after lethal TBI. Ultrastructural observation illustrated that pretreatment of rats with MASM significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed that pretreatment with MASM had a dramatic effect on gene expression changes caused by TBI. Pretreatment with MASM prevented differential expression of 53% (765 genes of 1445 differentially expressed genes induced by TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 21 pathways, such as metabolic pathways, pathways in cancer, and mitogen-activated protein kinase (MAPK pathways. Our data indicated that pretreatment of rats with MASM modulated these pathways induced by TBI, suggesting that the pretreatment with MASM might provide the protective effects on lethal TBI mainly or partially through the modulation of these pathways, such as multiple MAPK pathways. Therefore, MASM has the potential to be used as an effective therapeutic or radioprotective agent to minimize irradiation damages and in combination with radiotherapy to improve the efficacy of cancer therapy.

  7. Recombinant thrombomodulin protects mice against histone-induced lethal thromboembolism.

    Directory of Open Access Journals (Sweden)

    Mayumi Nakahara

    Full Text Available INTRODUCTION: Recent studies have shown that histones, the chief protein component of chromatin, are released into the extracellular space during sepsis, trauma, and ischemia-reperfusion injury, and act as major mediators of the death of an organism. This study was designed to elucidate the cellular and molecular basis of histone-induced lethality and to assess the protective effects of recombinant thrombomodulin (rTM. rTM has been approved for the treatment of disseminated intravascular coagulation (DIC in Japan, and is currently undergoing a phase III clinical trial in the United States. METHODS: Histone H3 levels in plasma of healthy volunteers and patients with sepsis and DIC were measured using enzyme-linked immunosorbent assay. Male C57BL/6 mice were injected intravenously with purified histones, and pathological examinations were performed. The protective effects of rTM against histone toxicity were analyzed both in vitro and in mice. RESULTS: Histone H3 was not detectable in plasma of healthy volunteers, but significant levels were observed in patients with sepsis and DIC. These levels were higher in non-survivors than in survivors. Extracellular histones triggered platelet aggregation, leading to thrombotic occlusion of pulmonary capillaries and subsequent right-sided heart failure in mice. These mice displayed symptoms of DIC, including thrombocytopenia, prolonged prothrombin time, decreased fibrinogen, fibrin deposition in capillaries, and bleeding. Platelet depletion protected mice from histone-induced death in the first 30 minutes, suggesting that vessel occlusion by platelet-rich thrombi might be responsible for death during the early phase. Furthermore, rTM bound to extracellular histones, suppressed histone-induced platelet aggregation, thrombotic occlusion of pulmonary capillaries, and dilatation of the right ventricle, and rescued mice from lethal thromboembolism. CONCLUSIONS: Extracellular histones cause massive

  8. Effect of caffeine on the expression of a major X-ray induced protein in human tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, E.N.; Boothman, D.A. (Univ. of Pennsylvania School of Medicine, Philadelphia (USA))

    1991-03-01

    We have examined the effect of caffeine on the concomitant processes of the repair of potentially lethal damage (PLD) and the synthesis of X-ray-induced proteins in the human malignant melanoma cell line, Ul-Mel. Caffeine administered at a dose of 5mM after X radiation not only inhibited PLD repair but also markedly reduced the level of XIP269, a major X-ray-induced protein whose expression has been shown to correlate with the capacity to repair PLD. The expression of the vast majority of other cellular proteins, including seven other X-ray-induced proteins, remained unchanged following caffeine treatment. A possible role for XIP269 in cell cycle delay following DNA damage by X irradiation is discussed.

  9. 35S induced dominant lethals in immature Oocytes in mice

    International Nuclear Information System (INIS)

    Satyanarayana Reddy, K.; Reddy, P.; Reddy, O.S.

    1976-01-01

    CBA female mice were injected intraperitoneally with a dose of 20 μCi of sulphur-35 on 15.5 day post conception. Another group of pregnant mice injected with normal saline was kept as control. The pregnant females were allowed to litter and the mothers were separated from their offspring 4 weeks after littering. Eight weeks after treatment i.e. at the age of 22-24 weeks, the treated mothers were mated to control C 3 H/He males. The vaginal plugs were checked everyday morning and those mated were separated. The pregnants were killed on 14th day of gestation. The uterine contents were searched for live and dead embryos and the ovaries for corpora lutea. The pre, post and total loses were calculated in the treated females and compared with those of control. The statistical tests performed indicated that all losses are significant. The results indicate that 35 S can induce chromosomal breaks in immature oocytes and lead to the induction of dominant lethals. (author)

  10. Successful Treatment of Acute Lethal Dose of Acrylamide Poisoning

    Directory of Open Access Journals (Sweden)

    Ali Banagozar Mohammadi

    2015-03-01

    Full Text Available Background: Acrylamide (C3H5NO is a vinyl monomer. This water-soluble crystalline solid is a colorless, odorless agent which is used in scientific laboratories and some industries. Acrylamide has cellular oxidative effects. Acute or chronic poisoning with this agent happens as a result of skin, respiratory, or oral contacts. Clinical manifestations depend on the dose, duration, and frequency of contact. Management of these patients consists of conservative and palliative therapies to reduce the oxidative effects. Case: The case was a 29-year-old girl with a Master of Sciences degree in genetics who worked in a university research center with previous history of depression. She had ingested 100cc of 30% Acrylamide solution for intentional suicide attempt. The patient was successfully managed using N-acetyl cysteine, vitamin C, and melatonin. Conclusion: Early diagnosis and appropriate treatment with recommended agents together with supportive therapies can save the life of patients exposed to potentially lethal doses of acrylamide, although intentional or accidental.

  11. Lethal effect of glucose load on malignant cells

    International Nuclear Information System (INIS)

    Shmakova, N.L.; Yarmonenko, S.P.; Kozubek, S.

    1987-01-01

    Ehrlich ascites tumor (EAT) cells were treated with glucose load under anoxic conditions (for 15 or 60 min) and/or with γ radiation (20 Gy). The efficiency of the treatment was judged from the tumorigenic activity of EAT cell inocula. The markedly increased efficiency of the combined treatment of EAT cells using glucose load in anoxia and γ radiation is due to the additive action of both agents. The glucose load in anoxia leads to extensive desintegration of tumor cells. Further, the lethal effect of various pH values on EAT cells was investigated. Different pH values were obtained by means of both glucose load and phosphate buffers. The effect was investigated by determining the tumorigenic activity of EAT cells tested in vivo in mice and by determining the radiosensitivity of treated EAT cells. The results allowed us to conclude that the same values of pH lead to the same effect on EAT cells independently of the way by which the given pH value was reached. (author). 5 figs., 2 tabs., 12 refs

  12. Lethal Lullabies: A History of Opium Use in Infants.

    Science.gov (United States)

    Obladen, Michael

    2016-02-01

    Poppy extract accompanied the human infant for more than 3 millenia. Motives for its use included excessive crying, suspected pain, and diarrhea. In antiquity, infantile sleeplessness was regarded as a disease. When treatment with opium was recommended by Galen, Rhazes, and Avicenna, baby sedation made its way into early medical treatises and pediatric instructions. Dabbing maternal nipples with bitter substances and drugging the infant with opium were used to hasten weaning. A freerider of gum lancing, opiates joined the treatment of difficult teething in the 17th century. Foundling hospitals and wet-nurses used them extensively. With industrialization, private use was rampant among the working class. In German-speaking countries, poppy extracts were administered in soups and pacifiers. In English-speaking countries, proprietary drugs containing opium were marketed under names such as soothers, nostrums, anodynes, cordials, preservatives, and specifics and sold at the doorstep or in grocery stores. Opium's toxicity for infants was common knowledge; thousands of cases of lethal intoxication had been reported from antiquity. What is remarkable is that the willingness to use it in infants persisted and that physicians continued to prescribe it for babies. Unregulated trade, and even that protected by governments, led to greatly increased private use of opiates during the 19th century. Intoxication became a significant factor in infant mortality. As late as 1912, the International Hague Convention forced governments to implement legislation that effectively curtailed access to opium and broke the dangerous habit of sedating infants. © The Author(s) 2015.

  13. Internet suicide: communities of affirmation and the lethality of communication.

    Science.gov (United States)

    Niezen, Ronald

    2013-04-01

    As a tool of instant information dissemination and social networking, the Internet has made possible the formation and affirmation of public identities based on personality traits that are usually characterized by clinicians as pathological. The wide variety of online communities of affirmation reveals new conditions for permissiveness and inclusiveness in expressions of these socially marginal and clinically pathologized identities. Much the same kind of discourse common to these online communities is evident in some suicide forums. Web sites with suicide as their central raison d'être, taken together, encompass a wide range of ideas and commitments, including many that provide collective affirmation outside of (and often with hostility toward) professional intervention. The paradox of a potentially life-affirming effect of such forums runs counter to a stark dualism between online therapy versus "prochoice" forums and, by extension, to simple models of the influence of ideas on the lethality of suicide. Different forums either intensify or mitigate self-destructive tendencies in ways that are significant for understanding the place of communication in the occurrence of suicide and for therapeutic practice.

  14. USC-087 protects Syrian hamsters against lethal challenge with human species C adenoviruses.

    Science.gov (United States)

    Toth, Karoly; Spencer, Jacqueline F; Ying, Baoling; Tollefson, Ann E; Hartline, Caroll B; Richard, Eric T; Fan, Jiajun; Lyu, Jinglei; Kashemirov, Boris A; Harteg, Cheryl; Reyna, Dawn; Lipka, Elke; Prichard, Mark N; McKenna, Charles E; Wold, William S M

    2018-05-01

    Human adenoviruses (AdV) cause generally mild infections of the respiratory and GI tracts as well as some other tissues. However, AdV can cause serious infection in severely immunosuppressed individuals, especially pediatric patients undergoing allogeneic hematopoietic stem cell transplantation, where mortality rates are up to 80% with disseminated disease. Despite the seriousness of AdV disease, there are no drugs approved specifically to treat AdV infections. We report here that USC-087, an N-alkyl tyrosinamide phosphonate ester prodrug of HPMPA, the adenine analog of cidofovir, is highly effective against multiple AdV types in cell culture. USC-087 is also effective against AdV-C6 in our immunosuppressed permissive Syrian hamster model. In this model, hamsters are immunosuppressed by treatment with high dose cyclophosphamide. Injection of AdV-C6 (or AdV-C5) intravenously leads to a disseminated infection that resembles the disease seen in humans, including death. We have tested the efficacy of orally-administered USC-087 against the median lethal dose of intravenously administered AdV-C6. USC-087 completely prevented or significantly decreased mortality when administered up to 4 days post challenge. USC-087 also prevented or significantly decreased liver damage caused by AdV-C6 infection, and suppressed virus replication even when administered 4 days post challenge. These results imply that USC-087 is a promising candidate for drug development against HAdV infections. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Development of a detection sensor for lethal H2S gas.

    Science.gov (United States)

    Park, Young-Ho; Kim, Yong-Jae; Lee, Chang-Seop

    2012-07-01

    The gas which may be lethal to human body with short-term exposure in common industrial fields or workplaces in LAB may paralyze the olfactory sense and impose severe damages to central nervous system and lung. This study is concerned with the gas sensor which allows individuals to avoid the toxic gas that may be generated in the space with residues of organic wastes under 50 degrees C or above. This study investigates response and selectivity of the sensor to hydrogen sulfide gas with operating temperatures and catalysts. The thick-film semiconductor sensor for hydrogen sulfide gas detection was fabricated WO3/SnO2 prepared by sol-gel and precipitation methods. The nanosized SnO2 powder mixed with the various metal oxides (WO3, TiO2, and ZnO) and doped with transition metals (Au, Ru, Pd Ag and In). Particle sizes, specific surface areas and phases of sensor materials were investigated by SEM, BET and XRD analyses. The metal-WO3/SnO2 thick films were prepared by screen-printing method. The measured response to hydrogen sulfide gas is defined as the ratio (Ra/R,) of the resistance of WO3ISnO2 film in air to the resistance of WO3/SnO2 film in a hydrogen sulfide gas. It was shown that the highest response and selectivity of the sensor for hydrogen sulfide by doping with 1 wt% Ru and 10 wt% WO3 to SnO2 at the optimum operating temperature of 200 degrees C.

  16. Lethal and sublethal effects of marine sediment extracts on fish cells and chromosomes

    Science.gov (United States)

    Landolt, Marsha L.; Kocan, Richard M.

    1984-03-01

    The cost of conducting conventional chronic bioassays with every potentially toxic compound found in marine ecosystems is prohibitive; therefore short-term toxicity tests which can be used for rapid screening were developed. The tests employ cultured fish cells to measure lethal, sublethal or genotoxic effects of pure compounds and complex mixtures. The sensitivity of these tests has been proven under laboratory conditions; the following study used two of these tests, the anaphase aberration test and a cytotoxicity assay, under field conditions. Sediment was collected from 97 stations within Puget Sound, Washington. Serial washings of the sediment in methanol and dichloromethane yielded an organic extract which was dried, dissolved in DMSO and incubated as a series of dilutions with rainbow trout gonad (RTG-2) cells. The toxic effects of the extract were measured by examining the rate of cell proliferation and the percentage of damaged anaphase figures. Anaphase figures were considered to be abnormal if they exhibited non-disjunctions, chromosome fragments, or chromosome bridges. A second cell line (bluegill fry, BF-2) was also tested for cell proliferation and was included because, unlike the RTG-2 cell line, it contains little or no mixed function oxygenase activity. Of 97 stations tested, 35 showed no genotoxic activity, 42 showed high genotoxic activity (P≤.01) and the remainder were intermediate. Among the toxic sites were several deep water stations adjacent to municipal sewage outfalls and four urban waterways contaminated by industrial and municipal effluents. Extracts from areas that showed genotoxic effects also inhibited cell proliferation and were cytotoxic to RTG-2 cells. Few effects were noted in the MFO deficient BF-2 cells. Short term in vitro tests provide aquatic toxicologists with a versatile and cost effective tool for screening complex environments. Through these tests one can identify compounds or geographic regions that exhibit high

  17. Lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes.

    Directory of Open Access Journals (Sweden)

    Cristian Cillóniz

    2009-10-01

    Full Text Available The enormous toll on human life during the 1918-1919 Spanish influenza pandemic is a constant reminder of the potential lethality of influenza viruses. With the declaration by the World Health Organization of a new H1N1 influenza virus pandemic, and with continued human cases of highly pathogenic H5N1 avian influenza virus infection, a better understanding of the host response to highly pathogenic influenza viruses is essential. To this end, we compared pathology and global gene expression profiles in bronchial tissue from macaques infected with either the reconstructed 1918 pandemic virus or the highly pathogenic avian H5N1 virus A/Vietnam/1203/04. Severe pathology was observed in respiratory tissues from 1918 virus-infected animals as early as 12 hours after infection, and pathology steadily increased at later time points. Although tissues from animals infected with A/Vietnam/1203/04 also showed clear signs of pathology early on, less pathology was observed at later time points, and there was evidence of tissue repair. Global transcriptional profiles revealed that specific groups of genes associated with inflammation and cell death were up-regulated in bronchial tissues from animals infected with the 1918 virus but down-regulated in animals infected with A/Vietnam/1203/04. Importantly, the 1918 virus up-regulated key components of the inflammasome, NLRP3 and IL-1beta, whereas these genes were down-regulated by A/Vietnam/1203/04 early after infection. TUNEL assays revealed that both viruses elicited an apoptotic response in lungs and bronchi, although the response occurred earlier during 1918 virus infection. Our findings suggest that the severity of disease in 1918 virus-infected macaques is a consequence of the early up-regulation of cell death and inflammatory related genes, in which additive or synergistic effects likely dictate the severity of tissue damage.

  18. Clostridium sordellii lethal toxin kills mice by inducing a major increase in lung vascular permeability.

    Science.gov (United States)

    Geny, Blandine; Khun, Huot; Fitting, Catherine; Zarantonelli, Leticia; Mazuet, Christelle; Cayet, Nadège; Szatanik, Marek; Prevost, Marie-Christine; Cavaillon, Jean-Marc; Huerre, Michel; Popoff, Michel R

    2007-03-01

    When intraperitoneally injected into Swiss mice, Clostridium sordellii lethal toxin reproduces the fatal toxic shock syndrome observed in humans and animals after natural infection. This animal model was used to study the mechanism of lethal toxin-induced death. Histopathological and biochemical analyses identified lung and heart as preferential organs targeted by lethal toxin. Massive extravasation of blood fluid in the thoracic cage, resulting from an increase in lung vascular permeability, generated profound modifications such as animal dehydration, increase in hematocrit, hypoxia, and finally, cardiorespiratory failure. Vascular permeability increase induced by lethal toxin resulted from modifications of lung endothelial cells as evidenced by electron microscopy. Immunohistochemical analysis demonstrated that VE-cadherin, a protein participating in intercellular adherens junctions, was redistributed from membrane to cytosol in lung endothelial cells. No major sign of lethal toxin-induced inflammation was observed that could participate in the toxic shock syndrome. The main effect of the lethal toxin is the glucosylation-dependent inactivation of small GTPases, in particular Rac, which is involved in actin polymerization occurring in vivo in lungs leading to E-cadherin junction destabilization. We conclude that the cells most susceptible to lethal toxin are lung vascular endothelial cells, the adherens junctions of which were altered after intoxication.

  19. Lethality of Rendang packaged in multilayer retortable pouch with sterilization process

    Science.gov (United States)

    Praharasti, A. S.; Kusumaningrum, A.; Frediansyah, A.; Nurhikmat, A.; Khasanah, Y.; Suprapedi

    2017-01-01

    Retort Pouch had become a choice to preserve foods nowadays, besides the used of the can. Both had their own advantages, and Retort Pouch became more popular for the reason of cheaper and easier to recycle. General Method usually used to estimate the lethality of commercial heat sterilization process. Lethality value wa s used for evaluating the efficacy of the thermal process. This study aimed to find whether different layers of pouch materials affect the lethality value and to find differences lethality in two types of multilayer retort pouch, PET/Aluminum Foil/Nylon/RCPP and PET/Nylon/Modified Aluminum/CPP. The result showed that the different layer arrangement was resulted different Sterilization Value (SV). PET/Nylon/Modified Aluminum/CPP had better heat penetration, implied by the higher value of lethality. PET/Nylon/Modified Aluminum/CPP had the lethality value of 6,24 minutes, whereas the lethality value of PET/Aluminum Foil/Nylon/RCPP was 3,54 minutes.

  20. A bacterial cocaine esterase protects against cocaine-induced epileptogenic activity and lethality.

    Science.gov (United States)

    Jutkiewicz, Emily M; Baladi, Michelle G; Cooper, Ziva D; Narasimhan, Diwahar; Sunahara, Roger K; Woods, James H

    2009-09-01

    Cocaine toxicity results in cardiovascular complications, seizures, and death and accounts for approximately 20% of drug-related emergency department visits every year. Presently, there are no treatments to eliminate the toxic effects of cocaine. The present study hypothesizes that a bacterial cocaine esterase with high catalytic efficiency would provide rapid and robust protection from cocaine-induced convulsions, epileptogenic activity, and lethality. Cocaine-induced paroxysmal activity and convulsions were evaluated in rats surgically implanted with radiotelemetry devices (N=6 per treatment group). Cocaine esterase was administered 1 minute after a lethal dose of cocaine or after cocaine-induced convulsions to determine the ability of the enzyme to prevent or reverse, respectively, the effects of cocaine. The cocaine esterase prevented all cocaine-induced electroencephalographic changes and lethality. This effect was specific for cocaine because the esterase did not prevent convulsions and death induced by a cocaine analog, (-)-2beta-carbomethoxy-3beta-phenyltropane. The esterase prevented lethality even after cocaine-induced convulsions occurred. In contrast, the short-acting benzodiazepine, midazolam, prevented cocaine-induced convulsions but not the lethal effects of cocaine. The data showed that cocaine esterase successfully degraded circulating cocaine to prevent lethality and that cocaine-induced convulsions alone are not responsible for the lethal effects of cocaine in this model. Therefore, further investigation into the use of cocaine esterase for treating cocaine overdose and its toxic effects is warranted.

  1. Relative Risks for Lethal Prostate Cancer Based on Complete Family History of Prostate Cancer Death.

    Science.gov (United States)

    Albright, Frederick S; Stephenson, Robert A; Agarwal, Neeraj; Cannon-Albright, Lisa A

    2017-01-01

    There are few published familial relative risks (RR) for lethal prostate cancer. This study estimates RRs for lethal prostate cancer based on comprehensive family history data, with the goal of improving identification of those men at highest risk of dying from prostate cancer. We used a population-based genealogical resource linked to a statewide electronic SEER cancer registry and death certificates to estimate relative risks (RR) for death from prostate cancer based upon family history. Over 600,000 male probands were analyzed, representing a variety of family history constellations of lethal prostate cancer. RR estimates were based on the ratio of the observed to the expected number of lethal prostate cancer cases using internal rates. RRs for lethal prostate cancer based on the number of affected first-degree relatives (FDR) ranged from 2.49 (95% CI: 2.27, 2.73) for exactly 1 FDR to 5.30 (2.13, 10.93) for ≥3 affected FDRs. In an absence of affected FDRs, increased risk was also significant for increasing numbers of affected second-degree or third degree relatives. Equivalent risks were observed for similar maternal and paternal family history. This study provides population-based estimates of lethal prostate cancer risk based on lethal prostate cancer family history. Many family history constellations associated with two to greater than five times increased risk for lethal prostate cancer were identified. These lethal prostate cancer risk estimates hold potential for use in identification, screening, early diagnosis, and treatment of men at high risk for death from prostate cancer. Prostate77:41-48, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Modification of potentially lethal damage in irradiated Chinese hamster V79 cells after incorporation of halogenated pyrimidines

    NARCIS (Netherlands)

    Franken, N. A.; van Bree, C. V.; Kipp, J. B.; Barendsen, G. W.

    1997-01-01

    Radiosensitization of exponentially growing and plateau phase Chinese hamster V79 cells by incorporation of halogenated pyrimidines (HP) was investigated for different culture conditions that influenced repair. For this purpose cells were grown for 72 h with 0, 1, 2 and 4 microM of chloro-(CldUrd),

  3. Time course of photoreactivation of UV-induced chromosomal aberrations and lethal damage in interphase Xenopus cells

    International Nuclear Information System (INIS)

    Griggs, H.G.; Payne, J.D.

    1981-01-01

    Sets of G1, S, and G2 phase Xenopus cells were exposed to 15.0 Jm -2 UV and their ability to photoreactivate the induced cell killing and chromosomal aberrations was determined. Most of the lesions induced in G1 cells leading to cell death were converted to a non-photoreactivable state before the cells entered the S phase, while lesions leading to chromosomal aberrations were converted to a non-photoreactivable state as the cells entered the S phase. In S phase cells the UV-induced lesions leading to aberrations appeared to be converted to a non-photoreactivable state at a much faster rate than those leading to cell death. A significant fraction of the lesions induced in G2 cells, leading to cell death, were converted to a non-photoreactivable state before the progeny of the exposed cells reach the next S phase. Few, if any, lesions were induced in G2 cells that were expressed as aberrations at the first mitosis following exposure. The results suggest that the intracellular mechanism which expresses photoreactivable UV-induced lesions as cell death is not identical to the mechanism which expresses such lesions as chromosomal aberrations, and the two mechanisms operate with different efficiencies in different phases of the cell cycle. (author)

  4. Preparation of Nd-Fe-B/α-Fe nano-composite thick-film magnets on various substrates using PLD with high laser energy density above 10 J/cm2

    Science.gov (United States)

    Nakano, M.; Kondo, H.; Yamashita, A.; Yanai, T.; Itakura, M.; Fukunaga, H.

    2018-05-01

    PLD (Pulsed Laser Deposition) method with high laser energy density (LED) above 10 J/cm2 followed by a flash annealing enabled us to obtain isotropic nano-composite thick-film magnets with (BH)max ≧ 80 kJ/m3 on polycrystalline Ta substrates. We also have demonstrated that a dispersed structure composed of α-Fe together with Nd2Fe14B phases with the average grain diameter of approximately 20 nm could be formed on the Ta substrates. In this study, we tried to enhance the (BH)max value by controlling the microstructure due to the usage of different metal based substrates with each high melting point such as Ti, Nb, and W. Although it was difficult to vary the microstructure and to improve the magnetic properties of the films deposited on the substrates, we confirmed that isotropic thick-film magnets with (BH)max ≧ 80 kJ/m3 based on the nano-dispersed α-Fe and Nd2Fe14B phases could be obtained on various metal substrates with totally different polycrystalline structure. On the other hand, the use of a glass substrate lead to the deterioration of magnetic properties of a film prepared using the same preparation process.

  5. Genotoxic endpoints in the earthworms sub-lethal assay to evaluate natural soils contaminated by metals and radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Lourenco, Joana I., E-mail: joanalourenco@ua.pt [CESAM and Departamento de Biologia, Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); Pereira, Ruth O., E-mail: ruthp@ua.pt [CESAM and Departamento de Biologia, Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); Silva, Ana C., E-mail: ana.cmj@ua.pt [CESAM and Departamento de Biologia, Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); Morgado, Jose M., E-mail: jmtmorgado@gmail.com [Centro de Histocompatibilidade do Centro, Praceta Prof. Mota Pinto, Edificio S. Jeronimo, 4o piso, Apartado 9041, 3001-301 Coimbra (Portugal); Carvalho, Fernando P., E-mail: fernando.carvalho@itn.pt [Instituto Tecnologico Nuclear, Estrada Nacional 10, 2686-953 Sacavem (Portugal); Oliveira, Joao M., E-mail: joaomota@itn.pt [Instituto Tecnologico Nuclear, Estrada Nacional 10, 2686-953 Sacavem (Portugal); Malta, Margarida P., E-mail: margm@itn.pt [Instituto Tecnologico Nuclear, Estrada Nacional 10, 2686-953 Sacavem (Portugal); Paiva, Artur A., E-mail: apaiva@histocentro.min-saude.pt [Centro de Histocompatibilidade do Centro, Praceta Prof. Mota Pinto, Edificio S. Jeronimo, 4o piso, Apartado 9041, 3001-301 Coimbra (Portugal); Mendo, Sonia A., E-mail: smendo@ua.pt [CESAM and Departamento de Biologia, Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); Goncalves, Fernando J., E-mail: fjmg@ua.pt [CESAM and Departamento de Biologia, Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal)

    2011-02-15

    Eisenia andrei was exposed, for 56 days, to a contaminated soil from an abandoned uranium mine and to the natural reference soil LUFA 2.2. The organisms were sampled after 0, 1, 2, 7, 14 and 56 days of exposure, to assess metals bioaccumulation, coelomocytes DNA integrity and cytotoxicity. Radionuclides bioaccumulation and growth were also determined at 0 h, 14 and 56 days of exposure. Results have shown the bioaccumulation of metals and radionuclides, as well as, growth reduction, DNA damages and cytotoxicity in earthworms exposed to contaminated soil. The usefulness of the comet assay and flow cytometry, to evaluate the toxicity of contaminants such as metals and radionuclides in earthworms are herein reported. We also demonstrated that DNA strand breakage and immune cells frequency are important endpoints to be employed in the earthworm reproduction assay, for the evaluation of soil geno and cytotoxicity, as part of the risk assessment of contaminated areas. This is the first study that integrates DNA damage and cytotoxicity evaluation, growth and bioaccumulation of metals and radionuclides in a sub lethal assay, for earthworms exposed to soil contaminated with metals and radionuclides.

  6. Genotoxic endpoints in the earthworms sub-lethal assay to evaluate natural soils contaminated by metals and radionuclides

    International Nuclear Information System (INIS)

    Lourenco, Joana I.; Pereira, Ruth O.; Silva, Ana C.; Morgado, Jose M.; Carvalho, Fernando P.; Oliveira, Joao M.; Malta, Margarida P.; Paiva, Artur A.; Mendo, Sonia A.; Goncalves, Fernando J.

    2011-01-01

    Eisenia andrei was exposed, for 56 days, to a contaminated soil from an abandoned uranium mine and to the natural reference soil LUFA 2.2. The organisms were sampled after 0, 1, 2, 7, 14 and 56 days of exposure, to assess metals bioaccumulation, coelomocytes DNA integrity and cytotoxicity. Radionuclides bioaccumulation and growth were also determined at 0 h, 14 and 56 days of exposure. Results have shown the bioaccumulation of metals and radionuclides, as well as, growth reduction, DNA damages and cytotoxicity in earthworms exposed to contaminated soil. The usefulness of the comet assay and flow cytometry, to evaluate the toxicity of contaminants such as metals and radionuclides in earthworms are herein reported. We also demonstrated that DNA strand breakage and immune cells frequency are important endpoints to be employed in the earthworm reproduction assay, for the evaluation of soil geno and cytotoxicity, as part of the risk assessment of contaminated areas. This is the first study that integrates DNA damage and cytotoxicity evaluation, growth and bioaccumulation of metals and radionuclides in a sub lethal assay, for earthworms exposed to soil contaminated with metals and radionuclides.

  7. A reliable method for reconstituting thymectomized, lethally irradiated guinea pigs with bone marrow cells

    International Nuclear Information System (INIS)

    Terata, N.; Tanio, Y.; Zbar, B.

    1984-01-01

    The authors developed a reliable method for reconstituting thymectomized, lethally irradiated guinea pigs. Injection of 2.5-10 x 10 7 syngeneic bone marrow cells into adult thymectomized, lethally irradiated guinea pigs produced survival of 46-100% of treated animals. Gentamycin sulfate (5 mg/kg of body weight) for 10 days was required for optimal results. Acidified drinking water (pH 2.5) appeared to be required for optimal results. Thymectomized, lethally irradiated, bone marrow reconstituted ('B') guinea pigs had impaired ability to develop delayed cutaneous hypersensitivity to mycobacterial antigens and cutaneous basophil hypersensitivity to keyhole limpet hemocyanin; proliferative responses to phytohemagglutinin were impaired. (Auth.)

  8. Radiation damage to mushrooms

    International Nuclear Information System (INIS)

    Sattler, P.W.

    1986-01-01

    This document contains newspaper cuttings and correspondence with various ministries in Hessen on the subject of radiation damage to mushrooms from the Odenwald area. The reader is given, amongst other things, detailed information on radiation damage to different types of mushroom in 1986. (MG) [de

  9. Animal damage to birch

    Science.gov (United States)

    James S. Jordan; Francis M. Rushmore

    1969-01-01

    A relatively few animal species are responsible for most of the reported damage to the birches. White-tailed deer, yellow-bellied sapsuckers, porcupines, moose, and hares are the major animals involved. We will review reports of damage, discuss the underlying causes, and describe possible methods of control. For example, heavy deer browsing that eliminates birch...

  10. Animal damage management handbook.

    Science.gov (United States)

    Hugh C. Black

    1994-01-01

    This handbook treats animal damage management (ADM) in the West in relation to forest, range, and recreation resources; predator management is not addressed. It provides a comprehensive reference of safe, effective, and practical methods for managing animal damage on National Forest System lands. Supporting information is included in references after each chapter and...

  11. Nuclear damage - civil liability

    International Nuclear Information System (INIS)

    Simoes, A.C.

    1980-01-01

    An analysis is made of the civil liability for nuclear damage since there is a need to adjust the existing rules to the new situations created. The conventions that set up the new disciplining rules not considered in the common law for the liability of nuclear damage are also mentioned. (A.L.) [pt

  12. DNA damage and autophagy

    International Nuclear Information System (INIS)

    Rodriguez-Rocha, Humberto; Garcia-Garcia, Aracely; Panayiotidis, Mihalis I.; Franco, Rodrigo

    2011-01-01

    Both exogenous and endogenous agents are a threat to DNA integrity. Exogenous environmental agents such as ultraviolet (UV) and ionizing radiation, genotoxic chemicals and endogenous byproducts of metabolism including reactive oxygen species can cause alterations in DNA structure (DNA damage). Unrepaired DNA damage has been linked to a variety of human disorders including cancer and neurodegenerative disease. Thus, efficient mechanisms to detect DNA lesions, signal their presence and promote their repair have been evolved in cells. If DNA is effectively repaired, DNA damage response is inactivated and normal cell functioning resumes. In contrast, when DNA lesions cannot be removed, chronic DNA damage triggers specific cell responses such as cell death and senescence. Recently, DNA damage has been shown to induce autophagy, a cellular catabolic process that maintains a balance between synthesis, degradation, and recycling of cellular components. But the exact mechanisms by which DNA damage triggers autophagy are unclear. More importantly, the role of autophagy in the DNA damage response and cellular fate is unknown. In this review we analyze evidence that supports a role for autophagy as an integral part of the DNA damage response.

  13. Effects of β-glucan polysaccharide revealed by the dominant lethal assay and micronucleus assays, and reproductive performance of male mice exposed to cyclophosphamide

    Directory of Open Access Journals (Sweden)

    Rodrigo Juliano Oliveira

    2014-01-01

    Full Text Available β-glucan is a well-known polysaccharide for its chemopreventive effect. This study aimed to evaluate the chemopreventive ability of β-glucan in somatic and germ cells through the dominant lethal and micronucleus assays, and its influence on the reproductive performance of male mice exposed to cyclophosphamide. The results indicate that β-glucan is capable of preventing changes in DNA in both germ cells and somatic ones. Changes in germ cells were evaluated by the dominant lethal assay and showed damage reduction percentages of 46.46% and 43.79% for the doses of 100 and 150 mg/kg. For the somatic changes, evaluated by micronucleus assay in peripheral blood cells in the first week of treatment, damage reduction percentages from 80.63-116.32% were found. In the fifth and sixth weeks, the percentage ranged from 10.20-52.54% and -0.95-62.35%, respectively. Besides the chemopreventive efficiency it appears that the β-glucan, when combined with cyclophosphamide, is able to improve the reproductive performance of males verified by the significant reduction in rates of post-implantation losses and reabsorption in the mating of nulliparous females with males treated with cyclophosphamide.

  14. Exposure to Sub-lethal 2,4-Dichlorophenoxyacetic Acid Arrests Cell Division and Alters Cell Surface Properties in Escherichia coli

    Science.gov (United States)

    Bhat, Supriya V.; Kamencic, Belma; Körnig, André; Shahina, Zinnat; Dahms, Tanya E. S.

    2018-01-01

    Escherichia coli is a robust, easily adaptable and culturable bacterium in vitro, and a model bacterium for studying the impact of xenobiotics in the environment. We have used correlative atomic force – laser scanning confocal microscopy (AFM-LSCM) to characterize the mechanisms of cellular response to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). One of the most extensively used herbicides world-wide, 2,4-D is known to cause hazardous effects in diverse non-target organisms. Sub-lethal concentrations of 2,4-D caused DNA damage in E. coli WM1074 during short exposure periods which increased significantly over time. In response to 2,4-D, FtsZ and FtsA relocalized within seconds, coinciding with the complete inhibition of cell septation and cell elongation. Exposure to 2,4-D also resulted in increased activation of the SOS response. Changes to cell division were accompanied by concomitant changes to surface roughness, elasticity and adhesion in a time-dependent manner. This is the first study describing the mechanistic details of 2,4-D at sub-lethal levels in bacteria. Our study suggests that 2,4-D arrests E. coli cell division within seconds after exposure by disrupting the divisome complex, facilitated by dissipation of membrane potential. Over longer exposures, 2,4-D causes filamentation as a result of an SOS response to oxidative stress induced DNA damage. PMID:29472899

  15. Recombinant raccoon pox vaccine protects mice against lethal plague

    Science.gov (United States)

    Osorio, J.E.; Powell, T.D.; Frank, R.S.; Moss, K.; Haanes, E.J.; Smith, S.R.; Rocke, T.E.; Stinchcomb, D.T.

    2003-01-01

    Using a raccoon poxvirus (RCN) expression system, we have developed new recombinant vaccines that can protect mice against lethal plague infection. We tested the effects of a translation enhancer (EMCV-IRES) in combination with a secretory (tPA) signal or secretory (tPA) and membrane anchoring (CHV-gG) signals on in vitro antigen expression of F1 antigen in tissue culture and the induction of antibody responses and protection against Yersinia pestis challenge in mice. The RCN vector successfully expressed the F1 protein of Y. pestis in vitro. In addition, the level of expression was increased by the insertion of the EMCV-IRES and combinations of this and the secretory signal or secretory and anchoring signals. These recombinant viruses generated protective immune responses that resulted in survival of 80% of vaccinated mice upon challenge with Y. pestis. Of the RCN-based vaccines we tested, the RCN-IRES-tPA-YpF1 recombinant construct was the most efficacious. Mice vaccinated with this construct withstood challenge with as many as 1.5 million colony forming units of Y. pestis (7.7×104 LD50). Interestingly, vaccination with F1 fused to the anchoring signal (RCN-IRES-tPA-YpF1-gG) elicited significant anti-F1 antibody titers, but failed to protect mice from plague challenge. Our studies demonstrate, in vitro and in vivo, the potential importance of the EMCV-IRES and secretory signals in vaccine design. These molecular tools provide a new approach for improving the efficacy of vaccines. In addition, these novel recombinant vaccines could have human, veterinary, and wildlife applications in the prevention of plague.

  16. Analyzing temporal variation in the lethality of ETA

    Directory of Open Access Journals (Sweden)

    Sánchez-Cuenca, Ignacio

    2009-12-01

    Full Text Available This article analyzes time variation in the lethal violence of the terrorist organization ETA. Given the dynamic structure of the time series of fatalities, I look at the effect of a number of independent variables (the celebration of different types of elections, anti-ETA activity by extreme right-wing organizations and the GAL, police arrests, and other relevant events, such as the referendums on the Constitution and the Statute of Autonomy of Guernica. To do so, I have estimated several ARIMA models using the time series of fatalities between 1968 and 2007. Moreover, the results obtained are complemented by a historical-political analysis of the period of maximum violence, which took place during the Spanish transition to democracy.

    Este artículo analiza la variación temporal en la violencia letal de la organización terrorista ETA. Dada la estructura dinámica de la serie temporal de víctimas mortales, se estudia el efecto de una serie de variables independientes (celebración de distintos tipos de elecciones, actividad anti-ETA de la extrema derecha y del GAL, detenciones policiales y sucesos especiales como los referendos sobre la Constitución o el Estatuto de Autonomía de Guernica. Para ello, se estiman diversos modelos ARIMA con la serie trimestral de víctimas mortales entre 1968 y 2007. Además, se completan los resultados obtenidos con un análisis histórico-político del periodo de máxima violencia durante la transición a la democracia.

  17. Lethal action of soluble metallic salts on fishes

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, K E

    1927-01-01

    A study of pollution of Welsh rivers by lead-mine effluents revealed the fact that fishes were killed by the action of soluble salts of lead, which proved lethal at concentrations so low as pb i : 3,000,000. A physiological investigation of the action of lead-salts revealed the following facts: the action does not correspond to the normal toxic type. The graph of survival-times in different concentrations closely follows the equation: K = i/t log i/conc. The speed of the reaction is dependent upon the total quantity of metallic ion present, as well as upon the actual concentrations. The speed of the reaction varies in inverse relation to the size and weight of fishes employed. The most marked symptom is the formation of a film over gills and skin, by interaction of the metallic ion with a mucus-constituent. Death by suffocation is the final result. Where insufficient lead ion is present, the film is shed off, and complete recovery takes place. The speed of the reaction varies in direct relation to the temperature. Chemical analysis of residues shows that no trace of metallic ion penetrates into the body itself. The action is thus held to be purely external in process, chemical in type, and mechanical in effect; i.e., it is not a toxic action in the ordinary sense of the term. The action of soluble salts of zinc, iron, copper, cadmium, and mercury is shown to follow the same law as that of lead. Attention is directed to the economic importance of the facts, in connection with the pollution of rivers.

  18. MKLN1 splicing defect in dogs with lethal acrodermatitis.

    Directory of Open Access Journals (Sweden)

    Anina Bauer

    2018-03-01

    Full Text Available Lethal acrodermatitis (LAD is a genodermatosis with monogenic autosomal recessive inheritance in Bull Terriers and Miniature Bull Terriers. The LAD phenotype is characterized by poor growth, immune deficiency, and skin lesions, especially at the paws. Utilizing a combination of genome wide association study and haplotype analysis, we mapped the LAD locus to a critical interval of ~1.11 Mb on chromosome 14. Whole genome sequencing of an LAD affected dog revealed a splice region variant in the MKLN1 gene that was not present in 191 control genomes (chr14:5,731,405T>G or MKLN1:c.400+3A>C. This variant showed perfect association in a larger combined Bull Terrier/Miniature Bull Terrier cohort of 46 cases and 294 controls. The variant was absent from 462 genetically diverse control dogs of 62 other dog breeds. RT-PCR analysis of skin RNA from an affected and a control dog demonstrated skipping of exon 4 in the MKLN1 transcripts of the LAD affected dog, which leads to a shift in the MKLN1 reading frame. MKLN1 encodes the widely expressed intracellular protein muskelin 1, for which diverse functions in cell adhesion, morphology, spreading, and intracellular transport processes are discussed. While the pathogenesis of LAD remains unclear, our data facilitate genetic testing of Bull Terriers and Miniature Bull Terriers to prevent the unintentional production of LAD affected dogs. This study may provide a starting point to further clarify the elusive physiological role of muskelin 1 in vivo.

  19. Can Telescopes Help Leo Satellites Dodge Most Lethal Impacts?

    Science.gov (United States)

    GUDIEL, ANDREA; Carroll, Joseph; Rowe, David

    2018-01-01

    Authors: Joseph Carroll and David RoweABSTRACT LEO objects are tracked by radar because it works day and night, in all weather. This fits military interest in potentially hostile objects. There is less interest in objects too small to be credible active threats. But accidental hypervelocity impact by even 5-10 mm objects can disable most LEO satellites. Such “cm-class” objects greatly outnumber objects of military interest, and will cause most accidental impact losses.Under good viewing conditions, a sunlit 5mm sphere with 0.15 albedo at 800 km altitude is a 19th magnitude object. A ground-based 0.5m telescope tracking it against a 20 mag/arcsec2 sky can see it in seconds, and provide 1 million such objects in LEO, nearly all debris fragments, mostly cm-class and at 600-1200 km altitude.Maintaining a ~million-item catalog requires a world-wide network of several dozen telescope sites with several telescopes at each site. Each telescope needs a mount capable of ~1,000,000 fast slews/year without wearing out.The paper discusses recent advances that make such a service far more feasible:1. Automated tasking and remote control of distributed telescope networks,2. Direct-drive mounts that can make millions of fast slews without wearing out,3. Telescope optics with low focal curvature that are in focus across large imagers,4. CMOS imagers with 95% peak QE and 1.5e- noise at 2E8 pix/sec readout rates,5. Methods for uncued detection of most lethal LEO debris (eg., >5 mm at 800 km),6. Initial orbit determination using 3 alt-az fixes made during the discovery pass,7. High-speed photometry to infer debris spin axis, to predict drag area changes,8. Better conjunction predictions using explicit modeling of drag area variations.

  20. Very smooth FeSb.sub.2./sub.Te and Ce.sub.0.1./sub.Fe.sub.0.7./sub.Co.sub.3.3./sub.Sb.sub.12./sub. layers prepared by modified PLD

    Czech Academy of Sciences Publication Activity Database

    Remsa, Jan; Jelínek, Miroslav; Kocourek, Tomáš; Zeipl, Radek; Navrátil, Jiří

    2016-01-01

    Roč. 45, č. 3 (2016), s. 1921-1926 ISSN 0361-5235 R&D Projects: GA ČR(CZ) GA13-33056S Institutional support: RVO:68378271 ; RVO:61389013 Keywords : PLD * RTA * thermoelectric layer * Harman * FeSb 2 Te * Ce 0.1 Fe 0.7 Co 3.3 Sb 12 Subject RIV: BM - Solid Matter Physics ; Magnetism; CD - Macromolecular Chemistry (UMCH-V) Impact factor: 1.579, year: 2016

  1. Metabolite Damage and Metabolite Damage Control in Plants

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Andrew D. [Horticultural Sciences Department and; Henry, Christopher S. [Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois 60439, email:; Computation Institute, University of Chicago, Chicago, Illinois 60637; Fiehn, Oliver [Genome Center, University of California, Davis, California 95616, email:; de Crécy-Lagard, Valérie [Microbiology and Cell Science Department, University of Florida, Gainesville, Florida 32611, email: ,

    2016-04-29

    It is increasingly clear that (a) many metabolites undergo spontaneous or enzyme-catalyzed side reactions in vivo, (b) the damaged metabolites formed by these reactions can be harmful, and (c) organisms have biochemical systems that limit the buildup of damaged metabolites. These damage-control systems either return a damaged molecule to its pristine state (metabolite repair) or convert harmful molecules to harmless ones (damage preemption). Because all organisms share a core set of metabolites that suffer the same chemical and enzymatic damage reactions, certain damage-control systems are widely conserved across the kingdoms of life. Relatively few damage reactions and damage-control systems are well known. Uncovering new damage reactions and identifying the corresponding damaged metabolites, damage-control genes, and enzymes demands a coordinated mix of chemistry, metabolomics, cheminformatics, biochemistry, and comparative genomics. This review illustrates the above points using examples from plants, which are at least as prone to metabolite damage as other organisms.

  2. Chloride and sulphate toxicity to Hydropsyche exocellata (Trichoptera, Hydropsychidae): Exploring intraspecific variation and sub-lethal endpoints.

    Science.gov (United States)

    Sala, Miquel; Faria, Melissa; Sarasúa, Ignacio; Barata, Carlos; Bonada, Núria; Brucet, Sandra; Llenas, Laia; Ponsá, Sergio; Prat, Narcís; Soares, Amadeu M V M; Cañedo-Arguelles, Miguel

    2016-10-01

    The rivers and streams of the world are becoming saltier due to human activities. In spite of the potential damage that salt pollution can cause on freshwater ecosystems, this is an issue that is currently poorly managed. Here we explored intraspecific differences in the sensitivity of freshwater fauna to two major ions (Cl(-) and SO4(2-)) using the net-spinning caddisfly Hydropsyche exocellata Dufour 1841 (Trichoptera, Hydropsychidae) as a model organism. We exposed H. exocellata to saline solutions (reaching a conductivity of 2.5mScm(-1)) with Cl(-):SO4(2-) ratios similar to those occurring in effluents coming from the meat, mining and paper industries, which release dissolved salts to rivers and streams in Spain. We used two different populations, coming from low and high conductivity streams. To assess toxicity, we measured sub-lethal endpoints: locomotion, symmetry of the food-capturing nets and oxidative stress biomarkers. According to biomarkers and net building, the population historically exposed to lower conductivities (B10) showed higher levels of stress than the population historically exposed to higher conductivities (L102). However, the differences between populations were not strong. For example, net symmetry was lower in the B10 than in the L102 only 48h after treatment was applied, and biomarkers showed a variety of responses, with no discernable pattern. Also, treatment effects were rather weak, i.e. only some endpoints, and in most cases only in the B10 population, showed a significant response to treatment. The lack of consistent differences between populations and treatments could be related to the high salt tolerance of H. exocellata, since both populations were collected from streams with relatively high conductivities. The sub-lethal effects tested in this study can offer an interesting and promising tool to monitor freshwater salinization by combining physiological and behavioural bioindicators. Copyright © 2016 Elsevier B.V. All rights

  3. Stress response of the black coral Leiopathes glaberrima when exposed to sub-lethal amounts of crude oil and dispersant

    Directory of Open Access Journals (Sweden)

    Dannise V. Ruiz-Ramos

    2017-12-01

    Full Text Available The 2010 Deep Water Horizon oil well failure released billions of gallons of crude oil into the deep Gulf of Mexico, and, combined with chemical dispersants, this oil caused significant coral mortality. However, the mechanisms by which oil and dispersed oil impact deep marine fauna are not well understood. Here, we investigate the effects of oil and dispersed oil on a black coral common in the deep Gulf of Mexico, 'Leiopathes glaberrima. 'This coral occurs in several color morphs that show ecological and genetic differences. We hypothesized that dispersed oil would be more detrimental to coral health than oil alone and that this difference would be detectable in the gene expression response of the colonies even at sub-lethal concentrations. In two experiments, four and six colonies of red and white color morphs were exposed to oil, dispersant, and dispersed oil for a minimum of 96 hours. Visual assessment indicated that indeed dispersant and dispersed oil treatments were more damaging than oil alone, for target concentrations of 25 mg L–1. Decline in health was observed for all treatments, independently of color morphotype, but the decline was faster in the white colonies exposed to dispersant. The responses to the treatments were also investigated by monitoring gene expression after 24 hours of sub-lethal chemical exposure. Coral gene expression differed by chemical stressor. Interestingly, the polycyclic aromatic hydrocarbon biomarker gene, cytochrome P450, was only up-regulated in dispersed oil but not oil alone, suggesting that the dispersant increased the availability of such hydrocarbons in the tissue. The gene expression response was apparent at 24 hours when visual impacts were not (yet detectable. The use of chemical dispersants in oil-spill remediation may cause health declines in deep-water corals and deserves further study.

  4. sigE facilitates the adaptation of Bordetella bronchiseptica to stress conditions and lethal infection in immunocompromised mice

    Directory of Open Access Journals (Sweden)

    Barchinger Sarah E

    2012-08-01

    Full Text Available Abstract Background The cell envelope of a bacterial pathogen can be damaged by harsh conditions in the environment outside a host and by immune factors during infection. Cell envelope stress responses preserve the integrity of this essential compartment and are often required for virulence. Bordetella species are important respiratory pathogens that possess a large number of putative transcription factors. However, no cell envelope stress responses have been described in these species. Among the putative Bordetella transcription factors are a number of genes belonging to the extracytoplasmic function (ECF group of alternative sigma factors, some of which are known to mediate cell envelope stress responses in other bacteria. Here we investigate the role of one such gene, sigE, in stress survival and pathogenesis of Bordetella bronchiseptica. Results We demonstrate that sigE encodes a functional sigma factor that mediates a cell envelope stress response. Mutants of B. bronchiseptica strain RB50 lacking sigE are more sensitive to high temperature, ethanol, and perturbation of the envelope by SDS-EDTA and certain β-lactam antibiotics. Using a series of immunocompromised mice deficient in different components of the innate and adaptive immune responses, we show that SigE plays an important role in evading the innate immune response during lethal infections of mice lacking B cells and T cells. SigE is not required, however, for colonization of the respiratory tract of immunocompetent mice. The sigE mutant is more efficiently phagocytosed and killed by peripheral blood polymorphonuclear leukocytes (PMNs than RB50, and exhibits decreased cytotoxicity toward macrophages. These altered interactions with phagocytes could contribute to the defects observed during lethal infection. Conclusions Much of the work on transcriptional regulation during infection in B. bronchiseptica has focused on the BvgAS two-component system. This study reveals that the Sig

  5. Chloride and sulphate toxicity to Hydropsyche exocellata (Trichoptera, Hydropsychidae): Exploring intraspecific variation and sub-lethal endpoints

    International Nuclear Information System (INIS)

    Sala, Miquel; Faria, Melissa; Sarasúa, Ignacio; Barata, Carlos; Bonada, Núria; Brucet, Sandra; Llenas, Laia; Ponsá, Sergio; Prat, Narcís; Soares, Amadeu M.V.M.

    2016-01-01

    The rivers and streams of the world are becoming saltier due to human activities. In spite of the potential damage that salt pollution can cause on freshwater ecosystems, this is an issue that is currently poorly managed. Here we explored intraspecific differences in the sensitivity of freshwater fauna to two major ions (Cl"− and SO_4"2"−) using the net-spinning caddisfly Hydropsyche exocellata Dufour 1841 (Trichoptera, Hydropsychidae) as a model organism. We exposed H. exocellata to saline solutions (reaching a conductivity of 2.5 mS cm"−"1) with Cl"−:SO_4"2"− ratios similar to those occurring in effluents coming from the meat, mining and paper industries, which release dissolved salts to rivers and streams in Spain. We used two different populations, coming from low and high conductivity streams. To assess toxicity, we measured sub-lethal endpoints: locomotion, symmetry of the food-capturing nets and oxidative stress biomarkers. According to biomarkers and net building, the population historically exposed to lower conductivities (B10) showed higher levels of stress than the population historically exposed to higher conductivities (L102). However, the differences between populations were not strong. For example, net symmetry was lower in the B10 than in the L102 only 48 h after treatment was applied, and biomarkers showed a variety of responses, with no discernable pattern. Also, treatment effects were rather weak, i.e. only some endpoints, and in most cases only in the B10 population, showed a significant response to treatment. The lack of consistent differences between populations and treatments could be related to the high salt tolerance of H. exocellata, since both populations were collected from streams with relatively high conductivities. The sub-lethal effects tested in this study can offer an interesting and promising tool to monitor freshwater salinization by combining physiological and behavioural bioindicators. - Highlights: • We assessed Cl

  6. Chloride and sulphate toxicity to Hydropsyche exocellata (Trichoptera, Hydropsychidae): Exploring intraspecific variation and sub-lethal endpoints

    Energy Technology Data Exchange (ETDEWEB)

    Sala, Miquel [Centre Tecnològic Forestal de Catalunya - CTFC, Solsona, Catalunya (Spain); Faria, Melissa [CESAM, Departamento de Biologia, Universidade de Aveiro, 3810-193 Aveiro (Portugal); Sarasúa, Ignacio [Technische Universität München, Munich, Bayern (Germany); Barata, Carlos [Institute of Environmental Assessment and Water Research (IDAEA-CSIC), Barcelona (Spain); Bonada, Núria [Grup de Recerca Freshwater Ecology and Management (FEM), Departament d' Ecologia, Facultat de Biologia, Universitat de Barcelona (UB), Diagonal 643, 08028 Barcelona, Catalonia (Spain); Grup de Recerca Freshwater Ecology and Management (FEM), Departament d' Ecologia, Facultat de Biologia, Institut de Recerca de la Biodiversitat (IRBio), Universitat de Barcelona - UB, Diagonal 643, 08028 Barcelona, Catalonia (Spain); Brucet, Sandra [Aquatic Ecology Group, BETA Tecnio Centre, University of Vic - Central University of Catalonia, Vic, Catalonia (Spain); Catalan Institution for Research and Advanced Studies, ICREA, Barcelona 08010 (Spain); Llenas, Laia; Ponsá, Sergio [Aquatic Ecology Group, BETA Tecnio Centre, University of Vic - Central University of Catalonia, Vic, Catalonia (Spain); Prat, Narcís [Grup de Recerca Freshwater Ecology and Management (FEM), Departament d' Ecologia, Facultat de Biologia, Universitat de Barcelona (UB), Diagonal 643, 08028 Barcelona, Catalonia (Spain); Soares, Amadeu M.V.M. [CESAM, Departamento de Biologia, Universidade de Aveiro, 3810-193 Aveiro (Portugal); and others

    2016-10-01

    The rivers and streams of the world are becoming saltier due to human activities. In spite of the potential damage that salt pollution can cause on freshwater ecosystems, this is an issue that is currently poorly managed. Here we explored intraspecific differences in the sensitivity of freshwater fauna to two major ions (Cl{sup −} and SO{sub 4}{sup 2−}) using the net-spinning caddisfly Hydropsyche exocellata Dufour 1841 (Trichoptera, Hydropsychidae) as a model organism. We exposed H. exocellata to saline solutions (reaching a conductivity of 2.5 mS cm{sup −1}) with Cl{sup −}:SO{sub 4}{sup 2−} ratios similar to those occurring in effluents coming from the meat, mining and paper industries, which release dissolved salts to rivers and streams in Spain. We used two different populations, coming from low and high conductivity streams. To assess toxicity, we measured sub-lethal endpoints: locomotion, symmetry of the food-capturing nets and oxidative stress biomarkers. According to biomarkers and net building, the population historically exposed to lower conductivities (B10) showed higher levels of stress than the population historically exposed to higher conductivities (L102). However, the differences between populations were not strong. For example, net symmetry was lower in the B10 than in the L102 only 48 h after treatment was applied, and biomarkers showed a variety of responses, with no discernable pattern. Also, treatment effects were rather weak, i.e. only some endpoints, and in most cases only in the B10 population, showed a significant response to treatment. The lack of consistent differences between populations and treatments could be related to the high salt tolerance of H. exocellata, since both populations were collected from streams with relatively high conductivities. The sub-lethal effects tested in this study can offer an interesting and promising tool to monitor freshwater salinization by combining physiological and behavioural bioindicators

  7. Comparative influence of dose rate and radiation nature, on lethality after big mammals irradiation

    International Nuclear Information System (INIS)

    Destombe, C.; Le Fleche, Ph.; Grasseau, A.; Reynal, A.

    1997-01-01

    For the same dose and the 30 days lethality as biological criterion, the dose rate influence is more important than the radiation nature on the results of an big mammals total body irradiation. (authors)

  8. Anti-Cancer Drug Discovery Using Synthetic Lethal Chemogenetic (SLC) Analysis

    National Research Council Canada - National Science Library

    Bellows, David S

    2006-01-01

    I am developing a novel cell-based small-molecule screening approach that can identify inhibitors of any non-essential protein function through a surrogate synthetic lethal phenotype in the baker's...

  9. Anti-Cancer Drug Discovery Using Synthetic Lethal Chemogenetic (SLC) Analysis

    National Research Council Canada - National Science Library

    Bellows, David S

    2004-01-01

    I am developing a novel cell-based small-molecule screening approach that can identify inhibitors of any non-essential protein function through a surrogate synthetic lethal phenotype in the baker's...

  10. 76 FR 6054 - Use of Less-Than-Lethal Force: Delegation

    Science.gov (United States)

    2011-02-03

    ... report any medical problems encountered by subjects being subdued and arrested, and no medical problems.... Therefore, for accuracy in terminology, we replace the term ``non-lethal'' with the more accurate term...

  11. The Effects of Posture, Body Armor and Other Equipment on Rifleman Lethality

    National Research Council Canada - National Science Library

    Kramlich, Gary R., II

    2005-01-01

    ...? This study quantifies the effects of Soldier equipment on lethality through multi-factor logistic regression using data from range experiments with the 1st Brigade, 1st Infantry Division (Mechanized...

  12. Lethal and Sublethal Effects of Fenpropathrin on the Biological Performance of Scolothrips longicornis (Thysanoptera: Thripidae)

    DEFF Research Database (Denmark)

    Pakyari, Hajar; Enkegaard, Annie

    2013-01-01

    Determination of negative nontarget effects of pesticides on beneficial organisms by measuring only lethal effects is likely to underestimate effects of sublethal doses. In this study, the sublethal effects of fenpropathrin on the predatory thrips Scolothrips longicornis Priesner (Thysanoptera: T...

  13. Recurrent late cardiac tamponade following cardiac surgery : a deceiving and potentially lethal complication

    NARCIS (Netherlands)

    Harskamp, Ralf E.; Meuzelaar, Jacobus J.

    2010-01-01

    Background - Cardiac tamponade, characterized by inflow obstruction of the heart chambers by extracardiac compression, is a potentially lethal complication following cardiac surgery. Case report - We present a case of recurrent cardiac tamponade following valve surgery. At first presentation,

  14. Recurrent late cardiac tamponade following cardiac surgery: a deceiving and potentially lethal complication

    NARCIS (Netherlands)

    Harskamp, Ralf E.; Meuzelaar, Jacobus J.

    2010-01-01

    Cardiac tamponade, characterized by inflow obstruction of the heart chambers by extracardiac compression, is a potentially lethal complication following cardiac surgery. We present a case of recurrent cardiac tamponade following valve surgery. At first presentation, diagnosis was delayed because of

  15. Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations

    Science.gov (United States)

    Sardanyés, Josep; Simó, Carles; Martínez, Regina; Solé, Ricard V.; Elena, Santiago F.

    2014-04-01

    The distribution of mutational fitness effects (DMFE) is crucial to the evolutionary fate of quasispecies. In this article we analyze the effect of the DMFE on the dynamics of a large quasispecies by means of a phenotypic version of the classic Eigen's model that incorporates beneficial, neutral, deleterious, and lethal mutations. By parameterizing the model with available experimental data on the DMFE of Vesicular stomatitis virus (VSV) and Tobacco etch virus (TEV), we found that increasing mutation does not totally push the entire viral quasispecies towards deleterious or lethal regions of the phenotypic sequence space. The probability of finding regions in the parameter space of the general model that results in a quasispecies only composed by lethal phenotypes is extremely small at equilibrium and in transient times. The implications of our findings can be extended to other scenarios, such as lethal mutagenesis or genomically unstable cancer, where increased mutagenesis has been suggested as a potential therapy.

  16. DNA damage and polyploidization.

    Science.gov (United States)

    Chow, Jeremy; Poon, Randy Y C

    2010-01-01

    A growing body of evidence indicates that polyploidization triggers chromosomal instability and contributes to tumorigenesis. DNA damage is increasingly being recognized for its roles in promoting polyploidization. Although elegant mechanisms known as the DNA damage checkpoints are responsible for halting the cell cycle after DNA damage, agents that uncouple the checkpoints can induce unscheduled entry into mitosis. Likewise, defects of the checkpoints in several disorders permit mitotic entry even in the presence of DNA damage. Forcing cells with damaged DNA into mitosis causes severe chromosome segregation defects, including lagging chromosomes, chromosomal fragments and chromosomal bridges. The presence of these lesions in the cleavage plane is believed to abort cytokinesis. It is postulated that if cytokinesis failure is coupled with defects of the p53-dependent postmitotic checkpoint pathway, cells can enter S phase and become polyploids. Progress in the past several years has unraveled some of the underlying principles of these pathways and underscored the important role of DNA damage in polyploidization. Furthermore, polyploidization per se may also be an important determinant of sensitivity to DNA damage, thereby may offer an opportunity for novel therapies.

  17. Semi-lethal high temperature and heat tolerance of eight Camellia species

    OpenAIRE

    He, XY; Ye, H; Ma, JL; Zhang, RQ; Chen, GC; Xia, YY

    2012-01-01

    Annual leaf segments of eight Camellia species were used to study the heat tolerance by an electrical conductivity method, in combination with a Logistic equation to ascertain the semi-lethal high temperature by fitting the cell injury rate curve. Te relationship between the processing temperature and the cell injury rate in Camellia showed a typical "S" shaped curve, following the Logistic model. Te correlation coeficient was above 0.95. Te semi-lethal high temperature LT50 of the eight Came...

  18. Synthetic Lethal Therapeutic Approaches for ARID1A-Mutated Ovarian Cancer

    Science.gov (United States)

    2017-10-01

    Award Number: W81XWH-16-1-0496 TITLE: Synthetic lethal therapeutic approaches for ARID1A-mutated ovarian cancer PRINCIPAL INVESTIGATOR: Rugang...AND SUBTITLE Synthetic lethal therapeutic approaches for ARID1A-mutated ovarian cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0496 5c...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological

  19. Lethality of patients with rheumatoid arthritis depending on adalimumab administration: imitation modeling

    Directory of Open Access Journals (Sweden)

    D V Goryachev

    2009-01-01

    Full Text Available Lethality of pts with rheumatoid arthritis (RA exceeds mortality values in general population. Possibility of disease modifying anti-rheumatic drugs (DMARD influence on RA pts lethality has been widely discussed lately in scientific works. Objective. To determine possible lethality diminishment in Russian population of RA pts with one of biological drugs TNFα antagonist adalimumab. Material and methods. Model construction is based on the fact of lethality dependence on pt functional state assessed by HAQ. Model simulating progression of functional disability in pts with RA visiting medical institutions of Russia was made (RAISER study. 3 model variants for imitation of consecutive change of DMARDs including adalimumab were done. First consecution assessed DMARD change in the next chain: adalimumab-methotrexate-sulfasalazine-leflunomide-azathioprine-cyclosporine-palliative therapy. Second consecution: adalimumab administration after failure of first 3 DMARDs. Third consecution considered only change of synthetic DMARDs without adalimumab inclusion. Model imitated participation of 3000 pts in every consecution. Prognosis horizon was 12 years. Age of pts and initial HAQ distribution were get from results of epidemiological RAISER study. Calculation was done on the base of elevation of standardized lethality level (SLL in population of RA pts in average from 135% to 300%. SLL values from 80 to 320% were used depending on functional disability degree with converting to Russian values of age-specific lethality coefficient for 1999. Results. Lethality in treatment consecutions including adalimumab was significantly lower. To the end of 12th year in group not using adalimumab, using it at once and using it after 376 DMARDs respectively 65,1%, 71,6% and 71,1% of pts were still alive. Conclusion. Significant decrease of lethality with adalimumab inclusion in consecution of DMARD change during treatment of RA pts was demonstrated with imitation modeling

  20. Non-Lethal Weapons: A Technology Gap or Lack or Available Systems, Training, and Proper Application

    Science.gov (United States)

    2016-06-10

    102-104. 31 Ibid., 103-104. 32 Michael Wines , “The Aftermath in Moscow: Post-Mortem in Moscow; Russia Names Drug in Raid, Defending Use,” New York...during the past three decades have increased awareness of the benefit of non- lethal options, but increased advocacy within the services has not led to a...during the execution of suitable missions that could benefit from less than lethal technology. Research and Development Once the directorate

  1. Solar radiation and mitochondrial DNA damage

    International Nuclear Information System (INIS)

    Hill, H.Z.; Locitzer, J.; Nassrin, E.; Ogbonnaya, A.; Hubbard, K.

    2003-01-01

    The 16.6 kB human mitochondrial DNA contains two homologous 13 base pair direct repeats separated by about 5 kB. During asynchronous mitochondrial DNA replication, the distant repeat sequences are thought to anneal, resulting in the looping out of a portion of the non-template strand which is subsequently deleted as a result of interaction with reactive oxygen species (ROS). A normal daughter and a deleted daughter mitochondrion result from such insults. This deletion has been termed the common deletion as it is the most frequent of the known mitochondrial DNA deletions. The common deletion is present in high frequency in several mitochondrial disorders, accumulates with age in slow turnover tissues and is increased in sun-exposed skin. Berneburg, et al. (Photochem. Photobiol. 66: 271, 1997) induced the common deletion in normal human fibroblasts after repeated exposures to UVA. In this study, the common deletion has been shown to be induced by repeated non-lethal exposures to FS20 sunlamp irradiation. Increases in the common deletion were demonstrated using nested PCR which produced a 303 bp product that was compared to a 324 bp product that required the presence of the undeleted 5 kB region. The cells were exposed to 10 repeated doses ranging from 0.5 (UVB) - 0.24 (UVA) J/sq m to 14.4 (UVB) - 5.8 J/sq m (UVA) measured using a UVX digital radiometer and UVB and UVA detectors respectively. Comparison with the earlier study by Berneberg, et al. suggests that this type of simulated solar damage is considerably more effective in fewer exposures than UVA radiation alone. The common deletion provides a cytoplasmic end-point for ROS damage produced by low dose chronic irradiations and other low level toxic exposures and should prove useful in evaluating cytoplasmic damage produced by ionizing radiation as well

  2. RpoS plays a central role in the SOS induction by sub-lethal aminoglycoside concentrations in Vibrio cholerae.

    Science.gov (United States)

    Baharoglu, Zeynep; Krin, Evelyne; Mazel, Didier

    2013-01-01

    Bacteria encounter sub-inhibitory concentrations of antibiotics in various niches, where these low doses play a key role for antibiotic resistance selection. However, the physiological effects of these sub-lethal concentrations and their observed connection to the cellular mechanisms generating genetic diversification are still poorly understood. It is known that, unlike for the model bacterium Escherichia coli, sub-minimal inhibitory concentrations (sub-MIC) of aminoglycosides (AGs) induce the SOS response in Vibrio cholerae. SOS is induced upon DNA damage, and since AGs do not directly target DNA, we addressed two issues in this study: how sub-MIC AGs induce SOS in V. cholerae and why they do not do so in E. coli. We found that when bacteria are grown with tobramycin at a concentration 100-fold below the MIC, intracellular reactive oxygen species strongly increase in V. cholerae but not in E. coli. Using flow cytometry and gfp fusions with the SOS regulated promoter of intIA, we followed AG-dependent SOS induction. Testing the different mutation repair pathways, we found that over-expression of the base excision repair (BER) pathway protein MutY relieved this SOS induction in V. cholerae, suggesting a role for oxidized guanine in AG-mediated indirect DNA damage. As a corollary, we established that a BER pathway deficient E. coli strain induces SOS in response to sub-MIC AGs. We finally demonstrate that the RpoS general stress regulator prevents oxidative stress-mediated DNA damage formation in E. coli. We further show that AG-mediated SOS induction is conserved among the distantly related Gram negative pathogens Klebsiella pneumoniae and Photorhabdus luminescens, suggesting that E. coli is more of an exception than a paradigm for the physiological response to antibiotics sub-MIC.

  3. Materials Applications for Non-Lethal: Aqueous Foams

    International Nuclear Information System (INIS)

    GOOLSBY, TOMMY D.; SCOTT, STEVEN H.

    1999-01-01

    High expansion aqueous foam is an aggregation of bubbles that has the appearance of soap suds and is used to isolate individuals both visually and acoustically. It was developed in the 1920's in England to fight coal mine fires and has been widely used since for fire fighting and dust suppression. It was developed at Sandia National Laboratories (SNL) in the 1970's for nuclear safeguards and security applications. In the mid-1990s, the National Institute of Justice (NIJ), the research arm of the Department of Justice, began a project with SNL to determine the applicability of high expansion aqueous foam for correctional applications. NIJ funded the project as part of its search for new and better less-than-lethal weapons for responding to violent and dangerous individuals, where other means of force could lead to serious injuries. The phase one objectives of the project were to select a low-to-no toxicity foam concentrate (foaming agent) with physical characteristics suited for use in a single cell or large prison disturbances, and to determine if the selected foam concentrate could serve as a carrier for Oleoresin Capsicum (OC) irritant. The phase two objectives were to conduct an extensive toxicology review of the selected foam concentrate and OC irritant, and to conduct respiration simulation experiments in the selected high expansion aqueous foam. The phase three objectives were to build a prototype individual cell aqueous foam system and to study the feasibility of aqueous foams for large prison facility disturbances. The phase four and five objectives were to use the prototype system to do large scale foam physical characteristics testing of the selected foam concentrate, and to have the prototype single cell system further evaluated by correctional representatives. Prison rather than street scenarios were evaluated as the first and most likely place for using the aqueous foam since prisons have recurrent incidents where officers and inmates might be

  4. Materials Applications for Non-Lethal: Aqueous Foams

    Energy Technology Data Exchange (ETDEWEB)

    GOOLSBY,TOMMY D.; SCOTT,STEVEN H.

    1999-09-15

    High expansion aqueous foam is an aggregation of bubbles that has the appearance of soap suds and is used to isolate individuals both visually and acoustically. It was developed in the 1920's in England to fight coal mine fires and has been widely used since for fire fighting and dust suppression. It was developed at Sandia National Laboratories (SNL) in the 1970's for nuclear safeguards and security applications. In the mid-1990s, the National Institute of Justice (NIJ), the research arm of the Department of Justice, began a project with SNL to determine the applicability of high expansion aqueous foam for correctional applications. NIJ funded the project as part of its search for new and better less-than-lethal weapons for responding to violent and dangerous individuals, where other means of force could lead to serious injuries. The phase one objectives of the project were to select a low-to-no toxicity foam concentrate (foaming agent) with physical characteristics suited for use in a single cell or large prison disturbances, and to determine if the selected foam concentrate could serve as a carrier for Oleoresin Capsicum (OC) irritant. The phase two objectives were to conduct an extensive toxicology review of the selected foam concentrate and OC irritant, and to conduct respiration simulation experiments in the selected high expansion aqueous foam. The phase three objectives were to build a prototype individual cell aqueous foam system and to study the feasibility of aqueous foams for large prison facility disturbances. The phase four and five objectives were to use the prototype system to do large scale foam physical characteristics testing of the selected foam concentrate, and to have the prototype single cell system further evaluated by correctional representatives. Prison rather than street scenarios were evaluated as the first and most likely place for using the aqueous foam since prisons have recurrent incidents where officers and inmates might

  5. LSD and Genetic Damage

    Science.gov (United States)

    Dishotsky, Norman I.; And Others

    1971-01-01

    Reviews studies of the effects of lysergic acid diethylamide (LSD) on man and other organisms. Concludes that pure LSD injected in moderate doses does not cause chromosome or detectable genetic damage and is not a teratogen or carcinogen. (JM)

  6. Diabetes and nerve damage

    Science.gov (United States)

    Diabetic neuropathy; Diabetes - neuropathy; Diabetes - peripheral neuropathy ... In people with diabetes, the body's nerves can be damaged by decreased blood flow and a high blood sugar level. This condition is ...

  7. A lethal ovitrap-based mass trapping scheme for dengue control in Australia: I. Public acceptability and performance of lethal ovitraps.

    Science.gov (United States)

    Ritchie, S A; Rapley, L P; Williams, C; Johnson, P H; Larkman, M; Silcock, R M; Long, S A; Russell, R C

    2009-12-01

    We report on the first field evaluation of the public acceptability and performance of two types of lethal ovitrap (LO) in three separate trials in Cairns, Australia. Health workers were able to set standard lethal ovitraps (SLOs) in 75 and 71% of premise yards in the wet and dry season, respectively, and biodegradable lethal ovitraps (BLOs) in 93% of yards. Public acceptance, measured as retention of traps by residents, was high for both trap types, with porous (grass, soil and mulch) versus solid (tiles, concrete, wood and stone) substrates. The SLOs and the BLOs were readily acceptable to ovipositing Aedes aegypti L. (Diptera: Culicidae); the mean number of eggs/trap was 6 and 15, for the dry season and wet season SLO trial, respectively, and 15 for the BLO wet season trial. Indeed, 84-94% of premise yards had egg positive SLOs or BLOs. A high percentage of both wet and dry season SLOs (29 and 70%, respectively) and BLOs (62%) that were dry after 4 weeks were egg positive, indicating the traps had functioned. Lethal strips from SLOs and BLOs that had been exposed for 4 weeks killed 83 and 74%, respectively, of gravid Ae. aegypti in laboratory assays. These results indicate that mass trapping schemes using SLOs and BLOs are not rejected by the public and effectively target gravid Ae. aegypti. The impact of the interventions on mosquito populations is described in a companion paper.

  8. Ribosomal elongation factor 4 promotes cell death associated with lethal stress.

    Science.gov (United States)

    Li, Liping; Hong, Yuzhi; Luan, Gan; Mosel, Michael; Malik, Muhammad; Drlica, Karl; Zhao, Xilin

    2014-12-09

    Ribosomal elongation factor 4 (EF4) is highly conserved among bacteria, mitochondria, and chloroplasts. However, the EF4-encoding gene, lepA, is nonessential and its deficiency shows no growth or fitness defect. In purified systems, EF4 back-translocates stalled, posttranslational ribosomes for efficient protein synthesis; consequently, EF4 has a protective role during moderate stress. We were surprised to find that EF4 also has a detrimental role during severe stress: deletion of lepA increased Escherichia coli survival following treatment with several antimicrobials. EF4 contributed to stress-mediated lethality through reactive oxygen species (ROS) because (i) the protective effect of a ΔlepA mutation against lethal antimicrobials was eliminated by anaerobic growth or by agents that block hydroxyl radical accumulation and (ii) the ΔlepA mutation decreased ROS levels stimulated by antimicrobial stress. Epistasis experiments showed that EF4 functions in the same genetic pathway as the MazF toxin, a stress response factor implicated in ROS-mediated cell death. The detrimental action of EF4 required transfer-messenger RNA (tmRNA, which tags truncated proteins for degradation and is known to be inhibited by EF4) and the ClpP protease. Inhibition of a protective, tmRNA/ClpP-mediated degradative activity would allow truncated proteins to indirectly perturb the respiratory chain and thereby provide a potential link between EF4 and ROS. The connection among EF4, MazF, tmRNA, and ROS expands a pathway leading from harsh stress to bacterial self-destruction. The destructive aspect of EF4 plus the protective properties described previously make EF4 a bifunctional factor in a stress response that promotes survival or death, depending on the severity of stress. Translation elongation factor 4 (EF4) is one of the most conserved proteins in nature, but it is dispensable. Lack of strong phenotypes for its genetic knockout has made EF4 an enigma. Recent biochemical work has

  9. Fabrication of 93.7 m long PLD-EuBCO + BaHfO_3 coated conductors with 103 A/cm W at 77 K under 3 T

    International Nuclear Information System (INIS)

    Yoshida, T.; Ibi, A.; Takahashi, T.; Yoshizumi, M.; Izumi, T.; Shiohara, Y.

    2015-01-01

    Highlights: • A 93.7 m long EuBCO + BHO CC with 103 A/cm W at 77 K under 3 T was obtained. • The 93.7 m long CC showed high I_c values and high n-values with high uniformity. • The average I_c value at 77 K under 3 T was estimated by that at 77 K under 0.3 T. - Abstract: Introduction of artificial pinning centers such as BaHfO_3 (BHO), BaZrO_3 (BZO) and BaSnO_3 (BSO) into REBa_2Cu_3O_7_−_δ (REBCO) coated conductor (CC) layers could improve the in-field critical currents (I_c) in wide ranges of temperatures and magnetic fields. In particular, a combination of EuBCO + BHO has been found to be effective for attaining high in-field I_c performance by means of IBAD/PLD process in short length samples. In this work, we have successfully fabricated a 93.7 m long EuBCO + BHO CC with 103 A/cm W at 77 K under a magnet field (B) of 3 T applied perpendicular to the CC (B//c). The 93.7 m long EuBCO + BHO CC had high uniformity of I_c values and n-values without any trend of fluctuations, independent of the external field up to 0.3 T. I_c–B–applied angle (θ) profiles of the 93.7 m long EuBCO + BHO CC sample showed the high in-field I_c values in all directions of applied magnetic fields especially B//c (at θ ∼ 180°, I_c = 157 A/cm W) at 77 K under 3 T. The profiles were about the same as those in a short length sample.

  10. AES, EELS and XPS characterization of Ti(C, N, O) films prepared by PLD using a Ti target in N2, CH4, O2 and CO as reactive gases

    International Nuclear Information System (INIS)

    Soto, G.

    2004-01-01

    Titanium-based films were grown on (1 0 0)-Si substrates by the pulsed laser deposition (PLD) method using a Ti target in reactive atmospheres. The films were grown in vacuum (Ti-film), O 2 (TiO x ), N 2 (TiN x ), CH 4 (TiC x ), CO (TiC x O y ), N 2 +CH 4 (TiC x N y ) and CO+N 2 (TiC x N y O z ). After depositions, every film is characterized in situ by Auger, electron-energy loss and X-ray photoelectron (XPS) spectroscopies. For the binary compounds the stoichiometry is regulated without difficulty by gas pressure during ablation. However, for ternary and quaternary compounds there is a tendency to produce chemically inhomogeneous films. For example, the ablation of Ti in a N 2 +CH 4 environment results in a TiNC:C composite. In this case, the overabundance of nitrogen influences the segregation of carbon. In the other hand, the O 2 +CH 4 mixture was ineffectively to produce TiC x O y films, yielding mostly TiO 2 with traces of embedded carbon. By using CO as reactive gas the TiC x O y films were completed. Also, a mixture of CO with N 2 was tested to produce quaternary TiC x N y O z compounds. Based on these results, it is recommended that better control on film stoichiometry and chemical homogeneity can be achieved by using reactive gases with predetermined C:N:O ratios

  11. Inner organ damages after acute radioactive poisoning

    International Nuclear Information System (INIS)

    Krasnyuk, Valeriy

    2008-01-01

    Full text: There are some difficulties in making early diagnosis on acute radioactive poisoning. Clinical disorders from a poison in November 2006 in London has not given an opportunity to doctors to reveal radiation as the reason of the acute injury before the death. The report purpose is to give more diagnostic possibilities to reveal early signs of acute radioactive poisoning. It provides an evaluation of clinical observation data on a difference of clinical symptoms after internal or external exposure, activities of some radioactive isotopes that are able to cause ARS with bone marrow failure or damages to different organs and tissues. The report contains descriptions of some clinical cases of radioactive poisonings. Prodromal responses after acute internal expose are significant only in cases of the following early death but are not typical for the most clinical cases of internal exposure. Lethal gastrointestinal or cutaneous damages are not characteristic. Early radiation vasculitis (blood vessel endotheliitis) sings: bloody rash on the trunk, blood in the urine, hemorrhages in the skin and mucous membranes at blood platelet count in excess of 40 x 10 9 l -1 . Death from lung radiation injury could be expected in all individuals from as little as 7 MBq of inhaled alpha emitter with energy of about 5 MeV and an effective half-life greater than 100 days. Death from severe bone marrow syndrome for the first month or death from liver insufficiency for the following 6 months is typical after ingestion or injection of radioactive materials at lethal doses. Hemolytic sings after acute exposure should be confirmed by the following clinical investigations. It is known the erythrocyte hemolysis and the following hemoglobin decay is a significant source of the endogenous CO that release from the hem. So estimation of CO and methemoglobin in the blood is a way for revealing of the higher erythrocyte destroy. If hemolytic syndrome is characteristic for early acute

  12. Action of the chlorophyllin on the genetic damage induced by gamma radiation in germinal cells of Drosophila Melanogaster

    International Nuclear Information System (INIS)

    Cruces, M.P.; Pimentel, A.E.; Moreno, A.; Moreno, R.

    2003-01-01

    The obtained results using somatic cells, they have evidenced that the chlorophyllin (CHLN) it can act inhibiting or increasing the damage caused by different mutagens. The objective of this investigation is to evaluate the effect of the CHLN on the damage induced by gamma radiation in germinal cells of Drosophila. Two tests were used, the lost of the X chromosome and the conventional test of lethal recessive bound to the sex (LRLS); both with a system of litters. The obtained results in both essays, indicated that the CHLN doesn't reduce the damage induced by the gamma radiation in none of the cellular monitored states. (Author)

  13. Potentially lethal effects of astrophysical high energy explosive events

    International Nuclear Information System (INIS)

    Zarauza, Dario; Martin, Osmel; Rolando Cardenas

    2007-01-01

    In this work we compare the biological extinction risks posed by different types of high energy explosive events, if they occur at distances close enough to inhabited planets. These events are several kinds of supernovae and gamma ray bursts. We mainly consider the ozone depletion, leaving other effects, as photon retransmission and muon showers, for future work. In order to estimate the damage on ozonosphere, we use a simple analytical model for ozone depletion. We also mention some hints to look for the signatures of these events on Earth biogeochemical record, and evaluate the possibility of applying these results to the astrobiologically interesting sample of stars gathered by Porto de Mello, del Peloso and Ghezzi. (Author)

  14. Fine Mapping and Transcriptome Analysis Reveal Candidate Genes Associated with Hybrid Lethality in Cabbage (Brassica Oleracea).

    Science.gov (United States)

    Xiao, Zhiliang; Hu, Yang; Zhang, Xiaoli; Xue, Yuqian; Fang, Zhiyuan; Yang, Limei; Zhang, Yangyong; Liu, Yumei; Li, Zhansheng; Liu, Xing; Liu, Zezhou; Lv, Honghao; Zhuang, Mu

    2017-06-05

    Hybrid lethality is a deleterious phenotype that is vital to species evolution. We previously reported hybrid lethality in cabbage ( Brassica oleracea ) and performed preliminary mapping of related genes. In the present study, the fine mapping of hybrid lethal genes revealed that BoHL1 was located on chromosome C1 between BoHLTO124 and BoHLTO130, with an interval of 101 kb. BoHL2 was confirmed to be between insertion-deletion (InDels) markers HL234 and HL235 on C4, with a marker interval of 70 kb. Twenty-eight and nine annotated genes were found within the two intervals of BoHL1 and BoHL2 , respectively. We also applied RNA-Seq to analyze hybrid lethality in cabbage. In the region of BoHL1 , seven differentially expressed genes (DEGs) and five resistance (R)-related genes (two in common, i.e., Bo1g153320 and Bo1g153380 ) were found, whereas in the region of BoHL2 , two DEGs and four R-related genes (two in common, i.e., Bo4g173780 and Bo4g173810 ) were found. Along with studies in which R genes were frequently involved in hybrid lethality in other plants, these interesting R-DEGs may be good candidates associated with hybrid lethality. We also used SNP/InDel analyses and quantitative real-time PCR to confirm the results. This work provides new insight into the mechanisms of hybrid lethality in cabbage.

  15. Lethal and Mutagenic Effects of Tritium Decay Produced by Tritiated Compounds Incorporated into Bacteria and Bacteriophages

    Energy Technology Data Exchange (ETDEWEB)

    Person, S. [Pennsylvania State University, University Park, PA (United States)

    1968-06-15

    The work discussed below is predominantly from the author's laboratory. Some effects of tritium decay on bacteria and bacteriophages, using labelled compounds that are incorporated preferentially into DNA, RNA or protein, have been studied. A relatively high killing efficiency, the probability that a single decay produces loss of colony-forming ability in bacteria or loss of plaque-forming ability in bacteriophages, is observed for thymidine- methyl-{sup 3}H decay, but this is thought to be due to S-particle ionization damage. The most definitive experiments involved a comparison of killing efficiencies for decays originating as thymidine-methyl-{sup 3}H in phage DNA and as amino acid-{sup 3}H in phage protein with the calculated {beta}-particle path length through, the DNA in the two cases. Experimental and calculated values are essentially the same. Radiation-dose calculations to many different bacterial sub-volumes were determined for several different distributions of radioactivity. The high killing efficiency for thymidine-methyl- {sup 3}H decay can be explained by {beta}-particle ionizations, providing DNA is the sensitive target molecule and it is organized in a central volume of the cell (see also Ref.[24]). Although both the lethal and mutagenic effect of thymidine-methyl-{sup 3}H and amino acid-{sup 3}H decays can readily be explained on the basis of {beta}-particle ionizations, the observed large mutation frequency produced by uracil-5{sup 3}H decay cannot. The majority of mutations produced by uracil-5{sup 3}H decays are due to a specific chemical rearrangement of the parent molecule, since decays from uracil-6{sup 3}H are 6 to 7-fold less mutagenic. It is clear that the decays leading to mutations for cells labelled with uracil-5{sup 3}H originate as cytosine-5{sup 3}H in bacterial DNA. Recent work shows that the specific chemical rearrangement causes a C --> T(u) genetic coding change. (author)

  16. Lethal Area 50 in Patients with Burn Injuries in North West, Iran

    Directory of Open Access Journals (Sweden)

    Ahmad Mirza Aghazadeh

    2018-03-01

    Full Text Available Introduction: In view of their considerably high rates of mortality and morbidity, burns are still viewed as one of the most important health-threatening environmental hazards imposing a significant burden on the health care system in low and middle-income countries. This study seeks to determine the lethal area fifty percent (LA50 in all burn patients admitted over a period of five years and the factors influencing mortality in burn injuries. Methods: This study was a cross-sectional carried out from 2010 to 2014 in Sina Hospital of Tabriz, 1226 participant including 319 women, 346 men, 272 girls, and 289 boys were selected through stratified sampling. The demographic and clinical data of patients ( their age, gender, burn type, TBSA, the season and consequences of burning were all extracted and then analyzed, using descriptive statistics (measures of central tendency and variability and inferential statistics(chi-square and linear regressionat a significance level of 0.05. The LA50 was calculated through determining the relationship between the total body surface area and mortality rate (The extent of the body burns measured and recorded based on Lando Chart in hospitals. Results: The highest (47.6% and the lowest (3.8% rates of burns were observed among those aged below 16 and above 65, respectively. The majority of the participants were residents of cities (55.4%, married (34.6%, illiterate (56.6%, and housewives (14.8%. Most burns were caused by accidents (98.4% at home (90.6%. Most patients had suffered first- and second-degree burns (68.4%, with no inhalation damages (99.5%. Hot liquids were the main culprit in most of the burns (58.7% and the upper extremities were the most frequently affected areas (34.8%. There was .99 rise in mortality for every percent increase in TBSA, and there seemed to be a significant relationship between the age level and the eventual outcome- the higher the age, the more likely for the incident to end in death

  17. Coal transportation road damage

    International Nuclear Information System (INIS)

    Burtraw, D.; Harrison, K.; Pawlowski, J.A.

    1994-01-01

    Heavy trucks are primarily responsible for pavement damage to the nation's highways. In this paper we evaluate the pavement damage caused by coal trucks. We analyze the chief source of pavement damage (vehicle weight per axle, not total vehicle weight) and the chief cost involved (the periodic overlay that is required when a road's surface becomes worn). This analysis is presented in two stages. In the first section we present a synopsis of current economic theory including simple versions of the formulas that can be: used to calculate costs of pavement wear. In the second section we apply this theory to a specific example proximate to the reference environment for the Fuel Cycle Study in New Mexico in order to provide a numerical measure of the magnitude of the costs

  18. Natural resource damage assessment

    International Nuclear Information System (INIS)

    Seddelmeyer, J.

    1991-01-01

    The assessment and collection of natural resource damages from petroleum and chemical companies unfortunate enough to have injured publicly owned natural resources is perhaps the most rapidly expanding area of environmental liability. The idea of recovering for injury to publicly owned natural resources is an extension of traditional common law tort concepts under which a person who negligently injures another or his property is called upon to compensate the injured party. Normally, once liability has been established, it is a fairly straightforward matter to calculate the various elements of loss, such as the cost to repair or replace damaged property, or medical expenses, and lost income. More difficult questions, such as the amount to be awarded for pain and suffering or emotional distress, are left to the jury, although courts limit the circumstances in which the jury is permitted to award such damages

  19. Repair of endogenous and ionizing radiation-induced DNA damages: mechanisms and biological functions

    International Nuclear Information System (INIS)

    Boiteux, S.

    2002-01-01

    The cellular DNA is continuously exposed to endogenous and exogenous stress. Oxidative stress due to cellular metabolism is the major cause of endogenous DNA damage. On the other hand, ionizing radiation (IR) is an important exogenous stress. Both induce similar DNA damages: damaged bases, abasic sites and strand breakage. Most of these lesions are lethal and/or mutagenic. The survival of the cell is managed by efficient and accurate DNA repair mechanisms that remove lesions before their replication or transcription. DNA repair pathways involved in the removal of IR-induced lesions are briefly described. Base excision repair (BER) is mostly involved in the removal of base damage, abasic sites and single strand breaks. In contrast, DNA double strand breaks are mostly repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). How DNA repair pathways prevent cancer process is also discussed. (author)

  20. Lethal action of canavanine in Escherichia coli; Etude de l'action lethale de la canavanine sur Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Simonnet, Gerard Marc

    1972-01-04

    proteines. La canavanine stimule la synthese de l'ARN dans les souches de bacteries RC{sup str} arg{sup -}, carencees en arginine; mais elle inhibe l'incorporation de l'uracile, l'UMP et d'UDP dans les souches RC{sup rel} arg{sup -}. En presence de canavanine, la replication de l'ADN suit le meme type de cinetique que dans les bacteries carencees en acide amine indispensable. L'ADN des bacteries incubees en presence de canavanine presente des alterations qui resultent de coupures de la molecule d'ADN. Il s'ensuit la formation de fragments d'ADN qui ne sedimentent pas a 10 000 xg avec les membranes cellulaires, ni a 150 000 xg en gradient de sucrose alcalin. L'action lethale de la canavanine doit etre le resultat de cette alteration de l'ADN. (auteur)

  1. The bureaucratization of war: moral challenges exemplified by the covert lethal drone

    Directory of Open Access Journals (Sweden)

    Richard Adams

    2013-12-01

    Full Text Available This article interrogates the bureaucratization of war, incarnate in the covert lethal drone. Bureaucracies are criticized typically for their complexity, inefficiency, and inflexibility. This article is concerned with their moral indifference. It explores killing, which is so highly administered, so morally remote, and of such scale, that we acknowledge a covert lethal program. This is a bureaucratized program of assassination in contravention of critical human rights. In this article, this program is seen to compromise the advance of global justice. Moreover, the bureaucratization of lethal force is seen to dissolve democratic ideals from within. The bureaucracy isolates the citizens from lethal force applied in their name. People are killed, in the name of the State, but without conspicuous justification, or judicial review, and without informed public debate. This article gives an account of the risk associated with the bureaucratization of the State's lethal power. Exemplified by the covert drone, this is power with formidable reach. It is power as well, which requires great moral sensitivity. Considering the drone program, this article identifies challenges, which will become more prominent and pressing, as technology advances.

  2. Plasma microRNA profiles distinguish lethal injury in acetaminophen toxicity: A research study

    Institute of Scientific and Technical Information of China (English)

    Jeanine Ward; Shashi Bala; Jan Petrasek; Gyongyi Szabo

    2012-01-01

    AIM:To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice.METHODS:Using plasma from APAP poisoned mice,either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed,we screened commercially available murine microRNA libraries (SABiosciences,Qiagen Sciences,MD) to evaluate for unique miRNA profiles between these two dosing parameters.RESULTS:We distinguished numerous,unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice.Of note,many of the greatest up- and downregulated miRNAs,namely 574-5p,466g,466f-3p,375,29c,and 148a,have been shown to be associated with asthma in prior studies.Interestingly,a relationship between APAP and asthma has been previously well described in the literature,with an as yet unknown mechanism of pathology.There was a statistically significant increase in alanine aminotransferase levels in the lethal compared to sublethal APAP dosing groups at the 12 h time point (P <0.001).There was 90% mortality in the lethally compared to sublethally dosed mice at the 48 h time point (P =0.011).CONCLUSION:We identified unique plasma miRNAs both up- and downregulated in APAP poisoning which are correlated to asthma development.

  3. Tolerization with BLP down-regulates HMGB1 a critical mediator of sepsis-related lethality.

    LENUS (Irish Health Repository)

    Coffey, J Calvin

    2012-02-03

    Tolerization with bacterial lipoprotein (BLP) affords a significant survival benefit in sepsis. Given that high mobility group box protein-1 (HMGB1) is a recognized mediator of sepsis-related lethality, we determined if tolerization with BLP leads to alterations in HMGB1. In vitro, BLP tolerization led to a reduction in HMGB1 gene transcription. This was mirrored at the protein level, as HMGB1 protein expression and release were reduced significantly in BLP-tolerized human THP-1 monocytic cells. BLP tolerance in vivo led to a highly significant, long-term survival benefit following challenge with lethal dose BLP in C57BL\\/6 mice. This was associated with an attenuation of HMGB1 release into the circulation, as evidenced by negligible serum HMGB1 levels in BLP-tolerized mice. Moreover, HMGB1 levels in peritoneal macrophages from BLP-tolerized mice were reduced significantly. Hence, tolerization with BLP leads to a down-regulation of HMGB1 protein synthesis and release. The improved survival associated with BLP tolerance could thus be explained by a reduction in HMGB1, were the latter associated with lethality in BLP-related sepsis. In testing this hypothesis, it was noted that neutralization of HMGB1, using anti-HMGB1 antibodies, abrogated BLP-associated lethality almost completely. To conclude, tolerization with BLP leads to a down-regulation of HMGB1, thus offering a novel means of targeting the latter. HMGB1 is also a mediator of lethality in BLP-related sepsis.

  4. The organisational structure of protein networks: revisiting the centrality-lethality hypothesis.

    Science.gov (United States)

    Raman, Karthik; Damaraju, Nandita; Joshi, Govind Krishna

    2014-03-01

    Protein networks, describing physical interactions as well as functional associations between proteins, have been unravelled for many organisms in the recent past. Databases such as the STRING provide excellent resources for the analysis of such networks. In this contribution, we revisit the organisation of protein networks, particularly the centrality-lethality hypothesis, which hypothesises that nodes with higher centrality in a network are more likely to produce lethal phenotypes on removal, compared to nodes with lower centrality. We consider the protein networks of a diverse set of 20 organisms, with essentiality information available in the Database of Essential Genes and assess the relationship between centrality measures and lethality. For each of these organisms, we obtained networks of high-confidence interactions from the STRING database, and computed network parameters such as degree, betweenness centrality, closeness centrality and pairwise disconnectivity indices. We observe that the networks considered here are predominantly disassortative. Further, we observe that essential nodes in a network have a significantly higher average degree and betweenness centrality, compared to the network average. Most previous studies have evaluated the centrality-lethality hypothesis for Saccharomyces cerevisiae and Escherichia coli; we here observe that the centrality-lethality hypothesis hold goods for a large number of organisms, with certain limitations. Betweenness centrality may also be a useful measure to identify essential nodes, but measures like closeness centrality and pairwise disconnectivity are not significantly higher for essential nodes.

  5. The frequency of allelic lethals and complementation maps in natural populations of drosophila melanogaster from Mexico

    Directory of Open Access Journals (Sweden)

    Salceda Victor M.

    2004-01-01

    Full Text Available Departing from a previous study on the genetic loads affecting the second chromosome of Drosophila melanogaster in four natural populations, 171 lethal chromosomes were recovered and maintained as a balanced stocks in the condition Cy L / 1 (l=lethal; of those lethais 24 correspond to population A, 50 to populations B and C and 47 to population D. later on an intra-population allelism test for the four populations was performed for each one. A total of 3807 inter lethal crosses were done yielding a total of i 10 allelic combinations, from them the respective percentage of allelism for each population was calculated and they are as follow: 3.98 % for population A, 1.80 % for population B, 3.67 % for population C and 2.96 % for population D. the observed values for the frequency of allelism in these populations are not significantly different from those reported by other authors in similar studies in natural and/or experimental populations. Beside these values the frequency for singles, doubles, triplets and even quadruplets present in each population were determined, they shown the presence of various complementation maps due to the clustering of few different lethals: also a large complementation map formed by a large cluster involving the presence of 26 different lethals found in population D all of them combined constituting a single unit was found.

  6. Ion - biomolecule interactions and radiation damage

    International Nuclear Information System (INIS)

    Schlathoelter, T.

    2004-01-01

    Full text: The biological effects of ionizing radiation in living cells are not a mere result of the direct impact of high energy quanta of radiation. Secondary particles such as low energy electrons, radicals and (multiply charged) ions are formed within the track. The interaction of these secondary particles with biologically relevant molecules is responsible for a large fraction of biological radiation damage to a cell, as well. Singly and multiply charged ions can be of importance as both, primary and secondary particles, and are known to cause severe biological damage. For instance, in heavy ion therapy and proton therapy the pronounced Bragg peak of fast (typically a few 100 MeV/u) ions in biological tissue is utilized. The Bragg peak is located at a depth, where the ions (mostly C q+ or protons) are slowed down to about 100 keV/u and have their maximum linear energy transfer (LET) to the medium. This depth is reasonably well defined and depends on the initial ion kinetic energy. Since the ions are rapidly stopped in this energy range, penetration beyond the Bragg peak is weak and it is thus possible to 'scan' the Bragg peak through a malignant tumour without excessive damage of the surrounding tissue by mere variation of the ion kinetic energy (i.e. the penetration depth). Severe biological damage is almost only possible, when the track of a primary quantum of ionizing radiation crosses the nucleus of a cell. Particularly the induction of double strand breaks of DNA or clustered DNA lesions is potentially lethal or mutagenic. A primary particle interacting with individual molecules within this environment leads to molecular excitation, ionization and fragmentation. In the process, the primary particle looses energy and slow secondary electrons and ions are formed, which might induce further damage. For a deep understanding of biological radiation damage on the level of individual molecules it is thus important to quantify excitation, ionization and

  7. Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

    International Nuclear Information System (INIS)

    Benko', Klara; Pintye, Eva; Szabo, Boglarka; Geresi, Krisztina; Megyeri, Attila; Benko, Ilona

    2008-01-01

    To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of γ--irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD 50 values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

  8. Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

    Science.gov (United States)

    Benkő, Klára; Pintye, Éva; Szabó, Boglárka; Géresi, Krisztina; Megyeri, Attila; Benkő, Ilona

    2008-12-01

    To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of γ—irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD50 values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

  9. Suspended animation-like state protects mice from lethal hypoxia.

    Science.gov (United States)

    Blackstone, Eric; Roth, Mark B

    2007-04-01

    Joseph Priestley observed the high burn rate of candles in pure oxygen and wondered if people would "live out too fast" if we were in the same environment. We hypothesize that sulfide, a natural reducer of oxygen that is made in many cell types, acts as a buffer to prevent unrestricted oxygen consumption. To test this, we administered sulfide in the form of hydrogen sulfide (H2S) to mice (Mus musculus). As we have previously shown, H2S decreases the metabolic rate of mice by approximately 90% and induces a suspended animation-like state. Mice cannot survive for longer than 20 min when exposed to 5% oxygen. However, if mice are first put into a suspended animation-like state by a 20-min pretreatment with H2S and then are exposed to low oxygen, they can survive for more than 6.5 h in 5% oxygen with no apparent detrimental effects. In addition, if mice are exposed to a 20-min pretreatment with H2S followed by 1 h at 5% oxygen, they can then survive for several hours at oxygen tensions as low as 3%. We hypothesize that prior exposure to H2S reduces oxygen demand, therefore making it possible for the mice to survive with low oxygen supply. These results suggest that H2S may be useful to prevent damage associated with hypoxia.

  10. Defense mechanisms against radiation induced teratogenic damage in mice

    International Nuclear Information System (INIS)

    Kato, F.; Ootsuyama, A.; Nomoto, S.; Norimura, T.

    2002-01-01

    Experimental studies with mice have established that fetuses at midgestational stage are highly susceptible to malformation at high, but not low, doses of radiation. When DNA damage is produced by a small amount of radiation, it is efficiently eliminated by DNA repair. However, DNA repair is not perfect. There must be defense mechanisms other than DNA repair. In order to elucidate the essential role of p53 gene in apoptotic tissue repair, we compared the incidence of radiation-induced malformations and deaths (deaths after day 10) in wild-type p53 (+/+) mice and null p53 (-/-) mice. For p53 (+/+) mice, an X-ray dose of 2 Gy given at a high dose-rate (450 mGy/min) to fetuses at 9.5 days of gestation was highly lethal and considerably teratogenic whereas it was only slightly lethal but highly teratogenic for p53 (-/-) fetuses. This reciprocal relationship of radiosensitivity to malformations and deaths supports the notion that fetal tissues have a p53 -dependent idguardianln of the tissue that aborts cells bearing radiation-induced teratogenic DNA damage. When an equal dose of 2 Gy given at a 400-fold lower dose-rate (1.2 mGy/min), this dose became not teratogenic for p53 (+/+) fetuses exhibiting p53 -dependent apoptosis, whereas this dose remained teratogenic for p53 (-/-) fetuses unable to carry out apoptosis. Furthermore, when the dose was divided into two equal dose fractions (1+1 Gy) at high dose rate, separated by 24 hours, the incidences of malformations were equal with control level for p53 (+/+), but higher for p53 (-/-) mice. Hence, complete elimination of teratogenic damage from irradiated tissues requires a concerted cooperation of two mechanisms; proficient DNA repair and p53-dependent apoptotic tissue repair

  11. Development of System Architecture to Investigate the Impact of Integrated Air and Missile Defense in a Distributed Lethality Environment

    Science.gov (United States)

    2017-12-01

    SYSTEM ARCHITECTURE TO INVESTIGATE THE IMPACT OF INTEGRATED AIR AND MISSILE DEFENSE IN A DISTRIBUTED LETHALITY ENVIRONMENT by Justin K. Davis...TO INVESTIGATE THE IMPACT OF INTEGRATED AIR AND MISSILE DEFENSE IN A DISTRIBUTED LETHALITY ENVIRONMENT 5. FUNDING NUMBERS 6. AUTHOR(S) Justin K...ARCHITECTURE TO INVESTIGATE THE IMPACT OF INTEGRATED AIR AND MISSILE DEFENSE IN A DISTRIBUTED LETHALITY ENVIRONMENT Justin K. Davis Lieutenant

  12. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

    OpenAIRE

    Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

    2012-01-01

    Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT) and cardiac-specific catalase overexpression mice were challenged...

  13. Nest-building behavior of Monk Parakeets and insights into potential mechanisms for reducing damage to utility poles

    Directory of Open Access Journals (Sweden)

    Kevin R. Burgio

    2014-09-01

    Full Text Available The Monk Parakeet (Myiopsitta monachus commonly uses utility poles as a substrate for building large, bulky nests. These nests often cause fires and electric power outages, creating public safety risks and increasing liability and maintenance costs for electric companies. Previous research has focused on lethal methods and chemical contraception to prevent nesting on utility poles and electrical substations. However, implementation of lethal methods has led to public protests and lawsuits, while chemical contraception may affect other than the targeted species, and must be continually reapplied for effectiveness. One non-lethal alternative, nest removal, is costly and may not be a sustainable measure if Monk Parakeet populations continue to grow. In order to identify cost-effective non-lethal solutions to problems caused by Monk Parakeet nesting, we studied their behavior as they built nests on utility poles. Monk Parakeets initiate nests by attaching sticks at the intersection of the pole and electric lines. We found that parakeets use the electric lines exclusively to gain access to the intersection of lines and pole during nest initiation, and continue to use the lines intensively throughout construction. Monk Parakeets also have more difficulty attaching sticks during the early stages of nest construction than when the nest is nearing completion. These findings suggest that intervention during the earlier stages of nest building, by excluding Monk Parakeets from electric lines adjacent to poles, may be an effective, non-lethal method of reducing or eliminating parakeets nesting on, and damaging, utility poles.

  14. Postnatal Deletion of Fat Storage-inducing Transmembrane Protein 2 (FIT2/FITM2) Causes Lethal Enteropathy.

    Science.gov (United States)

    Goh, Vera J; Tan, Jolene S Y; Tan, Bryan C; Seow, Colin; Ong, Wei-Yi; Lim, Yen Ching; Sun, Lei; Ghosh, Sujoy; Silver, David L

    2015-10-16

    Lipid droplets (LDs) are phylogenetically conserved cytoplasmic organelles that store neutral lipids within a phospholipid monolayer. LDs compartmentalize lipids and may help to prevent cellular damage caused by their excess or bioactive forms. FIT2 is a ubiquitously expressed transmembrane endoplasmic reticulum (ER) membrane protein that has previously been implicated in LD formation in mammalian cells and tissue. Recent data indicate that FIT2 plays an essential role in fat storage in an in vivo constitutive adipose FIT2 knock-out mouse model, but the physiological effects of postnatal whole body FIT2 depletion have never been studied. Here, we show that tamoxifen-induced FIT2 deletion using a whole body ROSA26CreER(T2)-driven FIT2 knock-out (iF2KO) mouse model leads to lethal intestinal pathology, including villus blunting and death of intestinal crypts, and loss of lipid absorption. iF2KO mice lose weight and die within 2 weeks after the first tamoxifen dose. At the cellular level, LDs failed to form in iF2KO enterocytes after acute oil challenge and instead accumulated within the ER. Intestinal bile acid transporters were transcriptionally dysregulated in iF2KO mice, leading to the buildup of bile acids within enterocytes. These data support the conclusion that FIT2 plays an essential role in regulating intestinal health and survival postnatally. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. The radiobiology of laser-driven particle beams: focus on sub-lethal responses of normal human cells

    International Nuclear Information System (INIS)

    Manti, L.; Perozziello, F.M.; Romagnani, L.; Borghesi, M.; Doria, D.; Candiano, G.; Cirrone, G.A.P.; Leanza, R.; Romano, F.; Scuderi, V.; Tramontana, A.; Chaudhary, P.; Gwynne, D.; Prise, K. M.

    2017-01-01

    Accelerated proton beams have become increasingly common for treating cancer. The need for cost and size reduction of particle accelerating machines has led to the pioneering investigation of optical ion acceleration techniques based on laser-plasma interactions as a possible alternative. Laser-matter interaction can produce extremely pulsed particle bursts of ultra-high dose rates (≥ 10 9 Gy/s), largely exceeding those currently used in conventional proton therapy. Since biological effects of ionizing radiation are strongly affected by the spatio-temporal distribution of DNA-damaging events, the unprecedented physical features of such beams may modify cellular and tissue radiosensitivity to unexplored extents. Hence, clinical applications of laser-generated particles need thorough assessment of their radiobiological effectiveness. To date, the majority of studies have either used rodent cell lines or have focussed on cancer cell killing being local tumour control the main objective of radiotherapy. Conversely, very little data exist on sub-lethal cellular effects, of relevance to normal tissue integrity and secondary cancers, such as premature cellular senescence. Here, we discuss ultra-high dose rate radiobiology and present preliminary data obtained in normal human cells following irradiation by laser-accelerated protons at the LULI PICO2000 facility at Laser Lab Europe, France.

  16. The Effect of A Single Sub-Lethal Dose of Whole Body Irradiation on the Small Intestine of Rats

    International Nuclear Information System (INIS)

    Al-Ramli, M. A.; Kubba, M. A.; Al-Bassam, L. S.; Belhaj, K.; Al-shawish, N. M.

    2007-01-01

    The effect of whole body radiation with a single sub-lethal dose at 4 Gy on rat small intestine was studied histologically and quantitatively. Irradiated animals were euthanized at 24 hours, 3, 7, 14, 21 and 28 days post- irradiation. Crypts of Leiberkuhn and peyer's patches were especially targeted by irradiation. The crypts showed severe cellular fragmentation in the germinal cellular compartments twenty Four hours after irradiation resulting in partial denudation of villi especially at their Tips. At three days, these cells resumed their proliferative activity with the appearance of unusually large numbers of mitotic figures. Cellular regeneration in the crypts and on the villous surface showed improvement with advancing time till day 28 when the villi had complete epithelial covering and the proliferative activity of the germinal cryptic cells returned to normal. The quantitative study included the measurement of about fifty villi at each time after irradiation. A significant decrease in villous length was noticed at twenty four hours post-irradiation compared to the control values. The length of villi plateaued at about this level till day twenty one when it slightly increased to reach a sub normal mean length on day 28. We concluded that whole body irradiation with a single dose at 4 Gy was enough to induce cryptic cellular necrosis with sloughing of epithelial villous columnar covering. This cellular damage was, however, sub- total since quick regenerative cellular activity was noticed three days post-irradiation. The decrease in the villous length paralleled the cryptic cellular damage whereas full recovery was not achieved despite obvious cellular regeneration.

  17. mapDamage

    DEFF Research Database (Denmark)

    Ginolhac, Aurélien; Rasmussen, Morten; Gilbert, Tom

    2011-01-01

    Ancient DNA extracts consist of a mixture of contaminant DNA molecules, most often originating from environmental microbes, and endogenous fragments exhibiting substantial levels of DNA damage. The latter introduce specific nucleotide misincorporations and DNA fragmentation signatures in sequenci...... of the SAMtools suite and R environment and has been validated on both GNU/Linux and MacOSX operating systems....

  18. Core damage risk indicators

    International Nuclear Information System (INIS)

    Szikszai, T.

    1994-01-01

    The purpose of this document is to show a method for the fast recalculation of the PSA. To avoid the information loose, it is necessary to simplify the PSA models, or at least reorganize them. The method, introduced in this document, require that preparation, so we try to show, how to do that. This document is an introduction. This is the starting point of the work related to the development of the risk indicators. In the future, with the application of this method, we are going to show an everyday use of the PSA results to produce the indicators of the core damage risk. There are two different indicators of the plant safety performance, related to the core damage risk. The first is the core damage frequency indicator (CDFI), and the second is the core damage probability indicator (CDPI). Of course, we cannot describe all of the possible ways to use these indicators, rather we will try to introduce the requirements to establish such an indicator system and the calculation process

  19. Dominant lethal mutations in male mice fed γ-irradiated diet

    International Nuclear Information System (INIS)

    Chauhan, P.S.; Aravindakshan, M.; Aiyer, A.S.; Sundaram, K.

    1975-01-01

    Three groups of Swiss male mice were fed a stock ration of an unirradiated or irradiated (2.5 Mrad) test diet for 8 wk. After the feeding period, the males were mated with groups of untreated female mice for 4 consecutive weeks. The females were autopsied at mid-term pregnancy for evaluation of dominant lethal mutations. Numbers of dead implantations, including deciduomas and dead embryos, showed no significant differences among the different groups, thus producing no evidence of any induced post-implantation lethality in mice fed on irradiated diet. Similarly, there was no indication of preimplantation lethality, since implantation rates remained comparable among different groups. Consumption of irradiated diet did not affect the fertility of mice. Total pre- and post-implantation loss, as indicated by the numbers of live implantations remained comparable among all the groups of mice. (author)

  20. Comparison of the lethal effects of chemical warfare nerve agents across multiple ages.

    Science.gov (United States)

    Wright, Linnzi K M; Lee, Robyn B; Vincelli, Nicole M; Whalley, Christopher E; Lumley, Lucille A

    2016-01-22

    Children may be inherently more vulnerable than adults to the lethal effects associated with chemical warfare nerve agent (CWNA) exposure because of their closer proximity to the ground, smaller body mass, higher respiratory rate, increased skin permeability and immature metabolic systems. Unfortunately, there have only been a handful of studies on the effects of CWNA in pediatric animal models, and more research is needed to confirm this hypothesis. Using a stagewise, adaptive dose design, we estimated the 24h median lethal dose for subcutaneous exposure to seven CWNA in both male and female Sprague-Dawley rats at six different developmental times. Perinatal (postnatal day [PND] 7, 14 and 21) and adult (PND 70) rats were more susceptible than pubertal (PND 28 and 42) rats to the lethal effects associated with exposure to tabun, sarin, soman and cyclosarin. Age-related differences in susceptibility were not observed in rats exposed to VM, Russian VX or VX. Published by Elsevier Ireland Ltd.

  1. Lethal and nonlethal violence against an intimate female partner: comparing male murderers to nonlethal abusers.

    Science.gov (United States)

    Dobash, R Emerson; Dobash, Russell P; Cavanagh, Kate; Medina-Ariza, Juanjo

    2007-04-01

    Men's lethal and nonlethal violence against an intimate female partner are compared. Various risk factors are examined to compare men's lethal and nonlethal violence against an intimate woman partner. Relative to abusers, men who kill are generally more conventional with respect to childhood backgrounds, education, employment, and criminal careers, are more likely to be possessive and jealous, and are more likely to be separated from their partner at the time of the event. Men who kill are more likely to have used violence against a previous partner, to have sexually assaulted and strangled the victim, and to have used a weapon or instrument. However, they were less likely to have been drunk at the time of the event and/or to have previously used violence against the woman they killed. Overall, the findings do not support the notion of a simple progression from nonlethal to lethal violence and raise some dilemmas for the growing area of risk assessment.

  2. QTL mapping of inbreeding-related cold sensitivity and conditional lethality in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Vermeulen, Corneel J.; Bijlsma, R.; Loeschcke, Volker

    2008-01-01

    of inbreeding-related and conditionally expressed lethality in Drosophila melanogaster. The lethal effect was triggered by exposure to a cold shock. We used a North Carolina crossing Design 3 to establish the mapping population, as well as to estimate the average dominance ratio and heritability. We found two......Inbreeding depression is a central theme within genetics, and is of specific interest for researchers within evolutionary and conservation genetics and animal and plant breeding. Inbreeding effects are thought to be caused by the joint expression of conditional and unconditional deleterious alleles....... Whenever the expression of deleterious alleles is conditional, this can result in extreme environmental sensitivity in certain inbred lineages. Analysis of conditional lethal effects can reveal some of the loci that are sensitive to inbreeding. We performed a QTL (quantitative trait locus) mapping study...

  3. Risk of nuclear damage

    International Nuclear Information System (INIS)

    Kienzl, K.

    1997-01-01

    Following the opening and words of welcome by Mr. Fritz Unterpertinger (unit director at the Austrian Federal Ministry for the Environment, Youth and Family; BMUJF) Mrs Helga Kromp-Kolb (professor at the Institute for Meteorology and Physics of the University of Natural Resources Science Vienna) illustrated the risks of nuclear damage in Europe by means of a nuclear risk map. She explained that even from a scientific or technical point of view the assessment of risks arising from nuclear power stations was fraught with great uncertainties. Estimates about in how far MCAs (maximum credible accident) could still be controlled by safety systems vary widely and so do assessments of the probability of a core melt. But there is wide agreement in all risk assessments conducted so far that MCAs might occur within a - from a human point of view - conceivable number of years. In this connection one has to bear in mind that the occurrence of such a major accident - whatever its probability may be - could entail immense damage and the question arises whether or not it is at all justifiable to expose the general public to such a risk. Klaus Rennings (Centre for European Economic Research, Mannheim, Germany) dealt with the economic aspects of nuclear risk assessment. He explained that there are already a number of studies available aiming to assess the risk of damage resulting from a core melt accident in economic terms. As to the probability of occurrence estimates vary widely between one incident in 3,333 and 250,000 year of reactor operation. It is assumed, however, that a nuclear accident involving a core melt in Germany would probably exceed the damage caused by the Chernobyl accident. The following speakers addressed the legal aspects of risks associated with nuclear installations. Mrs Monika Gimpel-Hinteregger (professor at the Institute for Civil Law in Graz) gave an overview on the applicable Austrian law concerning third party liability in the field of nuclear energy

  4. Assessing the Blunt Trauma Potential of Free Flying Projectiles for Development and Safety Certification of Non-Lethal Kinetic Impactors

    National Research Council Canada - National Science Library

    Widder, Jeffrey

    1997-01-01

    The primary performance objective for non-lethal, antipersonnel kinetic energy impact projectiles is to reliably deter or incapacitate without causing injuries that require medical treatment beyond...

  5. Frequencies of aneuploidy and dominant lethal mutations in young female mice induced by low dose γ-rays

    International Nuclear Information System (INIS)

    Yao Suyan; Zhang Chaoyang; Dai Lianlian; Gao Changwen

    1991-01-01

    Relationship between aneuploidy, dominant lethal mutations and doses in young feral mice induced by low dose γ-rays was examined. The results suggest that the frequencies of aneuploidy of embryos increased at 0.15 Gy, but increases at over 0.50 Gy after irradiation in groups. The frequencies of aneuploidy and dominant lethal mutations increased with increasing doses and fitted linear relationship. This dose-response relationship of trisomic was not significant. The frequency of dominant lethal mutations induced by 60 Co γ irradiation is 5.59%. The effect of dominant lethal mutation is higher than that of the aneuploidy

  6. Why is intracellular ice lethal? A microscopical study showing evidence of programmed cell death in cryo-exposed embryonic axes of recalcitrant seeds of Acer saccharinum.

    Science.gov (United States)

    Wesley-Smith, James; Walters, Christina; Pammenter, N W; Berjak, Patricia

    2015-05-01

    Conservation of the genetic diversity afforded by recalcitrant seeds is achieved by cryopreservation, in which excised embryonic axes (or, where possible, embryos) are treated and stored at temperatures lower than -180 °C using liquid nitrogen. It has previously been shown that intracellular ice forms in rapidly cooled embryonic axes of Acer saccharinum (silver maple) but this is not necessarily lethal when ice crystals are small. This study seeks to understand the nature and extent of damage from intracellular ice, and the course of recovery and regrowth in surviving tissues. Embryonic axes of A. saccharinum, not subjected to dehydration or cryoprotection treatments (water content was 1·9 g H2O g(-1) dry mass), were cooled to liquid nitrogen temperatures using two methods: plunging into nitrogen slush to achieve a cooling rate of 97 °C s(-1) or programmed cooling at 3·3 °C s(-1). Samples were thawed rapidly (177 °C s(-1)) and cell structure was examined microscopically immediately, and at intervals up to 72 h in vitro. Survival was assessed after 4 weeks in vitro. Axes were processed conventionally for optical microscopy and ultrastructural examination. Immediately following thaw after cryogenic exposure, cells from axes did not show signs of damage at an ultrastructural level. Signs that cells had been damaged were apparent after several hours of in vitro culture and appeared as autophagic decomposition. In surviving tissues, dead cells were sloughed off and pockets of living cells were the origin of regrowth. In roots, regrowth occurred from the ground meristem and procambium, not the distal meristem, which became lethally damaged. Regrowth of shoots occurred from isolated pockets of surviving cells of peripheral and pith meristems. The size of these pockets may determine the possibility for, the extent of and the vigour of regrowth. Autophagic degradation and ultimately autolysis of cells following cryo-exposure and formation of small

  7. Molecular analysis of two mouse dilute locus deletion mutations: Spontaneous dilute lethal20J and radiation-induced dilute prenatal lethal Aa2 alleles

    International Nuclear Information System (INIS)

    Strobel, M.C.; Seperack, P.K.; Copeland, N.G.; Jenkins, N.A.

    1990-01-01

    The dilute (d) coat color locus of mouse chromosome 9 has been identified by more than 200 spontaneous and mutagen-induced recessive mutations. With the advent of molecular probes for this locus, the molecular lesion associated with different dilute alleles can be recognized and precisely defined. In this study, two dilute mutations, dilute-lethal20J (dl20J) and dilute prenatal lethal Aa2, have been examined. Using a dilute locus genomic probe in Southern blot analysis, we detected unique restriction fragments in dl20J and Aa2 DNA. Subsequent analysis of these fragments showed that they represented deletion breakpoint fusion fragments. DNA sequence analysis of each mutation-associated deletion breakpoint fusion fragment suggests that both genomic deletions were generated by nonhomologous recombination events. The spontaneous dl20J mutation is caused by an interstitial deletion that removes a single coding exon of the dilute gene. The correlation between this discrete deletion and the expression of all dilute-associated phenotypes in dl20J homozygotes defines the dl20J mutation as a functional null allele of the dilute gene. The radiation-induced Aa2 allele is a multilocus deletion that, by complementation analysis, affects both the dilute locus and the proximal prenatal lethal-3 (pl-3) functional unit. Molecular analysis of the Aa2 deletion breakpoint fusion fragment has provided access to a previously undefined gene proximal to d. Initial characterization of this new gene suggests that it may represent the genetically defined pl-3 functional unit

  8. Inactivation of CDK2 is synthetically lethal to MYCN over-expressing cancer cells

    Science.gov (United States)

    Molenaar, Jan J.; Ebus, Marli E.; Geerts, Dirk; Koster, Jan; Lamers, Fieke; Valentijn, Linda J.; Westerhout, Ellen M.; Versteeg, Rogier; Caron, Huib N.

    2009-01-01

    Two genes have a synthetically lethal relationship when the silencing or inhibiting of 1 gene is only lethal in the context of a mutation or activation of the second gene. This situation offers an attractive therapeutic strategy, as inhibition of such a gene will only trigger cell death in tumor cells with an activated second oncogene but spare normal cells without activation of the second oncogene. Here we present evidence that CDK2 is synthetically lethal to neuroblastoma cells with MYCN amplification and over-expression. Neuroblastomas are childhood tumors with an often lethal outcome. Twenty percent of the tumors have MYCN amplification, and these tumors are ultimately refractory to any therapy. Targeted silencing of CDK2 by 3 RNA interference techniques induced apoptosis in MYCN-amplified neuroblastoma cell lines, but not in MYCN single copy cells. Silencing of MYCN abrogated this apoptotic response in MYCN-amplified cells. Inversely, silencing of CDK2 in MYCN single copy cells did not trigger apoptosis, unless a MYCN transgene was activated. The MYCN induced apoptosis after CDK2 silencing was accompanied by nuclear stabilization of P53, and mRNA profiling showed up-regulation of P53 target genes. Silencing of P53 rescued the cells from MYCN-driven apoptosis. The synthetic lethality of CDK2 silencing in MYCN activated neuroblastoma cells can also be triggered by inhibition of CDK2 with a small molecule drug. Treatment of neuroblastoma cells with roscovitine, a CDK inhibitor, at clinically achievable concentrations induced MYCN-dependent apoptosis. The synthetically lethal relationship between CDK2 and MYCN indicates CDK2 inhibitors as potential MYCN-selective cancer therapeutics. PMID:19525400

  9. Calcium-Sensing Receptor Tumor Expression and Lethal Prostate Cancer Progression.

    Science.gov (United States)

    Ahearn, Thomas U; Tchrakian, Nairi; Wilson, Kathryn M; Lis, Rosina; Nuttall, Elizabeth; Sesso, Howard D; Loda, Massimo; Giovannucci, Edward; Mucci, Lorelei A; Finn, Stephen; Shui, Irene M

    2016-06-01

    Prostate cancer metastases preferentially target bone, and the calcium-sensing receptor (CaSR) may play a role in promoting this metastatic progression. We evaluated the association of prostate tumor CaSR expression with lethal prostate cancer. A validated CaSR immunohistochemistry assay was performed on tumor tissue microarrays. Vitamin D receptor (VDR) expression and phosphatase and tensin homolog tumor status were previously assessed in a subset of cases by immunohistochemistry. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and pathological tumor node metastasis stage were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of CaSR expression with lethal prostate cancer. The investigation was conducted in the Health Professionals Follow-up Study and Physicians' Health Study. We studied 1241 incident prostate cancer cases diagnosed between 1983 and 2009. Participants were followed up or cancer-specific mortality or development of metastatic disease. On average, men were followed up 13.6 years, during which there were 83 lethal events. High CaSR expression was associated with lethal prostate cancer independent of clinical and pathological variables (HR 2.0; 95% CI 1.2-3.3). Additionally, there was evidence of effect modification by VDR expression; CaSR was associated with lethal progression among men with low tumor VDR expression (HR 3.2; 95% CI 1.4-7.3) but not in cases with high tumor VDR expression (HR 0.8; 95% CI 0.2-3.0). Tumor CaSR expression is associated with an increased risk of lethal prostate cancer, particularly in tumors with low VDR expression. These results support further investigating the mechanism linking CaSR with metastases.

  10. Lethal and sub-lethal effects of select macrocyclic lactones insecticides on forager worker honey bees under laboratory experimental conditions.

    Science.gov (United States)

    Abdu-Allah, Gamal A M; Pittendrigh, Barry R

    2018-01-01

    Selective insecticide application is one important strategy for more precisely targeting harmful insects while avoiding or mitigating collateral damage to beneficial insects like honey bees. Recently, macrocyclic lactone-class insecticides have been introduced into the market place as selective bio-insecticides for controlling many arthropod pests, but how to target this selectivity only to harmful insects has yet to be achieved. In this study, the authors investigated the acute toxicity of fourmacrocyclic lactone insecticides (commercialized as abamectin, emamectin benzoate, spinetoram, and spinosad) both topically and through feeding studies with adult forager honey bees. Results indicated emamectin benzoate as topically 133.3, 750.0, and 38.3-fold and orally 3.3, 7.6, and 31.7-fold more toxic, respectively than abamectin, spinetoram and spinosad. Using Hazard Quotients for estimates of field toxicity, abamectin was measured as the safest insecticide both topically and orally for honey bees. Moreover, a significant reduction of sugar solution consumption by treatment group honey bees for orally applied emamectin benzoate and spinetoram suggests that these insecticides may have repellent properties.

  11. Discovery and Development of Therapeutic Drugs against Lethal Human RNA Viruses: a Multidisciplinary Assault.

    Science.gov (United States)

    1991-07-16

    AD-A239 742 AD GRANT NO: DAMD17-89-Z-9021 TITLE: DISCOVERY AND DEVELOPMENT OF THERAPEUTIC DRUGS AGAINST LETHAL HUMAN RNA VIRUSES: A MULTIDISCIPLINARY...62787A871 AB WrJDA317987 11. TITLE (Include Securty Classification) DISCOVERY AND DEVELOPMENT OF THERAPEUTIC DRUGS AGAINST LETHAL HUMAN RNA VIRUSES: A...G. R. Pettit, III, D.-S. Huang, and G. R. Pettit, 23rd Int’l. Horticulture Congress, Italy, 8/27 - 9/1/90. "Bryostatins Define the Role of Protein

  12. Dominant lethal mutations research in mice fed with irradiated black beams

    International Nuclear Information System (INIS)

    Andrade, Z.P.

    1982-01-01

    To evaluate the potential mutagenic effects of irradiated black beans (Phaseolus vulgaris) with conservation purpose, in germ cells of mice, dominant lethal assay were employed. Three groups of albino swiss male mice (S W-55) were fed with a normal ration, or unirradiated or irradiated (0,2; 0,5; 1; 5; 10; 15 e 20 KGy) test diets for eight weeks. After the feeding period the males were mated with groups of untreated females mice for four consecutive weeks. Numbers of pregnancy rates females were observed. The females were autopsied at mid-term pregnancy for evaluation of dominant lethal mutations. (author)

  13. The lethal injection quandary: how medicine has dismantled the death penalty.

    Science.gov (United States)

    Denno, Deborah W

    2007-10-01

    On February 20, 2006, Michael Morales was hours away from execution in California when two anesthesiologists declined to participate in his lethal injection procedure, thereby halting all state executions. The events brought to the surface the long-running schism between law and medicine, raising the question of whether any beneficial connection between the professions ever existed in the execution context. History shows it seldom did. Decades of botched executions prove it. This Article examines how states ended up with such constitutionally vulnerable lethal injection procedures, suggesting that physician participation in executions, though looked upon with disdain, is more prevalent--and perhaps more necessary--than many would like to believe. The Article also reports the results of this author's unique nationwide study of lethal injection protocols and medical participation. The study demonstrates that states have continued to produce grossly inadequate protocols that severely restrict sufficient understanding of how executions are performed and heighten the likelihood of unconstitutionality. The analysis emphasizes in particular the utter lack of medical or scientific testing of lethal injection despite the early and continuous involvement of doctors but ongoing detachment of medical societies. Lastly, the Article discusses the legal developments that led up to the current rush of lethal injection lawsuits as well as the strong and rapid reverberations that followed, particularly with respect to medical involvement. This Article concludes with two recommendations. First, much like what occurred in this country when the first state switched to electrocution, there should be a nationwide study of proper lethal injection protocols. An independent commission consisting of a diverse group of qualified individuals, including medical personnel, should conduct a thorough assessment of lethal injection, especially the extent of physician participation. Second, this

  14. Sterilization and lethal gamma radiation doses on adults and eggs of Sitotroga Cerealella (OLIVIER)

    International Nuclear Information System (INIS)

    Wiendl, F.M.; Bovi, O.A.; Arthur, V.

    1975-04-01

    The influence of lethal doses of radiation from a cobalt 60 gamma source on eggs, adults and fertitility of Sitotroga Cerealella (Olivier) is described. Eggs irradiated with a dose of 14 Krad still showed viability of 16.1%. On longevity doses up to 70 Krad were usually non lethal but some variation could be observed related to the larval diet. Females fertilized by males irradiated with a dose of 70 Krad produced 36% fertile eggs. When the females were irradiated with the same dose, their fertility dropped to 2.2% and when both sexes were irradiated with a 60 Krad dose, the fertility was 28.8%

  15. UV-induced lethal sectoring and pure mutant clones in yeast.

    Science.gov (United States)

    Hannan, M A; Duck, P; Nasim, A

    1976-08-01

    The induction of lethal sectoring and pure mutant clones by ultraviolet light has been studied in a homogeneous G1 population of Saccharomyces cerevisiae grown in a normal growth medium. At the lowest UV dose of 250 ergs, which corresponds to a shoulder in the survival curve, all mutants appeared as pure clones. At higher doses the frequency of mosaic mutants progressively increased. These results indicate a relationship between the highest frequency of complete mutants and the maximum repair activity. In addition, the frequency of lethal sectoring at all doses tested was too low to account for the origin of pure mutant clones.

  16. Effect of radiomodifying agents on the ratios of X-ray-induced lesions in cellular DNA: use in lethal lesion determination

    International Nuclear Information System (INIS)

    Radford, I.R.

    1986-01-01

    The effect of three radiomodifying agents, cysteamine, hyperthermia, and hypoxia, on the induction of the major classes of X-ray-induced DNA lesions, was studied using mouse L cells and Chinese hamster V79 cells. The use of filter elution techniques allowed most of these studies to be conducted at X-ray doses within the survival-curve range. Cysteamine was found to protect against DNA single-strand breakage (ssb), DNA base damage, and DNA-protein crosslinkage. Hyperthermia had no effect on the level of DNA ssb or DNA base damage, but in L cells (but not in V79 cells) it increased the level of DNA-protein crosslinkage relative to DNA ssb. Hypoxia protected against DNA ssb, had no significant effect on the level of DNA base damage, and enhanced the level of DNA-protein crosslinkage relative to DNA ssb. These results support the previous suggestion that the X-ray-induced lethal lesion is DNA double-strand breakage. Implications of these findings for the mechanisms of formation of X-ray-induced DNA lesions are also discussed. (author)

  17. Lethality Prediction for Escherichia Coli O157:H7 and Uropathogenic E. coli in Ground Chicken Treated with High Pressure Processing and Trans-Cinnamaldehyde.

    Science.gov (United States)

    Sheen, Shiowshuh; Huang, Chi-Yun; Ramos, Rommel; Chien, Shih-Yung; Scullen, O Joseph; Sommers, Christopher

    2018-03-01

    Pathogenic Escherichia coli, intestinal (O157:H7) as well as extraintestinal types (for example, Uropathogenic E. coli [UPEC]) are commonly found in many foods including raw chicken meat. The resistance of E. coli O157:H7 to UPEC in chicken meat under the stresses of high hydrostatic Pressure (HHP, also known as HPP-high pressure processing) and trans-cinnamaldehyde (an essential oil) was investigated and compared. UPEC was found slightly less resistant than O157:H7 in our test parameter ranges. With the addition of trans-cinnamaldehyde as an antimicrobial to meat, HPP lethality enhanced both O157:H7 and UPEC inactivation. To facilitate the predictive model development, a central composite design (CCD) was used to assess the 3-parameter effects, that is, pressure (300 to 400 MPa), trans-cinnamaldehyde dose (0.2 to 0.5%, w/w), and pressure-holding time (15 to 25 min), on the inactivation of E. coli O157:H7 and UPEC in ground chicken. Linear models were developed to estimate the lethality of E. coli O157:H7 (R 2 = 0.86) and UPEC (R 2 = 0.85), as well as dimensionless nonlinear models. All models were validated with data obtained from separated CCD combinations. Because linear models of O157:H7 and UPEC had similar R 2 and the significant lethality difference of CCD points was only 9 in 20; all data were combined to generate models to include both O157:H7 and UPEC. The results provide useful information/tool to predict how pathogenic E. coli may survive HPP in the presence of trans-cinnamaldehyde and to achieve a great than 5 log CFU/g reduction in chicken meat. The models may be used for process optimization, product development and to assist the microbial risk assessment. The study provided an effective means to reduce the high hydrostatic pressure level with incorporation of antimicrobial compound to achieve a 5-log reduction of pathogenic E. coli without damaging the raw meat quality. The developed models may be used to predict the high pressure processing

  18. An H5N1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with H7N9 influenza virus.

    Science.gov (United States)

    Leung, Ho-Chuen; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Zhao, Han-Jun; Cheung, Chung-Yan; Ng, Fai; Huang, Jian-Dong; Zheng, Bo-Jian

    2015-04-01

    In March 2013, a patient infected with a novel avian influenza A H7N9 virus was reported in China. Since then, there have been 458 confirmed infection cases and 177 deaths. The virus contains several human-adapted markers, indicating that H7N9 has pandemic potential. The outbreak of this new influenza virus highlighted the need for the development of universal influenza vaccines. Previously, we demonstrated that a tetrameric peptide vaccine based on the matrix protein 2 ectodomain (M2e) of the H5N1 virus (H5N1-M2e) could protect mice from lethal infection with different clades of H5N1 and 2009 pandemic H1N1 influenza viruses. In this study, we investigated the cross-protection of H5N1-M2e against lethal infection with the new H7N9 virus. Although five amino acid differences existed at positions 13, 14, 18, 20, and 21 between M2e of H5N1 and H7N9, H5N1-M2e vaccination with either Freund's adjuvant or the Sigma adjuvant system (SAS) induced a high level of anti-M2e antibody, which cross-reacted with H7N9-M2e peptide. A mouse-adapted H7N9 strain, A/Anhui/01/2013m, was used for lethal challenge in animal experiments. H5N1-M2e vaccination provided potent cross-protection against lethal challenge of the H7N9 virus. Reduced viral replication and histopathological damage of mouse lungs were also observed in the vaccinated mice. Our results suggest that the tetrameric H5N1-M2e peptide vaccine could protect against different subtypes of influenza virus infections. Therefore, this vaccine may be an ideal candidate for developing a universal vaccine to prevent the reemergence of avian influenza A H7N9 virus and the emergence of potential novel reassortants of influenza virus.

  19. DNA damage and mutagenesis of lambda phage induced by gamma-rays

    International Nuclear Information System (INIS)

    Bertram, Heidi

    1988-01-01

    Lambda phage DNA was gamma irradiated in aqueous solution and strand breakage determined. Twice as much minor structural damage per lethal hit was found in this DNA compared with DNA from irradiated phage suspensions. The in vitro irradiated DNA was repackaged into infectious particles. Induction of mutations in the cI or cII cistron was scored using SOS-induced host cells. In vitro prepared particles were found to have second-order kinetics for mutagenesis induced by gamma rays indicating two pre-mutational events were necessary to produce a mutation, but bacteria-free phage suspensions ('lys-phage') showed single hit kinetics for mutagenesis after irradiation. Increase in the mutation rate in the phage particles was mainly due to minor lesions, i.e. ssb, als and unidentified base damage. In lys-phage, mutagenesis might be enhanced by clustered DNA damage - configuration not existing in pack-phage. Loss of infectivity was analysed in comparison with structural damage. All lesions contributed to biological inactivation. Minor lesions were tolerated by lambda phage to a limited extent. Major lesions (e.g. dsb) contributed most to infectivity loss and were considered lethal events. (U.K.)

  20. Immunoassay of DNA damage

    International Nuclear Information System (INIS)

    Gasparro, F.P.; Santella, R.M.

    1988-01-01

    The direct photomodification of DNA by ultraviolet light or the photo-induced addition of exogenous compounds to DNA components results in alterations of DNA structure ranging from subtle to profound. There are two consequences of these conformational changes. First, cells in which the DNA has been damaged are capable of executing repair steps. Second, the DNA which is usually of very low immunogenicity now becomes highly antigenic. This latter property has allowed the production of a series of monoclonal antibodies that recognize photo-induced DNA damage. Monoclonal antibodies have been generated that recognize the 4',5'-monoadduct and the crosslink of 8-methoxypsoralen in DNA. In addition, another antibody has been prepared which recognizes the furan-side monoadduct of 6,4,4'-trimethylangelicin in DNA. These monoclonal antibodies have been characterized as to sensitivity and specificity using non-competitive and competitive enzyme-linked-immunosorbent assays (ELISA). (author)

  1. Neutron induced radiation damage

    International Nuclear Information System (INIS)

    Williams, M.M.R.

    1977-01-01

    We derive a general expression for the number of displaced atoms of type j caused by a primary knock-on of type i. The Kinchin-Pease model is used, but considerably generalised to allow for realistic atomic potentials. Two cases are considered in detail: the single particle problem causing a cascade and the neutron initiated problem which leads to multiple subcascades. Numerical results have been obtained for a variety of scattering laws. An important conclusion is that neutron initiated damage is much more severe than atom-initiated damage and leads to the number of displaced atoms being a factor of (A+1) 2 /4A larger than the single primary knock-on theory predicts. A is the ratio of the atomic mass to the neutron mass. The importance of this result to the theory of neutron sputtering is explained. (orig.) [de

  2. Immunoassay of DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Gasparro, F P; Santella, R M

    1988-09-01

    The direct photomodification of DNA by ultraviolet light or the photo-induced addition of exogenous compounds to DNA components results in alterations of DNA structure ranging from subtle to profound. There are two consequences of these conformational changes. First, cells in which the DNA has been damaged are capable of executing repair steps. Second, the DNA which is usually of very low immunogenicity now becomes highly antigenic. This latter property has allowed the production of a series of monoclonal antibodies that recognize photo-induced DNA damage. Monoclonal antibodies have been generated that recognize the 4',5'-monoadduct and the crosslink of 8-methoxypsoralen in DNA. In addition, another antibody has been prepared which recognizes the furan-side monoadduct of 6,4,4'-trimethylangelicin in DNA. These monoclonal antibodies have been characterized as to sensitivity and specificity using non-competitive and competitive enzyme-linked-immunosorbent assays (ELISA).

  3. Radiation damage in DNA

    International Nuclear Information System (INIS)

    Lafleur, V.

    1978-01-01

    A number of experiments are described with the purpose to obtain a better insight in the chemical nature and the biological significance of radiation-induced damage in DNA, with some emphasis on the significance of alkali-labile sites. It is shown that not only reactions of OH radicals but also of H radicals introduce breaks and other inactivating damage in single-standed phiX174 DNA. It is found that phosphate buffer is very suitable for the study of the reactions of H radicals with DNA, as the H 2 PO 4 - ions convert the hydrated electrons into H radicals. The hydrated electron, which does react with DNA, does not cause a detectable inactivation. (Auth.)

  4. OH radicals from the indirect actions of X-rays induce cell lethality and mediate the majority of the oxygen enhancement effect.

    Science.gov (United States)

    Hirayama, Ryoichi; Ito, Atsushi; Noguchi, Miho; Matsumoto, Yoshitaka; Uzawa, Akiko; Kobashi, Gen; Okayasu, Ryuichi; Furusawa, Yoshiya

    2013-11-01

    We examined OH radical-mediated indirect actions from X irradiation on cell killing in wild-type Chinese hamster ovary cell lines (CHO and AA8) under oxic and hypoxic conditions, and compared the contribution of direct and indirect actions under both conditions. The contribution of indirect action on cell killing can be estimated from the maximum degree of protection by dimethylsulfoxide, which suppresses indirect action by quenching OH radicals without affecting the direct action of X rays on cell killing. The contributions of indirect action on cell killing of CHO cells were 76% and 50% under oxic and hypoxic conditions, respectively, and those for AA8 cells were 85% and 47%, respectively. Therefore, the indirect action on cell killing was enhanced by oxygen during X irradiation in both cell lines tested. Oxygen enhancement ratios (OERs) at the 10% survival level (D10 or LD90) for CHO and AA8 cells were 2.68 ± 0.15 and 2.76 ± 0.08, respectively. OERs were evaluated separately for indirect and direct actions, which gave the values of 3.75 and 2.01 for CHO, and 4.11 and 1.32 for AA8 cells, respectively. Thus the generally accepted OER value of ∼3 is best understood as the average of the OER values for both indirect and direct actions. These results imply that both indirect and direct actions on cell killing require oxygen for the majority of lethal DNA damage, however, oxygen plays a larger role in indirect than for direct effects. Conversely, the lethal damage induced by the direct action of X rays are less affected by oxygen concentration.

  5. Trivalent pneumococcal protein recombinant vaccine protects against lethal Streptococcus pneumoniae pneumonia and correlates with phagocytosis by neutrophils during early pathogenesis.

    Science.gov (United States)

    Xu, Qingfu; Surendran, Naveen; Verhoeven, David; Klapa, Jessica; Ochs, Martina; Pichichero, Michael E

    2015-02-18

    Due to the fact that current polysaccharide-based pneumococcal vaccines have limited serotype coverage, protein-based vaccine candidates have been sought for over a decade to replace or complement current vaccines. We previously reported that a trivalent Pneumococcal Protein recombinant Vaccine (PPrV), showed protection against pneumonia and sepsis in an infant murine model. Here we investigated immunological correlates of protection of PPrV in the same model. C57BL/6J infant mice were intramuscularly vaccinated at age 1-3 weeks with 3 doses of PPrV, containing pneumococcal histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and detoxified pneumolysin mutant PlyD1. 3-4 weeks after last vaccination, serum and lung antibody levels to PPrV components were measured, and mice were intranasally challenged with a lethal dose of Streptococcus pneumoniae (Spn) serotype 6A. Lung Spn bacterial burden, number of neutrophils and alveolar macrophages, phagocytosed Spn by granulocytes, and levels of cytokines and chemokines were determined at 6, 12, 24, and 48h after challenge. PPrV vaccination conferred 83% protection against Spn challenge. Vaccinated mice had significantly elevated serum and lung antibody levels to three PPrV components. In the first stage of pathogenesis of Spn induced pneumonia (6-24h after challenge), vaccinated mice had lower Spn bacterial lung burdens and more phagocytosed Spn in the granulocytes. PPrV vaccination led to lower levels of pro-inflammatory cytokines IL-6, IL-1β, and TFN-α, and other cytokines and chemokines (IL-12, IL-17, IFN-γ, MIP-1b, MIP-2 and KC, and G-CSF), presumably due to a lower lung bacterial burden. Trivalent PPrV vaccination results in increased serum and lung antibody levels to the vaccine components, a reduction in Spn induced lethality, enhanced early clearance of Spn in lungs due to more rapid and thorough phagocytosis of Spn by neutrophils, and correspondingly a reduction in lung inflammation

  6. Cardiomyocyte-Specific Ablation of Med1 Subunit of the Mediator Complex Causes Lethal Dilated Cardiomyopathy in Mice.

    Science.gov (United States)

    Jia, Yuzhi; Chang, Hsiang-Chun; Schipma, Matthew J; Liu, Jing; Shete, Varsha; Liu, Ning; Sato, Tatsuya; Thorp, Edward B; Barger, Philip M; Zhu, Yi-Jun; Viswakarma, Navin; Kanwar, Yashpal S; Ardehali, Hossein; Thimmapaya, Bayar; Reddy, Janardan K

    2016-01-01

    Mediator, an evolutionarily conserved multi-protein complex consisting of about 30 subunits, is a key component of the polymerase II mediated gene transcription. Germline deletion of the Mediator subunit 1 (Med1) of the Mediator in mice results in mid-gestational embryonic lethality with developmental impairment of multiple organs including heart. Here we show that cardiomyocyte-specific deletion of Med1 in mice (csMed1-/-) during late gestational and early postnatal development by intercrossing Med1fl/fl mice to α-MyHC-Cre transgenic mice results in lethality within 10 days after weaning due to dilated cardiomyopathy-related ventricular dilation and heart failure. The csMed1-/- mouse heart manifests mitochondrial damage, increased apoptosis and interstitial fibrosis. Global gene expression analysis revealed that loss of Med1 in heart down-regulates more than 200 genes including Acadm, Cacna1s, Atp2a2, Ryr2, Pde1c, Pln, PGC1α, and PGC1β that are critical for calcium signaling, cardiac muscle contraction, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy and peroxisome proliferator-activated receptor regulated energy metabolism. Many genes essential for oxidative phosphorylation and proper mitochondrial function such as genes coding for the succinate dehydrogenase subunits of the mitochondrial complex II are also down-regulated in csMed1-/- heart contributing to myocardial injury. Data also showed up-regulation of about 180 genes including Tgfb2, Ace, Atf3, Ctgf, Angpt14, Col9a2, Wisp2, Nppa, Nppb, and Actn1 that are linked to cardiac muscle contraction, cardiac hypertrophy, cardiac fibrosis and myocardial injury. Furthermore, we demonstrate that cardiac specific deletion of Med1 in adult mice using tamoxifen-inducible Cre approach (TmcsMed1-/-), results in rapid development of cardiomyopathy and death within 4 weeks. We found that the key findings of the csMed1-/- studies described above are highly reproducible in TmcsMed1-/- mouse heart

  7. Radiation damage of uranium

    International Nuclear Information System (INIS)

    Lazarevic, Dj.

    1966-11-01

    Study of radiation damage covered the following: Kinetics of electric resistance of uranium and uranium alloy with 1% of molybdenum dependent on the second phase and burnup rate; Study of gas precipitation and diffusion of bubbles by transmission electron microscopy; Numerical analysis of the influence of defects distribution and concentration on the rare gas precipitation in uranium; study of thermal sedimentation of uranium alloy with molybdenum; diffusion of rare gas in metal by gas chromatography method

  8. Cavitation damage of ceramics

    International Nuclear Information System (INIS)

    Kovalenko, V.I.; Marinin, V.G.

    1988-01-01

    Consideration is given to results of investigation of ceramic material damage under the effect of cavitation field on their surface, formed in water under the face of exponential concentrator, connected with ultrasonic generator UZY-3-0.4. Amplitude of vibrations of concentrator face (30+-2)x10 -6 m, frequency-21 kHz. It was established that ceramics resistance to cavitation effect correlated with the product of critical of stress intensity factor and material hardness

  9. Nondestructive damage detection and evaluation technique for seismically damaged structures

    Science.gov (United States)

    Adachi, Yukio; Unjoh, Shigeki; Kondoh, Masuo; Ohsumi, Michio

    1999-02-01

    The development of quantitative damage detection and evaluation technique, and damage detection technique for invisible damages of structures are required according to the lessons from the 1995 Hyogo-ken Nanbu earthquake. In this study, two quantitative damage sensing techniques for highway bridge structures are proposed. One method is to measure the change of vibration characteristics of the bridge structure. According to the damage detection test for damaged bridge column by shaking table test, this method can successfully detect the vibration characteristic change caused by damage progress due to increment excitations. The other method is to use self-diagnosis intelligent materials. According to the reinforced concrete beam specimen test, the second method can detect the damage by rupture of intelligent sensors, such as optical fiber or carbon fiber reinforced plastic rod.

  10. The effect of dithiothreitol on radiation-induced genetic damage in Arabidopsis thaliana (L) Heynh

    International Nuclear Information System (INIS)

    Dellaert, L.M.W.

    1980-01-01

    A study was made on the effect of dithiothreitol (DTT; present during irradiation) on M 1 ovule sterility, M 2 embryonic lethals, M 2 chlorophyll mutants and M 2 viable mutants induced with fast neutrons or X-rays in Arabidopsis thaliana. DTT provides considerable protection against both fast-neutron and X-ray induced genetic damage. However, a higher protection was observed against M 1 ovule sterility, than against embryonic lethals, chlorophylls and viable mutants. This implies a significant DTT-induced spectral shift (0.01 < p < 0.05), i.e. a shift in the relative frequencies of the different genetic parameters. This spectral shift is explained on the basis of a specific DTT protection against radiation-induced strand breaks, and by differences in the ratio strand breaks/base damage for the genetic parameters concerned, i.e. a higher ratio for ovule sterility than for the other parameters. The induction of the genetic damage by ionizing radiation, either with or without DTT, is described by a mathematical model, which includes both strand breaks and base damage. The model shows that the resolving power of a test for a 'mutation'spectral shift depends on the relative values of the strandbreak reduction factor of -SH compounds and on the ratio strand breaks/base damage of the genetic parameters. For each genetic parameter the DTT damage reduction factor (DRF) is calculated per irradiation dose, and in addition the average (over-all doses) ratio strand breaks/base damage. (orig.)

  11. 76 FR 17439 - Nonessential Experimental Populations of Gray Wolves in the Northern Rocky Mountains; Lethal Take...

    Science.gov (United States)

    2011-03-29

    ... nonessential experimental population areas for the gray wolf under section 10(j) of the ESA: the Yellowstone...-0000-C3] Nonessential Experimental Populations of Gray Wolves in the Northern Rocky Mountains; Lethal Take of Wolves in the West Fork Elk Management Unit of Montana; Draft Environmental Assessment AGENCY...

  12. 76 FR 7875 - Nonessential Experimental Populations of Gray Wolves in the Northern Rocky Mountains; Lethal Take...

    Science.gov (United States)

    2011-02-11

    ... the central Idaho and Yellowstone area nonessential experimental populations of gray wolves in the...-0000-C3] Nonessential Experimental Populations of Gray Wolves in the Northern Rocky Mountains; Lethal Take of Wolves in the Lolo Elk Management Zone of Idaho; Draft Environmental Assessment AGENCY: Fish...

  13. When a Fly Has to Fly to Reproduce: Selection against Conditional Recessive Lethals in "Drosophila"

    Science.gov (United States)

    Plunkett, Andrea D.; Yampolsky, Lev Y.

    2010-01-01

    We propose an experimental model suitable for demonstrating allele frequency change in Drosophila melanogaster populations caused by selection against an easily scorable conditional lethal, namely recessive flightless alleles such as apterous and vestigial. Homozygotes for these alleles are excluded from reproduction because the food source used…

  14. [Gunshot wounds caused by non-lethal ammunition on the porcine model post-mortem].

    Science.gov (United States)

    Jabrocký, Peter; Pivko, Juraj; Vondráková, Mária; Tažký, Boris

    2013-10-01

    In this article we focus on the effects of so called non-lethal ammunition. We studied possible mechanism of firearm injury formation as a consequence of using firearm on the body, to present a more comprehensive material in wound ballistics. We pointed out possible actions of a projectile causes on human, respectively other animal organisms, as well as to a manner in which an injury is caused by rifles or shotguns using non-lethal ammunition with rubber projectiles. In the experiment, we have focused on macroscopic analysis of the tissue penetrated by a rubber projectile fired from a long firearm and pump-action shotgun while focusing on the anatomical-morphological analysis of entry wounds to determine the effectiveness respectively, the wounding potential of the projectile. The results of the experiment based on the macroscopic analysis of entry wounds, cavities and exit wounds, show that when a rubber projectile penetrates the body it causes loss of the tissue (i.e. the minus effect) and mechanical disruption of the tissue similar to lethal projectile. Based on the measures and ballistic computations we concluded that in specific cases, like for example in a close range hit, a penetration of vital organs can cause serious or even lethal injuries.

  15. The Influence of criminal history on the likelihood of committing lethal versus nonlethal violence

    NARCIS (Netherlands)

    Ganpat, Soenita M.; Liem, Marieke; van der Leun, Joanne; Nieuwbeerta, Paul

    2014-01-01

    This study focuses on the criminal history of serious violent offenders. Our aim is to determine: (a) to what extent the criminal history of lethally violent offenders differs from nonlethally violent offenders and (b) to what extent one's criminal history influences the likelihood that violence

  16. Myxoma virus M130R is a novel virulence factor required for lethal myxomatosis in rabbits.

    Science.gov (United States)

    Barrett, John W; Werden, Steven J; Wang, Fuan; McKillop, William M; Jimenez, June; Villeneuve, Danielle; McFadden, Grant; Dekaban, Gregory A

    2009-09-01

    Myxoma virus (MV) is a highly lethal, rabbit-specific poxvirus that induces a disease called myxomatosis in European rabbits. In an effort to understand the function of predicted immunomodulatory genes we have deleted various viral genes from MV and tested the ability of these knockout viruses to induce lethal myxomatosis. MV encodes a unique 15 kD cytoplasmic protein (M130R) that is expressed late (12h post infection) during infection. M130R is a non-essential gene for MV replication in rabbit, monkey or human cell lines. Construction of a targeted gene knockout virus (vMyx130KO) and infection of susceptible rabbits demonstrate that the M130R knockout virus is attenuated and that loss of M130R expression allows the rabbit host immune system to effectively respond to and control the lethal effects of MV. M130R expression is a bona fide poxviral virulence factor necessary for full and lethal development of myxomatosis.

  17. Proteomic characterization of a temperature-sensitive conditional lethal in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Pedersen, Kamilla Sofie; Codrea, M.C; Vermeulen, Corneel

    2010-01-01

    Genetic variation that is expressed only under specific environmental conditions can contribute to additional adverse effects of inbreeding if environmental conditions change. We present a proteomic characterization of a conditional lethal found in an inbred line of Drosophila melanogaster. The l...

  18. Differential replication of foot-and-mouth disease viruses in mice determine lethality

    Science.gov (United States)

    Adult C57BL/6J mice have been used to study foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a let...

  19. Lethal Encephalitozoon cuniculi genotype III infection in Steppe lemmings (Lagurus lagurus)

    Czech Academy of Sciences Publication Activity Database

    Hofmannová, L.; Sak, Bohumil; Jekl, V.; Mináriková, A.; Škorič, M.; Kváč, Martin

    2014-01-01

    Roč. 205, 1-2 (2014), s. 357-360 ISSN 0304-4017 R&D Projects: GA ČR(CZ) GAP505/11/1163 Institutional support: RVO:60077344 Keywords : Encephalitozoon cuniculi genotype III * Steppe lemmings * Lethal infection * PCR * Histology Subject RIV: EG - Zoology Impact factor: 2.460, year: 2014

  20. Non-lethality in reality: a defence technology assessment of its political and military potential

    NARCIS (Netherlands)

    Orbons, J.B.J.

    2013-01-01

    Het gebruik van non-lethal weapons (NLW’s, niet-dodelijke wapens zoals traangas en plastic kogels) bij het winnen van hearts and minds van de bevolking is alleen effectief als de bevolking een politiek perspectief wordt geboden. Zonder een aanvaardbaar politiek perspectief worden NLW’s toenemend

  1. Mutagenic Potential of Nitroguanidine in the Drosophila melanogaster Sex-Linked Recessive Lethal Test

    Science.gov (United States)

    1988-07-01

    Security Classification) Mtutagenic potential of nitroguan idine in the Drosophila melano- gaster sex-linked recessive lethal test 12. PERSONAL AUTHOR(S...Frederick, MD 21701-5012 Commander Commandant US Army Environmental Hygine Academy of Health Sciences. US Army Agency ATTN: AHS-CDM ATTN: Librarian, HSDH

  2. Sub-lethal effects of neonicitinoids on the alfalfa leafcutter bee, Megachile rotundata

    Science.gov (United States)

    Neonicotinoids are commonly used pesticides in U.S. agriculture. For many beneficial insect species, lethal effects of neonicotinoids are well-documented; however, much less is known about sublethal exposure. The alfalfa leaf cutter bee Megachile rotundata is a managed pollinator that constructs com...

  3. Radiation injuries of plasmatic membrane and lethal action of radiation on cells

    Energy Technology Data Exchange (ETDEWEB)

    Fomenko, B S; Akoev, I G [AN SSSR, Pushchino-na-Oke. Inst. Biologicheskoj Fiziki

    1984-01-01

    Data on modification of procaryotes and eukaryotes cell injuries using preparations not penetrating into cells and also membrane-specific drugs localized in cells in a lipid phase are generalized. A conclusion is drawn that radiation injuries of plasmatic membrane of prokaryotes and eukaryotes contribute considerably to lethal action of radiation on cells.

  4. Crowd Confrontation and Non-Lethal Weapons: A Literature Review and Conceptual Model

    Science.gov (United States)

    2008-03-01

    counterterrorist situations, when there is a need to incapacitate one or several terrorists operating from within a larger group of harmless individuals. In such...weapons include some microbes capable of degrading fuel, an herbicide (“Agent Orange”), as well as non-lethal anti-personnel mines. It is concluded

  5. The Slimeball: The Development of Broad-Scale Maritime Non-Lethal Weaponry

    Science.gov (United States)

    2009-04-01

    commercial applications from waste management to horticulture to baby diapers. By some estimates, it can absorb one thousand times its volume in water...www.nytimes.com/2008/10/31/world/africa/31pirates.html?pagewanted=1&_r=1. Goolsby, Tommy D. “Aqueous Foam as a Less-Than-Lethal Technology for Prison

  6. Crowd Behavior, Crowd Control, and the Use of Non-Lethal Weapons

    Science.gov (United States)

    2001-01-01

    that U.S. forces know these repertoires of actions when they operate in different cultures. Dr. Waddington provided the example of the Zulu tribe in...6 The History of Hostile Crowds and Riots...Mobs, and Non-lethal Weapons,” by Lieutenant Sid Heal. The History of Hostile Crowds and Riots Dr. Wendy Gilpin conducted background research on hostile

  7. Interaction of radiation, Dihydroxyanthraquinone, and Adriamycin on the induction of acute lethality in mice

    International Nuclear Information System (INIS)

    Kimler, B.F.; Cox, G.G.; Reddy, E.K.

    1984-01-01

    The acute lethality induced by combinations of radiation, Dihydroxyanthraquinone (DHAQ), and Adriamycin (ADR) was investigated in mice. Whole-body irradiation produced acute lethality, with an LD-50/30 of approximately 6.5 Gy. ADR and DHAQ produced LD-50/30's of 14 and 4 mg/kg, respectively. When 10 mg/kg doses were fractionated into 5 x 2 mg/kg daily doses, both drugs were equally or more efficient at producing mortality, 90% by day 30. When 4 Gy radiation was combined with 5 mg/kg ADR or 5 mg/kg DHAQ, a response no greater than that produced by drug alone was obtained. However, when 5 mg/kg ADR was administered concomitantly with 5 mg/kg DHAQ, there was a less-than-additive induction of lethality, resulting in only 21% mortality by day 20. ADR and DHAQ (at doses of 5 mg/kg) were combined but with a 1 day interval between drugs, the protective effect was lost and animals died earlier than after either agent alone. At present, no definite explanation is available for this unusual protective effect of ADR against acute lethality induced by DHAQ

  8. Radiation injuries of plasmatic membrane and lethal action of radiation on cells

    International Nuclear Information System (INIS)

    Fomenko, B.S.; Akoev, I.G.

    1984-01-01

    Data on modification of procaryotes and eukaryotes cell injuries using preparations not penetrating into cells and also membrane-specific drugs localized in cells in a lipid phase are generalized. A conclusion is drawn that radiation injuries of plasmatic membrane of prokaryotes and eukaryotes contribute considerably to lethal action of radiation on cells

  9. Soil physical properties regulate lethal heating during burning of woody residues

    Science.gov (United States)

    Matt Busse; Carol Shestak; Ken Hubbert; Eric Knapp

    2010-01-01

    Temperatures well in excess of the lethal threshold for roots (60°C) have been measured in forest soils when woody fuels are burned. Whether this heat pulse is strongly moderated by soil moisture or soil texture is not fully understood, however. We measured soil heat profi les during 60 experimental burns, identifying changes in maximum soil temperature and heat...

  10. Control of lethal browning by using ascorbic acid on shoot tip ...

    African Journals Online (AJOL)

    The use of ascorbic acid during explants preparation and the effect of different concentrations of ascorbic acid in controlling lethal browning and survival of the explants in local banana cv. Mzuzu banana were investigated. The explants were taken from young suckers. The shoot tips were cultured on Murashige and Skoog's ...

  11. Models for pulmonary lethality and morbidity after irradiation from internal and external sources

    International Nuclear Information System (INIS)

    Scott, B.R.; Filipy, R.E.; Hahn, E.F.

    1989-05-01

    This report provides a hazard-function model for estimating the risk of death from radiation pneumonitis and/or pulmonary fibrosis following a light-water nuclear power accident. A similar model is also provided for estimating the prevalence of respiratory functional morbidity among those that survive death from acute effects. Hazard-function models for lethality and for morbidity were constructed using the cumulative hazard estimator H, which is related to the risk estimator R through the equation R = 1-exp(-H). The estimator H can be calculated using information provided in the report. The method of calculation depends on the exposure scenario. In general, the total normalized dose X for lethality or for morbidity is calculated. For lethality, X = 1 corresponds to a median lethal dose (LD 50 ); for morbidity, X = 1 corresponds to a median effective dose (ED 50 ). H is related to X by the equation H = 1n(2)X/sup V/, where V depends on the type of radiation (or radiations) involved. Contributions to X can arise from each of two main modes of exposure: (1) brief exposure of the lung, at a relatively high dose rate, to mainly external gammas, followed by (2) chronic internal alpha, and/or beta, and/or gamma irradiation of the lung. Equations are provided for calculating the contributions to X from both modes of exposure. 73 refs., 16 figs., 2 tabs

  12. Comparative study of different sexis mutability: recessive sex-linked and dominant lethals in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Vatti, K.V.; Dzhaparidze, L.A.; Mamon, L.A.

    1980-01-01

    The frequency of recessive sex-linked lethal mutations (RSLLM) and those realizing in embryogenesis of dominant lethals, which form in oo- and spermatogenesis of Drosophila and fly productivity under the effect of X-rays and N-nitroso-N methylourea (NMU), is studied. In the case of effect of both mutagens RSLLM form in spermatocytes with higher frequency as compared with oocytes. Dominant lethal mutations (DLM) during irradiation are also often registered in spermatocytes. NMU induces DLM in mitotic male cells with a very high frequency but is not effective during the effect on oocytes. When both mutagens affect males and X-rays affect females, the decrease of productivity is mainly conditioned by DLM. As NMU does not induce DLM in females realizing in embryogenesis but reduces productivity, a later lethal realization connected with their different nature is supposed. Differences in mole and female mutability found in the course of X-ray and NMU effect are discussed in connection with peculiarities of their mitotic cells and the nature of effect of mutagens applied [ru

  13. 9 CFR 430.4 - Control of Listeria monocytogenes in post-lethality exposed ready-to-eat products.

    Science.gov (United States)

    2010-01-01

    ... post-lethality exposed ready-to-eat products. 430.4 Section 430.4 Animals and Animal Products FOOD... Control of Listeria monocytogenes in post-lethality exposed ready-to-eat products. (a) Listeria... comes into direct contact with a food contact surface which is contaminated with L. monocytogenes. (b...

  14. Military Robotics and Collateral Damage

    National Research Council Canada - National Science Library

    Kott, Robert Douglass ;Alexander

    2004-01-01

    .... Such concepts raise important questions in terms of their impact on collateral damage. In a broader context, western warfare in general places a continuously growing emphasis on issues of collateral damage...

  15. A comparative study of proliferative nodules and lethal melanomas in congenital nevi from children.

    Science.gov (United States)

    Yélamos, Oriol; Arva, Nicoleta C; Obregon, Roxana; Yazdan, Pedram; Wagner, Annette; Guitart, Joan; Gerami, Pedram

    2015-03-01

    Differentiating proliferative nodules (PNs) from melanomas arising in congenital nevi (CN) is a considerable challenge for dermatopathologists. Most of the specimens dermatopathologists assess that deal with this differential diagnosis involve proliferations of melanocytes arising in the dermis. In this study, we compare the clinical, histologic, and molecular findings of these 2 conditions. In our database, we found 22 examples of PNs arising in the dermis of CN and 2 cases of lethal melanomas arising from the dermis/epidermis of CN of children. Importantly, we found that among dermal melanocytic proliferations arising from CN in children, PNs are far more common than lethal melanomas. Clinically, multiplicity of lesions favored a diagnosis of PNs, whereas ulceration was infrequent in PNs compared with lethal melanomas. Histologically, PNs showed several distinct patterns including expansile nodules of epithelioid melanocytes with mitotic counts lower than that seen in the melanomas (1.67 vs. 12.5 mitoses/mm), a small round blue cell pattern often highly mitotically active, neurocristic-like, blue nevus-like, a nevoid melanoma-like pattern, or an undifferentiated spindle cell pattern. The lethal melanomas both featured expansile nodules of epithelioid melanocytes with high mitotic counts (range, 5 to 20 mitoses/mm) and an ulcerated overlying epidermis. At the molecular level, the PNs showed mostly whole chromosomal copy number aberrations, which in some cases were accompanied by rare partial chromosomal aberrations, whereas both lethal melanomas showed highly elevated copy number aberrations involving 6p25 without gains of the long arm of chromosome 6.

  16. Strong lethality and teratogenicity of strobilurins on Xenopus tropicalis embryos: Basing on ten agricultural fungicides

    International Nuclear Information System (INIS)

    Li, Dan; Liu, Mengyun; Yang, Yongsheng; Shi, Huahong; Zhou, Junliang; He, Defu

    2016-01-01

    Agricultural chemical inputs have been considered as a risk factor for the global declines in amphibian populations, yet the application of agricultural fungicides has increased dramatically in recent years. Currently little is known about the potential toxicity of fungicides on the embryos of amphibians. We studied the effects of ten commonly used fungicides (four strobilurins, two SDHIs, two triazoles, fludioxonil and folpet) on Xenopus tropicalis embryos. Lethal and teratogenic effects were respectively examined after 48 h exposure. The median lethal concentrations (LC50s) and the median teratogenic concentrations (TC50s) were determined in line with actual exposure concentrations. These fungicides except two triazoles showed obvious lethal effects on embryos; however LC50s of four strobilurins were the lowest and in the range of 6.81–196.59 μg/L. Strobilurins, SDHIs and fludioxonil induced severe malformations in embryos. Among the ten fungicides, the lowest TC50s were observed for four strobilurins in the range of 0.61–84.13 μg/L. The teratogenicity shared similar dose–effect relationship and consistent phenotypes mainly including microcephaly, hypopigmentation, somite segmentation and narrow fins. The findings indicate that the developmental toxicity of currently-used fungicides involved with ecologic risks on amphibians. Especially strobilurins are highly toxic to amphibian embryos at μg/L level, which is close to environmentally relevant concentrations. - Highlights: • Effects of ten agricultural fungicides were tested on Xenopus tropicalis embryos. • Strobilurin fungicides showed strong lethal and teratogenic effects on embryos. • Lowest LC50 and TC50 were observed for strobilurins in ten fungicides. • μg/L level of toxic concentrations for strobilurins was environmentally relevant. • Teratogenicity shared similar dose–effect relationship and main phenotypes. - Strobilurins induced strong lethality and teratogenicity on Xenopus

  17. Sensitization of ultraviolet radiation damage in bacteria and mammalian cells

    International Nuclear Information System (INIS)

    Fisher, G.J.; Watts, M.E.; Patel, K.B.; Adams, G.E.

    1978-01-01

    Bacteria (Serratia marcescens) and mammalian cells (Chinese hamsters V79-379A) were irradiated in monolayers with ultraviolet light at 254 nm or 365 nm in the presence or absence of radiosensitizing drugs. At 254 nm, killing is very efficient (Dsub(37) approximately equal 1 J m -2 exposure, or approximately equal 6 x 10 4 photons absorbed by DNA per bacterium), and sensitizers have no effect. At 365 nm, cells are not killed in buffer, but are inactivated in the presence of nifurpipone or misonidazole. Lethal exposures (approximately equal 5 x 10 3 J m -2 at 10 nM misonidazole) correspond to about 10 7 photons absorbed by sensitizer molecules per bacterium. Toxicity of stable photoproducts of the drugs is not involved, nor is oxygen required. Hence the transient species formed by photo-excitation of radiosensitizer molecules are capable of killing cells in the absence of other types of radiation damage. (author)

  18. Repair of uv damaged DNA in systemic lupus erythematosus. [Mice

    Energy Technology Data Exchange (ETDEWEB)

    Beighlie, D J; Teplitz, R L

    1975-06-01

    The NZB NZW hybrid mouse is an animal model of human systemic lupus erythematosus (SLE). Two breeding schemes were devised using NZB, NZW, B/W, and CBA mice, which permit definitive decisions regarding genetic and/or viral origin of the disease. It is proposed that at least two factors must be involved: a genetic abnormality producing hyper-responsiveness to nucleic acid antigens, and a DNA repair defect which results in liberation of DNA and RNA when cells are lethally injured. Evidence is presented for a DNA repair deficit in human SLE lymphocytes following in vitro irradiation with ultraviolet (uv) light. Lymphocytes from adult New Zealand and control mice were found to lack normal amounts of endonuclease necessary for repairing uv damage.

  19. Radiation damage in semiconductor detectors

    International Nuclear Information System (INIS)

    Kraner, H.W.

    1981-12-01

    A survey is presented of the important damage-producing interactions in semiconductor detectors and estimates of defect numbers are made for MeV protons, neutrons and electrons. Damage effects of fast neutrons in germanium gamma ray spectrometers are given in some detail. General effects in silicon detectors are discussed and damage constants and their relationship to leakage current is introduced

  20. Protective roles of bacterioruberin and intracellular KCl in the resistance of Halobacterium salinarium against DNA-damaging agents

    International Nuclear Information System (INIS)

    Shahmohammadi, H.R.; Asgarani, E.; Terato, Hiroaki; Saito, Takeshi; Ohyama, Yoshihiko; Gekko, Kunihiko; Yamamoto, Osamu; Ide, Hiroshi

    1998-01-01

    Halobacterium salinarium, a member of the extremely halophilic archaebacteria, contains a C 50 -carotenoid namely bacterioruberin. We have previously reported the high resistance of this organism against the lethal actions of DNA-damaging agents including ionizing radiation and ultraviolet light (UV). In this study, we have examined whether bacterioruberin and the highly concentrated salts in this bacterium play protective roles against the lethal actions of ionizing radiation, UV, hydrogen peroxide, and mitomycin-C (MMC). The colourless mutant of H. salinarium deficient in bacterioruberin was more sensitive than the red-pigmented wild-type to all tested DNA-damaging agents except MMC. Circular dichroism (CD) spectra of H. salinarium chromosomal DNA at various concentrations of KCl (0-3.5 M) were similar to that of B-DNA, indicating that no conformational changes occurred as a result of high salt concentrations. However, DNA strand-breaks induced by ionizing radiation were significantly reduced by the presence of either bacterioruberin or concentrated KCl, presumably due to scavenging of free radicals. These results suggest that bacterioruberin and intracellular KCl of H. salinarium protect this organism against the lethal effects of oxidative DNA-damaging agents. (author)