Induction of dominant lethals in male mice treated as embryos with 35S

International Nuclear Information System (INIS)

Reddy, K.S.; Reddy, P.P.; Reddy, O.S.

1980-01-01

Pregnant female mice were injected (ip) with 20 μCi of 35 S or 0.5 ml of saline (control) on 3.5 day of gestation. The animals were allowed to litter and the (CBA female x C 3 H/He male) F 1 males treated as embryos were tested at maturity (8-10 weeks) for dominant lethal incidence. Each male was mated to 3 untreated virgin females for a period of 3 weeks. The pregnant animals were killed at mid gestation and the uterine contents and corpora lutea were examined. There was a significant increase in the frequency of dominant lethals both at pre- and post-implantation stages in the treated group when compared to controls. As a result a significant increase in dead implantations/female and reduction in live implantations/female were noticed in the treated group. Thus the results clearly delineate the genetic effects of sulfur-35 in mice. (auth.)

Mutagenicity assayed by dominant lethality testing in mice fed a combined gamma-irradiated diet

International Nuclear Information System (INIS)

Rupova, I.; Katsarova, Ts.; Bajrakova, A.; Baev, I.; Tencheva, S.

1980-01-01

Mice fed a combined gamma-irradiated diet were examined for a mutagenic effect using the dominant lethality test. Their feed contained the following irradiated ingredients: 20% maize, 10% dried plums, and 5% walnut kernels. Taking into account cycle duration in spermatogenesis and oogenesis, males were fed this special diet throughout 56 days, and females throughout 21 days. The experiments involved three animal groups: (1) fed the special diet containing irradiated ingredients; (2) fed the special diet but with the ingredients nonirradiated; and (3) fed standard vivarium diet. Matings to provide the first generation were between one parent fed the special diet and a partner fed standard diet. With an adequate number of implants examined on day 16 of gestation, embryonic death rate was not found to be increased; hence, induction of dominant lethality from consumption of irradiated diet failed to be demonstrated

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.

The effects of radiation dose-rate and quality on the induction of dominant lethals in mouse spermatids

International Nuclear Information System (INIS)

Searle, A.G.; Beechey, G.V.

1981-01-01

Hybrid male mice were given 3 Gy (300 rad) doses of X- or γ-irradiation at dose-rates of either 0.6 or 0.002 Gy/min for each radiation. Germ-cells treated as spermatids were tested for dominant lethality. Effects on spermatogonia were evaluated by studying testis-weight, sperm-count and sperm abnormalities. The rate of induction of dominant lethal mutations was 2.1 times as high after acute X-irradiation as after protracted γ-irradiation. Most of this difference resulted from the change in radiation quality, since the relative effectiveness of X- versus γ-irradiation was 1.9 at low and 1.6 at high dose rates. For each radiation, however, fewer dominant lethals were induced at low dose-rates than at high (low/high ratios of 0.8 and 0.9 respectively) although differences did not reach a significant level. There were no statistically significant effects of dose rate on testis-weight of sperm-count in the X-ray series, but there were significantly less severe effects on both with protraction of the γ-irradiation. Evidence for effects of radiation quality on these characters was conflicting. Frequencies of abnormal spermatozoa were markedly increased 7 weeks after irradiation but there were no consistent effects of radiation intensity or quality. (orig.)

What Are Reasons for the Large Gender Differences in the Lethality of Suicidal Acts? An Epidemiological Analysis in Four European Countries.

Science.gov (United States)

Mergl, Roland; Koburger, Nicole; Heinrichs, Katherina; Székely, András; Tóth, Mónika Ditta; Coyne, James; Quintão, Sónia; Arensman, Ella; Coffey, Claire; Maxwell, Margaret; Värnik, Airi; van Audenhove, Chantal; McDaid, David; Sarchiapone, Marco; Schmidtke, Armin; Genz, Axel; Gusmão, Ricardo; Hegerl, Ulrich

2015-01-01

In Europe, men have lower rates of attempted suicide compared to women and at the same time a higher rate of completed suicides, indicating major gender differences in lethality of suicidal behaviour. The aim of this study was to analyse the extent to which these gender differences in lethality can be explained by factors such as choice of more lethal methods or lethality differences within the same suicide method or age. In addition, we explored gender differences in the intentionality of suicide attempts. Methods. Design: Epidemiological study using a combination of self-report and official data. Setting: Mental health care services in four European countries: Germany, Hungary, Ireland, and Portugal. Data basis: Completed suicides derived from official statistics for each country (767 acts, 74.4% male) and assessed suicide attempts excluding habitual intentional self-harm (8,175 acts, 43.2% male). Main Outcome Measures and Data Analysis. We collected data on suicidal acts in eight regions of four European countries participating in the EU-funded "OSPI-Europe"-project (www.ospi-europe.com). We calculated method-specific lethality using the number of completed suicides per method * 100 / (number of completed suicides per method + number of attempted suicides per method). We tested gender differences in the distribution of suicidal acts for significance by using the χ2-test for two-by-two tables. We assessed the effect sizes with phi coefficients (φ). We identified predictors of lethality with a binary logistic regression analysis. Poisson regression analysis examined the contribution of choice of methods and method-specific lethality to gender differences in the lethality of suicidal acts. Suicidal acts (fatal and non-fatal) were 3.4 times more lethal in men than in women (lethality 13.91% (regarding 4106 suicidal acts) versus 4.05% (regarding 4836 suicidal acts)), the difference being significant for the methods hanging, jumping, moving objects, sharp objects

What Are Reasons for the Large Gender Differences in the Lethality of Suicidal Acts? An Epidemiological Analysis in Four European Countries.

Directory of Open Access Journals (Sweden)

Roland Mergl

Full Text Available In Europe, men have lower rates of attempted suicide compared to women and at the same time a higher rate of completed suicides, indicating major gender differences in lethality of suicidal behaviour. The aim of this study was to analyse the extent to which these gender differences in lethality can be explained by factors such as choice of more lethal methods or lethality differences within the same suicide method or age. In addition, we explored gender differences in the intentionality of suicide attempts.Methods. Design: Epidemiological study using a combination of self-report and official data. Setting: Mental health care services in four European countries: Germany, Hungary, Ireland, and Portugal. Data basis: Completed suicides derived from official statistics for each country (767 acts, 74.4% male and assessed suicide attempts excluding habitual intentional self-harm (8,175 acts, 43.2% male. Main Outcome Measures and Data Analysis. We collected data on suicidal acts in eight regions of four European countries participating in the EU-funded "OSPI-Europe"-project (www.ospi-europe.com. We calculated method-specific lethality using the number of completed suicides per method * 100 / (number of completed suicides per method + number of attempted suicides per method. We tested gender differences in the distribution of suicidal acts for significance by using the χ2-test for two-by-two tables. We assessed the effect sizes with phi coefficients (φ. We identified predictors of lethality with a binary logistic regression analysis. Poisson regression analysis examined the contribution of choice of methods and method-specific lethality to gender differences in the lethality of suicidal acts.Suicidal acts (fatal and non-fatal were 3.4 times more lethal in men than in women (lethality 13.91% (regarding 4106 suicidal acts versus 4.05% (regarding 4836 suicidal acts, the difference being significant for the methods hanging, jumping, moving objects, sharp

X-ray induced dominant lethal mutations in mature and immature oocytes of guinea-pigs and golden hamsters

International Nuclear Information System (INIS)

Cox, B.D.; Lyon, M.F.

1975-01-01

The induction of dominant lethal mutations by doses of 100-400 rad X-rays in oocytes of the guinea-pig and golden hamster was studied using criteria of embryonic mortality. For both species higher yields were obtained from mature than from immature oocytes. Data on fertility indicated that in the golden hamster immature oocytes were more sensitive to killing by X-rays than mature oocytes but that the converse was true in the guinea-pig. The dose-response relationship for mutation to dominant lethals in pre-ovulatory oocytes of guinea-pigs and golden hamsters was linear, both when based on pre- and post-implantation loss only. The rate per unit dose was higher for the golden hamster, and the old golden hamsters were possibly slightly more sensitive than young ones

Influence on DNA repair inhibitors on dominant lethal factors after gamma irradiation

International Nuclear Information System (INIS)

Engl, D.

1978-01-01

Experiments were performed in order to test the hypothesis of a correlation between ionizing radiation and DNA repair inhibition under in vivo conditions. In a biometrically planned dominant lethal test on mice, the repair inhibition on the male gametes by butazolidine, TWEEN 80 and vitamin A was studied after gamma irradiation at 20 rad/10 min. No effect was observed in the case of butazolidine and TWEEN 80, whereas the influence of a high concentration of vitamin A (1 million IE/kg) was just at the statistical significancy threshold. (G.G.)

35S induced dominant lethals in male germ cells of mouse

International Nuclear Information System (INIS)

Satyanarayana Reddy, K.; Reddy, P.D.; Reddi, O.S.

1977-01-01

(CBA female x C 3 H/He male) F 1 males born to 35 S (20 μCi) treated animals during major organogenesis period were tested for dominant lethal mutations at maturity. The pre-implantation loss showed an increase from 6.88% in the control to 10.92% in 35 S treated animals. Similarly the post-implantation loss has increased from 3.96% (control) to 7.40%. As a result of the increased pre- and post-losses the total loss showed a significant increase (17.51%) in F 1 males born to 35 S treated animals when compared to controls (10.57%). Thus the results clearly show that 35 S is mutagenic in male germ cells of mouse. (author)

Insect radiosensitivity: dose curves and dose-fractionation studies of dominant lethal mutations in the mature sperm of 4 insect species

International Nuclear Information System (INIS)

LaChance, L.E.; Graham, C.K.

1984-01-01

Males of 4 species of insects: Musca domestica L. (housefly) (Diptera), Oncopeltus fasciatus (Dallas) (milkweed bug) (Hemiptera), Anagasta kuhniella (Zeller) (mealmoth) (Lepidoptera) and Heliothis virescens (Fab.) (tobacco budworm) (Lepidoptera) were irradiated as adults. Dose-response curves for the induction of dominant lethal mutations in the mature sperm were constructed. The curves were analyzed mathematically and compared with theoretical computer simulated curves requiring 1, 2, 4, 8 and 16 'hits' for the induction of a dominant lethal mutation. The 4 species belonging to 3 different orders of insects showed a wide range in radiation sensitivity and vastly different dose-response curves. When the data were analyzed by several mathematical models the authors found that a logistic response curve gave reasonably good fit with vastly different parameters for the 4 species. Dose-fractionation experiments showed no reduction in the frequency of lethal mutations induced in any species when an acute dose was fractionated into 2 equal exposures separated by an 8-h period. (Auth.)

Parental Conflict and Dominance in Late Adolescent Maladjustment: A Triple Interaction Model.

Science.gov (United States)

Schwarz, J. Conrad; Getter, Herbert

1980-01-01

Ninety-two undergraduates were administered three questionnaires on parental conflict and dominance in late adolescent maladjustment. Results indicated that more neurotic daughters come from high conflict families with dominant fathers, while more neurotic sons come from high conflict families with dominant mothers. (Author/CL)

Studies on chromosomal aberrations and dominant lethal mutations induced by x irradiation in germ cells of male mice

International Nuclear Information System (INIS)

Wang Xianli; Wang Mingdong; Wang Bin; Sun Shuqing

1992-01-01

After male mice irradiated by 2 Gy X rays mated to normal virginal females superovulated with PMSG and HCG, pronuclei chromosome spreading of first-cleavage embryos were prepared and chromosomal aberrations of paternal pronuclei were observed. The results showed that the frequency of chromosomal aberrations was highest irradiated at spermatic stage among different stages of spermatogenesis. The sequence of radiosensitivity in spermatogenesis was as follows: spermatids > mature sperm > spermatocyte > spermatogonia and stem spermatogonia. The frequencies of paternal chromosomal aberrations resulted from irradiation at spermatids and mature sperms were significantly higher than that in control. The reciprocal translocations of stem spermatogonia induced by 2 Gy X rays in those male mice were also examined in the preparations of diakinesis-metaphase I. The frequency of reciprocal translocations were 0.0429 per cell and significantly higher than that in control. The proportion of unbalanced gametes, resulting in lethal embryos after fertilization, was 0.02145 to be predicted. At the same time, the dominant lethality induced by X rays in stem spermatogonia was measured, being 0.0371. The frequency of dead fetuses in irradiation group was about twice as in control. The regression analysis was found that the reciprocal translocations was markedly related to the dominant lethality

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)

Prolonged Permian Triassic ecological crisis recorded by molluscan dominance in Late Permian offshore assemblages.

Science.gov (United States)

Clapham, Matthew E; Bottjer, David J

2007-08-07

The end-Permian mass extinction was the largest biotic crisis in the history of animal life, eliminating as many as 95% of all species and dramatically altering the ecological structure of marine communities. Although the causes of this pronounced ecosystem shift have been widely debated, the broad consensus based on inferences from global taxonomic diversity patterns suggests that the shift from abundant brachiopods to dominant molluscs was abrupt and largely driven by the catastrophic effects of the end-Permian mass extinction. Here we analyze relative abundance counts of >33,000 fossil individuals from 24 silicified Middle and Late Permian paleocommunities, documenting a substantial ecological shift to numerical dominance by molluscs in the Late Permian, before the major taxonomic shift at the end-Permian mass extinction. This ecological change was coincident with the development of fluctuating anoxic conditions in deep marine basins, suggesting that numerical dominance by more tolerant molluscs may have been driven by variably stressful environmental conditions. Recognition of substantial ecological deterioration in the Late Permian also implies that the end-Permian extinction was the climax of a protracted environmental crisis. Although the Late Permian shift to molluscan dominance was a pronounced ecological change, quantitative counts of 847 Carboniferous-Cretaceous collections from the Paleobiology Database indicate that it was only the first stage in a stepwise transition that culminated with the final shift to molluscan dominance in the Late Jurassic. Therefore, the ecological transition from brachiopods to bivalves was more protracted and complex than their simple Permian-Triassic switch in diversity.

Prolonged Permian–Triassic ecological crisis recorded by molluscan dominance in Late Permian offshore assemblages

Science.gov (United States)

Clapham, Matthew E.; Bottjer, David J.

2007-01-01

The end-Permian mass extinction was the largest biotic crisis in the history of animal life, eliminating as many as 95% of all species and dramatically altering the ecological structure of marine communities. Although the causes of this pronounced ecosystem shift have been widely debated, the broad consensus based on inferences from global taxonomic diversity patterns suggests that the shift from abundant brachiopods to dominant molluscs was abrupt and largely driven by the catastrophic effects of the end-Permian mass extinction. Here we analyze relative abundance counts of >33,000 fossil individuals from 24 silicified Middle and Late Permian paleocommunities, documenting a substantial ecological shift to numerical dominance by molluscs in the Late Permian, before the major taxonomic shift at the end-Permian mass extinction. This ecological change was coincident with the development of fluctuating anoxic conditions in deep marine basins, suggesting that numerical dominance by more tolerant molluscs may have been driven by variably stressful environmental conditions. Recognition of substantial ecological deterioration in the Late Permian also implies that the end-Permian extinction was the climax of a protracted environmental crisis. Although the Late Permian shift to molluscan dominance was a pronounced ecological change, quantitative counts of 847 Carboniferous–Cretaceous collections from the Paleobiology Database indicate that it was only the first stage in a stepwise transition that culminated with the final shift to molluscan dominance in the Late Jurassic. Therefore, the ecological transition from brachiopods to bivalves was more protracted and complex than their simple Permian–Triassic switch in diversity. PMID:17664426

/sup 35/S induced dominant lethals in immature oocytes in mice

Energy Technology Data Exchange (ETDEWEB)

Satyanarayana Reddy, K; Reddy, P P; Reddi, O S [Osmania Univ., Hyderabad (India). Dept. of Genetics

1977-03-01

CBA female mice were injected intraperitoneally with a dose of 20..mu..Ci 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 offsprings 4 weeks after littering. Eight weeks after treatment i.e. at the age of 22 to 24 weeks, the treated mothers were mated with control C/sub 3/H/He males. The vaginal plugs were checked every morning and those which mated were separated. The pregnant females were killed on the 14th day of gestation. The uterine contents were examined for live and dead embryos and the ovaries for corpora lutea. The pre- and post-implantation losses and total loss were calculated in the treated females and compared with those of controls. Embryonic death was significantly higher among treated animals. The results indicated that /sup 35/S can induced dominant lethal mutations in immature oocytes.

Induction of dominant lethal mutations by alkylating agnets in germ-cells of the silkworm, Bombyx mori

International Nuclear Information System (INIS)

Murota, Tetsuo; Murakami, Akio.

1977-01-01

The comparison of the intensity of activity was made by measuring radiation equivalent chemical (REC) dose in the experiment of the induction of dominant lethal mutation, using the germ cells of pupae five days before the moths will be hatched. The alkylating agents employed in the experiment are methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), diethyl sulfate (DSC) and mitomycine-C (MC). X-ray irradiation was employed in order to indicate the capability of inducing mutation of the alkylating agents with the radiation equivalent chemical dose (REC dose). The dose-hatchability curves for the alkylating agents showed sigmoidal fashion as observed in X-ray, regardless of germ cells. The REC value at LD (50) was estimated by comparing the relative mutagenic capability of these chemicals. In sperm, EMS and DES with concentration of 1.0 x 10 -7 M/g showed the same lethality as about 2.3 kR and 0.6 kR of X-ray. However, no significant reduction of embryonic lethality after the treatment of pupae with MC (up to 2.1 x 10 -7 M/g) and MMS (up to 1.0 x 10 -6 M/g) was observed. As the results, the order of mutagenic effectiveness was as follows: EMS>DES>MMS approximately equal to MC. When oocytes in the mid-pupae were treated with MMS, EMS and MC with concentration of 1.0 x 10 -7 M/g, MMS and EMS showed the same effects as 12.8 kR and 0.6 kR. Surprisingly, MC showed the same lethality as 232.3 kR. This extremely high sensitivity of oocytes to MC may be ascribed to the inhibiting effect of the drug on the meiotic division. (Iwakiri, K.)

Evaluation of freshly irradiated wheat for dominant lethal mutations in Wistar rats

International Nuclear Information System (INIS)

Pawan, S.C.; Aravindakshan, M.; Kumar, N.S.; Subba Rao, V.; Aiyar, A.S.; Sundaram, K.

1977-01-01

Three independent, serially performed experiments involving acute and chronic feeding of freshly irradiated wheat (75 krad, gamma-irradiation) were carried out in Wistar rats. In the first experiment groups of 10 males were given wheat for 1 week; irradiated wheat was consumed by the animals within 24 h of irradiation. In the other two experiments feeding of males was continued for 6 (10 males per group) and 12 (13 males per group) weeks, respectively, and the irradiated wheat was fed within 7 days of irradiation. At the end of each treatment period each male was paired with 3 females for 7 days and sequentially at weekly intervals for 5 or 8 weeks. Females were killed and examined for live and dead implantations and corpora lutea. There were no differences between groups with regard to fertility nor was there any inter-group difference as regards pre- and post-implantation losses whether the rats were fed irradiated or non-irradiated wheat. This suggested that even feeding of freshly irradiated wheat does not induce any dominant lethal mutations in rats

Evaluation of freshly irradiated wheat for dominant lethal mutations in Wistar rats

Energy Technology Data Exchange (ETDEWEB)

Pawan, S C; Aravindakshan, M; Kumar, N S; Subba Rao, V; Aiyar, A S; Sundaram, K [Bhabha Atomic Research Centre, Bombay (India). Bio-medical Group

1977-01-01

Three independent, serially performed experiments involving acute and chronic feeding of freshly irradiated wheat (75 krad, gamma-irradiation) were carried out in Wistar rats. In the first experiment groups of 10 males were given wheat for 1 week; irradiated wheat was consumed by the animals within 24 h of irradiation. In the other two experiments feeding of males was continued for 6 (10 males per group) and 12 (13 males per group) weeks, respectively, and the irradiated wheat was fed within 7 days of irradiation. At the end of each treatment period each male was paired with 3 females for 7 days and sequentially at weekly intervals for 5 or 8 weeks. Females were killed and examined for live and dead implantations and corpora lutea. There were no differences between groups with regard to fertility nor was there any inter-group difference as regards pre- and post-implantation losses whether the rats were fed irradiated or non-irradiated wheat. This suggested that even feeding of freshly irradiated wheat does not induce any dominant lethal mutations in rats.

On the mutagenicity of methadone hydrochloride. Induced dominant lethal mutation and spermatocyte chromosomal aberrations in treated males.

Science.gov (United States)

Badr, F M; Rabouh, S A; Badr, R S

1979-11-01

The mutagenicity of methadone hydrochloride was tested in male mice using the dominant lethal mutation technique and the spermatocyte test of treated mice. Male mice of C3H inbred strain received one of the following doses, 1, 2, 4 or 6 mg/kg body weight once a day for 3 consecutive days. Another group of mice served as control and received saline instead. Treated males were then mated to virgin females at 3-day intervals for a period of 45 days. Pregnant females were dissected at mid-term and the corpora lutea and intrauterine contents were recorded. The spermatocytes of treated males were examined 45-50 d after treatments with methadone and abnormal pairing configurations were scored. The methadone treatment was found to increase the rate of preimplantation deaths consistently in all post-meiotic stages with all doses used. In addition, the higher doses, 4 and 6 mg, affected spermatogonia stages. Quantitatively, the dose-response relationship cannot be demonstrated though the spectrum of effect increased with higher doses as more spermatogenesis stages became more sensitive to the treatment. In many cases the frequency of live implants showed a positive correlation with preimplantation deaths in contrast with the frequency of early deaths which showed only sporadic variation. The mutation indices based on total embryonic death indicate that methadone hydrochloride affected several stages of germ-cell maturation namely, spermatozoa (M.I. 14-35), late spermatids (M.I. 15-48), early spermatids (M.I. 14-50), late spermatocytes (M.I. 15-43) and spermatogonial stages (M.I. 12-63). Chromosome analysis at diakinesis-metaphase 1 revealed significant increase in the frequency of sex chromosome and autosome univalents with different doses of methadone. The smallest dose applied was quite effective and the data represent direct dose-response relationship. Of the multivalent configuration, the most frequent type was chain quadrivalents. The frequencies of total translocations

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.

Dominant Lethal Pathologies in Male Mice Engineered to Contain an X-Linked DUX4 Transgene

Directory of Open Access Journals (Sweden)

Abhijit Dandapat

2014-09-01

Full Text Available Facioscapulohumeral muscular dystrophy (FSHD is an enigmatic disease associated with epigenetic alterations in the subtelomeric heterochromatin of the D4Z4 macrosatellite repeat. Each repeat unit encodes DUX4, a gene that is normally silent in most tissues. Besides muscular loss, most patients suffer retinal vascular telangiectasias. To generate an animal model, we introduced a doxycycline-inducible transgene encoding DUX4 and 3′ genomic DNA into a euchromatic region of the mouse X chromosome. Without induction, DUX4 RNA was expressed at low levels in many tissues and animals displayed a variety of unexpected dominant leaky phenotypes, including male-specific lethality. Remarkably, rare live-born males expressed DUX4 RNA in the retina and presented a retinal vascular telangiectasia. By using doxycycline to induce DUX4 expression in satellite cells, we observed impaired myogenesis in vitro and in vivo. This mouse model, which shows pathologies due to FSHD-related D4Z4 sequences, is likely to be useful for testing anti-DUX4 therapies in FSHD.

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

Revertant mutation releases confined lethal mutation, opening Pandora's box: a novel genetic pathogenesis.

Directory of Open Access Journals (Sweden)

Yasushi Ogawa

2014-05-01

Full Text Available When two mutations, one dominant pathogenic and the other "confining" nonsense, coexist in the same allele, theoretically, reversion of the latter may elicit a disease, like the opening of Pandora's box. However, cases of this hypothetical pathogenic mechanism have never been reported. We describe a lethal form of keratitis-ichthyosis-deafness (KID syndrome caused by the reversion of the GJB2 nonsense mutation p.Tyr136X that would otherwise have confined the effect of another dominant lethal mutation, p.Gly45Glu, in the same allele. The patient's mother had the identical misssense mutation which was confined by the nonsense mutation. The biological relationship between the parents and the child was confirmed by genotyping of 15 short tandem repeat loci. Haplotype analysis using 40 SNPs spanning the >39 kbp region surrounding the GJB2 gene and an extended SNP microarray analysis spanning 83,483 SNPs throughout chromosome 13 in the family showed that an allelic recombination event involving the maternal allele carrying the mutations generated the pathogenic allele unique to the patient, although the possibility of coincidental accumulation of spontaneous point mutations cannot be completely excluded. Previous reports and our mutation screening support that p.Gly45Glu is in complete linkage disequilibrium with p.Tyr136X in the Japanese population. Estimated from statisitics in the literature, there may be approximately 11,000 p.Gly45Glu carriers in the Japanese population who have this second-site confining mutation, which acts as natural genetic protection from the lethal disease. The reversion-triggered onset of the disesase shown in this study is a previously unreported genetic pathogenesis based on Mendelian inheritance.

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

Radiation-induced dominant skeletal mutations in mice

International Nuclear Information System (INIS)

Selby, P.B.

1979-01-01

Skeletons were chosen for the attempt to determine the overall damage by radiation to one body system largely bacause they can be prepared readily for detailed study. Dominant mutations were of special interest because they are the type of mutations that would account for almost all damage induced in the early generations. The male offsprings derived from spermatogonial irradiation were used in the mutation-rate experiment, and the mutation frequency of 1.4% per gamete was found. The general dominant skeletal mutations are 1) the fusions of bones or other changes in individual bones, 2) the gross changes in bone shapes, usually caused by incomplete or too extensive bone growth, or 3) the shifts in the relative positions of bones. The recessive lethality in the period between implantation and birth can be recognized by the expected high death rate of implants in approximately 1/4 of the crosses that are between heterozygotes for a given mutation. The recessive lethal mutations may account for an important fraction of human genetic disorders owing to their dominant deleterious effects which represent only a small fraction, but because of their easy detection, they have been studied more than other dominants. At least 45, or 27%, of 164 dominant visibles in mice, ignoring those concerned with enzyme polymorphisms and immunological traits, appear to be recessive lethals. (Yamashita, S.)

Late Quaternary glaciation history of monsoon-dominated Dingad basin, central Himalaya, India

Science.gov (United States)

Shukla, Tanuj; Mehta, Manish; Jaiswal, Manoj K.; Srivastava, Pradeep; Dobhal, D. P.; Nainwal, H. C.; Singh, Atul K.

2018-02-01

The study presents the Late Quaternary glaciation history of monsoon-dominated Dokriani Glacier valley, Dingad basin, central Himalaya, India. The basin is tested for the mechanism of landforms preservation in high relief and abundant precipitation regimes of the Higher Himalaya. Field geomorphology and remote sensing data, supported by Optical Stimulated Luminescence (OSL) dating enabled identification of five major glacial events of decreasing magnitude. The oldest glacial stage, Dokriani Glacial Stage I (DGS-I), extended down to ∼8 km (2883 m asl) from present-day snout (3965 m asl) followed by other four glaciations events viz. DGS-II, DGS-III, DGS-IV and DGS-V terminating at ∼3211, 3445, 3648 and ∼3733 m asl respectively. The DGS-I glaciation (∼25-∼22 ka BP) occurred during early Marine Isotope Stage (MIS) -2, characterized as Last Glacial Maximum (LGM) extension of the valley. Similarly, DGS-II stage (∼14-∼11 ka BP) represents the global cool and dry Older Dryas and Younger Dryas event glaciation. The DGS-III glaciation (∼8 ka BP) coincides with early Holocene 8.2 ka cooling event, the DGS-IV glaciations (∼4-3.7 ka BP) corresponds to 4.2 ka cool and drier event, DGS-V (∼2.7-∼1 ka BP) represents the cool and moist late Holocene glacial advancement of the valley. This study suggests that the Dokriani Glacier valley responded to the global lowering of temperature and variable precipitation conditions. This study also highlights the close correlation between the monsoon-dominated valley glaciations and Northern Hemisphere cooling events influenced by North Atlantic climate.

Dominant lethal mutations in Drosophila melanogaster natural populations flown on board ISS.

Science.gov (United States)

Larina, Olga; Bekker, Anna

The resistance to mutagenic impacts represents an important issue of manned space missions. However the reasons of its individual variability as well as the factors which could induce mutations in space flight are not fully understood. Drosophila studies accomplished by several research teams at real space flights, revealed pronounced increase of mutations in somatic and reproductive cells, nonetheless, quite an opposite spaceflight effects also occurred, i.e., mei-41 laboratory strain showed postflight mutation rates lower than that in ground control. In order to monitor the influence of space flight on the mutational process, 4 series of space experiment with D. melanogaster wild type populations were performed at International Space Station (ISS). The appliance “Drosophila-2” used for breeding of drosophila in spaceflight conditions, enabled to conduct synchronous studies with two samples of fly populations. First instar drosophila larvae were placed into the experimental appliance 12 hours before the start of transport spacecraft. The duration of experiments was 7.9 through 19.7 days. In 19.7-day experiment, two generations of the flies were raised during the space flight, and then delivered to the earth. The frequency of dominant lethal mutations (DLM) was evaluated as the percentage of embryonic death in the progeny of experimental drosophila samples. DLM tests in VV-09 and Chas-09 natural populations, performed after the exposure to 10.9-day flight, showed the increase of DLM rate in Chas-09 (0.077 in flight series vs. 0.43 in earth-based control) while post-flight DLM value in VV-09 did not diverge from on-earth sample (0.025 and 0.027 correspondingly). The same results for VV-09 were obtained after the 14.7-day and 7.9-day flights with the only exception: 7.9-day flight experiment employed DLM measurements in two VV-09 spaceflight samples, differing by the age of the flies, and the above DLM rates were detected in “younger” VV-09 sample only. DLM

[Dominating motivation in systemic memory mechanisms].

Science.gov (United States)

Sudakov, K V

2005-01-01

The materials provided in the article support the key role of dominating motivation in the systemic processes of fixation and opening of memory mechanisms. The activating mechanisms of dominating motivations in the systemic architectonics of behavioural acts provide the basis for development of a multicomponent acceptor apparatus of an action outcomes broadly represented in various analysing brain sections. As result of enhancement of action outcomes on acceptors structures, molecular behaviour engrammes form within the functional systems. It is these molecular engrammes that are opened by dominating motivations in the same spatial-temporal sequence in which training takes place, and determine deliberate actions of animals. It was demonstrated that dominating motivation opens genetic information with an approximating-exploratory reaction under strong activation of early genes expression, in particular, of c-fos gene protein. Inherent motivation reactions are not blocked by inhibitors of proteins synthesis, by cycloheximide, in particular. In the process of training animals, i.e., satisfaction of the demands which are the basis of dominating motivations, expression of early genes in reduced, while expression of late genes is initiated. In this case, blockators of protein synthesis begin to produce strong inhibiting impact on behaviour of animals.

Chimeric anti-staphylococcal enterotoxin B antibodies and lovastatin act synergistically to provide in vivo protection against lethal doses of SEB.

Directory of Open Access Journals (Sweden)

Mulualem E Tilahun

Full Text Available Staphylococcal enterotoxin B (SEB is one of a family of toxins secreted by Staphylococcus aureus that act as superantigens, activating a large fraction of the T-cell population and inducing production of high levels of inflammatory cytokines that can cause toxic shock syndrome (TSS and death. Extracellular engagement of the TCR of T-cells and class II MHC of antigen presenting cells by SEB triggers the activation of many intracellular signaling processes. We engineered chimeric antibodies to block the extracellular engagement of cellular receptors by SEB and used a statin to inhibit intracellular signaling. Chimeric human-mouse antibodies directed against different neutralizing epitopes of SEB synergistically inhibited its activation of human T-cells in vitro. In the in vivo model of lethal toxic shock syndrome (TSS in HLA-DR3 transgenic mice, two of these antibodies conferred significant partial protection when administered individually, but offered complete protection in a synergistic manner when given together. Similarly, in vivo, lovastatin alone conferred only partial protection from TSS similar to single anti-SEB antibodies. However, used in combination with one chimeric neutralizing anti-SEB antibody, lovastatin provided complete protection against lethal TSS in HLA-DR3 transgenic mice. These experiments demonstrate that in vivo protection against lethal doses of SEB can be achieved by a statin of proven clinical safety and chimeric human-mouse antibodies, agents now widely used and known to be of low immunogenicity in human hosts.

The Earliest Colubroid-Dominated Snake Fauna from Africa: Perspectives from the Late Oligocene Nsungwe Formation of Southwestern Tanzania

Science.gov (United States)

McCartney, Jacob A.; Stevens, Nancy J.; O’Connor, Patrick M.

2014-01-01

The extant snake fauna has its roots in faunal upheaval occurring across the Paleogene - Neogene transition. On northern continents, this turnover is well established by the late early Miocene. However, this transition is poorly documented on southern landmasses, particularly on continental Africa, where no late Paleogene terrestrial snake assemblages are documented south of the equator. Here we describe a newly discovered snake fauna from the Late Oligocene Nsungwe Formation in the Rukwa Rift Basin of Tanzania. The fauna is small but diverse with eight identifiable morphotypes, comprised of three booids and five colubroids. This fauna includes Rukwanyoka holmani gen. et sp. nov., the oldest boid known from mainland Africa. It also provides the oldest fossil evidence for the African colubroid clade Elapidae. Colubroids dominate the fauna, comprising more than 75% of the recovered material. This is likely tied to local aridification and/or seasonality and mirrors the pattern of overturn in later snake faunas inhabiting the emerging grassland environments of Europe and North America. The early emergence of colubroid dominance in the Rukwa Rift Basin relative to northern continents suggests that the pattern of overturn that resulted in extant faunas happened in a more complex fashion on continental Africa than was previously realized, with African colubroids becoming at least locally important in the late Paleogene, either ahead of or as a consequence of the invasion of colubrids. The early occurrence of elapid snakes in the latest Oligocene of Africa suggests the clade rapidly spread from Asia to Africa, or arose in Africa, before invading Europe. PMID:24646522

The earliest colubroid-dominated snake fauna from Africa: perspectives from the Late Oligocene Nsungwe Formation of southwestern Tanzania.

Directory of Open Access Journals (Sweden)

Jacob A McCartney

Full Text Available The extant snake fauna has its roots in faunal upheaval occurring across the Paleogene-Neogene transition. On northern continents, this turnover is well established by the late early Miocene. However, this transition is poorly documented on southern landmasses, particularly on continental Africa, where no late Paleogene terrestrial snake assemblages are documented south of the equator. Here we describe a newly discovered snake fauna from the Late Oligocene Nsungwe Formation in the Rukwa Rift Basin of Tanzania. The fauna is small but diverse with eight identifiable morphotypes, comprised of three booids and five colubroids. This fauna includes Rukwanyoka holmani gen. et sp. nov., the oldest boid known from mainland Africa. It also provides the oldest fossil evidence for the African colubroid clade Elapidae. Colubroids dominate the fauna, comprising more than 75% of the recovered material. This is likely tied to local aridification and/or seasonality and mirrors the pattern of overturn in later snake faunas inhabiting the emerging grassland environments of Europe and North America. The early emergence of colubroid dominance in the Rukwa Rift Basin relative to northern continents suggests that the pattern of overturn that resulted in extant faunas happened in a more complex fashion on continental Africa than was previously realized, with African colubroids becoming at least locally important in the late Paleogene, either ahead of or as a consequence of the invasion of colubrids. The early occurrence of elapid snakes in the latest Oligocene of Africa suggests the clade rapidly spread from Asia to Africa, or arose in Africa, before invading Europe.

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,

The population genetics of X-autosome synthetic lethals and steriles.

Science.gov (United States)

Lachance, Joseph; Johnson, Norman A; True, John R

2011-11-01

Epistatic interactions are widespread, and many of these interactions involve combinations of alleles at different loci that are deleterious when present in the same individual. The average genetic environment of sex-linked genes differs from that of autosomal genes, suggesting that the population genetics of interacting X-linked and autosomal alleles may be complex. Using both analytical theory and computer simulations, we analyzed the evolutionary trajectories and mutation-selection balance conditions for X-autosome synthetic lethals and steriles. Allele frequencies follow a set of fundamental trajectories, and incompatible alleles are able to segregate at much higher frequencies than single-locus expectations. Equilibria exist, and they can involve fixation of either autosomal or X-linked alleles. The exact equilibrium depends on whether synthetic alleles are dominant or recessive and whether fitness effects are seen in males, females, or both sexes. When single-locus fitness effects and synthetic incompatibilities are both present, population dynamics depend on the dominance of alleles and historical contingency (i.e., whether X-linked or autosomal mutations occur first). Recessive synthetic lethality can result in high-frequency X-linked alleles, and dominant synthetic lethality can result in high-frequency autosomal alleles. Many X-autosome incompatibilities in natural populations may be cryptic, appearing to be single-locus effects because one locus is fixed. We also discuss the implications of these findings with respect to standing genetic variation and the origins of Haldane's rule.

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

Continental Drift in the Treatment of Dominant Firms: Article 102 TFEU in Contrast to § 2 Sherman Act

NARCIS (Netherlands)

Larouche, P.; Schinkel, M.P.

2013-01-01

In this paper we compare the concepts of monopolization and abuse of dominance as in §2 of the Sherman Act and Article 102 of the TFEU, respectively. After identifying a number of distinctive features in wording and interpretation - including the special responsibility of the dominant firm,

Effects-Based Operations: The End of Dominant Maneuver?

National Research Council Canada - National Science Library

Cheek, Gary

2002-01-01

... without dominant ground maneuver. The paper concludes that such thinking misreads a historical warfare lethality trend in a potentially dangerous effort to vindicate the Air Force doctrine of strategic attack...

Late payment of freight and hire - power to award interest under the 1998 Act.

OpenAIRE

Okoli, Chukwuma

2014-01-01

Comments on the Commercial Court judgment in Martrade Shipping & Transport GmbH v United Enterprises Corp on whether to award interest under the Late Payment of Commercial Debts (Interest) Act 1998 in a dispute about a charterparty, which was governed by English law and referred to London arbitration, but otherwise had no significant connection with the UK.

Comparison of efficacy of long-acting bronchodilators in emphysema dominant and emphysema nondominant chronic obstructive pulmonary disease

Directory of Open Access Journals (Sweden)

Fujimoto K

2011-04-01

Full Text Available Keisaku Fujimoto1, Yoshiaki Kitaguchi2, Shintaro Kanda2, Kazuhisa Urushihata2, Masayuki Hanaoka2, Keishi Kubo21Department of Biomedical Laboratory Sciences, 2First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, JapanBackground: The purpose of this study was to clarify the association between morphological phenotypes according to the predominance of emphysema and efficacy of long-acting muscarinic antagonist and β2 agonist bronchodilators in patients with chronic obstructive pulmonary disease (COPD.Methods: Seventy-two patients with stable COPD treated with tiotropium (n = 41 or salmeterol (n = 31 were evaluated for pulmonary function, dynamic hyperinflation following metronome-paced incremental hyperventilation, six-minute walking distance, and St George’s Respiratory Questionnaire (SGRQ before and 2–3 months following treatment with tiotropium or salmeterol. They were then visually divided into an emphysema dominant phenotype (n = 25 in the tiotropium-treated group and n = 22 in the salmeterol-treated group and an emphysema nondominant phenotype on high-resolution computed tomography, and the efficacy of the two drugs in each phenotype was retrospectively analyzed.Results: Tiotropium significantly improved airflow limitation, oxygenation, and respiratory impedance in both the emphysema dominant and emphysema nondominant phenotypes, and improved dynamic hyperinflation, exercise capacity, and SGRQ in the emphysema dominant phenotype but not in the emphysema nondominant phenotype. Salmeterol significantly improved total score for SGRQ in the emphysema phenotype, but no significant effects on other parameters were found for either of the phenotypes.Conclusion: These findings suggest that tiotropium is more effective than salmeterol for airflow limitation regardless of emphysema dominance, and also can improve dynamic hyperinflation in the emphysema dominant phenotype, which results in further

Late Quaternary Halimeda bioherms and aragonitic faecal pellet-dominated sediments on the carbonate platform of the western continental shelf of India

Digital Repository Service at National Institute of Oceanography (India)

Rao, V.P; Veerayya, M.; Nair, R.R.; Dupeuble, P; Lamboy, M.

brought by river runoff and shelf edge currents favoured the growth of algal bioherms dominated by Halimeda between 13,700 (?) and 8300 yr B.P. The absence of Late Holocene and modern carbonates on the platform may be due to the combined influence...

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: ...

Paleovegetation reconstruction of fossil forests dominated by Metasequoia and Glyptostrobus from the late Pliocene Kobiwako Group, central Japan

OpenAIRE

CHIYOMI, YAMAKAWA; ARATA, MOMOHARA; TOMOO, NUNOTANI; MIDORI, MATSUMOTO; YASUYUKI, WATANO; Lake Biwa Museum; Graduate School of Horticulture, Chiba University; Lake Biwa Museum; Graduate School of Science, Chiba University; Graduate School of Science, Chiba University

2008-01-01

A late Pliocene (1.8-1.9 Ma) wetland fossil forest community that was dominated by Metasequoia and Glyptostrobus was reconstructed based on the species composition of the stumps and other plant macrofossil assemblages. The plant fossils were recovered from a fossil forest preserved in deposits of the Kobiwako Group that are exposed in the Echi River, Shiga Prefecture, central Japan. Fossil wood of Metasequoia and Glyptostrobus was distinguished based on anatomical characteristics. Apportionme...

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

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.

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.

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...

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.

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, ...

Mouse survival motor neuron alleles that mimic SMN2 splicing and are inducible rescue embryonic lethality early in development but not late.

Directory of Open Access Journals (Sweden)

Suzan M Hammond

Full Text Available Spinal muscular atrophy (SMA is caused by low survival motor neuron (SMN levels and patients represent a clinical spectrum due primarily to varying copies of the survival motor neuron-2 (SMN2 gene. Patient and animals studies show that disease severity is abrogated as SMN levels increase. Since therapies currently being pursued target the induction of SMN, it will be important to understand the dosage, timing and cellular requirements of SMN for disease etiology and potential therapeutic intervention. This requires new mouse models that can induce SMN temporally and/or spatially. Here we describe the generation of two hypomorphic Smn alleles, Smn(C-T-Neo and Smn(2B-Neo. These alleles mimic SMN2 exon 7 splicing, titre Smn levels and are inducible. They were specifically designed so that up to three independent lines of mice could be generated, herein we describe two. In a homozygous state each allele results in embryonic lethality. Analysis of these mutants indicates that greater than 5% of Smn protein is required for normal development. The severe hypomorphic nature of these alleles is caused by inclusion of a loxP-flanked neomycin gene selection cassette in Smn intron 7, which can be removed with Cre recombinase. In vitro and in vivo experiments demonstrate these as inducible Smn alleles. When combined with an inducible Cre mouse, embryonic lethality caused by low Smn levels can be rescued early in gestation but not late. This provides direct genetic evidence that a therapeutic window for SMN inductive therapies may exist. Importantly, these lines fill a void for inducible Smn alleles. They also provide a base from which to generate a large repertoire of SMA models of varying disease severities when combined with other Smn alleles or SMN2-containing mice.

Inhalation reproductive toxicology studies: Male dominant lethal study of n-hexane in Swiss (CD-1) mice: Final report

Energy Technology Data Exchange (ETDEWEB)

Mast, T.J.; Rommereim, R.L.; Evanoff, J.J.; Sasser, L.B.; Decker, J.R.; Stoney, K.H.; Weigel, R.J.; Westerberg, R.B.

1988-08-01

The straight-chain hydrocarbon, n-hexane, is a volatile, ubiquitous solvent routinely used in industrial environments; consequently, the opportunity for industrial, environmental or accidental exposure to hexane vapors is significant. Although myelinated nerve tissue is the primary target organ of hexane, the testes have also been identified as being sensitive to hexacarbon exposure. The objective of this study was to evaluate male dominant lethal effects in Swiss (CD-1) mice after exposure to 0, 200, 1000, or 5000 ppM n-hexane, 20 h/day for 5 consecutive days. Each exposure concentration consisted of 30 randomly selected, proven male breeders; 4 groups. The mice were weighed just prior to the first day of exposure and at weekly intervals until sacrifice. Ten males in each dose group were sacrificed one day after the cessation of exposure, and their testes and epididymides were removed for evaluation of the germinal epithelium. The remaining male mice, 20 per group, were individually housed in hanging wire-mesh breeding cages where they were mated with unexposed, virgin females for eight weekly intervals; new females were provided each week. The mated females were sacrificed 12 days after the last day of cohabitation and their reproductive status and the number and viability of the implants were recorded. The appearance and behavior of the male mice were unremarkable throughout the study period and no evidence of n-hexane toxicity was observed. 18 refs., 3 figs., 11 tabs.

Inhalation reproductive toxicology studies: Male dominant lethal study of n-hexane in Swiss (CD-1) mice: Final report

International Nuclear Information System (INIS)

Mast, T.J.; Rommereim, R.L.; Evanoff, J.J.; Sasser, L.B.; Decker, J.R.; Stoney, K.H.; Weigel, R.J.; Westerberg, R.B.

1988-08-01

The straight-chain hydrocarbon, n-hexane, is a volatile, ubiquitous solvent routinely used in industrial environments; consequently, the opportunity for industrial, environmental or accidental exposure to hexane vapors is significant. Although myelinated nerve tissue is the primary target organ of hexane, the testes have also been identified as being sensitive to hexacarbon exposure. The objective of this study was to evaluate male dominant lethal effects in Swiss (CD-1) mice after exposure to 0, 200, 1000, or 5000 ppM n-hexane, 20 h/day for 5 consecutive days. Each exposure concentration consisted of 30 randomly selected, proven male breeders; 4 groups. The mice were weighed just prior to the first day of exposure and at weekly intervals until sacrifice. Ten males in each dose group were sacrificed one day after the cessation of exposure, and their testes and epididymides were removed for evaluation of the germinal epithelium. The remaining male mice, 20 per group, were individually housed in hanging wire-mesh breeding cages where they were mated with unexposed, virgin females for eight weekly intervals; new females were provided each week. The mated females were sacrificed 12 days after the last day of cohabitation and their reproductive status and the number and viability of the implants were recorded. The appearance and behavior of the male mice were unremarkable throughout the study period and no evidence of n-hexane toxicity was observed. 18 refs., 3 figs., 11 tabs

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

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.)

MicroRNA Expression Profile in Bovine Granulosa Cells of Preovulatory Dominant and Subordinate Follicles during the Late Follicular Phase of the Estrous Cycle.

Directory of Open Access Journals (Sweden)

Samuel Gebremedhn

Full Text Available In bovine, ovarian follicles grow in a wave-like fashion with commonly 2 or 3 follicular waves emerging per estrous cycle. The dominant follicle of the follicular wave which coincides with the LH-surge becomes ovulatory, leaving the subordinate follicles to undergo atresia. These physiological processes are controlled by timely and spatially expressed genes and gene products, which in turn are regulated by post-transcriptional regulators. MicroRNAs, a class of short non-coding RNA molecules, are one of the important posttranscriptional regulators of genes associated with various cellular processes. Here we investigated the expression pattern of miRNAs in granulosa cells of bovine preovulatory dominant and subordinate follicles during the late follicular phase of bovine estrous cycle using Illumina miRNA deep sequencing. In addition to 11 putative novel miRNAs, a total of 315 and 323 known miRNAs were detected in preovulatory dominant and subordinate follicles, respectively. Moreover, in comparison with the subordinate follicles, a total of 64 miRNAs were found to be differentially expressed in preovulatory dominant follicles, of which 34 miRNAs including the miR-132 and miR-183 clusters were significantly enriched, and 30 miRNAs including the miR-17-92 cluster, bta-miR-409a and bta-miR-378 were significantly down regulated in preovulatory dominant follicles. In-silico pathway analysis revealed that canonical pathways related to oncogenesis, cell adhesion, cell proliferation, apoptosis and metabolism were significantly enriched by the predicted target genes of differentially expressed miRNAs. Furthermore, Luciferase reporter assay analysis showed that one of the differentially regulated miRNAs, the miR-183 cluster miRNAs, were validated to target the 3'-UTR of FOXO1 gene. Moreover FOXO1 was highly enriched in granulosa cells of subordinate follicles in comparison with the preovulatory dominant follicles demonstrating reciprocal expression pattern

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.

A dominant-negative mutation of mouse Lmx1b causes glaucoma and is semi-lethal via LDB1-mediated dimerization [corrected].

Directory of Open Access Journals (Sweden)

Sally H Cross

2014-05-01

Full Text Available Mutations in the LIM-homeodomain transcription factor LMX1B cause nail-patella syndrome, an autosomal dominant pleiotrophic human disorder in which nail, patella and elbow dysplasia is associated with other skeletal abnormalities and variably nephropathy and glaucoma. It is thought to be a haploinsufficient disorder. Studies in the mouse have shown that during development Lmx1b controls limb dorsal-ventral patterning and is also required for kidney and eye development, midbrain-hindbrain boundary establishment and the specification of specific neuronal subtypes. Mice completely deficient for Lmx1b die at birth. In contrast to the situation in humans, heterozygous null mice do not have a mutant phenotype. Here we report a novel mouse mutant Icst, an N-ethyl-N-nitrosourea-induced missense substitution, V265D, in the homeodomain of LMX1B that abolishes DNA binding and thereby the ability to transactivate other genes. Although the homozygous phenotypic consequences of Icst and the null allele of Lmx1b are the same, heterozygous Icst elicits a phenotype whilst the null allele does not. Heterozygous Icst causes glaucomatous eye defects and is semi-lethal, probably due to kidney failure. We show that the null phenotype is rescued more effectively by an Lmx1b transgene than is Icst. Co-immunoprecipitation experiments show that both wild-type and Icst LMX1B are found in complexes with LIM domain binding protein 1 (LDB1, resulting in lower levels of functional LMX1B in Icst heterozygotes than null heterozygotes. We conclude that Icst is a dominant-negative allele of Lmx1b. These findings indicate a reassessment of whether nail-patella syndrome is always haploinsufficient. Furthermore, Icst is a rare example of a model of human glaucoma caused by mutation of the same gene in humans and mice.

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

Radiobiological considerations of late effects arising from radiotherapy

International Nuclear Information System (INIS)

Kogelnik, H.D.; Kaercher, K.H.

1977-01-01

A variety of clinical and experimental data are reviewed to investigate the different factors leading to appearance of late complications. Higher individual doses per fraction are related to an increase in the incidence and severity of late effects and massive dose techniques result in catastrophic late complications. There is no apparent relation between the severity of initial skin reactions and late effects, indicating that matching of acute radiation reactions on skin or mucous membranes cannot be extrapolated to late damage in connective tissues and organs. The probability of late tissue injury increases with the volume of tissue irradiated. Several phenomena, e.g. parenchymal cell depletion, vascular injury and fibrocyte dysfunction, are likely to operate together as well as separately in the pathogenesis of late effects. The late complications of radiotherapy develop in cells with a slow proliferation, and this is consistent with the hypothesis that parenchymal cell killing may be the basis for the injury. The response of cells with a slow proliferation to a course of fractionated irradiation differs from that of rapidly proliferative cells in three biological processes: repair of potentially lethal damage, redistribution and regeneration. (author)

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

Late onset autosomal dominant cerebellar ataxia a family description and linkage analysis with the hla system

Directory of Open Access Journals (Sweden)

Walter O. Arruda

1991-09-01

Full Text Available A family suffering an autosomal dominant form of late onset hereditary cerebellar ataxia is described. Eight affected family members were personally studied, and data from another four were obtained through anamnesis. The mean age of onset was 37.1±5.4 years (27-47 years. The clinical picture consisted basically of a pure ataxic cerebellar syndrome. CT-scan disclosed diffuse cerebellar atrophy with relative sparing of the brainstem (and no involvement of supratentorial structures. Neurophysiological studies (nerve conduction, VEP and BAEP were normal. Twenty-six individuals were typed for HLA histocompatibility antigens. Lod scores were calculated with the computer program LINKMAP. Close linkage of the ataxia gene with the HLA system in this family could be excluded - 0==0,02, z=(-2,17 - and the overall analysis of the lod scores suggest another chromossomal location than chromosome 6.

Implementation of directive 2011/7/EU on combating late payment in commercial transactions in the Republic of Macedonia: The Financial Discipline Act

Directory of Open Access Journals (Sweden)

Josimovski Aleksandar

2015-01-01

Full Text Available In the Republic of Macedonia, the legislator has tried to solve the problem of late payment in commercial transactions by enacting the Financial Discipline Act. The justifications for enacting this Act were the illiquidity of the business sector and the implementation of the EU Directive on combating late payment in commercial transactions. Yet, the Act includes several differences in comparison to the regime envisaged in the Directive. The time limits governing the performance of monetary liabilities in transactions between economic operators (undertakings are identical with those in the EU Directive; however, the Act does not regulate payment in installment and does not provide for an extension of time limits unless expressly agreed. On the other hand, public authorities have a few privileges: time limits for commercial transactions between public authorities and economic operators are identical with the time limits for transactions between economic operators (whereas in the Directive time limits for public authorities are shorter; contracts on perennial procurement are exempt from compliance with this Act; and particular categories of public authorities should comply with the general time limits for commercial transactions as of 1 January 2016. Additionally, considering the prescribed misdemeanor sanctions applicable in cases where the debtor has failed to pay within the prescribed time limits, the purpose of the Financial Discipline Act remains unclear. Has it been enacted to increase or to reduce the liquidity in the national economy?.

Fine mapping of dominant X-linked incompatibility alleles in Drosophila hybrids.

Science.gov (United States)

Matute, Daniel R; Gavin-Smyth, Jackie

2014-04-01

Sex chromosomes have a large effect on reproductive isolation and play an important role in hybrid inviability. In Drosophila hybrids, X-linked genes have pronounced deleterious effects on fitness in male hybrids, which have only one X chromosome. Several studies have succeeded at locating and identifying recessive X-linked alleles involved in hybrid inviability. Nonetheless, the density of dominant X-linked alleles involved in interspecific hybrid viability remains largely unknown. In this report, we study the effects of a panel of small fragments of the D. melanogaster X-chromosome carried on the D. melanogaster Y-chromosome in three kinds of hybrid males: D. melanogaster/D. santomea, D. melanogaster/D. simulans and D. melanogaster/D. mauritiana. D. santomea and D. melanogaster diverged over 10 million years ago, while D. simulans (and D. mauritiana) diverged from D. melanogaster over 3 million years ago. We find that the X-chromosome from D. melanogaster carries dominant alleles that are lethal in mel/san, mel/sim, and mel/mau hybrids, and more of these alleles are revealed in the most divergent cross. We then compare these effects on hybrid viability with two D. melanogaster intraspecific crosses. Unlike the interspecific crosses, we found no X-linked alleles that cause lethality in intraspecific crosses. Our results reveal the existence of dominant alleles on the X-chromosome of D. melanogaster which cause lethality in three different interspecific hybrids. These alleles only cause inviability in hybrid males, yet have little effect in hybrid females. This suggests that X-linked elements that cause hybrid inviability in males might not do so in hybrid females due to differing sex chromosome interactions.

Incompatibility between X chromosome factor and pericentric heterochromatic region causes lethality in hybrids between Drosophila melanogaster and its sibling species.

Science.gov (United States)

Cattani, M Victoria; Presgraves, Daven C

2012-06-01

The Dobzhansky-Muller model posits that postzygotic reproductive isolation results from the evolution of incompatible epistatic interactions between species: alleles that function in the genetic background of one species can cause sterility or lethality in the genetic background of another species. Progress in identifying and characterizing factors involved in postzygotic isolation in Drosophila has remained slow, mainly because Drosophila melanogaster, with all of its genetic tools, forms dead or sterile hybrids when crossed to its sister species, D. simulans, D. sechellia, and D. mauritiana. To circumvent this problem, we used chromosome deletions and duplications from D. melanogaster to map two hybrid incompatibility loci in F(1) hybrids with its sister species. We mapped a recessive factor to the pericentromeric heterochromatin of the X chromosome in D. simulans and D. mauritiana, which we call heterochromatin hybrid lethal (hhl), which causes lethality in F(1) hybrid females with D. melanogaster. As F(1) hybrid males hemizygous for a D. mauritiana (or D. simulans) X chromosome are viable, the lethality of deficiency hybrid females implies that a dominant incompatible partner locus exists on the D. melanogaster X. Using small segments of the D. melanogaster X chromosome duplicated onto the Y chromosome, we mapped a dominant factor that causes hybrid lethality to a small 24-gene region of the D. melanogaster X. We provide evidence suggesting that it interacts with hhl(mau). The location of hhl is consistent with the emerging theme that hybrid incompatibilities in Drosophila involve heterochromatic regions and factors that interact with the heterochromatin.

Synergism between caffeine and γ-radiation in the induction of dominant lethal mutations in oocytes and spermatozoa of Musca domestica

International Nuclear Information System (INIS)

Targa, H.J.

1983-01-01

Caffeine was studied with regard to its synergism with γ-radiation in the induction of dominant lethal mutations in S14 oocytes and mature spermatozoa of M. domestica. In S14 oocytes an increase in the frequency of such a type of mutation was observed only when the exposure to γ-radiation followed a pretreatment with a diet containing 0.2% of caffeine. Negative results were obtained with (a) post-treatment with the same kind of diet, (b) pretreatment with diets containing 0.1 and 0.02% of caffeine and (c) exposure to the radiation 6 h after interruption of the feeding treatment with the diet containing 0.2% of caffeine. Such influence of the conditions under which the treatment is performed and the synergistic effects is probably related to the food intake pattern and the rapid metabolism of the caffeine. When the 0.2% caffeine pretreatment was combined with an exposure of the oocytes to variable doses of γ-radiation, the increments in the mutations observed seemed to be negatively correlated to the radiation doses used. Also, under such conditions, the dose/survival relationship fits well an exponential curve expressed by in y=-0.866chi. With mature spermatozoa, synergism by caffeine was found only when the females, after having been mated with the irradiated males, were fed for 24 h on a diet supplemented with 0.2% of caffeine. (orig.)

Late Onset Isolated Traumatic Pneumomediastinum in a Child: A Case Report

Directory of Open Access Journals (Sweden)

Ali Kemal Erenler

2013-04-01

Full Text Available Pneumomediastinum (PM is defined as the presence of gas or free air in mediastinum. Pneumomediastinum may ocur either by trauma or spontaneously. Traumatic PM is frequently seen after blunt thoracic trauma, head trauma, after endoscopy-bronchoscopy (osephagus perforation, tracheobronchial injury and due to mechanical ventilation. Pneumomediastinum after blunt trauma is a lethal injury that generally occurs in adults with concomittant injuries such as rib fractures, hemo-pneumothorax and thoracic vascular injuries after high-energy traumas. We represent case report of a late onset isolated traumatic PM in a child and aim to underline the difficulty and importance of diagnosis of this lethal injury in the emergency department.

Late endosomal cholesterol accumulation leads to impaired intra-endosomal trafficking.

Directory of Open Access Journals (Sweden)

Komla Sobo

Full Text Available BACKGROUND: Pathological accumulation of cholesterol in late endosomes is observed in lysosomal storage diseases such as Niemann-Pick type C. We here analyzed the effects of cholesterol accumulation in NPC cells, or as phenocopied by the drug U18666A, on late endosomes membrane organization and dynamics. METHODOLOGY/PRINCIPAL FINDINGS: Cholesterol accumulation did not lead to an increase in the raft to non-raft membrane ratio as anticipated. Strikingly, we observed a 2-3 fold increase in the size of the compartment. Most importantly, properties and dynamics of late endosomal intralumenal vesicles were altered as revealed by reduced late endosomal vacuolation induced by the mutant pore-forming toxin ASSP, reduced intoxication by the anthrax lethal toxin and inhibition of infection by the Vesicular Stomatitis Virus. CONCLUSIONS/SIGNIFICANCE: These results suggest that back fusion of intralumenal vesicles with the limiting membrane of late endosomes is dramatically perturbed upon cholesterol accumulation.

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)

Loss of ATM kinase activity leads to embryonic lethality in mice

DEFF Research Database (Denmark)

Daniel, J.A.; Pellegrini, M.; Filsuf, D.

2012-01-01

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...

Noninvasive risk stratification of lethal ventricular arrhythmias and sudden cardiac death after myocardial infarction

Directory of Open Access Journals (Sweden)

Kenji Yodogawa, MD

2014-08-01

Full Text Available Prediction of lethal ventricular arrhythmias leading to sudden cardiac death is one of the most important and challenging problems after myocardial infarction (MI. Identification of MI patients who are prone to ventricular tachyarrhythmias allows for an indication of implantable cardioverter-defibrillator placement. To date, noninvasive techniques such as microvolt T-wave alternans (MTWA, signal-averaged electrocardiography (SAECG, heart rate variability (HRV, and heart rate turbulence (HRT have been developed for this purpose. MTWA is an indicator of repolarization abnormality and is currently the most promising risk-stratification tool for predicting malignant ventricular arrhythmias. Similarly, late potentials detected by SAECG are indices of depolarization abnormality and are useful in risk stratification. However, the role of SAECG is limited because of its low predictive accuracy. Abnormal HRV and HRT patterns reflect autonomic disturbances, which may increase the risk of lethal ventricular arrhythmias, but the existing evidence is insufficient. Further studies of noninvasive assessment may provide a new insight into risk stratification in post-MI patients.

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).

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.

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

A Danish family with dominant deafness-onychodystrophy syndrome.

Science.gov (United States)

Vind-Kezunovic, Dina; Torring, Pernille M

2013-01-01

The rare hereditary disorder "dominant deafness and onychodystrophy (DDOD) syndrome" (OMIM 124480) has been described in a few case reports. No putative DDOD gene or locus has been mapped and the cause of the disorder remains unknown. We present here three male family members in three generations with sensori-neural deafness, onychodystrophy and brachydactyly inherited via autosomal dominant transmission. The family members presented with absent fingernails on the first and fifth digits. As to the feet, there were absent nails on second to fifth toes in two family members, whereas the third family member only had absent nails on the fifth toe. The proband had late dentition and his father a history of late dentition, but otherwise the teeth appeared normal. Comparative genomic hybridization array analysis (Agilent 400k oligoarray) of the proband did not detect any copy number variation. This Danish family fits within the spectrum of dominant deafness and onychodystrophy syndrome and further characterises this rare disorder.

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

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

Use of the Cone Penetration Testing (CPT) method to interpret late Quaternary tide-dominated successions: A case study from the eastern China coastal plain

Science.gov (United States)

Zhang, Xia; Lin, Chun-Ming; Dalrymple, Robert W.; Gao, Shu; Canas, Daniel T.

2018-06-01

We evaluate the applicability of cone penetration testing (CPT), calibrated using adjacent cores, as a tool for the sedimentological and stratigraphic examination of late Quaternary tide-dominated successions in the eastern China coastal plain. The results indicate that the sedimentary facies and sequence-stratigraphic surfaces can be readily distinguished using CPT profiles in the Qiantang River incised-valley system because of their distinctive mechanical behavior. The lithologic character of the various facies, which is controlled mainly by sediment supply, dynamic processes and post-depositional diagenesis, is the key factor affecting how well the CPT technique works. Within this particular macrotidal environment, which is dominated by non-cohesive sand and silt in the tidal channels, the accumulation of fluid mud is rare. Consequently, the tidal-channel deposits exhibit the geotechnical properties of coarse-grained sediments, and can be easily distinguished from the mud-dominated facies. However, in the nearby Changjiang delta system which is characterized by very high suspended-sediment concentrations and an abundance of fine-grained cohesive sediments, the presence of channel-bottom fluid muds makes it difficult to recognize channel deposits, because of the lack of a sharp lithologic contrast at their base. Consequently, the CPT method might not be as universally effective in tide-dominated systems as it appears to be in wave-dominated settings. Care is needed in the interpretation of the results from tide-dominated successions because of the widespread presence of fluid muds, the heterolithic nature of tidal deposits, the rheological similarity between adjacent facies, and the averaging of geotechnical properties between the alternating finer and coarser layers.

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

Studies on Drosophila radiosensitive strains

International Nuclear Information System (INIS)

Varentsova, E.P.; Zakharov, I.A.

1976-01-01

45 of radiosensitive strains of Drosophila melanogaster were isolated by Curly/Lobe technique after EMS treatment of Livadia population males. The lethality of non-Curly late larvae after gamma-irradiation (4000r) characterized radiosensitivity strains. Most of them exhibited higher frequency of the spontaneous dominant lethals (up to 69%). The males of 6 strains were semi-sterile. 5 of these strains exhibited higher frequency of X-chromosome non-disjunction

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.

Confocal observations of late-acting self-incompatibility in Theobroma cacao L.

Science.gov (United States)

Ford, Caroline S; Wilkinson, Mike J

2012-09-01

Cocoa (Theobroma cacao) has an idiosyncratic form of late-acting self-incompatibility that operates through the non-fusion of incompatible gametes. Here, we used high-resolution confocal microscopy to define fine level changes to the embryo sac of the strongly self-incompatible cocoa genotype SCA 24 in the absence of pollination, and following compatible and incompatible pollination. All sperm nuclei had fused with the female nuclei by 48 h following compatible pollinations. However, following incompatible pollinations, we observed divergence in the behaviour of sperm nuclei following release into the embryo sac. Incomplete sperm nucleus migration occurred in approximately half of the embryo sacs, where the sperm nuclei had so far failed to reach the female gamete nuclei. Sperm nuclei reached but did not fuse with the female gamete nuclei in the residual cases. We argue that the cellular mechanisms governing sperm nucleus migration to the egg nucleus and those controlling subsequent nuclear fusion are likely to differ and should be considered independently. Accordingly, we recommend that future efforts to characterise the genetic basis of LSI in cocoa should take care to differentiate between these two events, both of which contribute to failed karyogamy. Implications of these results for continuing efforts to gain better understanding of the genetic control of LSI in cocoa are discussed.

A screen for F1 hybrid male rescue reveals no major-effect hybrid lethality loci in the Drosophila melanogaster autosomal genome.

Science.gov (United States)

Cuykendall, Tawny N; Satyaki, P; Ji, Shuqing; Clay, Derek M; Edelman, Nathaniel B; Kimchy, Alexandra; Li, Ling-Hei; Nuzzo, Erin A; Parekh, Neil; Park, Suna; Barbash, Daniel A

2014-10-27

Hybrid sons between Drosophila melanogaster females and D. simulans males die as 3rd instar larvae. Two genes, D. melanogaster Hybrid male rescue (Hmr) on the X chromosome, and D. simulans Lethal hybrid rescue (Lhr) on chromosome II, interact to cause this lethality. Loss-of-function mutations in either gene suppress lethality, but several pieces of evidence suggest that additional factors are required for hybrid lethality. Here we screen the D. melanogaster autosomal genome by using the Bloomington Stock Center Deficiency kit to search for additional regions that can rescue hybrid male lethality. Our screen is designed to identify putative hybrid incompatibility (HI) genes similar to Hmr and Lhr which, when removed, are dominant suppressors of lethality. After screening 89% of the autosomal genome, we found no regions that rescue males to the adult stage. We did, however, identify several regions that rescue up to 13% of males to the pharate adult stage. This weak rescue suggests the presence of multiple minor-effect HI loci, but we were unable to map these loci to high resolution, presumably because weak rescue can be masked by genetic background effects. We attempted to test one candidate, the dosage compensation gene male specific lethal-3 (msl-3), by using RNA interference with short hairpin microRNA constructs targeted specifically against D. simulans msl-3 but failed to achieve knockdown, in part due to off-target effects. We conclude that the D. melanogaster autosomal genome likely does not contain additional major-effect HI loci. We also show that Hmr is insufficient to fully account for the lethality associated with the D. melanogaster X chromosome, suggesting that additional X-linked genes contribute to hybrid lethality. Copyright © 2014 Cuykendall et al.

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.

Targeted blockade in lethal West Nile virus encephalitis indicates a crucial role for very late antigen (VLA-4-dependent recruitment of nitric oxide-producing macrophages

Directory of Open Access Journals (Sweden)

Getts Daniel R

2012-10-01

Full Text Available Abstract Infiltration of Ly6Chi monocytes from the blood is a hallmark of viral encephalitis. In mice with lethal encephalitis caused by West Nile virus (WNV, an emerging neurotropic flavivirus, inhibition of Ly6Chi monocyte trafficking into the brain by anti-very late antigen (VLA-4 integrin antibody blockade at the time of first weight loss and leukocyte influx resulted in long-term survival of up to 60% of infected mice, with subsequent sterilizing immunity. This treatment had no effect on viral titers but appeared to be due to inhibition of Ly6Chi macrophage immigration. Although macrophages isolated from the infected brain induced WNV-specific CD4+ T-cell proliferation, T cells did not directly contribute to pathology, but are likely to be important in viral control, as antibody-mediated T-cell depletion could not reproduce the therapeutic benefit of anti-VLA-4. Instead, 70% of infiltrating inflammatory monocyte-derived macrophages were found to be making nitric oxide (NO. Furthermore, aminoguanidine-mediated inhibition of induced NO synthase activity in infiltrating macrophages significantly prolonged survival, indicating involvement of NO in the immunopathology. These data show for the first time the therapeutic effects of temporally targeting pathogenic NO-producing macrophages during neurotropic viral encephalitis.

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.

A hepatic protein, fetuin-A, occupies a protective role in lethal systemic inflammation.

Directory of Open Access Journals (Sweden)

Wei Li

2011-02-01

Full Text Available A liver-derived protein, fetuin-A, was first purified from calf fetal serum in 1944, but its potential role in lethal systemic inflammation was previously unknown. This study aims to delineate the molecular mechanisms underlying the regulation of hepatic fetuin-A expression during lethal systemic inflammation (LSI, and investigated whether alterations of fetuin-A levels affect animal survival, and influence systemic accumulation of a late mediator, HMGB1.LSI was induced by endotoxemia or cecal ligation and puncture (CLP in fetuin-A knock-out or wild-type mice, and animal survival rates were compared. Murine peritoneal macrophages were challenged with exogenous (endotoxin or endogenous (IFN-γ stimuli in the absence or presence of fetuin-A, and HMGB1 expression and release was assessed. Circulating fetuin-A levels were decreased in a time-dependent manner, starting between 26 h, reaching a nadir around 24-48 h, and returning towards base-line approximately 72 h post onset of endotoxemia or sepsis. These dynamic changes were mirrored by an early cytokine IFN-γ-mediated inhibition (up to 50-70% of hepatic fetuin-A expression. Disruption of fetuin-A expression rendered animals more susceptible to LSI, whereas supplementation of fetuin-A (20-100 mg/kg dose-dependently increased animal survival rates. The protection was associated with a significant reduction in systemic HMGB1 accumulation in vivo, and parallel inhibition of IFN-γ- or LPS-induced HMGB1 release in vitro.These experimental data suggest that fetuin-A is protective against lethal systemic inflammation partly by inhibiting active HMGB1 release.

A dominantly acting murine allele of Mcm4 causes chromosomal abnormalities and promotes tumorigenesis.

Directory of Open Access Journals (Sweden)

Bruce N Bagley

Full Text Available Here we report the isolation of a murine model for heritable T cell lymphoblastic leukemia/lymphoma (T-ALL called Spontaneous dominant leukemia (Sdl. Sdl heterozygous mice develop disease with a short latency and high penetrance, while mice homozygous for the mutation die early during embryonic development. Sdl mice exhibit an increase in the frequency of micronucleated reticulocytes, and T-ALLs from Sdl mice harbor small amplifications and deletions, including activating deletions at the Notch1 locus. Using exome sequencing it was determined that Sdl mice harbor a spontaneously acquired mutation in Mcm4 (Mcm4(D573H. MCM4 is part of the heterohexameric complex of MCM2-7 that is important for licensing of DNA origins prior to S phase and also serves as the core of the replicative helicase that unwinds DNA at replication forks. Previous studies in murine models have discovered that genetic reductions of MCM complex levels promote tumor formation by causing genomic instability. However, Sdl mice possess normal levels of Mcms, and there is no evidence for loss-of-heterozygosity at the Mcm4 locus in Sdl leukemias. Studies in Saccharomyces cerevisiae indicate that the Sdl mutation produces a biologically inactive helicase. Together, these data support a model in which chromosomal abnormalities in Sdl mice result from the ability of MCM4(D573H to incorporate into MCM complexes and render them inactive. Our studies indicate that dominantly acting alleles of MCMs can be compatible with viability but have dramatic oncogenic consequences by causing chromosomal abnormalities.

A dominantly acting murine allele of Mcm4 causes chromosomal abnormalities and promotes tumorigenesis.

Science.gov (United States)

Bagley, Bruce N; Keane, Thomas M; Maklakova, Vilena I; Marshall, Jonathon G; Lester, Rachael A; Cancel, Michelle M; Paulsen, Alex R; Bendzick, Laura E; Been, Raha A; Kogan, Scott C; Cormier, Robert T; Kendziorski, Christina; Adams, David J; Collier, Lara S

2012-01-01

Here we report the isolation of a murine model for heritable T cell lymphoblastic leukemia/lymphoma (T-ALL) called Spontaneous dominant leukemia (Sdl). Sdl heterozygous mice develop disease with a short latency and high penetrance, while mice homozygous for the mutation die early during embryonic development. Sdl mice exhibit an increase in the frequency of micronucleated reticulocytes, and T-ALLs from Sdl mice harbor small amplifications and deletions, including activating deletions at the Notch1 locus. Using exome sequencing it was determined that Sdl mice harbor a spontaneously acquired mutation in Mcm4 (Mcm4(D573H)). MCM4 is part of the heterohexameric complex of MCM2-7 that is important for licensing of DNA origins prior to S phase and also serves as the core of the replicative helicase that unwinds DNA at replication forks. Previous studies in murine models have discovered that genetic reductions of MCM complex levels promote tumor formation by causing genomic instability. However, Sdl mice possess normal levels of Mcms, and there is no evidence for loss-of-heterozygosity at the Mcm4 locus in Sdl leukemias. Studies in Saccharomyces cerevisiae indicate that the Sdl mutation produces a biologically inactive helicase. Together, these data support a model in which chromosomal abnormalities in Sdl mice result from the ability of MCM4(D573H) to incorporate into MCM complexes and render them inactive. Our studies indicate that dominantly acting alleles of MCMs can be compatible with viability but have dramatic oncogenic consequences by causing chromosomal abnormalities.

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

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.

Dominant Drop mutants are gain-of-function alleles of the muscle segment homeobox gene (msh) whose overexpression leads to the arrest of eye development.

Science.gov (United States)

Mozer, B A

2001-05-15

Dominant Drop (Dr) mutations are nearly eyeless and have additional recessive phenotypes including lethality and patterning defects in eye and sensory bristles due to cis-regulatory lesions in the cell cycle regulator string (stg). Genetic analysis demonstrates that the dominant small eye phenotype is the result of separate gain-of-function mutations in the closely linked muscle segment homeobox (msh) gene, encoding a homeodomain transcription factor required for patterning of muscle and nervous system. Reversion of the Dr(Mio) allele was coincident with the generation of lethal loss-of-function mutations in msh in cis, suggesting that the dominant eye phenotype is the result of ectopic expression. Molecular genetic analysis revealed that two dominant Dr alleles contain lesions upstream of the msh transcription start site. In the Dr(Mio) mutant, a 3S18 retrotransposon insertion is the target of second-site mutations (P-element insertions or deletions) which suppress the dominant eye phenotype following reversion. The pattern of 3S18 expression and the absence of msh in eye imaginal discs suggest that transcriptional activation of the msh promoter accounts for ectopic expression. Dr dominant mutations arrest eye development by blocking the progression of the morphogenetic furrow leading to photoreceptor cell loss via apoptosis. Gal4-mediated ubiquitous expression of msh in third-instar larvae was sufficient to arrest the morphogenetic furrow in the eye imaginal disc and resulted in lethality prior to eclosion. Dominant mutations in the human msx2 gene, one of the vertebrate homologs of msh, are associated with craniosynostosis, a disease affecting cranial development. The Dr mutations are the first example of gain-of-function mutations in the msh/msx gene family identified in a genetically tractible model organism and may serve as a useful tool to identify additional genes that regulate this class of homeodomain proteins. Copyright 2001 Academic Press.

Psychosocial influences on prisoner suicide: a case-control study of near-lethal self-harm in women prisoners.

Science.gov (United States)

Marzano, Lisa; Hawton, Keith; Rivlin, Adrienne; Fazel, Seena

2011-03-01

We examined the psychosocial influences on female prisoner suicide by carrying out a study of near-lethal self-harm. We interviewed 60 women prisoners who had recently engaged in near-lethal self-harm (cases) and 60 others who had never carried out near-lethal acts in prison (controls) from all closed female prison establishments in England and Wales, using mixed quantitative and qualitative methods. We gathered information on socio-demographic and criminological variables, life events and childhood trauma, exposure to suicidal behaviour, contributory and precipitating factors for near-lethal self-harm, social support and psychological characteristics. While socio-demographic factors were only modestly associated with near-lethal self-harm, being on remand, in single cell accommodation, and reporting negative experiences of imprisonment were strong correlates. Recent life events and past trauma, including different forms of childhood abuse, were also significantly associated with near-lethal self-harm, as were a family history of suicide and high scores on measures of depression, aggression, impulsivity and hostility, and low levels of self-esteem and social support. Our findings underline the importance of both individual and prison-related factors for suicide in custody, and hence the need for a comprehensive approach to suicide prevention in women's prisons. Given the multiple needs of female prisoners at-risk of self-harm and suicide, complex psychosocial interventions are likely to be required, including interventions for abused and bereaved women, and initiatives to improve staff-prisoner relationships and reduce bullying. The findings of this research may provide insights into factors leading to suicidal behaviour in other forensic and institutional settings, such as detention centres and psychiatric hospitals, and may assist in developing suicide prevention policies for prisoners and other at-risk populations. Copyright © 2011 Elsevier Ltd. All rights

USP22 regulates oncogenic signaling pathways to drive lethal cancer progression.

Science.gov (United States)

Schrecengost, Randy S; Dean, Jeffry L; Goodwin, Jonathan F; Schiewer, Matthew J; Urban, Mark W; Stanek, Timothy J; Sussman, Robyn T; Hicks, Jessica L; Birbe, Ruth C; Draganova-Tacheva, Rossitza A; Visakorpi, Tapio; DeMarzo, Angelo M; McMahon, Steven B; Knudsen, Karen E

2014-01-01

Increasing evidence links deregulation of the ubiquitin-specific proteases 22 (USP22) deubitiquitylase to cancer development and progression in a select group of tumor types, but its specificity and underlying mechanisms of action are not well defined. Here we show that USP22 is a critical promoter of lethal tumor phenotypes that acts by modulating nuclear receptor and oncogenic signaling. In multiple xenograft models of human cancer, modeling of tumor-associated USP22 deregulation demonstrated that USP22 controls androgen receptor accumulation and signaling, and that it enhances expression of critical target genes coregulated by androgen receptor and MYC. USP22 not only reprogrammed androgen receptor function, but was sufficient to induce the transition to therapeutic resistance. Notably, in vivo depletion experiments revealed that USP22 is critical to maintain phenotypes associated with end-stage disease. This was a significant finding given clinical evidence that USP22 is highly deregulated in tumors, which have achieved therapeutic resistance. Taken together, our findings define USP22 as a critical effector of tumor progression, which drives lethal phenotypes, rationalizing this enzyme as an appealing therapeutic target to treat advanced disease.

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...

Late Ordovician pelecypod faunas from the Cincinnati, Ohio area

Energy Technology Data Exchange (ETDEWEB)

Frey, R.C.

1985-01-01

The distribution of pelecypod faunas in the Late Ordovician strata exposed in the Cincinnati, Ohio area, points to a close relationship between lithofacies type and the life habits of these Ordovician bivalves. Muddy clastic shallow marine facies of Edenian, Maysvillian, and early Richmondian age support faunas dominated by endobyssate filter-feeding species, including a variety of modiomorphids and the genus Ambonychia, plus infaunal filter-feeding orthonotids, and in faunal deposit-feeding palaeotaxodonts. These pelecypod groups occur in claystones with a fauna of calymenid and asaphid trilobites, nautiloids, cyclomyan monoplacophorans, and occasionally crinoids and asterozoans. Younger Richmondian strata in the area are predominantly carbonate platform facies and support pelecypod faunas dominated by robust endobyssate and epibyssate ambonychiids, cyrtodontids, and colpomyids. These pelecypods are associated with diverse assemblage of articulate brachiopods, trepostome ectoprocts, solitary rugose corals, and mollusks in skeletal limestones representing storm-reworked thickets or ramos ectoprocts. This fundamental dichotomy in Late Ordovician pelecypod faunas is recognized not only in the Cincinnati area, but in Late Ordovician strata exposed on Manitoulin Island in Ontario and eastward into Quebec. Reconstructions of the life habits of these pelecypods demonstrates the dominance of the endobyssate mode of life in these Early Paleozoic pelecypods.

Early-acting inbreeding depression and reproductive success in the highbush blueberry, Vaccinium corymbosum L.

Science.gov (United States)

Krebs, S L; Hancock, J F

1990-06-01

Tetraploid Vaccinium corymbosum genotypes exhibit wide variability in seed set following self- and cross-pollinations. In this paper, a post-zygotic mechanism (seed abortion) under polygenic control is proposed as the basis for fertility differences in this species. A pollen chase experiment indicated that self-pollen tubes fertilize ovules, but are also 'outcompeted' by foreign male gametes in pollen mixtures. Matings among cultivars derived from a pedigree showed a linear decrease in seed number per fruit, and increase in seed abortion, with increasing relatedness among parents. Selfed (S1) progeny from self-fertile parents were largely self-sterile. At zygotic levels of inbreeding of F>0.3 there was little or no fertility, suggesting that an inbreeding threshold regulates reproductive success in V. corymbosum matings. Individuals below the threshold are facultative selfers, while those above it are obligate outcrossers. Inbreeding also caused a decrease in pollen viability, and reduced female fertility more rapidly than male fertility. These phenomena are discussed in terms of two models of genetic load: (1) mutational load - homozygosity for recessive embryolethal or sub-lethal mutations and (2) segregational load - loss of allelic interactions essential for embryonic vigor. Self-infertility in highbush blueberries is placed in the context of 'late-acting' self-incompatibility versus 'early-acting' inbreeding depression in angiosperms.

Functional diversity of non-lethal effects, chemical camouflage, and variation in fish avoidance in colonizing beetles.

Science.gov (United States)

Resetarits, William J; Pintar, Matthew R

2016-12-01

Predators play an extremely important role in natural communities. In freshwater systems, fish can dominate sorting both at the colonization and post-colonization stage. Specifically, for many colonizing species, fish can have non-lethal, direct effects that exceed the lethal direct effects of predation. Functionally diverse fish species with a range of predatory capabilities have previously been observed to elicit functionally equivalent responses on oviposition in tree frogs. We tested this hypothesis of functional equivalence of non-lethal effects for four predatory fish species, using naturally colonizing populations of aquatic beetles. Among taxa other than mosquitoes, and with the exception of the chemically camouflaged pirate perch, Aphredoderus sayanus, we provide the first evidence of variation in colonization or oviposition responses to different fish species. Focusing on total abundance, Fundulus chrysotus, a gape-limited, surface-feeding fish, elicited unique responses among colonizing Hydrophilidae, with the exception of the smallest and most abundant taxa, Paracymus, while Dytiscidae responded similarly to all avoided fish. Neither family responded to A. sayanus. Analysis of species richness and multivariate characterization of the beetle assemblages for the four fish species and controls revealed additional variation among the three avoided species and confirmed that chemical camouflage in A. sayanus results in assemblages essentially identical to fishless controls. The origin of this variation in beetle responses to different fish is unknown, but may involve variation in cue sensitivity, different behavioral algorithms, or differential responses to species-specific fish cues. The identity of fish species occupying aquatic habitats is crucial to understanding community structure, as varying strengths of lethal and non-lethal effects, as well as their interaction, create complex landscapes of predator effects and challenge the notion of functional

Protein complexes and cholesterol in the control of late endosomal dynamicsCholesterol and multi-protein complexes in the control of late endosomal dynamics

NARCIS (Netherlands)

Kant, Rik Henricus Nicolaas van der

2013-01-01

Late endosomal transport is disrupted in several diseases such as Niemann-Pick type C, ARC syndrome and Alzheimer’s disease. This thesis describes the regulation of late endosomal dynamics by cholesterol and multi-protein complexes. We find that cholesterol acts as a cellular tomtom that steers the

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.

[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.

Transgenic Drosophila simulans strains prove the identity of the speciation gene Lethal hybrid rescue.

Science.gov (United States)

Prigent, Stéphane R; Matsubayashi, Hiroshi; Yamamoto, Masa-Toshi

2009-10-01

Speciation genes are responsible for genetic incompatibilities in hybrids of incipient species and therefore participate in reproductive isolation leading to complete speciation. Hybrid males between Drosophila melanogaster females and D. simulans males die at late larval or prepupal stages due to a failure in chromosome condensation during mitosis. However a mutant male of D. simulans, named Lethal hybrid rescue (Lhr), produces viable hybrid males when crossed to females of D. melanogaster. Recently the Lhr gene has been proposed as corresponding to the CG18468 gene in D. melanogaster. However this identification relied on sequence characteristics more than on a precise mapping and the use of the GAL4/UAS system to drive the transgene in D. melanogaster might have increased the complexity of interaction. Thus here we propose an independent identification of the Lhr gene based on a more precise mapping and transgenic experiments in D. simulans. We have mapped the Lhr gene by using Single Nucleotide Polymorphisms (SNPs) and identified within the candidate region the gene homologous to CG18468 as the Lhr gene as it was previously reported. Transgenic experiments in D. simulans with the native promoter of CG18468 prove that it is the Lhr gene of D. simulans by inducing the lethality of the hybrid males.

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 ...

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

Lethal firearm-related violence against Canadian women: did tightening gun laws have an impact on women's health and safety?

Science.gov (United States)

McPhedran, Samara; Mauser, Gary

2013-01-01

Domestic violence remains a significant public health issue around the world, and policy makers continually strive to implement effective legislative frameworks to reduce lethal violence against women. This article examines whether the 1995 Firearms Act (Bill C-68) had a significant impact on female firearm homicide victimization rates in Canada. Time series of gender-disaggregated data from 1974 to 2009 were examined. Two different analytic approaches were used: the autoregressive integrated moving average (ARIMA) modelling and the Zivot-Andrews (ZA) structural breakpoint tests. There was little evidence to suggest that increased firearms legislation in Canada had a significant impact on preexisting trends in lethal firearm violence against women. These results do not support the view that increasing firearms legislation is associated with a reduced incidence of firearm-related female domestic homicide victimization.

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

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

From nature-dominated to human-dominated environmental changes

Science.gov (United States)

Messerli, Bruno; Grosjean, Martin; Hofer, Thomas; Núñez, Lautaro; Pfister, Christian

2000-01-01

To what extent is it realistic and useful to view human history as a sequence of changes from highly vulnerable societies of hunters and gatherers through periods with less vulnerable, well buffered and highly productive agrarian-urban societies to a world with regions of extreme overpopulation and overuse of life support systems, so that vulnerability to climatic-environmental changes and extreme events is again increasing? This question cannot be fully answered in our present state of knowledge, but at least we can try to illustrate, with three case studies from different continents, time periods and ecosystems, some fundamental changes in the relationship between natural processes and human activities that occur, as we pass from a nature-dominated to a human dominated environment. 1. Early-mid Holocene: Nature dominated environment — human adaptation, mitigation, and migration. In the central Andes, the Holocene climate changed from humid (10,800-8000 BP) to extreme arid (8000-3600 BP) conditions. Over the same period, prehistoric hunting communities adopted a more sedentary pattern of resource use by settling close to the few perennial water bodies, where they began the process of domesticating camelids around 5000 BP and irrigation from about 3100 BP. 2. Historical period: An agrarian society in transition from an "enduring" to an innovative human response. Detailed documentary evidence from Western Europe may be used to reconstruct quite precisely the impacts of climatic variations on agrarian societies. The period considered spans a major transition from an apparently passive response to the vagaries of the environment during the 16th century to an active and innovative attitude from the onset of the agrarian revolution in the late 18th century through to the present day. The associated changes in technology and in agricultural practices helped to create a society better able to survive the impact of climatic extremes. 3. The present day: A human dominated

What Are Reasons for the Large Gender Differences in the Lethality of Suicidal Acts? An Epidemiological Analysis in Four European Countries

NARCIS (Netherlands)

Mergl, Roland; Koburger, Nicole; Heinrichs, Katherina; Szekely, Andras; Toth, Monika Ditta; Coyne, James; Quintao, Sonia; Arensman, Ella; Coffey, Claire; Maxwell, Margaret; Vaernik, Airi; van Audenhove, Chantal; McDaid, David; Sarchiapone, Marco; Schmidtke, Armin; Genz, Axel; Gusmao, Ricardo; Hegerl, Ulrich

2015-01-01

Background In Europe, men have lower rates of attempted suicide compared to women and at the same time a higher rate of completed suicides, indicating major gender differences in lethality of suicidal behaviour. The aim of this study was to analyse the extent to which these gender differences in

Mutations in LOXHD1, a Recessive-Deafness Locus, Cause Dominant Late-Onset Fuchs Corneal Dystrophy

Science.gov (United States)

Riazuddin, S. Amer; Parker, David S.; McGlumphy, Elyse J.; Oh, Edwin C.; Iliff, Benjamin W.; Schmedt, Thore; Jurkunas, Ula; Schleif, Robert; Katsanis, Nicholas; Gottsch, John D.

2012-01-01

Fuchs corneal dystrophy (FCD) is a genetic disorder of the corneal endothelium and is the most common cause of corneal transplantation in the United States. Previously, we mapped a late-onset FCD locus, FCD2, on chromosome 18q. Here, we present next-generation sequencing of all coding exons in the FCD2 critical interval in a multigenerational pedigree in which FCD segregates as an autosomal-dominant trait. We identified a missense change in LOXHD1, a gene causing progressive hearing loss in humans, as the sole variant capable of explaining the phenotype in this pedigree. We observed LOXHD1 mRNA in cultured human corneal endothelial cells, whereas antibody staining of both human and mouse corneas showed staining in the corneal epithelium and endothelium. Corneal sections of the original proband were stained for LOXHD1 and demonstrated a distinct increase in antibody punctate staining in the endothelium and Descemet membrane; punctate staining was absent from both normal corneas and FCD corneas negative for causal LOXHD1 mutations. Subsequent interrogation of a cohort of >200 sporadic affected individuals identified another 15 heterozygous missense mutations that were absent from >800 control chromosomes. Furthermore, in silico analyses predicted that these mutations reside on the surface of the protein and are likely to affect the protein's interface and protein-protein interactions. Finally, expression of the familial LOXHD1 mutant allele as well as two sporadic mutations in cells revealed prominent cytoplasmic aggregates reminiscent of the corneal phenotype. All together, our data implicate rare alleles in LOXHD1 in the pathogenesis of FCD and highlight how different mutations in the same locus can potentially produce diverse phenotypes. PMID:22341973

Excessive prices as abuse of dominance?

DEFF Research Database (Denmark)

la Cour, Lisbeth; Møllgaard, Peter

2007-01-01

firm abused its position by charging excessive prices. We also test whether tightening of the Danish competition act has altered the pricing behaviour on the market. We discuss our results in the light of a Danish competition case against the dominant cement producer that was abandoned by the authority...

Therapeutic efficacy of antibodies lacking Fcγ receptor binding against lethal dengue virus infection is due to neutralizing potency and blocking of enhancing antibodies [corrected].

Directory of Open Access Journals (Sweden)

Katherine L Williams

2013-02-01

Full Text Available Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS are life-threatening complications following infection with one of the four serotypes of dengue virus (DENV. At present, no vaccine or antiviral therapies are available against dengue. Here, we characterized a panel of eight human or mouse-human chimeric monoclonal antibodies (MAbs and their modified variants lacking effector function and dissected the mechanism by which some protect against antibody-enhanced lethal DENV infection. We found that neutralizing modified MAbs that recognize the fusion loop or the A strand epitopes on domains II and III of the envelope protein, respectively, act therapeutically by competing with and/or displacing enhancing antibodies. By analyzing these relationships, we developed a novel in vitro suppression-of-enhancement assay that predicts the ability of modified MAbs to act therapeutically against antibody-enhanced disease in vivo. These studies provide new insight into the biology of DENV pathogenesis and the requirements for antibodies to treat lethal DENV disease.

A Late Mesozoic short-lived shift from fluid-dominated to sediment-dominated mantle metasomatism in the northeast South China Block and its tectonic implications

Science.gov (United States)

Pan, Fa-Bin; Jin, Chong; Jia, Bao-Jian; Liu, Rong; He, Xiaobo; Gao, Zhong; Tao, Lu; Zhou, Xiao-Chun; Zhang, Li-Qi

2018-06-01

Early Cretaceous northwest (NW)-trending dolerite and amphibole lamprophyre dykes exposed in NW Zhejiang Province provide a number of new insights into the nature of the subcontinental mantle on the northeast (NE) South China Block (SCB). These dykes have a high Al2O3 (14.04-17.89 wt%) and K2O (0.66-2.69 wt%) contents but relatively low Na2O (2.48-4.61 wt%) and TiO2 (1.33-2.79 wt%) makeup alongside moderate K2O/Na2O ratios between 0.26 and 1.04. These amphibole lamprophyre dykes also have higher MgO, Cr, and Ni contents than those of comparable dolerites that have SiO2 content ranging from 46.32 to 49.87 wt%. The most striking feature of these intrusions is that they contain higher contents of Rb, Th, U, Nb, Ta, and LREE compared to their dolerite counterparts, although both amphibole lamprophyres and dolerites do exhibit similar geochemical patterns that are indicative of subduction-related origins. These features imply that an ambient peridotitic mantle that acted as the source for the amphibole lamprophyre magma source may have reacted with silicate-rich melts leading to olivine consumption while maintaining orthopyroxene. The geochemical composition of these dolerites are likely influenced to a variable extent by the fractionation of olivine, orthopyroxene, clinopyroxene, Fe-Ti oxides, and apatite, while their amphibole lamprophyre counterparts have been modified to a minor degree by amphibole fractionation. Measured Sr-Nd isotopic compositions suggest relatively constant Nd isotopic compositions (-0.36 to +1.52) with more variable Sr isotopic compositions (0.7071 to 0.7306). We hence propose that both the dolerite and amphibole lamprophyre dykes in this region are the products of mantle source metasomatism by the subducted Paleo-Pacific slab. The dolerite dykes are mainly associated with slab-derived fluids, while the lamprophyre dykes are related to both slab-derived fluids and sediment melts. Evidence in support of metasomatism comprising distinct two

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.

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.

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

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.

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)

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

49 CFR 89.23 - Interest, late payment penalties, and collection charges.

Science.gov (United States)

2010-10-01

... received. Interest shall be calculated only on the principal of the debt (simple interest). The rate of... 49 Transportation 1 2010-10-01 2010-10-01 false Interest, late payment penalties, and collection... THE FEDERAL CLAIMS COLLECTION ACT Collection of Claims § 89.23 Interest, late payment penalties, and...

Antibacterial activity of essential oils: potential applications in food

NARCIS (Netherlands)

Burt, S.A.

2007-01-01

Due to its antibacterial activity, oregano oil has lately become interesting as a potential 'natural' food preservative. Oregano oil was found to be a fast acting and effective inhibitor of a strain of Escherichia coli O157:H7, the causative agent of a serious gastro-enteritis, and was lethal to

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.

Bulk viscous matter-dominated Universes: asymptotic properties

Energy Technology Data Exchange (ETDEWEB)

Avelino, Arturo [Departamento de Física, Campus León, Universidad de Guanajuato, León, Guanajuato (Mexico); García-Salcedo, Ricardo [Centro de Investigacion en Ciencia Aplicada y Tecnologia Avanzada - Legaria del IPN, México D.F. (Mexico); Gonzalez, Tame [Departamento de Ingeniería Civil, División de Ingeniería, Universidad de Guanajuato, Guanajuato (Mexico); Nucamendi, Ulises [Instituto de Física y Matemáticas, Universidad Michoacana de San Nicolás de Hidalgo, Edificio C-3, Ciudad Universitaria, CP. 58040 Morelia, Michoacán (Mexico); Quiros, Israel, E-mail: avelino@fisica.ugto.mx, E-mail: rigarcias@ipn.mx, E-mail: tamegc72@gmail.com, E-mail: ulises@ifm.umich.mx, E-mail: iquiros6403@gmail.com [Departamento de Matemáticas, Centro Universitario de Ciencias Exactas e Ingenierías (CUCEI), Corregidora 500 S.R., Universidad de Guadalajara, 44420 Guadalajara, Jalisco (Mexico)

2013-08-01

By means of a combined use of the type Ia supernovae and H(z) data tests, together with the study of the asymptotic properties in the equivalent phase space — through the use of the dynamical systems tools — we demonstrate that the bulk viscous matter-dominated scenario is not a good model to explain the accepted cosmological paradigm, at least, under the parametrization of bulk viscosity considered in this paper. The main objection against such scenarios is the absence of conventional radiation and matter-dominated critical points in the phase space of the model. This entails that radiation and matter dominance are not generic solutions of the cosmological equations, so that these stages can be implemented only by means of unique and very specific initial conditions, i. e., of very unstable particular solutions. Such a behavior is in marked contradiction with the accepted cosmological paradigm which requires of an earlier stage dominated by relativistic species, followed by a period of conventional non-relativistic matter domination, during which the cosmic structure we see was formed. Also, we found that the bulk viscosity is positive just until very late times in the cosmic evolution, around z < 1. For earlier epochs it is negative, been in tension with the local second law of thermodynamics.

Feelings of women regarding end-of-life decision making after ultrasound diagnosis of a lethal fetal malformation.

Science.gov (United States)

Benute, Gláucia R G; Nomura, Roseli M Y; Liao, Adolfo W; Brizot, Maria de Lourdes; de Lucia, Mara C S; Zugaib, M

2012-08-01

this study investigated the feelings of women regarding end-of-life decision making after ultrasound diagnosis of a lethal fetal malformation. The aim of this study was to present the decision making process of women that chose for pregnancy termination and to present selected speeches of women about their feelings. open psychological interviews conducted by a psychologist immediately after the diagnosis of fetal malformation by ultrasound. Analysis of the results was performed through a content analysis technique. the study was carried out at a public university hospital in Brazil. 249 pregnant women who had received the diagnosis of a severe lethal fetal malformation. fetal anencephaly was the most frequent anomaly detected in 135 cases (54.3%). Termination of pregnancy was decided by 172 (69.1%) patients and legally authorised by the judiciary (66%). The reason for asking for termination was to reduce suffering in all of them. In the 77 women who chose not to terminate pregnancy (30.9%), the reasons were related to feelings of guilt (74%). the results support the importance of psychological counselling for couples when lethal fetal malformation is diagnosed. The act of reviewing moral and cultural values and elements of the unconscious provides assurance in the decision-making process and mitigates the risk of emotional trauma and guilt that can continue long after the pregnancy is terminated. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ecogeomorphology of Spartina patens-dominated tidal marshes: Soil organic matter accumulation, marsh elevation dynamics, and disturbance

Science.gov (United States)

Cahoon, D.R.; Ford, M.A.; Hensel, P.F.; Fagherazzi, Sergio; Marani, Marco; Blum, Linda K.

2004-01-01

Marsh soil development and vertical accretion in Spartina patens (Aiton) Muhl.-dominated tidal marshes is largely dependent on soil organic matter accumulation from root-rhizome production and litter deposition. Yet there are few quantitative data sets on belowground production and the relationship between soil organic matter accumulation and soil elevation dynamics for this marsh type. Spartina patens marshes are subject to numerous stressors, including sea-level rise, water level manipulations (i.e., flooding and draining) by impoundments, and prescribed burning. These stressors could influence long-term marsh sustainability by their effect on root production, soil organic matter accumulation, and soil elevation dynamics. In this review, we summarize current knowledge on the interactions among vegetative production, soil organic matter accumulation and marsh elevation dynamics, or the ecogeomorphology, of Spartina patens-dominated tidal marshes. Additional studies are needed of belowground production/decomposition and soil elevation change (measured simultaneously) to better understand the links among soil organic matter accumulation, soil elevation change, and disturbance in this marsh type. From a management perspective, we need to better understand the impacts of disturbance stressors, both lethal and sub-lethal, and the interactive effect of multiple stressors on soil elevation dynamics in order to develop better management practices to safeguard marsh sustainability as sea level rises.

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.

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.

Climate and vegetational regime shifts in the late Paleozoic ice age earth.

Science.gov (United States)

DiMichele, W A; Montañez, I P; Poulsen, C J; Tabor, N J

2009-03-01

The late Paleozoic earth experienced alternation between glacial and non-glacial climates at multiple temporal scales, accompanied by atmospheric CO2 fluctuations and global warming intervals, often attended by significant vegetational changes in equatorial latitudes of Pangaea. We assess the nature of climate-vegetation interaction during two time intervals: middle-late Pennsylvanian transition and Pennsylvanian-Permian transition, each marked by tropical warming and drying. In case study 1, there is a catastrophic intra-biomic reorganization of dominance and diversity in wetland, evergreen vegetation growing under humid climates. This represents a threshold-type change, possibly a regime shift to an alternative stable state. Case study 2 is an inter-biome dominance change in western and central Pangaea from humid wetland and seasonally dry to semi-arid vegetation. Shifts between these vegetation types had been occurring in Euramerican portions of the equatorial region throughout the late middle and late Pennsylvanian, the drier vegetation reaching persistent dominance by Early Permian. The oscillatory transition between humid and seasonally dry vegetation appears to demonstrate a threshold-like behavior but probably not repeated transitions between alternative stable states. Rather, changes in dominance in lowland equatorial regions were driven by long-term, repetitive climatic oscillations, occurring with increasing intensity, within overall shift to seasonal dryness through time. In neither case study are there clear biotic or abiotic warning signs of looming changes in vegetational composition or geographic distribution, nor is it clear that there are specific, absolute values or rates of environmental change in temperature, rainfall distribution and amount, or atmospheric composition, approach to which might indicate proximity to a terrestrial biotic-change threshold.

Diversification of C(4) grasses (Poaceae) does not coincide with their ecological dominance.

Science.gov (United States)

Bouchenak-Khelladi, Yanis; Slingsby, Jasper A; Verboom, G Anthony; Bond, William J

2014-02-01

The radiation of a lineage and its rise to ecological dominance are distinct phenomena and driven by different processes. For example, paleoecological data has been used to show that the Cretaceous angiosperm radiation did not coincide with their rise to dominance. Using a phylogenetic approach, we here explored the evolution of C4 grasses and evaluated whether the diversification of this group and its rise to ecological dominance in the late Miocene were decoupled. We assembled a matrix including 675 grass species of the PACMAD clade and 2784 characters (ITS and ndhF) to run a molecular dating analysis using three fossils as reference calibrations. We coded species as C3 vs. C4 and reconstructed ancestral states under maximum likelihood. We used the program BiSSE to test whether rates of diversification are correlated with photosynthetic pathway and whether the radiation of C4 lineages preceded or coincided with their rise to ecological dominance from ∼10 Ma. C4 grass lineages first originated around 35 Ma at the time of the Eocene-Oligocene transition. Accelerated diversification of C4 lineages did not coincide with their rise to ecological dominance. C4-dominated grasslands have expanded only since the Late Miocene and Pliocene. The initial diversification of their biotic elements can be tracked back as far as the Eocene-Oligocene transition. We suggest that shifts in taxonomic diversification and ecological dominance were stimulated by different factors, as in the case of the early angiosperms in the Cretaceous.

The HIV Act - better late than never.

Science.gov (United States)

Divan, Vivek

2018-01-01

Although over 15 years in the making, the HIV legislation has recently been passed in India. This Act is unique in many respects, and hopefully a precursor to broader health sector legislation. The process of law making in this instance included a robust consultative process with civil society and other stakeholders involved with HIV. Some of the unique aspects of the Act, as it was eventually passed, include an anti-discrimination provision to cover violations by the private sector, and concrete provisions to ensure informed consent while seeking HIV-related testing and treatment, and confidentiality of HIV status. However, the law fails to recognise the enhanced vulnerability to HIV that some people - sex workers, transgender people, men who have sex with men, and people who use drugs - face, which should have been addressed by extending anti-discrimination guarantees to these communities, thereby providing a legal tool to access health, employment, educational, and other sectors; while also serving public health imperatives to encourage marginalised people towards health-seeking behaviour without fear of stigma and mistreatment. Yet, at least the legislation does protect these criminalised communities from punishment when they access or are provided HIV-related services and commodities, which could otherwise be tantamount to a crime. Another drawback of the law is the diluted obligation of the State to provide antiretroviral treatment to those in need. The legislation also provides options to redress grievances, which are localised, less formal and intimidating, and more accessible than courts, thereby recognising that implementation and actualisation of rights is critical to the success of the law, and efforts to control HIV.

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.

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.

Structure and novel functional mechanism of Drosophila SNF in sex-lethal splicing.

Directory of Open Access Journals (Sweden)

Jicheng Hu

Full Text Available Sans-fille (SNF is the Drosophila homologue of mammalian general splicing factors U1A and U2B'', and it is essential in Drosophila sex determination. We found that, besides its ability to bind U1 snRNA, SNF can also bind polyuridine RNA tracts flanking the male-specific exon of the master switch gene Sex-lethal (Sxl pre-mRNA specifically, similar to Sex-lethal protein (SXL. The polyuridine RNA binding enables SNF directly inhibit Sxl exon 3 splicing, as the dominant negative mutant SNF(1621 binds U1 snRNA but not polyuridine RNA. Unlike U1A, both RNA recognition motifs (RRMs of SNF can recognize polyuridine RNA tracts independently, even though SNF and U1A share very high sequence identity and overall structure similarity. As SNF RRM1 tends to self-associate on the opposite side of the RNA binding surface, it is possible for SNF to bridge the formation of super-complexes between two introns flanking Sxl exon 3 or between a intron and U1 snRNP, which serves the molecular basis for SNF to directly regulate Sxl splicing. Taken together, a new functional model for SNF in Drosophila sex determination is proposed. The key of the new model is that SXL and SNF function similarly in promoting Sxl male-specific exon skipping with SNF being an auxiliary or backup to SXL, and it is the combined dose of SXL and SNF governs Drosophila sex determination.

Epistasis modifies the dominance of loci causing hybrid male sterility in the Drosophila pseudoobscura species group.

Science.gov (United States)

Chang, Audrey S; Noor, Mohamed A F

2010-01-01

Speciation, the evolution of reproductive isolation between populations, serves as the driving force for generating biodiversity. Postzygotic barriers to gene flow, such as F(1) hybrid sterility and inviability, play important roles in the establishment and maintenance of biological species. F(1) hybrid incompatibilities in taxa that obey Haldane's rule, the observation that the heterogametic sex suffers greater hybrid fitness problems than the homogametic sex, are thought to often result from interactions between recessive-acting X-linked loci and dominant-acting autosomal loci. Because they play such prominent roles in producing hybrid incompatibilities, we examine the dominance and nature of epistasis between alleles derived from Drosophila persimilis that confer hybrid male sterility in the genetic background of its sister species, D. pseudoobscura bogotana. We show that epistasis elevates the apparent dominance of individually recessive-acting QTL such that they can contribute to F(1) hybrid sterility. These results have important implications for assumptions underlying theoretical models of hybrid incompatibilities and may offer a possible explanation for why, to date, identification of dominant-acting autosomal "speciation genes" has been challenging.

Late Neogene leaf assemblage from Bełchatów Lignite Mine (central Poland

Directory of Open Access Journals (Sweden)

Worobiec Grzegorz

2014-12-01

Full Text Available Leaf macroremains collected in the Bełchatów Lignite Mine (central Poland were investigated. The fossil assemblage consists of leaves of Acer, Betula, Carpinus, Dicotylophyllum, Fagus, ?Magnolia, “Parrotia”, Pinus, Quercus, and Zelkova. Mesophytic (zonal elements dominate, with admixture of riparian (azonal leaf taxa. The floristic composition points to late Neogene (late Miocene to late Pliocene age and suggests favourable temperate climate with mild winters.

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...

Status Decreases Dominance in the West but Increases Dominance in the East.

Science.gov (United States)

Kuwabara, Ko; Yu, Siyu; Lee, Alice J; Galinsky, Adam D

2016-02-01

In the experiments reported here, we integrated work on hierarchy, culture, and the enforcement of group cooperation by examining patterns of punishment. Studies in Western contexts have shown that having high status can temper acts of dominance, suggesting that high status may decrease punishment by the powerful. We predicted that high status would have the opposite effect in Asian cultures because vertical collectivism permits the use of dominance to reinforce the existing hierarchical order. Across two experiments, having high status decreased punishment by American participants but increased punishment by Chinese and Indian participants. Moreover, within each culture, the effect of status on punishment was mediated by feelings of being respected. A final experiment found differential effects of status on punishment imposed by Asian Americans depending on whether their Asian or American identity was activated. Analyzing enforcement through the lens of hierarchy and culture adds insight into the vexing puzzle of when and why people engage in punishment. © The Author(s) 2015.

Can Mustard Gas Induce Late Onset Polyneuropathy?

Directory of Open Access Journals (Sweden)

SJ. Mousavi

2007-11-01

Full Text Available Background:Mustard gas, lethal in high doses, affects multiple organs such as skin, eye and respiratory system. We studied the development of late onset mustardinduced polyneuropathy among chemically wounded Iranian veterans.Methods:In this descriptive study,100 chemically wounded Iranian veterans with severe eye involvement were examined for any signs and symptoms of polyneuropathy by an internist.20 patients were suspected to have neurological symptoms or signs.These patients were examined by a neurologist again. 13 showed abnormal neurological symptoms. Electrodiagnostic exams were performed for this group by another physician.Results:13 veterans had abnormal neurological exam results with prominent sensory signs and symptoms in almost all of them. Brisk deep tendon reflexes were found in 3 cases. Electrodiagnostic studies were compatible with axonal type distal sensory polyneuropathy in 6 subjects. Conclusion: To the best of our knowledge, this is the first report of late onset polyneuropathy among chemically-wounded victims who were exposed to mustard gas. The pathophysiology of this form of neuropathy is still unknown. Unlike most toxic neuropathies,obvious clinical signs and symptoms appeared several years after exposure. No specific treatment for.polyneuropathy due to chemical weapons exposure has been described to date.

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.

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.

A survey of new temperature-sensitive, embryonic-lethal mutations in C. elegans: 24 alleles of thirteen genes.

Directory of Open Access Journals (Sweden)

Sean M O'Rourke

2011-03-01

Full Text Available To study essential maternal gene requirements in the early C. elegans embryo, we have screened for temperature-sensitive, embryonic lethal mutations in an effort to bypass essential zygotic requirements for such genes during larval and adult germline development. With conditional alleles, multiple essential requirements can be examined by shifting at different times from the permissive temperature of 15°C to the restrictive temperature of 26°C. Here we describe 24 conditional mutations that affect 13 different loci and report the identity of the gene mutations responsible for the conditional lethality in 22 of the mutants. All but four are mis-sense mutations, with two mutations affecting splice sites, another creating an in-frame deletion, and one creating a premature stop codon. Almost all of the mis-sense mutations affect residues conserved in orthologs, and thus may be useful for engineering conditional mutations in other organisms. We find that 62% of the mutants display additional phenotypes when shifted to the restrictive temperature as L1 larvae, in addition to causing embryonic lethality after L4 upshifts. Remarkably, we also found that 13 out of the 24 mutations appear to be fast-acting, making them particularly useful for careful dissection of multiple essential requirements. Our findings highlight the value of C. elegans for identifying useful temperature-sensitive mutations in essential genes, and provide new insights into the requirements for some of the affected loci.

Pay Equity Act, 17 May 1988.

Science.gov (United States)

1988-01-01

This document contains major provisions of the 1988 Pay Equity Act of Prince Edward Island, Canada. (Nova Scotia enacted similar legislation in 1988.) This act defines "female-dominated class" or "male-dominated class" as a class with 60% or more female or male incumbents, respectively. The objective of this act is to achieve pay equity among public sector employers and employees by identifying systemic gender discrimination through a comparison of the relative wages and value of the work performed by female- and male-dominated classes. The value of work is to be determined by considering the skill, effort, and responsibility required by the work as well as the conditions under which it is performed. A difference in wages between a female- and male-dominated class performing work of equal or comparable value can be justified by a formal performance appraisal system or formal seniority system that does not discriminate on the basis of gender or by a skills shortage which requires a temporary inflation in wages to attract workers for a certain position. No wages shall be reduced to implement pay equity. Implementation of pay equity will include the work of bargaining agents to achieve agreement on salient points. Pay equity may be implemented in four stages over a period of 24 months.

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

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.

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.

CD4+ T cells targeting dominant and cryptic epitopes from Bacillus anthracis Lethal Factor

Directory of Open Access Journals (Sweden)

Stephanie eAscough

2016-01-01

Full Text Available Anthrax is an endemic infection in many countries, particularly in the developing world. The causative agent, Bacillus anthracis, mediates disease through the secretion of binary exotoxins. Until recently, research into adaptive immunity targeting this bacterial pathogen has largely focused on the humoral response to these toxins. There is, however, growing recognition that cellular immune responses involving IFNγ producing CD4+ T cells also contribute significantly to a protective memory response. An established concept in adaptive immunity to infection is that during infection of host cells, new microbial epitopes may be revealed, leading to immune recognition of so called ‘cryptic’ or ‘subdominant’ epitopes. We analysed the response to both cryptic and immunodominant T cell epitopes derived from the toxin component lethal factor and presented by a range of HLA-DR alleles. Using IFNγ-ELISPOT assays we characterised epitopes that elicited a response following immunisation with synthetic peptide and the whole protein and tested their capacities to bind purified HLA-DR molecules in vitro. We found that DR1 transgenics demonstrated T cell responses to a greater number of domain III cryptic epitopes than other HLA-DR transgenics, and that this pattern was repeated with the immunodominant epitopes, a greater proportion of these epitopes induced a T cell response when presented within the context of the whole protein. Immunodominant epitopes LF457-476 and LF467-487 were found to induce a T cell response to the peptide, as well as to the whole native LF protein in DR1 and DR15, but not in DR4 trangenics. The analysis of Domain I revealed the presence of several unique cryptic epitopes all of which showed a strong to moderate relative binding affinity to HLA-DR4 molecules. However, none of the cryptic epitopes from either domain III or I displayed notably high binding affinities across all HLA-DR alleles assayed. These responses were

Illocutionary Acts on Liz Gilbert's Dialogue in Eat Pray Love Movie

OpenAIRE

Sri Juriati Ownie, Riandi and

2015-01-01

This thesis deals with the type of illocutionary acts on Liz Gilbert's dialogue inEat Pray Love movie. The objectives of the study were to describe the types ofillocutionary acts used by Liz Gilbert in Eat Pray Love movie, the dominant typeof illocutionary acts used by Liz Gilbert in Eat Pray Love movie and the reasonwhy the dominant type of illocutionary acts occur on Liz Gilbert's dialogue in EatPray Love movie. This research was conducted by using descriptive qualitativedesign. Descriptive...

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.

Induction of high tolerance to artemisinin by sub-lethal administration: A new in vitro model of P. falciparum.

Directory of Open Access Journals (Sweden)

Serena De Lucia

Full Text Available Artemisinin resistance is a major threat to malaria control efforts. Resistance is characterized by an increase in the Plasmodium falciparum parasite clearance half-life following treatment with artemisinin-based combination therapies (ACTs and an increase in the percentage of surviving parasites. The remarkably short blood half-life of artemisinin derivatives may contribute to drug-resistance, possibly through factors including sub-lethal plasma concentrations and inadequate exposure. Here we selected for a new strain of artemisinin resistant parasites, termed the artemisinin resistant strain 1 (ARS1, by treating P. falciparum Palo Alto (PA cultures with sub-lethal concentrations of dihydroartemisinin (DHA. The resistance phenotype was maintained for over 1 year through monthly maintenance treatments with low doses of 2.5 nM DHA. There was a moderate increase in the DHA IC50 in ARS1 when compared with parental strain PA after 72 h of drug exposure (from 0.68 nM to 2 nM DHA. In addition, ARS1 survived treatment physiologically relevant DHA concentrations (700 nM observed in patients. Furthermore, we confirmed a lack of cross-resistance against a panel of antimalarials commonly used as partner drugs in ACTs. Finally, ARS1 did not contain Pfk13 propeller domain mutations associated with ART resistance in the Greater Mekong Region. With a stable growth rate, ARS1 represents a valuable tool for the development of new antimalarial compounds and studies to further elucidate the mechanisms of ART resistance.

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.

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.

Sedimentology and sequence stratigraphy of the Lopingian (Late Permian) coal measures in southwestern China

Energy Technology Data Exchange (ETDEWEB)

Wang, Hao [School of Geosciences and Surveying Engineering, China University of Mining and Technology, Beijing (China); School of Earth and Environment, University of Leeds (United Kingdom); Shao, Longyi; Hao, Liming; Zhang, Pengfei [School of Geosciences and Surveying Engineering, China University of Mining and Technology, Beijing (China); Glasspool, Ian J. [Department of Geology, Field Museum of Natural History, Chicago, Illinois (United States); Wheeley, James R.; Hilton, Jason [School of Geography, Earth and Environmental Sciences, University of Birmingham (United Kingdom); Wignall, Paul B. [School of Earth and Environment, University of Leeds (United Kingdom); Yi, Tongsheng [Guizhou Bureau of Coal Geological Exploration, Guiyang, Guizhou (China); Zhang, Mingquan [Coal Geology and Prospecting Institute of Yunnan Province, Kunming, Yunnan (China)

2011-01-01

The Lopingian coal measures of southwestern China were deposited within a range of facies associations spanning a spectrum of settings from fluvial to marine carbonate platform. The transitional to terrestrial coal measures are dominated by siliciclastics, but they also contain fifteen laterally extensive marine bands (limestone beds and mudstone). These bands act as marker horizons that enable correlation between fully marine and terrestrial facies. Examination of this range of facies and their sedimentology has enabled the development of a high-resolution sequence stratigraphic framework. Set against the established backdrop of second-order Lopingian transgression, sixteen fourth-order sequences and three composite sequences (third-order) are recognized. Results show that, in the composite sequences, peat accumulation in the seaward parts of the study area predominantly correlates with early transgressive sequence sets (TSS), while in more landward areas it correlates with the middle TSS to late highstand sequence sets (HSS). Differences in peat-accumulation regimes within the sequence stratigraphic framework are attributed to variations in subsidence and background siliciclastic input rates in different depositional settings, with these combining to produce differences in the rate of accommodation change. The preservation of coal resources in the middle to late HSS in this area was most likely related to the rise of the regional base level throughout the Lopingian. (author)

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…

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

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.

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

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

Effect of gamma radiation on mutability in male gametes of Japanese quail (Coturnix coturnix japonica)

Energy Technology Data Exchange (ETDEWEB)

Baumgartner, J [Vyskumny Ustav Chovu a Slachtenia Hydiny, Laboratorim Genetiky, Ivanka pri Dunaji (Czechoslovakia)

1978-01-01

An analysis of the mutability of developmental stages of male gametes of the japanese quail (Coturnix coturnix japonica), after irradiation with /sup 60/Co exposures (5.16; 15.48; and 30.96)x10/sup -2/C kg/sup -1/, i.e. 200, 600 and 1200 R, at an exposure rate of 8.59x10/sup -5/C kg/sup -1/s/sup -1/, i.e. O.33 R s/sup -1/, has shown that the rate of overall induced dominant lethality as well as the rate of mutation were highest in spermatocytes of the second order at all exposures. Starting from an exposure of 200 R the following values were found for lethal interference per 1 gamete for 1 R: spermatozoa 2.0x10/sup -3/, spermatides 1.95x10/sup -3/, spermatocytes II 6.1x10/sup -3/, spermatocytes I 4.06x10/sup -3/, spermatogonia in the process of differentiation 6.8x10/sup -3/. When analysing overall embryonic lethality, according to early and late lethality, dominant lethal mutations mainly manifested themsel--ves in the oviductal and germinal developmental periods, so that these periods can be considered as sensitive indices of genetic changes. The spermatogenic epithelium of the japanese quail was found to be greatly radioresistant since not even an exposure to 1200 R caused complete and permanent sterility.

The production of IL-1, IL-3, CSA by bone marrow nuclears during bone marrow haemopoiesis after lethal irradiation and syngenic bone marrow transplantation

International Nuclear Information System (INIS)

Dygaj, A.M.; Buznik, D.V.; Bogdashin, I.V.; Agafonov, V.I.

1994-01-01

The production of haemopoietic factors (IL-1, IL-3, CSA) by adherent and unadherent cells of lethally irradiate CBA mice bone marrow and after syngenic myelokaryocyte transplantation was studied. Radioresistant myelokaryocytes capable to produce haemopoetic factors IL-1, CSA as early as 24 hr after irradiation were found in adherent cell fraction. The synthesis of humoral factors (IL-3, CSA) by unadherent bone marrow elements was realised in a late of experiment (3-6 days) that was connected with forming of functionally valuable cell forms from transplanted or viable stem cells

Predator control promotes invasive dominated ecological states.

Science.gov (United States)

Wallach, Arian D; Johnson, Christopher N; Ritchie, Euan G; O'Neill, Adam J

2010-08-01

Invasive species are regarded as one of the top five drivers of the global extinction crisis. In response, extreme measures have been applied in an attempt to control or eradicate invasives, with little success overall. We tested the idea that state shifts to invasive dominance are symptomatic of losses in ecosystem resilience, due to the suppression of apex predators. This concept was investigated in Australia where the high rate of mammalian extinctions is largely attributed to the destructive influence of invasive species. Intensive pest control is widely applied across the continent, simultaneously eliminating Australia's apex predator, the dingo (Canis lupus dingo). We show that predator management accounts for shifts between two main ecosystem states. Lethal control fractures dingo social structure and leads to bottom-up driven increases in invasive mesopredators and herbivores. Where control is relaxed, dingoes re-establish top-down regulation of ecosystems, allowing for the recovery of biodiversity and productivity.

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

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)

Self-gravity in Magnetized Neutrino-dominated Accretion Disks

Energy Technology Data Exchange (ETDEWEB)

Shahamat, Narjes; Abbassi, Shahram, E-mail: abbassi@um.ac.ir [Department of Physics, School of Science, Ferdowsi University of Mashhad, Mashhad, P.O. Box 91775-1436 (Iran, Islamic Republic of)

2017-08-10

In the present work we study self-gravity effects on the vertical structure of a magnetized neutrino-dominated accretion disk as a central engine for gamma-ray bursts (GRBs). Some of the disk physical timescales that are supposed to play a pivotal role in the late-time evolutions of the disk, such as viscous, cooling, and diffusion timescales, have been studied. We are interested in investigating the possibility of the occurrence of X-ray flares, observed in late-time GRBs’ extended emission through the “magnetic barrier” and “fragmentation” processes in our model. The results lead us to interpret self-gravity as an amplifier for Blandford–Payne luminosity (BP power) and the generated magnetic field, but a suppressor for neutrino luminosity and magnetic barrier processes via highlighting the fragmentation mechanism in the outer disk, especially for the higher mass accretion rates.

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.

Domination, Eternal Domination, and Clique Covering

Directory of Open Access Journals (Sweden)

Klostermeyer William F.

2015-05-01

Full Text Available Eternal and m-eternal domination are concerned with using mobile guards to protect a graph against infinite sequences of attacks at vertices. Eternal domination allows one guard to move per attack, whereas more than one guard may move per attack in the m-eternal domination model. Inequality chains consisting of the domination, eternal domination, m-eternal domination, independence, and clique covering numbers of graph are explored in this paper.

Expression of inactive glutathione peroxidase 4 leads to embryonic lethality, and inactivation of the Alox15 gene does not rescue such knock-in mice.

Science.gov (United States)

Brütsch, Simone Hanna; Wang, Chi Chiu; Li, Lu; Stender, Hannelore; Neziroglu, Nilgün; Richter, Constanze; Kuhn, Hartmut; Borchert, Astrid

2015-02-01

Glutathione peroxidases (Gpx) and lipoxygenases (Alox) are functional counterplayers in the metabolism of hydroperoxy lipids that regulate cellular redox homeostasis. Gpx4 is a moonlighting protein that has been implicated not only as an enzyme in anti-oxidative defense, gene expression regulation, and programmed cell death, but also as a structural protein in spermatogenesis. Homozygous Gpx4 knock-out mice are not viable, but molecular reasons for intrauterine lethality are not completely understood. This study was aimed at investigating whether the lack of catalytic activity or the impaired function as structural protein is the dominant reason for embryonic lethality. We further explored whether the pro-oxidative enzyme mouse 12/15 lipoxygenase (Alox15) plays a major role in embryonic lethality of Gpx4-deficient mice. To achieve these goals, we first created knock-in mice, which express a catalytically inactive Gpx4 mutant (Sec46Ala). As homozygous Gpx4-knock-out mice Sec46Ala-Gpx4(+/+) knock-in animals are not viable but undergo intrauterine resorption between embryonic day 6 and 7 (E6-7). In contrast, heterozygous knock-in mice (Sec46Ala-Gpx4(-/+)) are viable, fertile and do not show major phenotypic alterations. Interestingly, homozygous Alox15 deficiency did not rescue the U46A-Gpx4(+/+) mice from embryonic lethality. In fact, when heterozygous U46A-Gpx4(-/+) mice were stepwise crossed into an Alox15-deficent background, no viable U46A-Gpx4(+/+)+Alox15(-/-) individuals were obtained. However, we were able to identify U46A-Gpx4(+/+)+Alox15(-/-) embryos in the state of resorption around E7. These data suggest that the lack of catalytic activity is the major reason for the embryonic lethality of Gpx4(-/-) mice and that systemic inactivation of the Alox15 gene does not rescue homozygous knock-in mice expressing catalytically silent Gpx4.

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.

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.

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.)

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.

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.)

‎ Late Recovery from Stuttering: The Role of Hand ‎Dominancy, Fine Motor and ‎Inhibition Control

Directory of Open Access Journals (Sweden)

Hiwa Mohammadi

2016-02-01

Full Text Available Objective: There are controversial reports about factors that affect recovery from stuttering. In the ‎present study, the effect of hand dominancy, fine motor and inhibition control on late ‎recovery from stuttering was investigated among a group of Kurdish-Persian children who ‎stuttered in Iran.‎Method: Twenty-two Kurdish-Persian children aged 7-14 years who stuttered were followed for 6 ‎years. Based on the evaluation of three experienced speech therapists and parental judgments, ‎these children were classified into recovered or persistent groups. Data about fine motor ‎control of hand and inhibition control were obtained, using Purdue Pegboard and Victoria ‎Strop Color Word Tests, respectively. Risk factors including sex, age, and family history of ‎stuttering, handedness, inhibitory control and fine motor control of hand were compared ‎between the groups and modeled to predict recovery from stuttering using logistic regression.‎Results: From the 22 participants, 5 (22.7% recovered from stuttering. The recovered and persistent ‎groups did not show significant differences in the interference effect. By dividing the scores ‎of the Purdue Pegboard tests to the right and left hand, we created a new Handedness Index ‎‎(HI. HI was significantly higher in the recovered group. The score of right hand was higher ‎than the left in the recovered group, but no difference was found between the two hands in ‎the persistent group. Among the investigated risk factors, only HI could predict the recovery ‎from or persistency of stuttering with 94% sensitivity and 84% specificity.‎Conclusion: Handedness Index can predict the recovery from stuttering significantly among children who ‎stutter.‎

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.

A Socio-technical Mapping and Analysis of Dominant Design Materialization

DEFF Research Database (Denmark)

Christiansen, John K.; Varnes, Claus

the importance of high market shares for defining a wining dominating design, but despite the electric vehicle’s higher market share in the years 1899-1900 it was surpassed by the internal combustion vehicle. The socio-technical analysis departs from a narrative based on historical accounts on the competition...... between the electric vehicle and the internal combustion vehicle from late 1890 - until 1909. The analysis shows that the electric vehicle did not successfully attract new allies or overcome resistance from anti-programs to the same degree as the internal combustion vehicle. Findings suggest that some...... of the issues with few allies and anti-programs that emerged already during the late 1890'ties is still active in today's market and haunts the electric vehicle....

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)

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 ...

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

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

Is Late or Non-Payment a Significant Problem to Malaysian Contractors?

Directory of Open Access Journals (Sweden)

M.E. Che Munaaim

2007-12-01

Full Text Available Some developed countries have drawn lip construction-specific statutory security of payment acts/legislations typically known as Construction Contracts Act to eliminate poor payment practices and to assist continuous uninterrupted construction works. Malaysia too cannot pretend not to have these problems. This paper presents findings of a study conducted amongst Malaysian contractors with the aims to determine the seriousness of late and non- payment problems; to identify the main causes and effects of late and non-payment; and to identify ways to sustain the payment flows in the Malaysian construction industry. The study focused on contractual payments from the paymaster (government or private to the contractors. The main factors for late and nonpayment in the construction industry identified from the study include: delay in certification, paymaster's poor financial management, local culture/attitude, pay master's failure to implement good governance in business, underpayment of certified amounts by the pay master and the use of 'pay when paid' clauses in contracts. The research findings show that late and non-payment can create cash flow problems, stress and financial hardship on the contractors. Amongst the most appropriate solutions to overcome the problem of late and non-payment faced by local contractors include: a right to regular periodic payment, a right to a defined time frame (or payment and a right to a speedy dispute resolution mechanism. Promptness of submitting, processing, issuing interim payment certificates and honouring the certificates are extremely important issues in relation to progress payment claims. Perhaps, an increased sense of professionalism in construction industry could overcome some of the problems related to late and non- payment issues.

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.

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.

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

Cornulitids (tubeworms) from the Late Ordovician Hirnantia fauna of Morocco

Science.gov (United States)

Gutiérrez-Marco, Juan Carlos; Vinn, Olev

2018-01-01

Two species of cornulitids, Cornulites gondwanensis sp. nov. and C. aff. shallochensis Reed are described from the Hirnantian of Morocco, within an assemblage representative of the Hirnantia brachiopod fauna occurring near the Ordovician South Pole. The dominance of aggregated and solitary free forms could be explained by particular sedimentary environments preceding the Hirnantian glaciation and the latest Ordovician Extinction Event. The diversity of cornulitids in the Late Ordovician of Gondwana and related terranes was relatively low, and less diverse than the cornulitids of Laurentia and Baltica. Hirnantian cornulitids from Morocco do not resemble Late Ordovician cornulitids of Baltica and Laurentia. Moroccan cornulitids seem to be closely allied to some older Gondwanan cornulitids, especially Sardinian ones. They resemble species described from the Late Ordovician and Llandovery of Scotland suggesting a palaeobiogeographic link.

Hyperinsulinaemic hypoglycaemia and diabetes mellitus due to dominant ABCC8/KCNJ11 mutations.

LENUS (Irish Health Repository)

Kapoor, R R

2011-10-01

Dominantly acting loss-of-function mutations in the ABCC8\\/KCNJ11 genes can cause mild medically responsive hyperinsulinaemic hypoglycaemia (HH). As controversy exists over whether these mutations predispose to diabetes in adulthood we investigated the prevalence of diabetes in families with dominantly inherited ATP-sensitive potassium (K(ATP)) channel mutations causing HH in the proband.

Is Late or Non-Payment a Significant Problem to Malaysian Contractors?

OpenAIRE

M.E. Che Munaaim; M.S. Mohd Danuri; H. Abdul-Rahman

2007-01-01

Some developed countries have drawn lip construction-specific statutory security of payment acts/legislations typically known as Construction Contracts Act to eliminate poor payment practices and to assist continuous uninterrupted construction works. Malaysia too cannot pretend not to have these problems. This paper presents findings of a study conducted amongst Malaysian contractors with the aims to determine the seriousness of late and non- payment problems; to identify the main causes and ...

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.

Multiple determinants controlling activation of yeast replication origins late in S phase.

Science.gov (United States)

Friedman, K L; Diller, J D; Ferguson, B M; Nyland, S V; Brewer, B J; Fangman, W L

1996-07-01

Analysis of a 131-kb segment of the left arm of yeast chromosome XIV beginning 157 kb from the telomere reveals four highly active origins of replication that initiate replication late in S phase. Previous work has shown that telomeres act as determinants for late origin activation. However, at least two of the chromosome XIV origins maintain their late activation time when located on large circular plasmids, indicating that late replication is independent of telomeres. Analysis of the replication time of plasmid derivatives containing varying amounts of chromosome XIV DNA show that a minimum of three chromosomal elements, distinct from each tested origin, contribute to late activation time. These late determinants are functionally equivalent, because duplication of one set of contributing sequences can compensate for the removal of another set. Furthermore, insertion of an origin that is normally early activated into this domain results in a shift to late activation, suggesting that the chromosome XIV origins are not unique in their ability to respond to the late determinants.

Mean Field Games with a Dominating Player

Energy Technology Data Exchange (ETDEWEB)

Bensoussan, A., E-mail: axb046100@utdallas.edu [The University of Texas at Dallas, International Center for Decision and Risk Analysis, Jindal School of Management (United States); Chau, M. H. M., E-mail: michaelchaumanho@gmail.com; Yam, S. C. P., E-mail: scpyam@sta.cuhk.edu.hk [The Chinese University of Hong Kong, Department of Statistics (Hong Kong, People’s Republic of China) (China)

2016-08-15

In this article, we consider mean field games between a dominating player and a group of representative agents, each of which acts similarly and also interacts with each other through a mean field term being substantially influenced by the dominating player. We first provide the general theory and discuss the necessary condition for the optimal controls and equilibrium condition by adopting adjoint equation approach. We then present a special case in the context of linear-quadratic framework, in which a necessary and sufficient condition can be asserted by stochastic maximum principle; we finally establish the sufficient condition that guarantees the unique existence of the equilibrium control. The proof of the convergence result of finite player game to mean field counterpart is provided in Appendix.

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.

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.

Selection is stronger in early-versus-late stages of divergence in a Neotropical livebearing fish.

Science.gov (United States)

Ingley, Spencer J; Johnson, Jerald B

2016-03-01

How selection acts to drive trait evolution at different stages of divergence is of fundamental importance in our understanding of the origins of biodiversity. Yet, most studies have focused on a single point along an evolutionary trajectory. Here, we provide a case study evaluating the strength of divergent selection acting on life-history traits at early-versus-late stages of divergence in Brachyrhaphis fishes. We find that the difference in selection is stronger in the early-diverged population than the late-diverged population, and that trait differences acquired early are maintained over time. © 2016 The Author(s).

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.

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…

Characterization of two second-site mutations preventing wild type protein aggregation caused by a dominant negative PMA1 mutant.

Directory of Open Access Journals (Sweden)

Pilar Eraso

Full Text Available The correct biogenesis and localization of Pma1 at the plasma membrane is essential for yeast growth. A subset of PMA1 mutations behave as dominant negative because they produce aberrantly folded proteins that form protein aggregates, which in turn provoke the aggregation of the wild type protein. One approach to understand this dominant negative effect is to identify second-site mutations able to suppress the dominant lethal phenotype caused by those mutant alleles. We isolated and characterized two intragenic second-site suppressors of the PMA1-D378T dominant negative mutation. We present here the analysis of these new mutations that are located along the amino-terminal half of the protein and include a missense mutation, L151F, and an in-frame 12bp deletion that eliminates four residues from Cys409 to Ala412. The results show that the suppressor mutations disrupt the interaction between the mutant and wild type enzymes, and this enables the wild type Pma1 to reach the plasma membrane.

Domination versus disjunctive domination in graphs | Henning ...

African Journals Online (AJOL)

Domination versus disjunctive domination in graphs. Michael A Henning, Sinclair A Marcon. Abstract. A dominating set in a graph G is a set S of vertices of G such that every vertex not in S is adjacent to a vertex of S. The domination number of G is the minimum cardinality of a dominating set of G. For a positive integer b, ...

Climate and landscape in Italy during Late Epigravettian. The Late Glacial small mammal sequence of Riparo Tagliente (Stallavena di Grezzana, Verona, Italy)

Science.gov (United States)

Berto, Claudio; Luzi, Elisa; Canini, Guido Montanari; Guerreschi, Antonio; Fontana, Federica

2018-03-01

The site of Riparo Tagliente (north-eastern Italy) contains one of the main Upper Pleistocene archaeological sequences of south-western Europe. It also represents a key site for the study of human adaptation to Late Glacial environmental changes in the southern Alpine area. These climatic and environmental conditions are here reconstructed based on small mammal assemblages, using the Bioclimatic model and Habitat Weighting methods. Climate proxies indicate a rise in temperature during the transition between HE1 and the Bølling-Allerød interstadial, while the landscape surrounding the shelter was still dominated by open grasslands. By comparing the data obtained from Riparo Tagliente with other coeval small mammal faunas from the Italian Peninsula and Europe we contribute to the reconstruction of the processes of faunal renewal registered during the Late Glacial across the continent and of the climatic and environmental context in which the Late Epigravettian hunter-gatherer groups lived.

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.

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

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.

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.

Diffusion of subsidized ACTs in accredited drug shops in Tanzania: determinants of stocking and characteristics of early and late adopters.

Science.gov (United States)

Larson, Peter S; Yadav, Prashant; Alphs, Sarah; Arkedis, Jean; Massaga, Julius; Sabot, Oliver; Cohen, Jessica L

2013-12-18

Many households in sub-Saharan Africa utilize the private sector as a primary source of treatment for malaria episodes. Expanding access to effective treatment in private drug shops may help reduce incidence of severe disease and mortality. This research leveraged a longitudinal survey of stocking of subsidized artemisinin combination therapies (ACTs), an effective anti-malarial, in Accredited Drug Dispensing Outlets (ADDOs) in two regions of Tanzania. This provided a unique opportunity to explore shop and market level determinants of product diffusion in a developing country retail market. 356 ADDOs in the Rukwa and Mtwara regions of Tanzania were surveyed at seven points between Feb 2011 and May 2012. Shop level audits were used to measure the availability of subsidized ACTs at each shop. Data on market and shop level factors were collected during the survey and also extracted from GIS layers. Regression and network based methodologies were used. Shops classified as early and late adopters, following Rogers' model of product diffusion, were compared. The Bass model of product diffusion was applied to determine whether shops stocked ACTs out of a need to imitate market competitors or a desire to satisfy customer needs. Following the introduction of a subsidy for ACTs, stocking increased from 12% to nearly 80% over the seven survey rounds. Stocking was influenced by higher numbers of proximal shops and clinics, larger customer traffic and the presence of a licensed pharmacist. Early adopters were characterized by a larger percentage of customers seeking care for malaria, a larger catchment and sourcing from specific wholesalers/suppliers. The Bass model of product diffusion indicated that shops were adopting products in response to competitor behavior, rather than customer demand. Decisions to stock new pharmaceutical products in Tanzanian ADDOs are influenced by a combination of factors related to both market competition and customer demand, but are particularly

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...

Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

Science.gov (United States)

Terryn, Sanne; Francart, Aurélie; Rommelaere, Heidi; Stortelers, Catelijne; Van Gucht, Steven

2016-01-01

Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP. PMID:27483431

Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection.

Directory of Open Access Journals (Sweden)

Sanne Terryn

2016-08-01

Full Text Available Post-exposure prophylaxis (PEP against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days and decreased mortality (60% versus 19% survival rate, when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP.

Compound-specific isotope records of late-quaternary environmental change in southeastern North Carolina

Science.gov (United States)

Lane, Chad S.; Taylor, Audrey K.; Spencer, Jessica; Jones, Kaylee B.

2018-02-01

Reconstructions of late Quaternary paleohydrology are rare from the U.S. Atlantic coastal plain (ACP). Here we present compound-specific hydrogen (δ2Halkane) and carbon (δ13Calkane) isotope analyses of terrestrially-derived n-alkanes from Jones Lake and Singletary Lake in eastern North Carolina spanning the last ∼50,000 years. Combined with pollen, charcoal, and bulk geochemical analyses, the δ2Halkane data indicate arid conditions during the late-Pleistocene, but differing edaphic conditions at the sites perhaps related to differing water table depths. The δ13Calkane data indicate a significant C4 plant component during the late Pleistocene, but other proxies indicate a sparsely-vegetated landscape. The Pleistocene-Holocene transition is marked by rapid fluctuations in δ2Halkane values that are similar to the patterns of Bølling Allerød and Younger Dryas isotope data from Greenland indicating sensitivity of the regional climate to short-lived, high-amplitude climatic events. The δ2Halkane data indicate a mesic early Holocene that supported colonization by Quercus-dominated ecosystems. Evidence of middle Holocene aridity in eastern Tennessee and western North Carolina contrasts with evidence of mesic conditions on the ACP, a geographic pattern similar to modern teleconnected precipitation responses to the Pacific Decadal Oscillation. A transition to Pinus-dominated ecosystems ∼5500 cal yr B.P. is accompanied by a large increase charcoal, but is not coincident with any large changes in δ2Halkane values, indicating that hydrologic change was likely not responsible for sustained late-Holocene dominance of Pinus. The lack of a change in middle Holocene hydrology and the spatiotemporally heterogeneous nature of the Quercus-Pinus transition on the ACP indicate prehistoric anthropogenic land management practices may represent the most parsimonious explanation for the regionally pervasive ecological change.

Lethal Zika Virus Disease Models in Young and Older Interferon α/β Receptor Knock Out Mice

Directory of Open Access Journals (Sweden)

Andrea Marzi

2018-04-01

Full Text Available The common small animal disease models for Zika virus (ZIKV are mice lacking the interferon responses, but infection of interferon receptor α/β knock out (IFNAR−/− mice is not uniformly lethal particularly in older animals. Here we sought to advance this model in regard to lethality for future countermeasure efficacy testing against more recent ZIKV strains from the Asian lineage, preferably the American sublineage. We first infected IFNAR−/− mice subcutaneously with the contemporary ZIKV-Paraiba strain resulting in predominantly neurological disease with ~50% lethality. Infection with ZIKV-Paraiba by different routes established a uniformly lethal model only in young mice (4-week old upon intraperitoneal infection. However, intraperitoneal inoculation of ZIKV-French Polynesia resulted in uniform lethality in older IFNAR−/− mice (10–12-weeks old. In conclusion, we have established uniformly lethal mouse disease models for efficacy testing of antivirals and vaccines against recent ZIKV strains representing the Asian lineage.

Fluid Intelligence and Cognitive Reflection in a Strategic Environment: Evidence from Dominance-Solvable Games.

Science.gov (United States)

Hanaki, Nobuyuki; Jacquemet, Nicolas; Luchini, Stéphane; Zylbersztejn, Adam

2016-01-01

Dominance solvability is one of the most straightforward solution concepts in game theory. It is based on two principles: dominance (according to which players always use their dominant strategy) and iterated dominance (according to which players always act as if others apply the principle of dominance). However, existing experimental evidence questions the empirical accuracy of dominance solvability. In this study, we study the relationships between the key facets of dominance solvability and two cognitive skills, cognitive reflection, and fluid intelligence. We provide evidence that the behaviors in accordance with dominance and one-step iterated dominance are both predicted by one's fluid intelligence rather than cognitive reflection. Individual cognitive skills, however, only explain a small fraction of the observed failure of dominance solvability. The accuracy of theoretical predictions on strategic decision making thus not only depends on individual cognitive characteristics, but also, perhaps more importantly, on the decision making environment itself.

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)

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.

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.

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

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

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.

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).

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.)

Optimal barrier zones for stopping the invasion of Aedes aegypti mosquitoes via transgenic or sterile insect techniques

KAUST Repository

Lee, S. Seirin

2013-03-27

Biological invasions have dramatically altered the natural world by threatening native species and their communities. Moreover, when the invading species is a vector for human disease, there are further substantive public health and economic impacts. The development of transgenic technologies is being explored in relation to new approaches for the biological control of insect pests. We investigate the use of two control strategies, classical sterile insect techniques and transgenic late-acting bisex lethality (Release of Insects carrying a Dominant Lethal), for controlling invasion of the mosquito Aedes aegypti using a spatial stage-structured mathematical model. In particular, we explore the use of a barrier zone of sterile/transgenic insects to prevent or impede the invasion of mosquitoes. We show that the level of control required is not only highly sensitive to the rate at which the sterile/transgenic males are released in the barrier zone but also to the spatial range of release. Our models characterise how the distribution of sterile/transgenic mosquitoes in the barrier zone can be controlled so as to minimise the number of mass-produced insects required for the arrest of species invasion. We predict that, given unknown rates of mosquito dispersal, management strategies should concentrate on larger release areas rather than more intense release rates for optimal control. © 2013 Springer Science+Business Media Dordrecht.

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

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.

Fossil evidence for open, Proteaceae-dominated heathlands and fire in the Late Cretaceous of Australia.

Science.gov (United States)

Carpenter, Raymond J; Macphail, Michael K; Jordan, Gregory J; Hill, Robert S

2015-12-01

The origin of biomes is of great interest globally. Molecular phylogenetic and pollen evidence suggest that several plant lineages that now characterize open, burnt habitats of the sclerophyll biome, became established during the Late Cretaceous of Australia. However, whether this biome itself dates to that time is problematic, fundamentally because of the near-absence of relevant, appropriately aged, terrestrial plant macro- or mesofossils. We recovered, identified, and interpreted the ecological significance of fossil pollen, foliar and other remains from a section of core drilled in central Australia, which we dated as Late Campanian-Maastrichtian. The sediments contain plant fossils that indicate nutrient-limited, open, sclerophyllous vegetation and abundant charcoal as evidence of fire. Most interestingly, >30 pollen taxa and at least 12 foliage taxa are attributable to the important Gondwanan family Proteaceae, including several minute, amphistomatic, and sclerophyllous foliage forms consistent with subfamily Proteoideae. Microfossils, including an abundance of Sphagnales and other wetland taxa, provided strong evidence of a fenland setting. The local vegetation also included diverse Ericaceae and Liliales, as well as a range of ferns and gymnosperms. The fossils provide strong evidence in support of hypotheses of great antiquity for fire and open vegetation in Australia, point to extraordinary persistence of Proteaceae that are now emblematic of the Mediterranean-type climate southwestern Australian biodiversity hotspot and raise the profile of open habitats as centers of ancient lineages. © 2015 Botanical Society of America.

Prolonged Permian–Triassic ecological crisis recorded by molluscan dominance in Late Permian offshore assemblages

OpenAIRE

Clapham, Matthew E.; Bottjer, David J.

2007-01-01

The end-Permian mass extinction was the largest biotic crisis in the history of animal life, eliminating as many as 95% of all species and dramatically altering the ecological structure of marine communities. Although the causes of this pronounced ecosystem shift have been widely debated, the broad consensus based on inferences from global taxonomic diversity patterns suggests that the shift from abundant brachiopods to dominant molluscs was abrupt and largely driven by the catastrophic effec...

No interaction between X-ray induced lesions in maternal and paternal chromosomes in inseminated eggs of Drosophila melanogaster

International Nuclear Information System (INIS)

Wuergler, F.E.; Graf, U.; Jeanneret, P.

1978-01-01

X-ray induced premutational lesions persist in mature gametes of drosophila until fertilization. Repairable lesions in sperm and oocyte chromosomes are repaired exclusively by maternal repair systems in the inseminated egg. Interactions between irradiated genomes in inseminated eggs might result in additional lethality if breaks induced in separate nuclei, which would normally be repaired, could interact to form dicentric chromosomes. Adult drosophila flies were X-irradiated (up to 5 kR), individual females crossed to three or four males, and the dose-response curves for dominant lethals (embryonic lethality) compared. The results indicate thet the potentially lethal damage present in irradiated sperm chromosomes was expressed independently of whether or not the oocyte was also irradiated. There were no (or only very few) interactions between maternal and paternal chromosome complements, and the maternal repair systems acting on radiation-induced chromosome breaks in sperm were resistant to X-rays. (U.K.)

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.

Radiation dominated relativistic current sheets

International Nuclear Information System (INIS)

Jaroschek, C.H.

2008-01-01

Relativistic Current Sheets (RCS) feature plasma instabilities considered as potential key to magnetic energy dissipation and non-thermal particle generation in Poynting flux dominated plasma flows. We show in a series of kinetic plasma simulations that the physical nature of non-linear RCS evolution changes in the presence of incoherent radiation losses: In the ultra-relativistic regime (i.e. magnetization parameter sigma = 104 defined as the ratio of magnetic to plasma rest frame energy density) the combination of non-linear RCS dynamics and synchrotron emission introduces a temperature anisotropy triggering the growth of the Relativistic Tearing Mode (RTM). As direct consequence the RTM prevails over the Relativistic Drift Kink (RDK) Mode as competitive RCS instability. This is in contrast to the previously studied situation of weakly relativistic RCS (sigma ∼ 1) where the RDK is dominant and most of the plasma is thermalized. The simulations witness the typical life cycle of ultra-relativistic RCS evolving from a violent radiation induced collapse towards a radiation quiescent state in rather classical Sweet-Parker topology. Such a transition towards Sweet-Parker configuration in the late non-linear evolution has immediate consequences for the efficiency of magnetic energy dissipation and non-thermal particle generation. Ceasing dissipation rates directly affect our present understanding of non-linear RCS evolution in conventional striped wind scenarios. (author)

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.

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...

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

miR-9a mediates the role of Lethal giant larvae as an epithelial growth inhibitor in Drosophila

Directory of Open Access Journals (Sweden)

Scott G. Daniel

2018-01-01

Full Text Available Drosophila lethal giant larvae (lgl encodes a conserved tumor suppressor with established roles in cell polarity, asymmetric division, and proliferation control. Lgl's human orthologs, HUGL1 and HUGL2, are altered in human cancers, however, its mechanistic role as a tumor suppressor remains poorly understood. Based on a previously established connection between Lgl and Fragile X protein (FMRP, a miRNA-associated translational regulator, we hypothesized that Lgl may exert its role as a tumor suppressor by interacting with the miRNA pathway. Consistent with this model, we found that lgl is a dominant modifier of Argonaute1 overexpression in the eye neuroepithelium. Using microarray profiling we identified a core set of ten miRNAs that are altered throughout tumorigenesis in Drosophila lgl mutants. Among these are several miRNAs previously linked to human cancers including miR-9a, which we found to be downregulated in lgl neuroepithelial tissues. To determine whether miR-9a can act as an effector of Lgl in vivo, we overexpressed it in the context of lgl knock-down by RNAi and found it able to reduce the overgrowth phenotype caused by Lgl loss in epithelia. Furthermore, cross-comparisons between miRNA and mRNA profiling in lgl mutant tissues and human breast cancer cells identified thrombospondin (tsp as a common factor altered in both fly and human breast cancer tumorigenesis models. Our work provides the first evidence of a functional connection between Lgl and the miRNA pathway, demonstrates that miR-9a mediates Lgl's role in restricting epithelial proliferation, and provides novel insights into pathways controlled by Lgl during tumor progression.

Assessing the Relevance of Anomie Theory for Explaining Spatial Variation in Lethal Criminal Violence: An Aggregate-Level Analysis of Homicide within the United States

Directory of Open Access Journals (Sweden)

Eric P. Baumer

2008-11-01

Full Text Available One of the most influential statements in the anomie theory tradition has been Merton’s argument that the volume of instrumental property crime should be higher where there is a greater imbalance between the degree of commitment to monetary success goals and the degree of commitment to legitimate means of pursuing such goals. Contemporary anomie theories stimulated by Merton’s perspective, most notably Messner and Rosenfeld’s institutional anomie theory, have expanded the scope conditions by emphasizing lethal criminal violence as an outcome to which anomie theory is highly relevant, and virtually all contemporary empirical studies have focused on applying the perspective to explaining spatial variation in homicide rates. In the present paper, we argue that current explications of Merton’s theory and IAT have not adequately conveyed the relevance of the core features of the anomie perspective to lethal violence. We propose an expanded anomie model in which an unbalanced pecuniary value system – the core causal variable in Merton’s theory and IAT – translates into higher levels of homicide primarily in indirect ways by increasing levels of firearm prevalence, drug market activity, and property crime, and by enhancing the degree to which these factors stimulate lethal outcomes. Using aggregate-level data collected during the mid-to-late 1970s for a sample of relatively large social aggregates within the U.S., we find a significant effect on homicide rates of an interaction term reflecting high levels of commitment to monetary success goals and low levels of commitment to legitimate means. Virtually all of this effect is accounted for by higher levels of property crime and drug market activity that occur in areas with an unbalanced pecuniary value system. Our analysis also reveals that property crime is more apt to lead to homicide under conditions of high levels of structural disadvantage. These and other findings underscore the

Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy.

Science.gov (United States)

Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

2012-11-07

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. Wild type (WT) and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.)). Cardiomyocyte contractile and intracellular Ca(2+) properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca(2+) handling), the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, possibly through regulation of autophagy and mitochondrial function.

Limiting factors for vegetation development during the early late glacial in Denmark

DEFF Research Database (Denmark)

Mortensen, Morten Fischer; Odgaard, Bent Vad; Jessen, Cathrine

Slotseng, a small basin in southern Jutland, is the first Danish site with a bio- and chronostratigraphy that unambiguously reflects the environment of the earliest late glacial, the Bølling period. Results of pollen and macrofossil analyses show that the vegetation of the Bølling and Older Dryas...... periods at Slotseng was dominated by Betula nana and Dryas octopetala and associated with many herbs of open habitats. Late-glacial pollen records are frequently interpreted only in the context of climate change. However, the forcing mechanisms of vegetational change may shift over time between e...... to climate change suggests that other factors limited vegetational development. These factors included soil instability, aridity and low soil nitrogen.. This study highlights the multitude of climatic, physical, chemical and biological interactions important for the formation of pollen records of late...

Observations on the variability of linear polarization in late-type dwarf stars

Energy Technology Data Exchange (ETDEWEB)

Huovelin, J.; Linnaluoto, S.; Tuominen, I.; Virtanen, H.

1989-04-01

Broadband (UBV) linear polarimetric observations of a sample of late-type (F7-K5) dwarfs are reported. The observations include ten stars and extend over a maximum of 20 nights. Seven stars show significant temporal variability of polarization, which could be interpreted as rotational modulation due to slowly varying magnetic regions. Magnetic intensification in saturated Zeeman sensitive absorption lines is suggested as the dominant effect connecting linear polarization with magnetic activity in the most active single late-type dwarfs, while the wavelength dependence in the less active stars could also be due to a combination of Rayleigh and Thomson scattering.

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

CD4+ T lymphocytes injected into severe combined immunodeficient (SCID) mice lead to an inflammatory and lethal bowel disease

DEFF Research Database (Denmark)

Claesson, Mogens Helweg; Rudolphi, A; Kofoed, S

1996-01-01

Transfer of 2 x 10(5) congenic or semiallogenic purified TCR alphabeta+ CD4+ T cells to SCID mice leads to an infiltration of the recipient gut lamina propria and epithelium with a donor-derived CD4+ T cell subset which induces a lethal inflammatory bowel disease (IBD) in the recipients....... In contrast, IBD was not observed in SCID mice transplanted with unfractionated splenic cells. The earliest detectable pathological changes after CD4+ T cell transfer were proliferation and hypertrophy of the entire colonic epithelial layer, including increased mitotic activity, increased expression...... plasma cells were present in the lamina propria of both the small and large intestine. We conclude that low numbers of intraveneously transferred CD4+ T cells induce IBD in SCID mice. In the late stages of CD4+ T cell-induced IBD, the colonic lamina propria becomes infiltrated with macrophages...

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.

Snapin-regulated late endosomal transport is critical for efficient autophagy-lysosomal function in neurons.

Science.gov (United States)

Cai, Qian; Lu, Li; Tian, Jin-Hua; Zhu, Yi-Bing; Qiao, Haifa; Sheng, Zu-Hang

2010-10-06

Neuron maintenance and survival require late endocytic transport from distal processes to the soma where lysosomes are predominantly localized. Here, we report a role for Snapin in attaching dynein to late endosomes through its intermediate chain (DIC). snapin(-/-) neurons exhibit aberrant accumulation of immature lysosomes, clustering and impaired retrograde transport of late endosomes along processes, reduced lysosomal proteolysis due to impaired delivery of internalized proteins and hydrolase precursors from late endosomes to lysosomes, and impaired clearance of autolysosomes, combined with reduced neuron viability and neurodegeneration. The phenotypes are rescued by expressing the snapin transgene, but not the DIC-binding-defective Snapin-L99K mutant. Snapin overexpression in wild-type neurons enhances late endocytic transport and lysosomal function, whereas expressing the mutant defective in Snapin-DIC coupling shows a dominant-negative effect. Altogether, our study highlights new mechanistic insights into how Snapin-DIC coordinates retrograde transport and late endosomal-lysosomal trafficking critical for autophagy-lysosomal function, and thus neuronal homeostasis. Copyright © 2010 Elsevier Inc. All rights reserved.

Total Domination Versus Paired-Domination in Regular Graphs

Directory of Open Access Journals (Sweden)

Cyman Joanna

2018-05-01

Full Text Available A subset S of vertices of a graph G is a dominating set of G if every vertex not in S has a neighbor in S, while S is a total dominating set of G if every vertex has a neighbor in S. If S is a dominating set with the additional property that the subgraph induced by S contains a perfect matching, then S is a paired-dominating set. The domination number, denoted γ(G, is the minimum cardinality of a dominating set of G, while the minimum cardinalities of a total dominating set and paired-dominating set are the total domination number, γt(G, and the paired-domination number, γpr(G, respectively. For k ≥ 2, let G be a connected k-regular graph. It is known [Schaudt, Total domination versus paired domination, Discuss. Math. Graph Theory 32 (2012 435–447] that γpr(G/γt(G ≤ (2k/(k+1. In the special case when k = 2, we observe that γpr(G/γt(G ≤ 4/3, with equality if and only if G ≅ C5. When k = 3, we show that γpr(G/γt(G ≤ 3/2, with equality if and only if G is the Petersen graph. More generally for k ≥ 2, if G has girth at least 5 and satisfies γpr(G/γt(G = (2k/(k + 1, then we show that G is a diameter-2 Moore graph. As a consequence of this result, we prove that for k ≥ 2 and k ≠ 57, if G has girth at least 5, then γpr(G/γt(G ≤ (2k/(k +1, with equality if and only if k = 2 and G ≅ C5 or k = 3 and G is the Petersen graph.

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)

Human polyomavirus JCV late leader peptide region contains important regulatory elements

International Nuclear Information System (INIS)

Akan, Ilhan; Sariyer, Ilker Kudret; Biffi, Renato; Palermo, Victoria; Woolridge, Stefanie; White, Martyn K.; Amini, Shohreh; Khalili, Kamel; Safak, Mahmut

2006-01-01

Transcription is a complex process that relies on the cooperative interaction between sequence-specific factors and the basal transcription machinery. The strength of a promoter depends on upstream or downstream cis-acting DNA elements, which bind transcription factors. In this study, we investigated whether DNA elements located downstream of the JCV late promoter, encompassing the late leader peptide region, which encodes agnoprotein, play regulatory roles in the JCV lytic cycle. For this purpose, the entire coding region of the leader peptide was deleted and the functional consequences of this deletion were analyzed. We found that viral gene expression and replication were drastically reduced. Gene expression also decreased from a leader peptide point mutant but to a lesser extent. This suggested that the leader peptide region of JCV might contain critical cis-acting DNA elements to which transcription factors bind and regulate viral gene expression and replication. We analyzed the entire coding region of the late leader peptide by a footprinting assay and identified three major regions (region I, II and III) that were protected by nuclear proteins. Further investigation of the first two protected regions by band shift assays revealed a new band that appeared in new infection cycles, suggesting that viral infection induces new factors that interact with the late leader peptide region of JCV. Analysis of the effect of the leader peptide region on the promoter activity of JCV by transfection assays demonstrated that this region has a positive and negative effect on the large T antigen (LT-Ag)-mediated activation of the viral early and late promoters, respectively. Furthermore, a partial deletion analysis of the leader peptide region encompassing the protected regions I and II demonstrated a significant down-regulation of viral gene expression and replication. More importantly, these results were similar to that obtained from a complete deletion of the late leader

A strong loss-of-function mutation in RAN1 results in constitutive activation of the ethylene response pathway as well as a rosette-lethal phenotype

Science.gov (United States)

Woeste, K. E.; Kieber, J. J.; Evans, M. L. (Principal Investigator)

2000-01-01

A recessive mutation was identified that constitutively activated the ethylene response pathway in Arabidopsis and resulted in a rosette-lethal phenotype. Positional cloning of the gene corresponding to this mutation revealed that it was allelic to responsive to antagonist1 (ran1), a mutation that causes seedlings to respond in a positive manner to what is normally a competitive inhibitor of ethylene binding. In contrast to the previously identified ran1-1 and ran1-2 alleles that are morphologically indistinguishable from wild-type plants, this ran1-3 allele results in a rosette-lethal phenotype. The predicted protein encoded by the RAN1 gene is similar to the Wilson and Menkes disease proteins and yeast Ccc2 protein, which are integral membrane cation-transporting P-type ATPases involved in copper trafficking. Genetic epistasis analysis indicated that RAN1 acts upstream of mutations in the ethylene receptor gene family. However, the rosette-lethal phenotype of ran1-3 was not suppressed by ethylene-insensitive mutants, suggesting that this mutation also affects a non-ethylene-dependent pathway regulating cell expansion. The phenotype of ran1-3 mutants is similar to loss-of-function ethylene receptor mutants, suggesting that RAN1 may be required to form functional ethylene receptors. Furthermore, these results suggest that copper is required not only for ethylene binding but also for the signaling function of the ethylene receptors.

Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

Directory of Open Access Journals (Sweden)

Kandadi Machender R

2012-11-01

Full Text Available 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 with lethal toxin (2 μg/g, intraperotineally (i.p.. Cardiomyocyte contractile and intracellular Ca2+ properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Results Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca2+ handling, the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Conclusions Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca2+ anomalies, possibly through regulation of autophagy and mitochondrial function.

Loss of Apela Peptide in Mice Causes Low Penetrance Embryonic Lethality and Defects in Early Mesodermal Derivatives

Directory of Open Access Journals (Sweden)

Laina Freyer

2017-08-01

Full Text Available Apela (also known as Elabela, Ende, and Toddler is a small signaling peptide that activates the G-protein-coupled receptor Aplnr to stimulate cell migration during zebrafish gastrulation. Here, using CRISPR/Cas9 to generate a null, reporter-expressing allele, we study the role of Apela in the developing mouse embryo. We found that loss of Apela results in low-penetrance cardiovascular defects that manifest after the onset of circulation. Three-dimensional micro-computed tomography revealed a higher penetrance of vascular remodeling defects, from which some mutants recover, and identified extraembryonic anomalies as the earliest morphological distinction in Apela mutant embryos. Transcriptomics at late gastrulation identified aberrant upregulation of erythroid and myeloid markers in mutant embryos prior to the appearance of physical malformations. Double-mutant analyses showed that loss of Apela signaling impacts early Aplnr-expressing mesodermal populations independently of the alternative ligand Apelin, leading to lethal cardiac defects in some Apela null embryos.

Winter feeding, growth and condition of brown trout Salmo trutta in a groundwater-dominated stream

Science.gov (United States)

French, William E.; Vondracek, Bruce C.; Ferrington, Leonard C.; Finlay, Jacques C.; Dieterman, Douglas J.

2014-01-01

Winter can be a stressful period for stream-dwelling salmonid populations, often resulting in reduced growth and survival. Stream water temperatures have been identified as a primary mechanism driving reductions in fitness during winter. However, groundwater inputs can moderate water temperature and may reduce winter severity. Additionally, seasonal reductions in prey availability may contribute to decreased growth and survival, although few studies have examined food webs supporting salmonids under winter conditions. This study employed diet, stable isotope, and mark-recapture techniques to examine winter (November through March) feeding, growth, and condition of brown troutSalmo trutta in a groundwater-dominated stream (Badger Creek, Minnesota, USA). Growth was greater for fish ≤ 150 mm (mean = 4.1 mg g−1 day−1) than for those 151–276 mm (mean = 1.0 mg g−1 day−1) during the winter season. Overall condition from early winter to late winter did not vary for fish ≤150 mm (mean relative weight (Wr) = 89.5) and increased for those 151–276 mm (mean Wr = 85.8 early and 89.4 late). Although composition varied both temporally and by individual, brown trout diets were dominated by aquatic invertebrates, primarily Amphipods, Dipterans, and Trichopterans. Stable isotope analysis supported the observations of the dominant prey taxa in stomach contents and indicated the winter food web was supported by a combination of allochthonous inputs and aquatic macrophytes. Brown trout in Badger Creek likely benefited from the thermal regime and increased prey abundance present in this groundwater-dominated stream during winter.

7 CFR 792.10 - Late payment interest, penalty and administrative charges.

Science.gov (United States)

2010-01-01

... State and local governments. Interest on debts owed by such entities shall be charged to the extent... debts. The late payment interest rate shall be equal to the higher of the Treasury Department's current... Prompt Payment Act was chosen as an alternative rate to ensure that the Government would recoup interest...

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)

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.

Late Pleistocene dune activity in the central Great Plains, USA

Science.gov (United States)

Mason, J.A.; Swinehart, J.B.; Hanson, P.R.; Loope, D.B.; Goble, R.J.; Miao, X.; Schmeisser, R.L.

2011-01-01

Stabilized dunes of the central Great Plains, especially the megabarchans and large barchanoid ridges of the Nebraska Sand Hills, provide dramatic evidence of late Quaternary environmental change. Episodic Holocene dune activity in this region is now well-documented, but Late Pleistocene dune mobility has remained poorly documented, despite early interpretations of the Sand Hills dunes as Pleistocene relicts. New optically stimulated luminescence (OSL) ages from drill cores and outcrops provide evidence of Late Pleistocene dune activity at sites distributed across the central Great Plains. In addition, Late Pleistocene eolian sands deposited at 20-25 ka are interbedded with loess south of the Sand Hills. Several of the large dunes sampled in the Sand Hills clearly contain a substantial core of Late Pleistocene sand; thus, they had developed by the Late Pleistocene and were fully mobile at that time, although substantial sand deposition and extensive longitudinal dune construction occurred during the Holocene. Many of the Late Pleistocene OSL ages fall between 17 and 14 ka, but it is likely that these ages represent only the later part of a longer period of dune construction and migration. At several sites, significant Late Pleistocene or Holocene large-dune migration also probably occurred after the time represented by the Pleistocene OSL ages. Sedimentary structures in Late Pleistocene eolian sand and the forms of large dunes potentially constructed in the Late Pleistocene both indicate sand transport dominated by northerly to westerly winds, consistent with Late Pleistocene loess transport directions. Numerical modeling of the climate of the Last Glacial Maximum has often yielded mean monthly surface winds southwest of the Laurentide Ice Sheet that are consistent with this geologic evidence, despite strengthened anticyclonic circulation over the ice sheet. Mobility of large dunes during the Late Pleistocene on the central Great Plains may have been the result of

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.)

Medical dominance in Canada in historical perspective: the rise and fall of medicine?

Science.gov (United States)

Coburn, D; Torrance, G M; Kaufert, J M

1983-01-01

Freidson's concept of medical dominance is compared to the alternative conceptions of neo-Marxist writers. Dominance is then examined in historical perspective, using medicine in Canada (mainly Ontario) as a case study. Medicine emerged as the dominant health occupation in Canada in the late 19th and early 20th centuries, consolidating its power between World War I and the Saskatchewan doctors' strike of 1962. The authors argue that medical dominance has declined since that time due to such factors as the involvement of the state in health insurance, the rise of other health occupations, increasing public or at least elite skepticism, and possible internal fragmentation. The underlying social explanation for this historical process is sought in changes in the Canadian class structure, specifically the spread of the capitalist mode of production, the decline of the petite bourgeoisie, and the rise of the state. It is suggested that Freidson's specific accounts of the history of medicine must be incorporated for explanatory purposes within the broader neo-Marxist view of medicine as an intermediary rather than an ultimately determining institution.

Directional dominance on stature and cognition in diverse human populations

DEFF Research Database (Denmark)

Joshi, Peter K; Esko, Tonu; Mattsson, Hannele

2015-01-01

is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been....... confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance...

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.

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.

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

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)

Characterization of the flowing afterglows of an N{sub 2}-O{sub 2} reduced-pressure discharge: setting the operating conditions to achieve a dominant late afterglow and correlating the NO{sub {beta}} UV intensity variation with the N and O atom densities

Energy Technology Data Exchange (ETDEWEB)

Boudam, M K [Groupe de Physique des Plasmas, Universite de Montreal, CP 6128, Succursale Centre-Ville, Montreal H3C 3J7, Quebec (Canada); Saoudi, B [Groupe de Physique des Plasmas, Universite de Montreal, CP 6128, Succursale Centre-Ville, Montreal H3C 3J7, Quebec (Canada); Moisan, M [Groupe de Physique des Plasmas, Universite de Montreal, CP 6128, Succursale Centre-Ville, Montreal H3C 3J7, Quebec (Canada); Ricard, A [Centre de Physique Atomique de Toulouse (CPAT), 118, route de Narbonne, Universite Paul Sabatier, 31062-Toulouse (France)

2007-03-21

The flowing afterglow of an N{sub 2}-O{sub 2} discharge in the 0.6-10 Torr range is examined in the perspective of achieving sterilization of medical devices (MDs) under conditions ensuring maximum UV intensity with minimum damage to polymer-based MDs. The early afterglow is shown to be responsible for creating strong erosion damage, requiring that the sterilizer be operated in a dominant late-afterglow mode. These two types of afterglow can be characterized by optical emission spectroscopy: the early afterglow is distinguished by an intense emission from the N{sub 2}{sup +} 1st negative system (band head at 391.4 nm) while the late afterglow yields an overpopulation of the v' = 11 ro-vibrational level of the N{sub 2}(B) state, indicating a reduced contribution from the early afterglow N{sub 2} metastable species. We have studied the influence of operating conditions (pressure, O{sub 2} content in the N{sub 2}-O{sub 2} mixture, distance of the discharge from the entrance to the afterglow (sterilizer) chamber) in order to achieve a dominant late afterglow that also ensures maximum and almost uniform UV intensity in the sterilization chamber. As far as operating conditions are concerned, moving the plasma source sufficiently far from the chamber entrance is shown to be a practical means for significantly reducing the density of the characteristic species of the early afterglow. Using the NO titration method, we obtain the (absolute) densities of N and O atoms in the afterglow at the NO injection inlet, a few cm before the chamber entrance: the N atom density goes through a maximum at approximately 0.3-0.5% O{sub 2} and then decreases, while the O atom density increases regularly with the O{sub 2} percentage. The spatial variation of the N atom (relative) density in the chamber is obtained by recording the emission intensity from the 1st positive system at 580 nm: in the 2-5 Torr range, this density is quite uniform everywhere in the chamber. The (relative

Impacts of extensive driftnet fishery and late 1990s climate regime shift on dominant epipelagic nekton in the Transition Region and Subtropical Frontal Zone: Implications for fishery management

Science.gov (United States)

Ichii, T.; Nishikawa, H.; Igarashi, H.; Okamura, H.; Mahapatra, K.; Sakai, M.; Wakabayashi, T.; Inagake, D.; Okada, Y.

2017-01-01

We investigated the impacts of extensive anthropogenic (high seas driftnet squid fishery) and natural (late 1990s major climate regime shift) events on dominant epipelagic fish, squid, and shark in the central North Pacific Transition Region based on a driftnet survey covering the years 1979-2006. Fishing was conducted by Japan, Korea and Taiwan to target neon flying squid in the period 1979-1992, resulting in a decline in stocks of the target species and non-target species (Pacific pomfret and juvenile blue shark), which were by-catch of this fishery. The catch was found to be at the maximum sustainable yield (MSY) level for neon flying squid, the underfished level for juvenile blue shark, but the overfished level for Pacific pomfret. The MSY of Pacific pomfret indicated that this species is more susceptible to exploitation than previously considered. In response to the late 1990s regime shift, neon flying squid and Pacific saury showed low stock levels in 1999-2002 and 1998-2002, respectively, as a result of reduced productivity in their nursery grounds (the Subtropical Frontal Zone and Kuroshio Extension Bifurcation Region, respectively). On the other hand, Pacific pomfret showed no decreasing trend in stock during the low- and intermediate-productivity regimes because of the high productivity of their main spawning/nursery ground (Transition Zone Chlorophyll Front), which was independent of the regime shifts. Thus, squid and saury appear to be more susceptible to the regime shift than pomfret. We discuss the implications for stock management of the species-specific responses to the fishery and the regime shift.

Lethal Surveillance: Drones and the Geo-History of Modern War

Science.gov (United States)

Kindervater, Katharine Hall

Interdisciplinary both in scope and method, my dissertation, Lethal Surveillance: Drones and the Geo-History of Modern War, examines the history of drone technology from the start of the 20th century to the present in order to understand the significance of the increasing centrality of drones to current American military engagements and security practices more generally. Much of the scholarship on drones and many other contemporary military technologies tends to view the technology as radically new, missing both the historical development of these objects as well as the perspectives and rationalities that are embedded in their use. For this research, I focused on three main periods of drone research and development: the early years of World War I and II in the UK, the Cold War, and the 1990s. In studying this history of the drone, I found that two key trends emerge as significant: the increasing importance of information to warfare under the rubric of intelligence, reconnaissance and surveillance; and a shift toward more dynamic, speedier, and individualized targeting practices. I argue that the widespread use of drones today thus represents the culmination of attempts in war to effectively link these two trends, creating a practice I call lethal surveillance -- with the armed Predator effectively closing the loop between identifying and killing targets. The concept of lethal surveillance, which in my dissertation I place squarely within the histories of modern scientific thinking and Western liberal governance, allows us to see how techniques of Western state power and knowledge production are merging with practices of killing and control in new ways, causing significant changes to both the operations of the state and to practices of war. Framing the drone through the lens of lethal surveillance, therefore, allows us to see the longer histories the drone is embedded in as well as other security practices it is connected to.

40 CFR 798.5450 - Rodent dominant lethal assay.

Science.gov (United States)

2010-07-01

... mated to untreated virgin females. The various germ cell stages can be tested separately by the use of... treated group to the live implants per female in the control group. The increase of dead implants per female in the treated group over the dead implants per female in the control group reflects the post...

Influence Of Quinolone Lethality on Irradiated Anaerobic Growth of Escherichia Coli

International Nuclear Information System (INIS)

Ibrahim, I.M.; El-Kabbany, H.M.; El-Esseily, E.SH.

2012-01-01

Bacteriostatic and bactericidal activities were measured with wild type cells and isomerase mutants of Escherichia coli for ciprofloxacin, formation of quinolone-gyrase-DNA complexes, observed as a sodium dodecyl sulfate (SDS) dependent drop in cell lysate viscosity, occurred during aerobic and anaerobic growth and in the presence and in the absence of chloramphenicol. Quinolone activity against Escherichia coli was examined during aerobic growth, aerobic treatment with chloramphenicol, and anaerobic growth. Nalidixic acid, norfloxacin and ciprofloxacin were lethal for cultures growing aerobically, and the bacteriostatic activity of each quinolone was unaffected by anaerobic growth. However, lethal activity was distinct for each quinolone with cells treated aerobically with chloramphenicol or grown anaerobically. Nalidixic acid failed to kill cells under both conditions, norfloxacin killed cells when they were grown anaerobically but not when they were treated with chloramphenicol, ciprofloxacin killed cells under both conditions but required higher concentrations than those required with cells grown aerobically, C-methoxy fluoro quinolone was equally lethal under all conditions. However, lethal chromosome fragmentation, detected as a drop in viscosity in the absence of SDS, was occurred with nalidixic acid treatment only under aerobic conditions in the absence of chloramphenicol, thus, all quinolones tested appeared to form reversible bacteriostatic complexes containing broken DNA during aerobic growth, during anaerobic growth, and when protein synthesis is blocked. The ability to fragment chromosomes rapidly kill cells under these conditions depends on quinolone structure. The radiation of sublethal dose was 3 Gy at rate of 0.6 Gy/min was shown as non-significant result

Longitudinal development of the gut microbiome and metabolome in preterm neonates with late onset sepsis and healthy controls.

Science.gov (United States)

Stewart, Christopher J; Embleton, Nicholas D; Marrs, Emma C L; Smith, Daniel P; Fofanova, Tatiana; Nelson, Andrew; Skeath, Tom; Perry, John D; Petrosino, Joseph F; Berrington, Janet E; Cummings, Stephen P

2017-07-12

Late onset sepsis (LOS) in preterm infants is associated with considerable morbidity and mortality. While studies have implicated gut bacteria in the aetiology of the disease, functional analysis and mechanistic insights are generally lacking. We performed temporal bacterial (n = 613) and metabolomic (n = 63) profiling on extensively sampled stool from 7 infants with LOS and 28 matched healthy (no LOS or NEC) controls. The bacteria isolated in diagnostic blood culture usually corresponded to the dominant bacterial genera in the gut microbiome. Longitudinal changes were monitored based on preterm gut community types (PGCTs), where control infants had an increased number of PGCTs compared to LOS infants (P = 0.011). PGCT 6, characterised by Bifidobacteria dominance, was only present in control infants. Metabolite profiles differed between LOS and control infants at diagnosis and 7 days later, but not 7 days prior to diagnosis. Bifidobacteria was positively correlated with control metabolites, including raffinose, sucrose, and acetic acid. Using multi-omic analysis, we show that the gut microbiome is involved in the pathogenesis of LOS. While the causative agent of LOS varies, it is usually abundant in the gut. Bifidobacteria dominance was associated with control infants, and the presence of this organism may directly protect, or act as a marker for protection, against gut epithelial translocation. While the metabolomic data is preliminary, the findings support that gut development and protection in preterm infants is associated with increased in prebiotic oligosaccharides (e.g. raffinose) and the growth of beneficial bacteria (e.g. Bifidobacterium).

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.)

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.)

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.)

Point of no return: experimental determination of the lethal hydraulic threshold during drought for loblolly pine (Pinus taeda)

Science.gov (United States)

Hammond, W.; Yu, K.; Wilson, L. A.; Will, R.; Anderegg, W.; Adams, H. D.

2017-12-01

The strength of the terrestrial carbon sink—dominated by forests—remains one of the greatest uncertainties in climate change modelling. How forests will respond to increased variability in temperature and precipitation is poorly understood, and experimental study to better inform global vegetation models in this area is needed. Necessary for achieving­­­­ this goal is an understanding of how increased temperatures and drought will affect landscape level distributions of plant species. Quantifying physiological thresholds representing a point of no return from drought stress, including thresholds in hydraulic function, is critical to this end. Recent theoretical, observational, and modelling research has converged upon a threshold of 60 percent loss of hydraulic conductivity at mortality (PLClethal). However, direct experimental determination of lethal points in conductivity and cavitation during drought is lacking. We quantified thresholds in hydraulic function in Loblolly pine, Pinus taeda, a commercially important timber species. In a greenhouse experiment, we exposed saplings (n = 96 total) to drought and rewatered treatment groups at variable levels of increasing water stress determined by pre-selected targets in pre-dawn water potential. Treatments also included a watered control with no drought, and drought with no rewatering. We measured physiological responses to water stress, including hydraulic conductivity, native PLC, water potential, foliar color, canopy die-back, and dark-adapted chlorophyll fluorescence. Following the rewatering treatment, we observed saplings for at least two months to determine which survived and which died. Using these data we calculated lethal physiological thresholds in water potential, directly measured PLC, and PLC inferred from water potential using a hydraulic vulnerability curve. We found that PLClethal inferred from water potential agreed with the 60% threshold suggested by previous research. However, directly

Late effects of chronic low dose-rate γ-rays irradiation on mice

International Nuclear Information System (INIS)

Tanaka, Satoshi; Sasagawa, Sumiko; Ichinohe, Kazuaki; Matsumoto, Tsuneya; Otsu, Hiroshi; Sato, Fumiaki

2002-01-01

To evaluate late biological effects of chronic low dose-rate radiation, we are conducting two experiments. Experiment 1 - Late effects of chronic low dose-rate g-rays irradiation on SPF mice, using life-span and pathological changes as parameters. Continuous irradiation with g-rays for 400 days was performed using 137 Cs γ-rays at dose-rates of 20 mGy/day, 1 mGy/day and 0.05 mGy/day with accumulated doses equivalent to 8,000 mGy, 400 mGy and 20 mGy, respectively. All mice were kept until they died a natural death. As of 2002 March 31, 3,999 of the total 4,000 mice have died. Preliminary analyses of data show that 20 mGy/day suggested a shortened life span in both sexes. Partial results show that the most common lethal neoplasms in the pooled data of non-irradiated control and irradiated male mice, in order of frequency, were neoplasms of the lymphohematopoietic system, liver, and lung. In female mice, neoplasms of the lymphohematopoietic system, soft tissue, and endocrine system were common. Experiment 2 - Effects on the progeny of chronic low dose-rate g-ray irradiated SPF mice: pilot study, was started in 1999 and is currently in progress. (author)

The effect of IFSA 2013 on late payment of takāful benefits

Directory of Open Access Journals (Sweden)

Muhammad Ali Jinnah Ahmad

2017-07-01

Full Text Available Purpose - This paper aims to examine the implications of compensation on late payment of takāful benefit imposed in the Islamic Financial Services Act 2013 on the takāful industry in Malaysia. It also aims to identify the issues and challenges faced by takāful operators in the implementation of the compensation and propose solutions for the benefits of the takāful industry. Design/methodology/approach - This research uses the qualitative approach to understand the practices of claims in takāful and to analyze the implication of compensation on late payment of takāful benefit to the takāful industry in Malaysia. Data are collected through survey and interview with various takāful stakeholders. Findings - Some of the key findings in this research are that the compensation of late payment of takāful benefit has a positive impact to the takāful industry. The research also found some Sharīʿah operational issues in terms of its implementation among takāful operators. Research limitations/implications - The research focuses on compensation on late payment of takāful benefit claim in death and personal accident only. Practical implications - The research offers certainty to the takāful industry and an explanation to academic and legal fraternities on the implementation of compensation on late payment of takāful benefit according to Islamic Financial Services Act (IFSA 2013. Originality/value - The research provides a valuable contribution to the current practices of takāful operators, identifies some issues and challenges of its implementation and proposes the solution.

Changes in vegetation since the late glacial on peat bog in the Small Carpathians

International Nuclear Information System (INIS)

Ciernikova, M.

2014-01-01

Mires are ecosystems accumulating high amount of organic matter with preserved micro- and macro-fossils. Thus they can serve as natural archives allowing reconstruction of local vegetation and landscape development. Main aim of this study was to bring evidence of the whole Holocene history of mire birch woodland located on the ridge of the Male Karpaty Mts (SW Slovakia) using pollen analysis. One peat core was sampled from the middle part containing the whole Holocene sequence. The local development of study site started with small lake in a terrain depression, which arose at the end of the Late Glacial (Middle Dryas). The Late Glacial landscape was mosaic of birch-pine forests on suitable places and Artemisia steppes. Early Holocene is characterized by steep decline of pine and increase of Corylus and other mesophilous trees (Quercus, Tilia, Ulmus, Fraxinus). Fagus started dominate in middle Holocene (about 5000 cal BP). The recent vegetation established only several hundred years ago (ca 500 cal. BP), when birch started dominate. (author)

Testing of candidate non-lethal sampling methods for detection of Renibacterium salmoninarum in juvenile Chinook salmon Oncorhynchus tshawytscha

Science.gov (United States)

Elliott, Diane G.; McKibben, Constance L.; Conway, Carla M.; Purcell, Maureen K.; Chase, Dorothy M.; Applegate, Lynn M.

2015-01-01

Non-lethal pathogen testing can be a useful tool for fish disease research and management. Our research objectives were to determine if (1) fin clips, gill snips, surface mucus scrapings, blood draws, or kidney biopsies could be obtained non-lethally from 3 to 15 g Chinook salmon Oncorhynchus tshawytscha, (2) non-lethal samples could accurately discriminate between fish exposed to the bacterial kidney disease agent Renibacterium salmoninarum and non-exposed fish, and (3) non-lethal samples could serve as proxies for lethal kidney samples to assess infection intensity. Blood draws and kidney biopsies caused ≥5% post-sampling mortality (Objective 1) and may be appropriate only for larger fish, but the other sample types were non-lethal. Sampling was performed over 21 wk following R. salmoninarum immersion challenge of fish from 2 stocks (Objectives 2 and 3), and nested PCR (nPCR) and real-time quantitative PCR (qPCR) results from candidate non-lethal samples were compared with kidney tissue analysis by nPCR, qPCR, bacteriological culture, enzyme-linked immunosorbent assay (ELISA), fluorescent antibody test (FAT) and histopathology/immunohistochemistry. R. salmoninarum was detected by PCR in >50% of fin, gill, and mucus samples from challenged fish. Mucus qPCR was the only non-lethal assay exhibiting both diagnostic sensitivity and specificity estimates >90% for distinguishing between R. salmoninarum-exposed and non-exposed fish and was the best candidate for use as an alternative to lethal kidney sample testing. Mucus qPCR R. salmoninarum quantity estimates reflected changes in kidney bacterial load estimates, as evidenced by significant positive correlations with kidney R. salmoninaruminfection intensity scores at all sample times and in both fish stocks, and were not significantly impacted by environmentalR. salmoninarum concentrations.

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.

Paleoecology of the Late Pennsylvanian-age Calhoun coal bed and implications for long-term dynamics of wetland ecosystems

Energy Technology Data Exchange (ETDEWEB)

Willard, Debra A. [US Geological Survey, 926A National Center, Reston (VA 20192 USA); Phillips, Tom L. [Department of Plant Biology, University of Illinois, Urbana (IL 61801 USA); Lesnikowska, Alicia D. [Box 24, Rt. 2, Vineyard Haven (MA 02568 USA); DiMichele, William A. [Department of Paleobiology, NMNH, Smithsonian Institution, Washington (DC 20560 USA)

2007-01-02

Quantitative plant assemblage data from coal balls, miospores, megaspores, and compression floras from the Calhoun coal bed (Missourian) of the Illinois Basin (USA) are used to interpret spatial and temporal changes in plant communities in the paleo-peat swamp. Coal-ball and miospore floras from the Calhoun coal bed are dominated strongly by tree ferns, and pteridosperms and sigillarian lycopsids are subdominant, depending on geographic location within the coal bed. Although the overall composition of Calhoun peat-swamp assemblages is consistent both temporally and spatially, site-to-site differences and short-term shifts in species dominance indicate local topographic and hydrologic control on species composition within the broader context of the swamp. Statistical comparison of the Calhoun miospore assemblages with those from other Late Pennsylvanian coal beds suggests that the same basic species pool was represented in each peat-swamp landscape and that the relative patterns of dominance and diversity were persistent from site to site. Therefore, it appears that the relative patterns of proportional dominance stayed roughly the same from one coal bed to the next during Late Pennsylvanian glacially-driven climatic oscillations. (author)

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.

Anemia: friend or foe? Low hemoglobin is associated with decreased survival, loco-regional control and late complications: a secondary analysis of RTOG 85-27

International Nuclear Information System (INIS)

Lee, W. Robert; Berkey, B.; Marcial, V.; Fu, K.K.; Cooper, J. S.; Vikram, B.; Coia, L.R.; Rotman, M.; Ortiz, H.

1997-01-01

Purpose: Classical teaching holds that hypoxia reduces the lethal effects of ionizing radiation. Many reports have correlated low hemoglobin (Hgb) levels with reduced loco-regional control (LRC) following radiotherapy (RT) suggesting that anemia may be associated with tumor hypoxia. If hypoxia protects tumors from the lethal effects of ionizing radiation then it might protect normal tissues in a similar fashion. The purpose of the present study was to examine the effect of Hgb level on the LRC, survival and late complications in patients with advanced head and neck cancer treated with conventional radiotherapy with or without a hypoxic cell sensitizer. Methods: From March 1988 to September 1991, 521 patients with Stage III or IV squamous cell carcinoma of the head and neck were entered onto a randomized trial examining the addition of etanidazole (SR 2508) to conventional RT (66 Gy in 33 fractions to 74 Gy in 37 fractions, 5 days a week). Hgb levels were stratified as high (≥ 14.5 grams-percent for men, ≥ 13.0 grams-percent for women) or low (<14.5 for men, <13.0 for women). Loco-regional failure rates were calculated using the cumulative incidence approach. Overall survival was estimated according to the Kaplan-Meier method. Late RT toxicity was scored according to the RTOG morbidity scale. Differences in rates of LRC, survival and late complications were tested by the Cox proportional hazard model. The median follow-up of surviving patients was 57 months with a range of 1-7.5 years. Results: Of 504 eligible patients, 451 had Hgb measured prior to the second week of RT. One hundred and sixty-two patients (35.9%) were classified as having a high Hgb (HH) and 289 (64.1%) patients were classified as having a low Hgb (LH). Patients in the LH group had significantly lower survival and a trend towards lower LRC and late RT complications (see Table). Conclusion: Low Hgb levels are associated with a statistically significant reduction in survival and a trend towards

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)

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)

Development of non-lethal methods for investigation of actinide uptake by wildlife

Energy Technology Data Exchange (ETDEWEB)

Johansen, M.; Child, D.; Davis, E.; Harrison, J.; Hotchkis, M.; Payne, T.; Thiruvoth, S. [Australian Nuclear Science and Technology Org. (Australia); Wood, M. [University of Salford (United Kingdom)

2014-07-01

There is growing interest in the use of non-lethal methods in radioecology and an International Union of Radioecology Task Group has been established to facilitate international cooperation in this field (http://iur-uir.org/en/task-groups/id-19-non-lethal-methods-in-radioecology). In this paper, we evaluate the use of lethally-, and non-lethally obtained samples (various body tissues, excreta and blood withdrawals as well as parasites and found bones) as indicators of contamination. Samples of mammals and reptiles were collected from the semi-arid former weapons test site at Maralinga, Australia and analysed for thorium, plutonium, and uranium isotopes by accelerator mass spectrometry and alpha-spectrometry. Most samples were of low mass and presented analytical challenges as a result. The plutonium concentrations in blood withdrawn from the marginal ear veins of Oryctolagus cuniculus (European rabbit) were successfully analysed using small samples (0.2 -7.9 ml, below the ∼10 ml threshold for safe extraction of blood from these rabbits). The results demonstrate that small-volume blood samples can serve as indicators of the presence of plutonium absorbed within other tissues (e.g., muscle, bone). However, the magnitude of the blood plutonium masses were poorly correlated with those in muscle and bone due to the presence of a small number of outliers (without the outliers, correlations improved to r = +0.66 and r = +0.51 for muscle and bone respectively). The activity concentrations in parasitic ticks were relatively high compared with those of their hosts Pseudomys hermannsburgensis (sandy inland mouse) and Ctenophorus cristatus (crested dragon lizard). Successful measurement of tick samples indicates a potential for use of parasites as general indicators of contamination within host organisms. The concentrations of actinides in found bones of Macropus rufus (red kangaroo) and O. cuniculus demonstrated potential for their use as indicators of the areal extent of

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.

[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.

A complex dominance hierarchy is controlled by polymorphism of small RNAs and their targets.

Science.gov (United States)

Yasuda, Shinsuke; Wada, Yuko; Kakizaki, Tomohiro; Tarutani, Yoshiaki; Miura-Uno, Eiko; Murase, Kohji; Fujii, Sota; Hioki, Tomoya; Shimoda, Taiki; Takada, Yoshinobu; Shiba, Hiroshi; Takasaki-Yasuda, Takeshi; Suzuki, Go; Watanabe, Masao; Takayama, Seiji

2016-12-22

In diploid organisms, phenotypic traits are often biased by effects known as Mendelian dominant-recessive interactions between inherited alleles. Phenotypic expression of SP11 alleles, which encodes the male determinants of self-incompatibility in Brassica rapa, is governed by a complex dominance hierarchy 1-3 . Here, we show that a single polymorphic 24 nucleotide small RNA, named SP11 methylation inducer 2 (Smi2), controls the linear dominance hierarchy of the four SP11 alleles (S 44 > S 60 > S 40 > S 29 ). In all dominant-recessive interactions, small RNA variants derived from the linked region of dominant SP11 alleles exhibited high sequence similarity to the promoter regions of recessive SP11 alleles and acted in trans to epigenetically silence their expression. Together with our previous study 4 , we propose a new model: sequence similarity between polymorphic small RNAs and their target regulates mono-allelic gene expression, which explains the entire five-phased linear dominance hierarchy of the SP11 phenotypic expression in Brassica.

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...

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...

Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections.

Science.gov (United States)

Lilly, Elizabeth A; Ikeh, Melanie; Nash, Evelyn E; Fidel, Paul L; Noverr, Mairi C

2018-01-16

Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non- albicans Candida (NAC) species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans / S. aureus (i.e., coninfection) resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis / S. aureus -mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis -induced protection. C. dubliniensis / S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge). Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO]) survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1 hi polymorphonuclear leukocytes (PMNLs) in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1 + cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans / S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of

DELVING INTO SPEECH ACT A Case Of Indonesian EFL Young Learners

Directory of Open Access Journals (Sweden)

Swastika Septiani, S.Pd

2017-04-01

Full Text Available This study attempts to describe the use of speech acts applied in primary school. This study is intended to identify the speech acts performed in primary school, to find the most dominant speech acts performed in elementary school, to give brief description of how speech acts applied in primary school, and to know how to apply the result of the study in English teaching learning to young learners. The speech acts performed in primary school is classified based on Searle‘s theory of speech acts. The most dominant speech acts performed in primary school is Directive (41.17%, the second speech act mostly performed is Declarative (33.33%, the third speech act mostly performed is Representative and Expressive (each 11.76%, and the least speech act performed is Commisive (1.9%. The speech acts performed in elementary school is applied on the context of situation determined by the National Education Standards Agency (BSNP. The speech acts performed in fourth grade have to be applied in the context of classroom, and the speech acts performed in fifth grade have to be applied in the context of school, whereas the speech acts performed in sixth grade have to be applied in the context of the students‘ surroundings. The result of this study is highy expected to give significant contribution to English teaching learning to young learners. By acknowledging the characteristics of young learners, the way they learn English as a foreign language, the teachers are expected to have inventive strategies and various techniques to create a fun and condusive atmosphere in English class.

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...

IslandFAST: A Semi-numerical Tool for Simulating the Late Epoch of Reionization

Energy Technology Data Exchange (ETDEWEB)

Xu, Yidong; Chen, Xuelei [Key Laboratory for Computational Astrophysics, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China); Yue, Bin [National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China)

2017-08-01

We present the algorithm and main results of our semi-numerical simulation, islandFAST, which was developed from 21cmFAST and designed for the late stage of reionization. The islandFAST simulation predicts the evolution and size distribution of the large-scale underdense neutral regions (neutral islands), and we find that the late Epoch of Reionization proceeds very fast, showing a characteristic scale of the neutral islands at each redshift. Using islandFAST, we compare the impact of two types of absorption systems, i.e., the large-scale underdense neutral islands versus small-scale overdense absorbers, in regulating the reionization process. The neutral islands dominate the morphology of the ionization field, while the small-scale absorbers dominate the mean-free path of ionizing photons, and also delay and prolong the reionization process. With our semi-numerical simulation, the evolution of the ionizing background can be derived self-consistently given a model for the small absorbers. The hydrogen ionization rate of the ionizing background is reduced by an order of magnitude in the presence of dense absorbers.

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...

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

Sex Differences in the Regulation of Offensive Aggression and Dominance by Arginine-Vasopressin

Directory of Open Access Journals (Sweden)

Joseph I. Terranova

2017-11-01

Full Text Available Arginine-vasopressin (AVP plays a critical role in the regulation of offensive aggression and social status in mammals. AVP is found in an extensive neural network in the brain. Here, we discuss the role of AVP in the regulation of aggression in the limbic system with an emphasis on the critical role of hypothalamic AVP in the control of aggression. In males, activation of AVP V1a receptors (V1aRs in the hypothalamus stimulates offensive aggression, while in females activation of V1aRs inhibits aggression. Serotonin (5-HT also acts within the hypothalamus to modulate the effects of AVP on aggression in a sex-dependent manner. Activation of 5-HT1a receptors (5-HT1aRs inhibits aggression in males and stimulates aggression in females. There are also striking sex differences in the mechanisms underlying the acquisition of dominance. In males, the acquisition of dominance is associated with the activation of AVP-containing neurons in the hypothalamus. By contrast, in females, the acquisition of dominance is associated with the activation of 5-HT-containing neurons in the dorsal raphe. AVP and 5-HT also play critical roles in the regulation of a form of social communication that is important for the maintenance of dominance relationships. In both male and female hamsters, AVP acts via V1aRs in the hypothalamus, as well as in other limbic structures, to communicate social status through the stimulation of a form of scent marking called flank marking. 5-HT acts on 5-HT1aRs as well as other 5-HT receptors within the hypothalamus to inhibit flank marking induced by AVP in both males and females. Interestingly, while AVP and 5-HT influence the expression of aggression in opposite ways in males and females, there are no sex differences in the effects of AVP and 5-HT on the expression of social communication. Given the profound sex differences in the incidence of many psychiatric disorders and the increasing evidence for a relationship between aggressiveness/dominance

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...

Extreme ecosystem instability suppressed tropical dinosaur dominance for 30 million years.

Science.gov (United States)

Whiteside, Jessica H; Lindström, Sofie; Irmis, Randall B; Glasspool, Ian J; Schaller, Morgan F; Dunlavey, Maria; Nesbitt, Sterling J; Smith, Nathan D; Turner, Alan H

2015-06-30

A major unresolved aspect of the rise of dinosaurs is why early dinosaurs and their relatives were rare and species-poor at low paleolatitudes throughout the Late Triassic Period, a pattern persisting 30 million years after their origin and 10-15 million years after they became abundant and speciose at higher latitudes. New palynological, wildfire, organic carbon isotope, and atmospheric pCO2 data from early dinosaur-bearing strata of low paleolatitudes in western North America show that large, high-frequency, tightly correlated variations in δ(13)Corg and palynomorph ecotypes occurred within a context of elevated and increasing pCO2 and pervasive wildfires. Whereas pseudosuchian archosaur-dominated communities were able to persist in these same regions under rapidly fluctuating extreme climatic conditions until the end-Triassic, large-bodied, fast-growing tachymetabolic dinosaurian herbivores requiring greater resources were unable to adapt to unstable high CO2 environmental conditions of the Late Triassic.

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.

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)

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.

Incomplete development of the spleen and the deformity in the chimeras between asplenic mutant (Dominant hemimelia) and normal mice.

Science.gov (United States)

Suto, J; Wakayama, T; Imamura, K; Goto, S; Fukuta, K

1995-08-01

The semidominant gene Dh (Dominant hemimelia) induces skeletal and visceral abnormalities of various degrees and failure of the spleen in mice. The homozygous individual (Dh/Dh) seems to be lethal. The present experiment was designed to investigate the ability Dh cells to form a spleen and the genesis of the hind limb malformations by Dh/Dh and Dh/+ cells in chimeric mice. The Dh/Dh and Dh/+ embryos were produced in the F2 progeny of a cross between inbred strains of Dh/+ and DDD mice. They were aggregated with C3H/He or C57BL/6 embryos to make chimeras. Identification of Dh/Dh or Dh/+ embryos was carried out by Pep-3, and chimerism was analyzed by Gpi-1. Of 25 chimeras carrying the Dh gene, four mice formed a small spleen, two mice had a vestigial spleen, and the others no spleen. The tissues of the incompletely developed spleens were normal histologically and Dh cells were involved in the tissues of the spleen. In the chimeric mice, hindlimb malformation by the Dh gene was reduced in severity and the lethality of the homozygote (Dh/Dh) was rescued.

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.

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 ...

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

Alternative Splicing and Tissue-specific Elastin Misassembly Act as Biological Modifiers of Human Elastin Gene Frameshift Mutations Associated with Dominant Cutis Laxa*

Science.gov (United States)

Sugitani, Hideki; Hirano, Eiichi; Knutsen, Russell H.; Shifren, Adrian; Wagenseil, Jessica E.; Ciliberto, Christopher; Kozel, Beth A.; Urban, Zsolt; Davis, Elaine C.; Broekelmann, Thomas J.; Mecham, Robert P.

2012-01-01

Elastin is the extracellular matrix protein in vertebrates that provides elastic recoil to blood vessels, the lung, and skin. Because the elastin gene has undergone significant changes in the primate lineage, modeling elastin diseases in non-human animals can be problematic. To investigate the pathophysiology underlying a class of elastin gene mutations leading to autosomal dominant cutis laxa, we engineered a cutis laxa mutation (single base deletion) into the human elastin gene contained in a bacterial artificial chromosome. When expressed as a transgene in mice, mutant elastin was incorporated into elastic fibers in the skin and lung with adverse effects on tissue function. In contrast, only low levels of mutant protein incorporated into aortic elastin, which explains why the vasculature is relatively unaffected in this disease. RNA stability studies found that alternative exon splicing acts as a modifier of disease severity by influencing the spectrum of mutant transcripts that survive nonsense-mediated decay. Our results confirm the critical role of the C-terminal region of tropoelastin in elastic fiber assembly and suggest tissue-specific differences in the elastin assembly pathway. PMID:22573328

Differential replication of Foot-and-mouth disease viruses in mice determine lethality.

Science.gov (United States)

Cacciabue, Marco; García-Núñez, María Soledad; Delgado, Fernando; Currá, Anabella; Marrero, Rubén; Molinari, Paula; Rieder, Elizabeth; Carrillo, Elisa; Gismondi, María Inés

2017-09-01

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 lethal virus (A01L) caused death within 24-48h independently of the dose used. Both viruses caused a systemic infection with pathological changes in the exocrine pancreas. Virus A01L reached higher viral loads in plasma and organs of inoculated mice as well as increased replication in an ovine kidney cell line. Complete consensus sequences revealed 6 non-synonymous changes between A01L and A10NL genomes that might be linked to replication differences, as suggested by in silico prediction studies. Our results highlight the biological significance of discrete genomic variations and reinforce the usefulness of this animal model to study viral determinants of lethality. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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

Adolescent male chimpanzees do not form a dominance hierarchy with their peers.

Science.gov (United States)

Sandel, Aaron A; Reddy, Rachna B; Mitani, John C

2017-01-01

Dominance hierarchies are a prominent feature of the lives of many primate species. These hierarchies have important fitness consequences, as high rank is often positively correlated with reproduction. Although adult male chimpanzees strive for status to gain fitness benefits, the development of dominance relationships is not well understood. While two prior studies found that adolescent males do not display dominance relationships with peers, additional research at Ngogo in Kibale National Park, Uganda, indicates that adolescents there form a linear dominance hierarchy. These conflicting findings could reflect different patterns of rank acquisition across sites. An alternate possibility arises from a recent re-evaluation of age estimates at Ngogo and suggests that the report describing decided dominance relationships between adolescent males may have been due to the accidental inclusion of young adult males in the sample. To investigate these issues, we conducted a study of 23 adolescent male chimpanzees of known age during 12 months at Ngogo. Adolescent male chimpanzees exchanged pant grunts, a formal signal of submission, only 21 times. Recipients of pant grunts were late adolescent males, ranging between 14 and 16 years old. In contrast, younger adolescent males never received pant grunts from other males. Aggression between adolescent males was also rare. Analysis of pant grunts and aggressive interactions did not produce a linear dominance hierarchy among adolescent males. These data indicate that adolescent male chimpanzees do not form decided dominance relationships with their peers and are consistent with the hypothesis that the hierarchy described previously at Ngogo resulted from inaccurate age estimates of male chimpanzees. Because dominance relationships develop before adulthood in other primates, our finding that adolescent male chimpanzees do not do so is surprising. We offer possible explanations for why this is the case and suggest future studies

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

A review of the Late Cambrian (Furongian) palaeogeography in the western Mediterranean region, NW Gondwana

Science.gov (United States)

Álvaro, J. Javier; Ferretti, Annalisa; González-Gómez, Cristina; Serpagli, Enrico; Tortello, M. Franco; Vecoli, Marco; Vizcaïno, Daniel

2007-11-01

The Cambrian-Ordovician transition of the western Mediterranean region (NW Gondwana) is characterized by the record of major erosive unconformities with gaps that range from a chronostratigraphic stage to a series. The hiatii are diachronous and involved progressively younger strata along the Gondwanan margin, from SW (Morocco) to NE (Montagne Noire). They can be related to development of a multi-stage rifting (further North), currently connected to the opening of the Rheic Ocean, and concomitant erosion on southern rift shoulders. The platforms of this margin of Gondwana occupied temperate-water, mid latitudes and were dominated by siliciclastic sedimentation, while carbonate factories were only episodically active in the Montagne-Noire platform. The Upper Cambrian is devoid of significant gaps in the southern Montagne Noire and the Iberian Chains. There, the sedimentation took place in a transgressive-dominated depositional system, with common offshore deposits and clayey substrates, and was bracketed by two major regressive trends. The Late Cambrian is also associated with the record of volcanic activity ( e.g., in the Cantabrian and Ossa-Morena zones, and the northern Montagne Noire), and widespread development of a tectonic instability that led to the episodic establishment of palaeotopographies and record of slope-related facies associations. Several immigration events are recognized throughout the latest Middle Cambrian, Late Cambrian and Tremadocian. The trilobites show a stepwise replacement of Acado-Baltic-type families ( e.g., the conocoryphid-paradoxidid-solenopleurid assemblage) characterized by: (i) a late Languedocian (latest Middle Cambrian) co-occurrence of Middle Cambrian trilobite families with the first anomocarid, dorypygid and proasaphiscid invaders; (ii) a Late Cambrian immigration replacing previous faunas, composed of trilobites (aphelaspidids, catillicephalids, ceratopygids, damesellids, eulomids, idahoiids, linchakephalids, lisariids

Lethal coalitionary aggression and long-term alliance formation among Yanomamö men.

Science.gov (United States)

Macfarlan, Shane J; Walker, Robert S; Flinn, Mark V; Chagnon, Napoleon A

2014-11-25

Some cross-cultural evidence suggests lethal coalitionary aggression in humans is the product of residence and descent rules that promote fraternal interest groups, i.e., power groups of coresident males bonded by kinship. As such, human lethal coalitions are hypothesized to be homologous to chimpanzee (Pan troglodytes) border patrols. However, humans demonstrate a unique metagroup social structure in which strategic alliances allow individuals to form coalitions transcending local community boundaries. We test predictions derived from the fraternal interest group and strategic alliance models using lethal coalition data from a lowland South American population, the Yanomamö. Yanomamö men who kill an enemy acquire a special status, termed unokai. We examine the social characteristics of co-unokais or men who jointly kill others. Analyses indicate co-unokais generally are (i) from the same population but from different villages and patrilines, (ii) close age mates, and (iii) maternal half-first cousins. Furthermore, the incident rate for co-unokai killings increases if men are similar in age, from the same population, and from different natal communities. Co-unokais who have killed more times in the past and who are more genetically related to each other have a higher probability of coresidence in adulthood. Last, a relationship exists between lethal coalition formation and marriage exchange. In this population, internal warfare unites multiple communities, and co-unokais strategically form new residential groups and marriage alliances. These results support the strategic alliance model of coalitionary aggression, demonstrate the complexities of human alliance formation, and illuminate key differences in social structure distinguishing humans from other primates.

Sex-linked dominant

Science.gov (United States)

Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... can be either an autosomal chromosome or a sex chromosome. It also depends on whether the trait ...

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...

The role of pH in lethal effect of glucose load malignant cells

International Nuclear Information System (INIS)

Shmakova, N.L.; Yarmonenko, S.P.; Laser, K.; Fomenkova, T.E.; Kozubek, S.; Korogodin, V.I.

1985-01-01

The lethal effect of variuos pH values on Erlich ascites tumour (EAT) calls has been investigated. Different pH values were obtained by means of both glucose load and phosphate buffers. The effect has been investigated by observing cell death in vitro, determining cancerogenity of EAT cells and determining their radiosensitivity. The results of all methods enabled 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. The lethal effect markedly increased when the value of pH was lower than 5.6. It is concluded that the basis of the mechanism of glucose load lethal effect is their ''self-acidisation''. The measurement of pH in tumours is proposed as a basic test for determining the suitability of the use of hyperglycemia in clinics and for comparison of the efficiency of various modes of treatment

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.

Paleoenvironmental conditions in the late Paleogene, Sumatra, Indonesia

Science.gov (United States)

O'shea, Natalie; Arthur Bettis, E.; Zaim, Yahdi; Rizal, Yan; Aswan, Aswan; Gunnell, Gregg F.; Zonneveld, John-Paul; Ciochon, Russell L.

2015-11-01

A stratified paleosol sequence exposed in an open pit mine in central Sumatra provides a record of the paleoenvironmental conditions in the lower reaches of a large river system in the late Paleogene (latest Eocene or Oligocene). Morphological, geochemical, and stable isotope data suggest that the sequence represents a mosaic of local environmental conditions changing from estuarine to riverine up section. Weakly expressed soils formed on low-lying estuary surfaces, while more well expressed soils formed on higher, better drained surfaces. Peatlands (coal) with clayey subsoils were along the estuary margins. Well-expressed soils with evidence of clay translocation and chemical weathering become more common higher in the section where alluvial deposits associated with a meandering river are dominant. Stable carbon isotope ratios support a paleolandscape dominated by C3 plants with input by C4 vegetation limited to a few intervals. Finally, whole-rock geochemistry suggests moderate chemical weathering consistent with a tropical locality. This multi-proxy paleoenvironmental reconstruction suggests a highly productive lowland forest environment at this locality in the late Paleogene and provides the first direct examination of the terrestrial environment in Sumatra at this time. The limited fossil record in Island Southeast Asia during this time period is likely a result of poor bone and shell preservation in tropical forest environments combined with a general lack of systematic prospecting. However, our continuing work in this area has produced a relatively diverse assemblage of fossil vertebrates, now including fishes, amphibians, turtles, crocodiles, and mammals, as well as a growing diversity of fossil plants.

Dominant Capital and the New Wars

Directory of Open Access Journals (Sweden)

Shimshon Bichler

2015-08-01

to run into mounting difficulties in the late 1990s, and eventually collapsed in 2000. For differential accumulation to continue, dominant capital now needs inflation, and inflation requires instability and social crisis. It is within this broader dynamics of power accumulation that the new wars need to be understood.

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.

Beta-Adrenergic Receptors and Mechanisms in Asthma: The New Long-Acting Beta-Agonists

Directory of Open Access Journals (Sweden)

Robert G Townley

1996-01-01

Full Text Available The objective is to review β-adrenergic receptors and mechanisms in the immediate and late bronchial reaction in asthma and the new long-acting β-agonist. This will be discussed in light of the controversy of the potential adverse effect of regular use of long-acting β-agonists. We studied the effect of formoterol on the late asthmatic response (LAR and airway inflammation in guinea-pigs. Formoterol suppressed the LAR, antigen-induced airway inflammation and hyperresponsiveness, although isoproterenol failed to inhibit these parameters. β-Adrenergic hyporesponsiveness, and cholinergic and a- adrenergic hyperresponsiveness have been implicated in the pathogenesis of asthma. A decrease in β-adrenoreceptor function can result either from exogenously administered β-agonist or from exposure to allergens resulting in a late bronchial reaction. There is increasing evidence that eosinophils, macrophages, and lymphocytes which are of primary importance in the late bronchial reaction are also modulated by β2- adrenoreceptors. In functional studies of guinea-pig or human isolated trachea and lung parenchyma, PAF and certain cytokines significantly reduced the potency of isoproterenol to reverse methacholine- or histamine-induced contraction. The effect of glucocorticoids on pulmonary β-adrenergic receptors and responses suggests an important role for glucocorticoids to increase β-adrenergic receptors and responsiveness.

Rethinking critical reflection on care: late modern uncertainty and the implications for care ethics.

Science.gov (United States)

Vosman, Frans; Niemeijer, Alistair

2017-12-01

Care ethics as initiated by Gilligan, Held, Tronto and others (in the nineteen eighties and nineties) has from its onset been critical towards ethical concepts established in modernity, like 'autonomy', alternatively proposing to think from within relationships and to pay attention to power. In this article the question is raised whether renewal in this same critical vein is necessary and possible as late modern circumstances require rethinking the care ethical inquiry. Two late modern realities that invite to rethink care ethics are complexity and precariousness. Late modern organizations, like the general hospital, codetermined by various (control-, information-, safety-, accountability-) systems are characterized by complexity and the need for complexity reduction, both permeating care practices. By means of a heuristic use of the concept of precariousness, taken as the installment of uncertainty, it is shown that relations and power in late modern care organizations have changed, precluding the use of a straightforward domination idea of power. In the final section a proposition is made how to rethink the care ethical inquiry in order to take late modern circumstances into account: inquiry should always be related to the concerns of people and practitioners from within care practices.

Proteus syndrome in a child aged 14 years and 11 months

Directory of Open Access Journals (Sweden)

T. V. Elizarova

2017-01-01

Full Text Available Proteus syndrome is an extremely rare genetic disorder with problematic genetic identification. It has been hypothesized that it is related to a lethal dominant somatic mutation occurring at a post-zygotic stage of embryonic development. Clinical presentation of the disease has much in common with a  number of hereditary disorders and is frequently associated with malignancies. We present a clinical case of Proteus syndrome in a child aged 14 years and 11 months, in whom late diagnosis and late administration of specific treatment resulted in disease progression with the development of the end stage chronic renal disease. Only correct and early diagnosis allows for timely referral of a  patient to a specialized hospital for adequate care.

Advanced Communications Technology Satellite (ACTS): Four-Year System Performance

Science.gov (United States)

Acosta, Roberto J.; Bauer, Robert; Krawczyk, Richard J.; Reinhart, Richard C.; Zernic, Michael J.; Gargione, Frank

1999-01-01

The Advanced Communications Technology Satellite (ACTS) was conceived at the National Aeronautics and Space Administration (NASA) in the late 1970's as a follow-on program to ATS and CTS to continue NASA's long history of satellite communications projects. The ACTS project set the stage for the C-band satellites that started the industry, and later the ACTS project established the use of Ku-band for video distribution and direct-to-home broadcasting. ACTS, launched in September 1993 from the space shuttle, created a revolution in satellite system architecture by using digital communications techniques employing key technologies such as a fast hopping multibeam antenna, an on-board baseband processor, a wide-band microwave switch matrix, adaptive rain fade compensation, and the use of 900 MHz transponders operating at Ka-band frequencies. This paper describes the lessons learned in each of the key ACTS technology areas, as well as in the propagation investigations.

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 ...

The dominance behavioral system and manic temperament: motivation for dominance, self-perceptions of power, and socially dominant behaviors.

Science.gov (United States)

Johnson, Sheri L; Carver, Charles S

2012-12-15

The dominance behavioral system has been conceptualized as a biologically based system comprising motivation to achieve social power and self-perceptions of power. Biological, behavioral, and social correlates of dominance motivation and self-perceived power have been related to a range of psychopathological tendencies. Preliminary evidence suggests that mania and risk for mania (manic temperament) relate to the dominance system. Four studies examine whether manic temperament, measured with the Hypomanic Personality Scale (HPS), is related to elevations in dominance motivation, self-perceptions of power, and engagement in socially dominant behavior across multiple measures. In Study 1, the HPS correlated with measures of dominance motivation and the pursuit of extrinsically-oriented ambitions for fame and wealth among 454 undergraduates. In Study 2, the HPS correlated with perceptions of power and extrinsically-oriented lifetime ambitions among 780 undergraduates. In Study 3, the HPS was related to trait-like tendencies to experience hubristic (dominance-related) pride, as well as dominance motivation and pursuit of extrinsically-oriented ambitions. In Study 4, we developed the Socially Dominant Behavior Scale to capture behaviors reflecting high power. The scale correlated highly with the HPS among 514 undergraduates. The studies rely on self-ratings of manic temperament and dominance constructs, and findings have not yet been generalized to a clinical sample. Taken together, results support the hypothesis that manic temperament is related to a focus on achieving social dominance, ambitions related to achieving social recognition, perceptions of having achieved power, tendencies to experience dominance-related pride, and engagement in social behaviors consistent with this elevated sense of power. Copyright © 2012 Elsevier B.V. All rights reserved.

Speech Act Classification of German Advertising Texts

Directory of Open Access Journals (Sweden)

Артур Нарманович Мамедов

2015-12-01

Full Text Available This paper uses the theory of speech acts and the underlying concept of pragmalinguistics to determine the types of speech acts and their classification in the German advertising printed texts. We ascertain that the advertising of cars and accessories, household appliances and computer equipment, watches, fancy goods, food, pharmaceuticals, and financial, insurance, legal services and also airline advertising is dominated by a pragmatic principle, which is based on demonstrating information about the benefits of a product / service. This influences the frequent usage of certain speech acts. The dominant form of exposure is to inform the recipient-user about the characteristics of the advertised product. This information is fore-grounded by means of stylistic and syntactic constructions specific to the advertisement (participial constructions, appositional constructions which contribute to emphasize certain notional components within the framework of the advertising text. Stylistic and syntactic devices of reduction (parceling constructions convey the author's idea. Other means like repetitions, enumerations etc are used by the advertiser to strengthen his selling power. The advertiser focuses the attention of the consumer on the characteristics of the product seeking to convince him of the utility of the product and to influence his/ her buying behavior.

Ecological impacts of the late Quaternary megaherbivore extinctions.

Science.gov (United States)

Gill, Jacquelyn L

2014-03-01

As a result of the late Quaternary megafaunal extinctions (50,000-10,000 before present (BP)), most continents today are depauperate of megaherbivores. These extinctions were time-transgressive, size- and taxonomically selective, and were caused by climate change, human hunting, or both. The surviving megaherbivores often act as ecological keystones, which was likely true in the past. In spite of this and extensive research on the causes of the Late Quaternary Extinctions, the long-term ecological consequences of the loss of the Pleistocene megafauna remained unknown until recently, due to difficulties in linking changes in flora and fauna in paleorecords. The quantification of Sporormiella and other dung fungi have recently allowed for explicit tests of the ecological consequences of megafaunal extirpations in the fossil pollen record. In this paper, I review the impacts of the loss of keystone megaherbivores on vegetation in several paleorecords. A growing number of studies support the hypothesis that the loss of the Pleistocene megafauna resulted in cascading effects on plant community composition, vegetation structure and ecosystem function, including increased fire activity, novel communities and shifts in biomes. Holocene biota thus exist outside the broader evolutionary context of the Cenozoic, and the Late Quaternary Extinctions represent a regime shift for surviving plant and animal species.

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

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.

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…

Locus-specific ribosomal RNA gene silencing in nucleolar dominance.

Directory of Open Access Journals (Sweden)

Michelle S Lewis

2007-08-01

Full Text Available The silencing of one parental set of rRNA genes in a genetic hybrid is an epigenetic phenomenon known as nucleolar dominance. We showed previously that silencing is restricted to the nucleolus organizer regions (NORs, the loci where rRNA genes are tandemly arrayed, and does not spread to or from neighboring protein-coding genes. One hypothesis is that nucleolar dominance is the net result of hundreds of silencing events acting one rRNA gene at a time. A prediction of this hypothesis is that rRNA gene silencing should occur independent of chromosomal location. An alternative hypothesis is that the regulatory unit in nucleolar dominance is the NOR, rather than each individual rRNA gene, in which case NOR localization may be essential for rRNA gene silencing. To test these alternative hypotheses, we examined the fates of rRNA transgenes integrated at ectopic locations. The transgenes were accurately transcribed in all independent transgenic Arabidopsis thaliana lines tested, indicating that NOR localization is not required for rRNA gene expression. Upon crossing the transgenic A. thaliana lines as ovule parents with A. lyrata to form F1 hybrids, a new system for the study of nucleolar dominance, the endogenous rRNA genes located within the A. thaliana NORs are silenced. However, rRNA transgenes escaped silencing in multiple independent hybrids. Collectively, our data suggest that rRNA gene activation can occur in a gene-autonomous fashion, independent of chromosomal location, whereas rRNA gene silencing in nucleolar dominance is locus-dependent.

Presence of virus neutralizing antibodies in cerebral spinal fluid correlates with non-lethal rabies in dogs.

Directory of Open Access Journals (Sweden)

Clement W Gnanadurai

Full Text Available Rabies is traditionally considered a uniformly fatal disease after onset of clinical manifestations. However, increasing evidence indicates that non-lethal infection as well as recovery from flaccid paralysis and encephalitis occurs in laboratory animals as well as humans.Non-lethal rabies infection in dogs experimentally infected with wild type dog rabies virus (RABV, wt DRV-Mexico correlates with the presence of high level of virus neutralizing antibodies (VNA in the cerebral spinal fluid (CSF and mild immune cell accumulation in the central nervous system (CNS. By contrast, dogs that succumbed to rabies showed only little or no VNA in the serum or in the CSF and severe inflammation in the CNS. Dogs vaccinated with a rabies vaccine showed no clinical signs of rabies and survived challenge with a lethal dose of wild-type DRV. VNA was detected in the serum, but not in the CSF of immunized dogs. Thus the presence of VNA is critical for inhibiting virus spread within the CNS and eventually clearing the virus from the CNS.Non-lethal infection with wt RABV correlates with the presence of VNA in the CNS. Therefore production of VNA within the CNS or invasion of VNA from the periphery into the CNS via compromised blood-brain barrier is important for clearing the virus infection from CNS, thereby preventing an otherwise lethal rabies virus infection.

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.

Direct measurement of the lethal isotherm for radiofrequency ablation of myocardial tissue.

Science.gov (United States)

Wood, Mark; Goldberg, Scott; Lau, Melissa; Goel, Aneesh; Alexander, Daniel; Han, Frederick; Feinstein, Shawn

2011-06-01

The lethal isotherm for radiofrequency catheter ablation of cardiac myocardium is widely accepted to be 50°C, but this has not been directly measured. The purpose of this study was to directly measure the tissue temperature at the edge of radiofrequency lesions in real time using infrared thermal imaging. Fifteen radiofrequency lesions of 6 to 240 seconds in duration were applied to the left ventricular surface of isolated perfused pig hearts. At the end of radiofrequency delivery, a thermal image of the tissue surface was acquired with an infrared camera. The lesion was then stained and an optical image of the lesion was obtained. The thermal and optical images were electronically merged to allow determination of the tissue temperature at the edge of the lesion at the end of radiofrequency delivery. By adjusting the temperature overlay display to conform with the edge of the radiofrequency lesion, the lethal isotherm was measured to be 60.6°C (interquartile ranges, 59.7° to 62.4°C; range, 58.1° to 64.2°C). The areas encompassed by the lesion border in the optical image and the lethal isotherm in the thermal image were statistically similar and highly correlated (Spearman ρ=0.99, Pradiofrequency delivery or to lesion size (both P>0.64). The areas circumscribed by 50°C isotherms were significantly larger than the areas of the lesions on optical imaging (P=0.002). By direct measurement, the lethal isotherm for cardiac myocardium is near 61°C for radiofrequency energy deliveries radiofrequency ablation is important to clinical practice as well as mathematical modeling of radiofrequency lesions.

Soluble factor(s) from bone marrow cells can rescue lethally irradiated mice by protecting endogenous hematopoietic stem cells.

Science.gov (United States)

Zhao, Yi; Zhan, Yuxia; Burke, Kathleen A; Anderson, W French

2005-04-01

Ionizing radiation-induced myeloablation can be rescued via bone marrow transplantation (BMT) or administration of cytokines if given within 2 hours after radiation exposure. There is no evidence for the existence of soluble factors that can rescue an animal after a lethal dose of radiation when administered several hours postradiation. We established a system that could test the possibility for the existence of soluble factors that could be used more than 2 hours postirradiation to rescue animals. Animals with an implanted TheraCyte immunoisolation device (TID) received lethal-dose radiation and then normal bone marrow Lin- cells were loaded into the device (thereby preventing direct interaction between donor and recipient cells). Animal survival was evaluated and stem cell activity was tested with secondary bone marrow transplantation and flow cytometry analysis. Donor cell gene expression of five antiapoptotic cytokines was examined. Bone marrow Lin- cells rescued lethally irradiated animals via soluble factor(s). Bone marrow cells from the rescued animals can rescue and repopulate secondary lethally irradiated animals. Within the first 6 hours post-lethal-dose radiation, there is no significant change of gene expression of the known radioprotective factors TPO, SCF, IL-3, Flt-3 ligand, and SDF-1. Hematopoietic stem cells can be protected in lethally irradiated animals by soluble factors produced by bone marrow Lin- cells.

Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy

DEFF Research Database (Denmark)

Winkelmann, Juliane; Lin, Ling; Schormair, Barbara

2012-01-01

to HDAC2. It is also highly expressed in immune cells and required for the differentiation of CD4+ into T regulatory cells. Mutations in exon 20 of this gene were recently reported to cause hereditary sensory neuropathy with dementia and hearing loss (HSAN1). Our mutations are all located in exon 21......Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is characterized by late onset (30-40 years old) cerebellar ataxia, sensory neuronal deafness, narcolepsy-cataplexy and dementia. We performed exome sequencing in five individuals from three ADCA-DN kindreds and identified DNMT...

Reinvestigating an enigmatic Late Cretaceous monocot: morphology, taxonomy, and biogeography of Viracarpon

Directory of Open Access Journals (Sweden)

Kelly K.S. Matsunaga

2018-04-01

Full Text Available Angiosperm-dominated floras of the Late Cretaceous are essential for understanding the evolutionary, ecological, and geographic radiation of flowering plants. The Late Cretaceous–early Paleogene Deccan Intertrappean Beds of India contain angiosperm-dominated plant fossil assemblages known from multiple localities in central India. Numerous monocots have been documented from these assemblages, providing a window into an important but poorly understood time in their diversification. One component of the Deccan monocot diversity is the genus Viracarpon, known from anatomically preserved infructescences. Viracarpon was first collected over a century ago and has been the subject of numerous studies. However, resolution of its three-dimensional (3D morphology and anatomy, as well as its taxonomic affinities, has remained elusive. In this study we investigated the morphology and taxonomy of genus Viracarpon, combining traditional paleobotanical techniques and X-ray micro-computed tomography (μCT. Re-examination of type and figured specimens, 3D reconstructions of fruits, and characterization of structures in multiple planes of section using μCT data allowed us to resolve conflicting interpretations of fruit morphology and identify additional characters useful in refining potential taxonomic affinities. Among the four Viracarpon species previously recognized, we consider two to be valid (Viracarpon hexaspermum and Viracarpon elongatum, and the other two to be synonyms of these. Furthermore, we found that permineralized infructescences of Coahuilocarpon phytolaccoides from the late Campanian of Mexico correspond closely in morphology to V. hexaspermum. We argue that Viracarpon and Coahuilocarpon are congeneric and provide the new combination, Viracarpon phytolaccoides (Cevallos-Ferriz, Estrada-Ruiz & Perez-Hernandez Matsunaga, S.Y. Smith, & Manchester comb. nov. The significant geographic disjunction between these two occurrences indicates that the

A major QTL affects temperature sensitive adult lethality and inbreeding depression in life span in Drosophila melanogaster.

DEFF Research Database (Denmark)

Vermeulen, Corneel J.; Bijlsma, R.; Loeschcke, Volker

2008-01-01

of inbreeding effects in specific traits, such as age-specific mortality and life span, provide a good starting point, as a limited set of genes is expected to be involved. Results Here we report on a QTL mapping study on inbreeding related and temperature sensitive lethality in male Drosophila melanogaster...... and the molecular properties of genes that give rise to or modulate its deleterious effects is lacking. These questions warrant the detailed study of genetic loci giving rise to inbreeding depression. However, the complex and polygenic nature of general inbreeding depression makes this a daunting task. Study...... simple, being due mainly to a single recessive QTL on the left arm of chromosome 2. This locus colocalised with a QTL that conditioned variation in female life span, acting as an overdominant locus for this trait. Male life span was additionally affected by variation at the X-chromosome. Conclusion...

Genetic interaction motif finding by expectation maximization – a novel statistical model for inferring gene modules from synthetic lethality

Directory of Open Access Journals (Sweden)

Ye Ping

2005-12-01

Full Text Available Abstract Background Synthetic lethality experiments identify pairs of genes with complementary function. More direct functional associations (for example greater probability of membership in a single protein complex may be inferred between genes that share synthetic lethal interaction partners than genes that are directly synthetic lethal. Probabilistic algorithms that identify gene modules based on motif discovery are highly appropriate for the analysis of synthetic lethal genetic interaction data and have great potential in integrative analysis of heterogeneous datasets. Results We have developed Genetic Interaction Motif Finding (GIMF, an algorithm for unsupervised motif discovery from synthetic lethal interaction data. Interaction motifs are characterized by position weight matrices and optimized through expectation maximization. Given a seed gene, GIMF performs a nonlinear transform on the input genetic interaction data and automatically assigns genes to the motif or non-motif category. We demonstrate the capacity to extract known and novel pathways for Saccharomyces cerevisiae (budding yeast. Annotations suggested for several uncharacterized genes are supported by recent experimental evidence. GIMF is efficient in computation, requires no training and automatically down-weights promiscuous genes with high degrees. Conclusion GIMF effectively identifies pathways from synthetic lethality data with several unique features. It is mostly suitable for building gene modules around seed genes. Optimal choice of one single model parameter allows construction of gene networks with different levels of confidence. The impact of hub genes the generic probabilistic framework of GIMF may be used to group other types of biological entities such as proteins based on stochastic motifs. Analysis of the strongest motifs discovered by the algorithm indicates that synthetic lethal interactions are depleted between genes within a motif, suggesting that synthetic

Toxic Shock Syndrome Toxin-1-Mediated Toxicity Inhibited by Neutralizing Antibodies Late in the Course of Continual in Vivo and in Vitro Exposure

Directory of Open Access Journals (Sweden)

Norbert Stich

2014-05-01

Full Text Available Toxic shock syndrome (TSS results from the host’s overwhelming inflammatory response and cytokine storm mainly due to superantigens (SAgs. There is no effective specific therapy. Application of immunoglobulins has been shown to improve the outcome of the disease and to neutralize SAgs both in vivo and in vitro. However, in most experiments that have been performed, antiserum was either pre-incubated with SAg, or both were applied simultaneously. To mirror more closely the clinical situation, we applied a multiple dose (over five days lethal challenge in a rabbit model. Treatment with toxic shock syndrome toxin 1 (TSST-1 neutralizing antibody was fully protective, even when administered late in the course of the challenge. Kinetic studies on the effect of superantigen toxins are scarce. We performed in vitro kinetic studies by neutralizing the toxin with antibodies at well-defined time points. T-cell activation was determined by assessing T-cell proliferation (3H-thymidine incorporation, determination of IL-2 release in the cell supernatant (ELISA, and IL-2 gene activation (real-time PCR (RT-PCR. Here we show that T-cell activation occurs continuously. The application of TSST-1 neutralizing antiserum reduced IL-2 and TNFα release into the cell supernatant, even if added at later time points. Interference with the prolonged stimulation of proinflammatory cytokines is likely to be in vivo relevant, as postexposure treatment protected rabbits against the multiple dose lethal SAg challenge. Our results shed new light on the treatment of TSS by specific antibodies even at late stages of exposure.

Right hemispheric language dominance in a right-handed male with a right frontal tumor shown by functional transcranial Doppler sonography.

Science.gov (United States)

Haag, A; Preibisch, C; Sure, U; Knake, S; Heinze, S; Krakow, K; Rosenow, F; Hamer, H M

2006-02-01

A 38-year-old, right-handed man with late-onset right frontal epilepsy due to a ganglioglioma and atypical right hemispheric language dominance is described. Language dominance was investigated with functional transcranial Doppler sonography (fTCD), and language localization with functional magnetic resonance imaging (fMRI). During a word generation task, fTCD showed atypical right hemispheric language dominance, which was confirmed by fMRI using a semantic word comparison and a word stem completion task. This information helped to guide the resective procedure, which left the patient seizure-free and did not induce new deficits. Functional TCD appears to be a useful and reliable screening tool for determining hemispheric language dominance, even in patients with atypical language representation. Functional MRI may be used to confirm fTCD results and further localize eloquent cortex.

Restoring efficiency of hemopoietic cell transplantation in a mouse lethally irradiated by a total exposure to X rays

International Nuclear Information System (INIS)

Doria, Gino

1959-10-01

This research thesis reports the study of possibility of treatments (or restoration) of a mouse which has been submitted to a lethal dose of X rays. More particularly, the author compared the restoring efficiency of bone marrow and fetal liver injected in a mouse which had been lethally irradiated by a total exposure to X rays. He also studied the functional status of the hemopoietic graft, and the emergence of the secondary disease in mice which had been as well lethally irradiated and then restored by injection of bone marrow and fetal liver. The author then addressed the influence of the induction of immune tolerance of the host with respect to the donor on the survival of a mouse lethally irradiated and restored by homologue bone marrow [fr

Changes in forest structure since 1860 in ponderosa pine dominated forests in the Colorado and Wyoming Front Range, USA

Science.gov (United States)

Mike A. Battaglia; Benjamin Gannon; Peter M. Brown; Paula J. Fornwalt; Antony S. Cheng; Laurie S. Huckaby

2018-01-01

Management practices since the late 19th century, including fire exclusion and harvesting, have altered the structure of ponderosa pine (Pinus ponderosa Douglas ex P. Lawson & C. Lawson) dominated forests across the western United States. These structural changes have the potential to contribute to uncharacteristic wildfire behavior and effects. Locally-...

Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections

Science.gov (United States)

Lilly, Elizabeth A.; Ikeh, Melanie; Nash, Evelyn E.; Fidel, Paul L.

2018-01-01

ABSTRACT Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non-albicans Candida (NAC) species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans/S. aureus (i.e., coninfection) resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis/S. aureus-mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus. S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis-induced protection. C. dubliniensis/S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge). Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO]) survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1hi polymorphonuclear leukocytes (PMNLs) in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1+ cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans/S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of

Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections

Directory of Open Access Journals (Sweden)

Elizabeth A. Lilly

2018-01-01

Full Text Available Polymicrobial intra-abdominal infections (IAIs are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non-albicans Candida (NAC species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis. Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans/S. aureus (i.e., coninfection resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis/S. aureus-mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus. S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis-induced protection. C. dubliniensis/S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge. Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO] survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1hi polymorphonuclear leukocytes (PMNLs in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1+ cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans/S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of

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.

Lethal differences:

DEFF Research Database (Denmark)

Christensen, Ivan Lind

2011-01-01

Through a study of the history of the concepts of wealth and poverty, this paper investigates the onset of a transition in the conceptual architecture of epidemiological research concerning social differences in mortality rates from 1858 to 1914. It raises the question as to what the concepts...... of wealth and poverty meant to those who used them and what objects of interventions the conceptual architecture surrounding the concepts enabled the researchers to create. It argues that a transition began in the late 19th century in which an important framework for the understanding of causal relations...

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

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

Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge

Science.gov (United States)

Konduru, Krishnamurthy; Shurtleff, Amy C.; Bradfute, Steven B.; Nakamura, Siham; Bavari, Sina; Kaplan, Gerardo

2016-01-01

Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105−106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV) pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data further support

Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge.

Science.gov (United States)

Konduru, Krishnamurthy; Shurtleff, Amy C; Bradfute, Steven B; Nakamura, Siham; Bavari, Sina; Kaplan, Gerardo

2016-01-01

Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105-106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV) pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data further support

Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge.

Directory of Open Access Journals (Sweden)

Krishnamurthy Konduru

Full Text Available Ebola virus (EBOV, a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105-106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data

Dynamics of Mixed Dark Energy Domination in Teleparallel Gravity and Phase-Space Analysis

Directory of Open Access Journals (Sweden)

Emre Dil

2015-01-01

Full Text Available We consider a novel dark energy model to investigate whether it will provide an expanding universe phase. Here we propose a mixed dark energy domination which is constituted by tachyon, quintessence, and phantom scalar fields nonminimally coupled to gravity, in the absence of background dark matter and baryonic matter, in the framework of teleparallel gravity. We perform the phase-space analysis of the model by numerical methods and find the late-time accelerated attractor solutions implying the acceleration phase of universe.

Sedimentary architecture and chronostratigraphy of a late Quaternary incised-valley fill: A case study of the late Middle and Late Pleistocene Rhine system in the Netherlands

Science.gov (United States)

Peeters, J.; Busschers, F. S.; Stouthamer, E.; Bosch, J. H. A.; Van den Berg, M. W.; Wallinga, J.; Versendaal, A. J.; Bunnik, F. P. M.; Middelkoop, H.

2016-01-01

This paper describes the sedimentary architecture, chronostratigraphy and palaeogeography of the late Middle and Late Pleistocene (Marine Isotope Stage/MIS 6-2) incised Rhine-valley fill in the central Netherlands based on six geological transects, luminescence dating, biostratigraphical data and a 3D geological model. The incised-valley fill consists of a ca. 50 m thick and 10-20 km wide sand-dominated succession and includes a well-developed sequence dating from the Last Interglacial: known as the Eemian in northwest Europe. The lower part of the valley fill contains coarse-grained fluvio-glacial and fluvial Rhine sediments that were deposited under Late Saalian (MIS 6) cold-climatic periglacial conditions and during the transition into the warm Eemian interglacial (MIS 5e-d). This unit is overlain by fine-grained fresh-water flood-basin deposits, which are transgressed by a fine-grained estuarine unit that formed during marine high-stand. This ca. 10 m thick sequence reflects gradual drowning of the Eemian interglacial fluvial Rhine system and transformation into an estuary due to relative sea-level rise. The chronological data suggests a delay in timing of regional Eemian interglacial transgression and sea-level high-stand of several thousand years, when compared to eustatic sea-level. As a result of this glacio-isostatic controlled delay, formation of the interglacial lower deltaic system took only place for a relative short period of time: progradation was therefore limited. During the cooler Weichselian Early Glacial period (MIS 5d-a) deposition of deltaic sediments continued and extensive westward progradation of the Rhine system occurred. Major parts of the Eemian and Weichselian Early Glacial deposits were eroded and buried as a result of sea-level lowering and climate cooling during the early Middle Weichselian (MIS 4-3). Near complete sedimentary preservation occurred along the margins of the incised valley allowing the detailed reconstruction presented

Late neurological complications after irradiation of malignant tumors of the testis

DEFF Research Database (Denmark)

Knap, Marianne; Bentzen, Søren M.; Overgaard, Jens

2007-01-01

To identify and describe late neurological complications in a Danish testis cancer cohort treated by radiotherapy. Clinical retrospective material of 94 consecutive patients with malignant testicular tumours treated at Aarhus County Hospital from 1964 to 1973. The irradiated dose in the paraaortic...... field varied from 27 to 55 Gy given 5 or 6 days a week, from the back and front alternately. The biological equivalent dose of the spinal cord was calculated using the linear-quadratic model. Median follow-up was 25 years, range 7 to 33 years. Seven patients were identified with late neurological...... complications after irradiation. One developed symptoms 9 months after treatment, but in the six other cases we found a latency period between 10 and 20 years from radiotherapy until the initial neurological symptoms began. The clinical picture in all seven patients was dominated by muscle atrophy, flaccid...

Relating 2-Rainbow Domination To Roman Domination

Directory of Open Access Journals (Sweden)

Alvarado José D.

2017-11-01

Full Text Available For a graph G, let R(G and yr2(G denote the Roman domination number of G and the 2-rainbow domination number of G, respectively. It is known that yr2(G ≤ R(G ≤ 3/2yr2(G. Fujita and Furuya [Difference between 2-rainbow domination and Roman domination in graphs, Discrete Appl. Math. 161 (2013 806-812] present some kind of characterization of the graphs G for which R(G − yr2(G = k for some integer k. Unfortunately, their result does not lead to an algorithm that allows to recognize these graphs efficiently. We show that for every fixed non-negative integer k, the recognition of the connected K4-free graphs G with yR(G − yr2(G = k is NP-hard, which implies that there is most likely no good characterization of these graphs. We characterize the graphs G such that yr2(H = yR(H for every induced subgraph H of G, and collect several properties of the graphs G with R(G = 3/2yr2(G.

Acute, Sub-lethal Cyanide Poisoning in Mice is Ameliorated by Nitrite Alone: Complications Arising from Concomitant Administration of Nitrite and Thiosulfate as an Antidotal Combination

Science.gov (United States)

Cambal, Leah K.; Swanson, Megan R.; Yuan, Quan; Weitz, Andrew C.; Li, Hui-Hua; Pitt, Bruce R.; Pearce, Linda L.; Peterson, Jim

2011-01-01

Sodium nitrite alone is shown to ameliorate sub-lethal cyanide toxicity in mice when given from ~1 hour before until 20 minutes after the toxic dose as demonstrated by the recovery of righting ability. An optimum dose (12 mg/kg) was determined to significantly relieve cyanide toxicity (5.0 mg/kg) when administered to mice intraperitoneally. Nitrite so administered was shown to rapidly produce NO in the bloodsteam as judged by the dose dependent appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin. It is argued that antagonism of cyanide inhibition of cytochrome c oxidase by NO is the crucial antidotal activity rather than the methemoglobin-forming action of nitrite. Concomitant addition of sodium thiosulfate to nitrite-treated blood resulted in the detection of sulfidomethemoblobin by EPR spectroscopy. Sulfide is a product of thiosulfate hydrolysis and, like cyanide, is known to be a potent inhibitor of cytochrome c oxidase; the effects of the two inhibitors being essentially additive under standard assay conditions, rather than dominated by either one. The findings afford a plausible explanation for an observed detrimental effect in mice associated with the use of the standard nitrite-thiosulfate combination therapy at sub-lethal levels of cyanide intoxication. PMID:21534623

Lethal infection thresholds of Paenibacillus larvae for honeybee drone and worker larvae (Apis mellifera).

Science.gov (United States)

Behrens, Dieter; Forsgren, Eva; Fries, Ingemar; Moritz, Robin F A

2010-10-01

We compared the mortality of honeybee (Apis mellifera) drone and worker larvae from a single queen under controlled in vitro conditions following infection with Paenibacillus larvae, a bacterium causing the brood disease American Foulbrood (AFB). We also determined absolute P. larvae cell numbers and lethal titres in deceased individuals of both sexes up to 8 days post infection using quantitative real-time PCR (qPCR). Our results show that in drones the onset of infection induced mortality is delayed by 1 day, the cumulative mortality is reduced by 10% and P. larvae cell numbers are higher than in worker larvae. Since differences in bacterial cell titres between sexes can be explained by differences in body size, larval size appears to be a key parameter for a lethal threshold in AFB tolerance. Both means and variances for lethal thresholds are similar for drone and worker larvae suggesting that drone resistance phenotypes resemble those of related workers. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

Gender and AIDS: time to act.

Science.gov (United States)

Greig, Alan; Peacock, Dean; Jewkes, Rachel; Msimang, Sisonke

2008-08-01

Gender has long been recognized as being key to understanding and addressing HIV and AIDS. Gender roles and relations that structure and legitimate women's subordination and simultaneously foster models of masculinity that justify and reproduce men's dominance over women exacerbate the spread and impact of the epidemic. Notions of masculinity prevalent in many parts of the world that equate being a man with dominance over women, sexual conquest and risk-taking are associated with less condom use, more sexually transmitted infections, more partners, including more casual partners, more frequent sex, more abuse of alcohol and more transactional sex. They also contribute to men accessing treatment later than women and at greater cost to public health systems. The imperative of addressing the gender dimensions of AIDS has been clearly and repeatedly articulated. Many interventions have been shown to be effective in addressing gender-related risks and vulnerabilities including programmes designed to reach and engage men, improve women's legal and economic position, integrate gender-based violence prevention into HIV services, and increase girls' access to secondary and tertiary education. Despite this, the political will to act has been sorely lacking and not nearly enough has been done to hold governments and multilateral institutions to account. This paper argues that we can no longer simply pay lip service to the urgent need to act on what we know about gender and AIDS. Simply put, it is time to act.

A signature of epithelial-mesenchymal plasticity and stromal activation in primary tumor modulates late recurrence in breast cancer independent of disease subtype.

Science.gov (United States)

Cheng, Qing; Chang, Jeffrey T; Gwin, William R; Zhu, Jun; Ambs, Stefan; Geradts, Joseph; Lyerly, H Kim

2014-07-25

Despite improvements in adjuvant therapy, late systemic recurrences remain a lethal consequence of both early- and late-stage breast cancer. A delayed recurrence is thought to arise from a state of tumor dormancy, but the mechanisms that govern tumor dormancy remain poorly understood. To address the features of breast tumors associated with late recurrence, but not confounded by variations in systemic treatment, we compiled breast tumor gene expression data from 4,767 patients and established a discovery cohort consisting of 743 lymph node-negative patients who did not receive systemic neoadjuvant or adjuvant therapy. We interrogated the gene expression profiles of the 743 tumors and identified gene expression patterns that were associated with early and late disease recurrence among these patients. We applied this classification to a subset of 46 patients for whom expression data from microdissected tumor epithelium and stroma was available, and identified a distinct gene signature in the stroma and also a corresponding tumor epithelium signature that predicted disease recurrence in the discovery cohort. This tumor epithelium signature was then validated as a predictor for late disease recurrence in the entire cohort of 4,767 patients. We identified a novel 51-gene signature from microdissected tumor epithelium associated with late disease recurrence in breast cancer independent of the molecular disease subtype. This signature correlated with gene expression alterations in the adjacent tumor stroma and describes a process of epithelial to mesenchymal transition (EMT) and tumor-stroma interactions. Our findings suggest that an EMT-related gene signature in the tumor epithelium is related to both stromal activation and escape from disease dormancy in breast cancer. The presence of a late recurrence gene signature in the primary tumor also suggests that intrinsic features of this tumor regulate the transition of disseminated tumor cells into a dormant phenotype with

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.

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

How the early sporulation sigma factor sigmaF delays the switch to late development in Bacillus subtilis.

Science.gov (United States)

Karmazyn-Campelli, Céline; Rhayat, Lamya; Carballido-López, Rut; Duperrier, Sandra; Frandsen, Niels; Stragier, Patrick

2008-03-01

Sporulation in Bacillus subtilis is a primitive differentiation process involving two cell types, the forespore and the mother cell. Each cell implements two successive transcription programmes controlled by specific sigma factors. We report that activity of sigma(G), the late forespore sigma factor, is kept in check by Gin, the product of csfB, a gene controlled by sigma(F), the early forespore sigma factor. Gin abolishes sigma(G) transcriptional activity when sigma(G) is artificially synthesized during growth, but has no effect on sigma(F). Gin interacts strongly with sigma(G) but not with sigma(F) in a yeast two-hybrid experiment. The absence of Gin allows sigma(G) to be active during sporulation independently of the mother-cell development to which it is normally coupled. Premature sigma(G) activity leads to the formation of slow-germinating spores, and complete deregulation of sigma(G) synthesis is lethal when combined with gin inactivation. Gin allows sigma(F) to delay the switch to the late forespore transcription programme by preventing sigma(G) to take over before the cell has reached a critical stage of development. A similar strategy, following a completely unrelated route, is used by the mother cell.

The lethal giant larvae Gene in Tribolium castaneum: Molecular Properties and Roles in Larval and Pupal Development as Revealed by RNA Interference

Directory of Open Access Journals (Sweden)

Da Xiao

2014-04-01

Full Text Available We identified and characterized the TcLgl gene putatively encoding lethal giant larvae (Lgl protein from the red flour beetle (Tribolium castaneum. Analyses of developmental stage and tissue-specific expression patterns revealed that TcLgl was constitutively expressed. To examine the role of TcLgl in insect development, RNA interference was performed in early (1-day larvae, late (20-day larvae, and early (1-day pupae. The early larvae injected with double-stranded RNA of TcLgl (dsTcLgl at 100, 200, and 400 ng/larva failed to pupate, and 100% mortality was achieved within 20 days after the injection or before the pupation. The late larvae injected with dsTcLgl at these doses reduced the pupation rates to only 50.3%, 36.0%, and 18.2%, respectively. The un-pupated larvae gradually died after one week, and visually unaffected pupae failed to emerge into adults and died during the pupal stage. Similarly, when early pupae were injected with dsTcLgl at these doses, the normal eclosion rates were reduced to only 22.5%, 18.0%, and 11.2%, respectively, on day 7 after the injection, and all the adults with abnormal eclosion died in two days after the eclosion. These results indicate that TcLgl plays an essential role in insect development, especially during their metamorphosis.

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

Nonvascular contribution to ecosystem NPP in a subarctic heath during early and late growing season

DEFF Research Database (Denmark)

Campioli, Matteo; Samson, Roeland; Michelsen, Anders

2009-01-01

significant when vascular plants are less active and ecosystems act as a source of carbon (C). To clarify these dynamics, nonvascular and vascular aboveground NPP was compared for a subarctic heath during two contrasting periods of the growing season, viz. early-mid summer and late summer-early autumn...... measurements of shoot length increase. Vascular NPP was determined by harvesting shrub and herb apical growth and considering production due to stem secondary growth of shrubs. Hylocomium splendens and Pleurozium schreberi showed highest biomass growth in late summer, whereas for D. elongatum this occurred...... weight m-2 d-1, in early and late summer, respectively, whereas in the same periods vascular NPP was 3.6 and 1.1 g dry weight m-2 d-1. The contribution of nonvascular NPP to total aboveground NPP was therefore minor in early summer but substantial in late summer, when 25% of the C accumulated...

Topics on domination

CERN Document Server

Hedetniemi, ST

1991-01-01

The contributions in this volume are divided into three sections: theoretical, new models and algorithmic. The first section focuses on properties of the standard domination number &ggr;(G), the second section is concerned with new variations on the domination theme, and the third is primarily concerned with finding classes of graphs for which the domination number (and several other domination-related parameters) can be computed in polynomial time.

The paired-domination and the upper paired-domination numbers of graphs

Directory of Open Access Journals (Sweden)

Włodzimierz Ulatowski

2015-01-01

Full Text Available In this paper we continue the study of paired-domination in graphs. A paired-dominating set, abbreviated PDS, of a graph \\(G\\ with no isolated vertex is a dominating set of vertices whose induced subgraph has a perfect matching. The paired-domination number of \\(G\\, denoted by \\(\\gamma_{p}(G\\, is the minimum cardinality of a PDS of \\(G\\. The upper paired-domination number of \\(G\\, denoted by \\(\\Gamma_{p}(G\\, is the maximum cardinality of a minimal PDS of \\(G\\. Let \\(G\\ be a connected graph of order \\(n\\geq 3\\. Haynes and Slater in [Paired-domination in graphs, Networks 32 (1998, 199-206], showed that \\(\\gamma_{p}(G\\leq n-1\\ and they determine the extremal graphs \\(G\\ achieving this bound. In this paper we obtain analogous results for \\(\\Gamma_{p}(G\\. Dorbec, Henning and McCoy in [Upper total domination versus upper paired-domination, Questiones Mathematicae 30 (2007, 1-12] determine \\(\\Gamma_{p}(P_n\\, instead in this paper we determine \\(\\Gamma_{p}(C_n\\. Moreover, we describe some families of graphs \\(G\\ for which the equality \\(\\gamma_{p}(G=\\Gamma_{p}(G\\ holds.

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

Exploring Late Globalization

DEFF Research Database (Denmark)

Turcan, Romeo V.

2016-01-01

literature on late globalization from sociocultural and economic perspectives. It illustrates in a vignette the character and features of late globalization observable in the withdrawal from foreign locations or deinternationalization of universities, as late globalizing entitis. The paper discusses...

Lethal and mutagenic effects of ion beams and γ-rays in Aspergillus oryzae.

Science.gov (United States)

Toyoshima, Yoshiyuki; Takahashi, Akemi; Tanaka, Hisaki; Watanabe, Jun; Mogi, Yoshinobu; Yamazaki, Tatsuo; Hamada, Ryoko; Iwashita, Kazuhiro; Satoh, Katsuya; Narumi, Issay

2012-12-01

Aspergillus oryzae is a fungus that is used widely in traditional Japanese fermentation industries. In this study, the lethal and mutagenic effects of different linear energy transfer (LET) radiation in freeze-dried conidia of A. oryzae were investigated. The lethal effect, which was evaluated by a 90% lethal dose, was dependent on the LET value of the ionizing radiation. The most lethal ionizing radiation among that tested was (12)C(5+) ion beams with an LET of 121keV/μm. The (12)C(5+) ion beams had a 3.6-times higher lethal effect than low-LET (0.2keV/μm) γ-rays. The mutagenic effect was evaluated by the frequency of selenate resistant mutants. (12)C(6+) ion beams with an LET of 86keV/μm were the most effective in inducing selenate resistance. The mutant frequency following exposure to (12)C(6+) ion beams increased with an increase in dose and reached 3.47×10(-3) at 700Gy. In the dose range from 0 to 700Gy, (12)C(5+) ion beams were the second most effective in inducing selenate resistance, the mutant frequency of which reached a maximum peak (1.67×10(-3)) at 400Gy. To elucidate the characteristics of mutation induced by ionizing radiation, mutations in the sulphate permease gene (sB) and ATP sulfurylase gene (sC) loci, the loss of function of which results in a selenate resistant phenotype, were compared between (12)C(5+) ion beams and γ-rays. We detected all types of transversions and transitions. For frameshifts, the frequency of a +1 frameshift was the highest in all cases. Although the incidence of deletions >2bp was generally low, deletions >20bp were characteristic for (12)C(5+) ion beams. γ-rays had a tendency to generate mutants carrying a multitude of mutations in the same locus. Both forms of radiation also induced genome-wide large-scale mutations including chromosome rearrangements and large deletions. These results provide new basic insights into the mutation breeding of A. oryzae using ionizing radiation. Crown Copyright © 2012. Published

Late Quaternary paleoenvironmental records from the Chatanika River valley near Fairbanks (Alaska)

Science.gov (United States)

Schirrmeister, Lutz; Meyer, Hanno; Andreev, Andrei; Wetterich, Sebastian; Kienast, Frank; Bobrov, Anatoly; Fuchs, Margret; Sierralta, Melanie; Herzschuh, Ulrike

2016-09-01

Perennially-frozen deposits are considered as excellent paleoenvironmental archives similar to lacustrine, deep marine, and glacier records because of the long-term and good preservation of fossil records under stable permafrost conditions. A permafrost tunnel in the Vault Creek Valley (Chatanika River Valley, near Fairbanks) exposes a sequence of frozen deposits and ground ice that provides a comprehensive set of proxies to reconstruct the late Quaternary environmental history of Interior Alaska. The multi-proxy approach includes different dating techniques (radiocarbon-accelerator mass spectrometry [AMS 14C], optically stimulated luminescence [OSL], thorium/uranium radioisotope disequilibria [230Th/U]), as well as methods of sedimentology, paleoecology, hydrochemistry, and stable isotope geochemistry of ground ice. The studied sequence consists of 36-m-thick late Quaternary deposits above schistose bedrock. Main portions of the sequence accumulated during the early and middle Wisconsin periods. The lowermost unit A consists of about 9-m-thick ice-bonded fluvial gravels with sand and peat lenses. A late Sangamon (MIS 5a) age of unit A is assumed. Spruce forest with birch, larch, and some shrubby alder dominated the vegetation. High presence of Sphagnum spores and Cyperaceae pollen points to mires in the Vault Creek Valley. The overlying unit B consists of 10-m-thick alternating fluvial gravels, loess-like silt, and sand layers, penetrated by small ice wedges. OSL dates support a stadial early Wisconsin (MIS 4) age of unit B. Pollen and plant macrofossil data point to spruce forests with some birch interspersed with wetlands around the site. The following unit C is composed of 15-m-thick ice-rich loess-like and organic-rich silt with fossil bones and large ice wedges. Unit C formed during the interstadial mid-Wisconsin (MIS 3) and stadial late Wisconsin (MIS 2) as indicated by radiocarbon ages. Post-depositional slope processes significantly deformed both, ground

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...

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

Ecological effects of spring and late summer applications of lambda-cyhalothrin on freshwater microcosms.

Science.gov (United States)

Van Wijngaarden, R P A; Brock, T C M; van den Brink, P J; Gylstra, R; Maund, S J

2006-02-01

The aim of the study was to compare the effects of the pyrethroid insecticide lambda-cyhalothrin (treated at 10, 25, 50, 100, 250 ng active ingredient a.i./L) on a drainage ditch ecosystem in spring and late summer. Microcosms (water volume approximately 430 L) were established using enclosures in a 50-cm-deep experimental ditch system containing communities typical of macrophyte-dominated freshwater ecosystems. Effects on macroinvertebrates, zooplankton, phytoplankton, macrophytes, and community metabolism were assessed and evaluated using univariate and multivariate statistical techniques. The macroinvertebrate community responded most clearly to treatment and, as anticipated, insects and crustaceans were among the most sensitive organisms. Statistical analysis showed that the underlying community structure was significantly different between the spring and summer experiments. However, the most sensitive species (Chaoborus obscuripes and Gammarus pulex) were abundant in spring as well as in late summer. In spring and late summer, only slight and transient effects were observed at the community level in the 10-ng/L treatment. Overall, the study did not show substantial differences in the responses of sensitive taxa between spring and late summer treatments, and effects thresholds were similar irrespective of season of treatment.

CRUSTOSE CORALLINE ALGAL PAVEMENTS FROM LATE EOCENE COLLI BERICI OF NORTHERN ITALY

OpenAIRE

BASSI, DAVIDE

2017-01-01

The Eocene from the Prealpine region records the first phase of the crustose coralline algae flourishing in the Cenozoic. These algae are very frequent in the Marne di Priabona Formation (Late Eocene). This palaeoecological research involves ourcrop at Barbarano Vicentino(Vicenza) in the Colli Berici which is well known for its Paleogene stratigraphy. The coralline unit consists of a floatstone bank 6 m thick with rhodoliths and laminar crusts; it lies between macroforaminifer dominated limes...

Diatom and silicoflagellate biostratigraphy for the late Eocene: ODP 1090 (sub-Antarctic Atlantic)

Science.gov (United States)

Barron, John A.; Bukry, David B.; Gersonde, Rainer

2014-01-01

Abundant and well-preserved diatoms and silicofl agellate assemblages are documented through a complete late Eocene sequence, ODP Hole 1090B, recovered from the southern Agulhas Ridge in the sub-Antarctic South Atlantic. A sequence of Cestodiscus (diatom) species occurrence events involving C. pulchellus var. novazealandica, C. fennerae, C. antarcticus, C. convexus, C. trochus, and C. robustus is tied with paleomagnetic stratigraphy and provides the basis of proposing a new diatom zonation for the latest middle Eocene to early Oligocene (~37.6–33.4 Ma) of the sub-Antarctic South Atlantic. Comparison with previously published diatom occurrence charts suggested this zonation should be applicable throughout the low latitude regions of the world’s oceans. Silicofl agellates belong to the Dictyocha hexacantha and the overlying Corbisema apiculata Zones. The late Eocene succession of silicofl agellate species is dominated by Naviculopsis (20–60%). Naviculopsis constricta and N. foliacea dominate the D. hexacantha Zone, followed by the N. constricta, then N. biapiculata in the C. apiculata Zone. Cold-water Distephanus is most abundant in the latest Eocene along with N. biapiculata. The tops of zonal guide fossils Dictyocha hexacantha and Hannaites quadria (both 36.6 Ma) and Dictyocha spinosa (37.1 Ma) are tied with paleomagnetic stratigraphy.

Describing the organization of dominance relationships by dominance-directed tree method.

Science.gov (United States)

Izar, Patrícia; Ferreira, Renata G; Sato, Takechi

2006-02-01

Methods to describe dominance hierarchies are a key tool in primatology studies. Most current methods are appropriate for analyzing linear and near-linear hierarchies; however, more complex structures are common in primate groups. We propose a method termed "dominance-directed tree." This method is based on graph theory and set theory to analyze dominance relationships in social groups. The method constructs a transitive matrix by imposing transitivity to the dominance matrix and produces a graphical representation of the dominance relationships, which allows an easy visualization of the hierarchical position of the individuals, or subsets of individuals. The method is also able to detect partial and complete hierarchies, and to describe situations in which hierarchical and nonhierarchical principles operate. To illustrate the method, we apply a dominance tree analysis to artificial data and empirical data from a group of Cebus apella. Copyright 2006 Wiley-Liss, Inc.

Lethal modifications of DNA via the transmutation of 32P and 33P incorporated in the genome of the S13 bacteriophage

International Nuclear Information System (INIS)

Cols, P.; Apelgot, S.; Guille, E.

1988-01-01

When circular single-standard DNA of phage S13 is labelled with 32 P or 33 P, the transmutations very efficiently bring about a loss of phage infectiousness (efficiency = 1 for 32 P and 0.73 for 33 P). For both radionuclides, the lethal efficiencies as well as the lethal events are different. In the case of 32 P, the lethal event is the loss of the circular integrity of the DNA molecule, occurring as a consequence of a systematic single strand-break caused by each 32 P decay (100%). Conversely, in the case of 33 P, the lethal events are either a single strand-break (40%) or a local stereochemical modification (33%). The same primary event, the substitution at each 33 P decay of a phosphate by a sulfate molecule, leads to one of these lethal events in relation to the decay site. Moreover, neither the phage adsorption nor its genome injection into bacteria depends on the physical state of the genome, and thus lethality is revealed at only the genetic level. (orig.)

High-resolution sedimentological and subsidence analysis of the Late Neogene, Pannonian Basin, Hungary

Science.gov (United States)

Juhasz, E.; Muller, P.; Toth-Makk, A.; Hamor, T.; Farkas-Bulla, J.; Suto-Szentai, M.; Phillips, R.L.; Ricketts, B.

1996-01-01

Detailed sedimentological and paleontological analyses were carried out on more than 13,000 m of core from ten boreholes in the Late Neogene sediments of the Pannonian Basin, Hungary. These data provide the basis for determining the character of high-order depositional cycles and their stacking patterns. In the Late Neogene sediments of the Pannonian Basin there are two third-order sequences: the Late Miocene and the Pliocene ones. The Miocene sequence shows a regressive, upward-coarsening trend. There are four distinguishable sedimentary units in this sequence: the basal transgressive, the lower aggradational, the progradational and the upper aggradational units. The Pliocene sequence is also of aggradational character. The progradation does not coincide in time in the wells within the basin. The character of the relative water-level curves is similar throughout the basin but shows only very faint similarity to the sea-level curve. Therefore, it is unlikely that eustasy played any significant role in the pattern of basin filling. Rather, the dominant controls were the rapidly changing basin subsidence and high sedimentation rates, together with possible climatic factors.

Cytoplasmic superoxide dismutase and catalase activity and resistance to radiation lethality in murine tumor cells

International Nuclear Information System (INIS)

Davy, C.A.; Tesfay, Z.; Jones, J.; Rosenberg, R.C.; McCarthy, C.; Rosenberg, S.O.

1986-01-01

Reduced species of molecular oxygen are produced by the interaction of ionizing radiation with aqueous solutions containing molecular oxygen. The enzymes catalase and superoxide dismutase (SOD) are thought to function in vivo as scavengers of metabolically produced peroxide and superoxide respectively. SOD has been shown to protect against the lethal effects of ionizing radiation in vitro and in vivo. The authors have investigated the relationship between the cytosolic SOD catalase content and the sensitivity to radiation lethality of a number of murine cell lines (402AX, EL-4, MB-2T3, MB-4, MEL, P-815, SAI, SP-2, and SV-3T3). K/sub i/(CN - ) for murine Cu-Zn-SOD was determined to be 6.8 x 10 -6 M. No cytosolic Mn-SOD activity was found in any of the cell lines studied. No correlation was found between the cytosolic Cu-Zn-SOD or cytosolic catalase activity and the resistance to radiation lethality or the murine cell lines studied

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.

The dominance behavioral system and manic temperament: Motivation for dominance, self-perceptions of power, and socially dominant behaviors

OpenAIRE

Johnson, Sheri L.; Carver, Charles S.

2012-01-01

The dominance behavioral system has been conceptualized as a biologically based system comprising motivation to achieve social power and self-perceptions of power. Biological, behavioral, and social correlates of dominance motivation and self-perceived power have been related to a range of psychopathological tendencies. Preliminary evidence suggests that mania and risk for mania (manic temperament) relate to the dominance system.

Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

Directory of Open Access Journals (Sweden)

Liling Yang

2017-10-01

Full Text Available Background/Aims: Forsythia suspensa Vahl. (Oleaceae fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN, the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF

Identification of DNA-binding sites for the activator involved in late transcription of the temperate lactococcal phage TP901-1

DEFF Research Database (Denmark)

Pedersen, Margit; Kilstrup, Mogens; Hammer, Karin

2006-01-01

Alt, encoded by the lactococcal phage TP901-1, is needed for late transcription. We identify Alt as a DNA-binding protein, and footprint analysis shows that Alt binds to a region containing four imperfect direct repeats (ALT boxes) located -76 to -32 relative to the P-late transcriptional start...... site. The importance of the ALT boxes was confirmed by deletion of one or two ALT boxes and by introducing mutations in ALT boxes 1 and 4. Alt is proposed to act as a tetramer or higher multimer activating transcription of TP901-1 late genes by binding to the four ALT boxes, and bending of the DNA may...... be important for transcriptional activation of P-late. Furthermore, our results suggest that DNA replication may be required for late transcription in TP901-1. Additionally, we identify gp28 of the related lactococcal phage Tuc2009 as an activator and show that the activators required for late transcription...

A New Algorithm Using the Non-Dominated Tree to Improve Non-Dominated Sorting.

Science.gov (United States)

Gustavsson, Patrik; Syberfeldt, Anna

2018-01-01

Non-dominated sorting is a technique often used in evolutionary algorithms to determine the quality of solutions in a population. The most common algorithm is the Fast Non-dominated Sort (FNS). This algorithm, however, has the drawback that its performance deteriorates when the population size grows. The same drawback applies also to other non-dominating sorting algorithms such as the Efficient Non-dominated Sort with Binary Strategy (ENS-BS). An algorithm suggested to overcome this drawback is the Divide-and-Conquer Non-dominated Sort (DCNS) which works well on a limited number of objectives but deteriorates when the number of objectives grows. This article presents a new, more efficient algorithm called the Efficient Non-dominated Sort with Non-Dominated Tree (ENS-NDT). ENS-NDT is an extension of the ENS-BS algorithm and uses a novel Non-Dominated Tree (NDTree) to speed up the non-dominated sorting. ENS-NDT is able to handle large population sizes and a large number of objectives more efficiently than existing algorithms for non-dominated sorting. In the article, it is shown that with ENS-NDT the runtime of multi-objective optimization algorithms such as the Non-Dominated Sorting Genetic Algorithm II (NSGA-II) can be substantially reduced.

Dispersion of aircraft exhaust in the late wake

Energy Technology Data Exchange (ETDEWEB)

Duerbeck, T; Gerz, T; Doernbrack, A [Deutsche Forschungsanstalt fuer Luft- und Raumfahrt e.V. (DLR), Oberpfaffenhofen (Germany). Inst. fuer Physik der Atmosphaere

1998-12-31

The dispersion of aircraft emissions is investigated at cruising levels, i.e. in the free, stably stratified atmosphere near the tropopause. The study is based on large-eddy simulations in a domain of size 4.3 x 1.1{sup 2} km{sup 3} where the combined effects of typical atmospheric stratification, shear and turbulence are considered. The effect of a breaking gravity wave on the dispersion of the exhaust is analyzed. The mixing processes during the late wake flow are evaluated, i.e. in the dispersion and diffusion regimes when the organized flow by the wing tip vortices has ceased and the atmospheric motions gradually dominate the events. (R.P.) 7 refs.

Dispersion of aircraft exhaust in the late wake

Energy Technology Data Exchange (ETDEWEB)

Duerbeck, T.; Gerz, T.; Doernbrack, A. [Deutsche Forschungsanstalt fuer Luft- und Raumfahrt e.V. (DLR), Oberpfaffenhofen (Germany). Inst. fuer Physik der Atmosphaere

1997-12-31

The dispersion of aircraft emissions is investigated at cruising levels, i.e. in the free, stably stratified atmosphere near the tropopause. The study is based on large-eddy simulations in a domain of size 4.3 x 1.1{sup 2} km{sup 3} where the combined effects of typical atmospheric stratification, shear and turbulence are considered. The effect of a breaking gravity wave on the dispersion of the exhaust is analyzed. The mixing processes during the late wake flow are evaluated, i.e. in the dispersion and diffusion regimes when the organized flow by the wing tip vortices has ceased and the atmospheric motions gradually dominate the events. (R.P.) 7 refs.

Late Pliocene Depositional History and Paleoclimate Reconstructions of the Southwest Pacific

Science.gov (United States)

Royce, B.; Patterson, M. O.; Pietras, J.

2017-12-01

Drift deposits off the eastern margin of New Zealand are important archives for the paleoclimate and paleoceanographic history of the southwest Pacific. Ocean Drilling Program (ODP) Site 1123 is located on the North Chatham rise drift just North of the westerly wind driven Subtropical Front (STF) and provides a record of near continuous sediment deposition since the Miocene along the southwest Pacific deep western boundary current (DWBC). While the Miocene and Late Pleistocene portion of this record have been well studied, the Late Pliocene record is less well developed. Southern Ocean geological records demonstrate that Late Pliocene cooling is the transient time bracketing the warmer than present Early Pliocene and bipolar glaciation at 2.7 Ma. A newly developed, robust, and astronomically tuned long-term record of benthic δ13C from ODP Site 1123 spanning the Early to Late Pliocene implies a reduction in Southern Ocean ventilation and lowering of preformed values from waters sourced along the Antarctic margin during the Late Pliocene. Thus, Late Pliocene Southern Hemisphere cooling and sea ice expansion may have drastically reduced outgassing and increased the burial of heat into the deep ocean. South Atlantic records off the west coast of Africa demonstrate an increase in the flux of iron to the open ocean during this time potentially enhancing surface ocean productivity and providing an additional cooling mechanism. Currently, atmospheric transport of dust to the Southern Ocean is dominated by persistent mid-latitude circumpolar westerly winds; this is particularly relevant for dust sourced from New Zealand. The Late Pliocene to Early Pleistocene uplift of the North Island axial ranges and South Island southern alps potentially provided a greater amount of not only sediment to the deep ocean, but also wind blow dust to the Pacific sector of the Southern Ocean. We will present a detailed high-resolution sedimentological study on the development of the Chatham

Late Carboniferous to Late Permian carbon isotope stratigraphy

DEFF Research Database (Denmark)

Buggisch, Werner; Krainer, Karl; Schaffhauser, Maria

2015-01-01

An integrated study of the litho-, bio-, and isotope stratigraphy of carbonates in the Southern Alps was undertaken in order to better constrain δ13C variations during the Late Carboniferous to Late Permian. The presented high resolution isotope curves are based on 1299 δ13Ccarb and 396 δ13Corg...

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

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.

Comparison of the Valuations of Alternatives Based on Cumulative Prospect Theory and Almost Stochastic Dominance

Directory of Open Access Journals (Sweden)

Ewa Michalska

2012-01-01

Full Text Available There are commonly accepted and objective decision rules, which are consistent with rationality, for example stochastic dominance rules. But, as can be seen in many research studies in behavioral economics, decision makers do not always act rationally. Rules based on cumulative prospect theory or almost stochastic dominance are relatively new tools which model real choices. Both approaches take into account some behavioral factors. The aim of this paper is to check the consistency of orders of the valuations of random alternatives based on these behavioral rules. The order of the alternatives is generated by a preference relation over the decision set. In this paper, we show that the methodology for creating rankings based on total orders can be used for the preference relations considered, because they enable comparison of all the elements in a set of random alternatives. For almost second degree stochastic dominance, this is possible due to its particular properties, which stochastic dominance does not possess. (original abstract

Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis.

Science.gov (United States)

Savoy, A C; Lupan, D M; Manalo, P B; Roberts, J S; Schlageter, A M; Weinhold, L C; Kozel, T R

1997-01-01

Passive immunization with monoclonal antibodies (MAbs) specific for the major capsular polysaccharide of Cryptococcus neoformans alters the course of murine cryptococcosis. During studies of passive immunization for treatment of murine cryptococcosis, we noted the occurrence of an acute, lethal toxicity. Toxicity was characterized by scratching, lethargy, respiratory distress, collapse, and death within 20 to 60 min after injection of antibody. The toxic effect was observed only in mice with a cryptococcal infection and was reduced or absent in the early and late stages of disease. The clinical course and histopathology were consistent with those for shock. There was considerable variation between mouse strains in susceptibility to toxicity. Swiss Webster mice from the Charles River colony were most susceptible, followed by C3H/He, BALB/c, and C57BL/6 mice. DBA/2 mice and Swiss Webster mice from the Simonsen colony were resistant. Acute toxicity was mimicked by injection of preformed complexes of MAb and purified polysaccharide. The toxic effect was also produced by injection of MAbs into mice that were preloaded with polysaccharide. The toxic effect was not blocked by treatment of mice with chloropheniramine or anti-tumor necrosis factor alpha antibodies or by depletion of complement components via pretreatment with cobra venom factor. Toxicity was reduced by treatment of mice with high doses of epinephrine, dexamethasone, or chlorpromazine. Finally, the toxic effect was completely blocked by treatment of mice with the platelet-activating factor antagonist WEB 2170 BS or by pretreatment of mice with the liposome-encapsulated drug dichloromethylene diphosphonate, a procedure which depletes macrophages from the spleen and liver. PMID:9125564

The social dominance paradox.

Science.gov (United States)

Cook, Jennifer Louise; den Ouden, Hanneke E M; Heyes, Cecilia M; Cools, Roshan

2014-12-01

Dominant individuals report high levels of self-sufficiency, self-esteem, and authoritarianism. The lay stereotype suggests that such individuals ignore information from others, preferring to make their own choices. However, the nonhuman animal literature presents a conflicting view, suggesting that dominant individuals are avid social learners, whereas subordinates focus on learning from private experience. Whether dominant humans are best characterized by the lay stereotype or the animal view is currently unknown. Here, we present a "social dominance paradox": using self-report scales and computerized tasks, we demonstrate that socially dominant people explicitly value independence, but, paradoxically, in a complex decision-making task, they show an enhanced reliance (relative to subordinate individuals) on social learning. More specifically, socially dominant people employed a strategy of copying other agents when the agents' responses had a history of being correct. However, in humans, two subtypes of dominance have been identified: aggressive and social. Aggressively dominant individuals, who are as likely to "get their own way" as socially dominant individuals but who do so through the use of aggressive or Machiavellian tactics, did not use social information, even when it was beneficial to do so. This paper presents the first study of dominance and social learning in humans and challenges the lay stereotype in which all dominant individuals ignore others' views. The more subtle perspective we offer could have important implications for decision making in both the boardroom and the classroom. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sub-lethal effects of Vip3A toxin on survival, development and fecundity of Heliothis virescens and Plutella xylostella.

Science.gov (United States)

Gulzar, Asim; Wright, Denis J

2015-11-01

The assessment of sub-lethal effects is important to interpret the overall insecticide efficacy in controlling insect pest populations. In addition to the lethal effect, sub-lethal effects may also occur in exposed insects. Vegetative insecticidal proteins (Vips) have shown a broad spectrum of insecticidal activity against many insect pest species. In this study the sub-lethal effects of the Bacillus thuringiensis vegetative insecticidal toxin Vip3A on the development and reproduction of Heliothis virescens F. and Plutella xylostella L. were evaluated in the laboratory. The results indicated that the sub-lethal concentration of Vip3A increased the duration of the larval and pupal stages as compared with the control treatment for both species. The percent pupation and percent adult emergence were significantly lower for Vip3A-treated insects. The proportion of pairs that produced eggs and the longevity of adults were not significantly different between treatments. H. virescens and P. xylostella treated with Vip3A showed an 11 and 17 % decrease in their intrinsic rate of increase (rm) respectively compared with untreated insects. The results from this study will be helpful to develop the strategy to incorporate Vip 3A containing crops in an integrated pest management programme.

THE ENVIRONMENTAL DEPENDENCE OF THE FRACTION OF 'UNCONVENTIONAL' GALAXIES: RED LATE TYPES AND BLUE EARLY TYPES

International Nuclear Information System (INIS)

Deng Xinfa; He Jizhou; Wu Ping; Ding Yingping

2009-01-01

From the Main galaxy sample of the Sloan Digital Sky Survey Data Release 6, we construct two volume-limited samples with the luminosity -20.0 ≤ M r ≤ -18.5 and -22.40 ≤ M r ≤ -20.16, respectively, to explore the environmental dependence of the fraction of 'unconventional' galaxies: red late types and blue early types. We use the density estimator within the distance to the fifth nearest neighbor, and construct two samples at both extremes of density and perform comparative studies between them for each volume-limited sample. Results of two volume-limited samples show the same conclusions: the fraction of red late-type galaxies rises considerably with increasing local density, and that one of the blue early-type galaxies declines substantially with increasing local density. In addition, we note that bluer galaxies preferentially are late types, but the red galaxies are not dominated by early types.

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)

Effect of diuron on germ cells of mice.

Science.gov (United States)

Agrawal, R C; Mehrota, N K

1997-11-01

Diuron in both, acute (340 and 170 mg/kg body wt) and chronic (3400 ppm) doses induced dominant lethal mutations in male Swiss albino mice. The results suggest that diuron is mutagenic in dominant lethal test system.

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

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

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

[Lethal effect after transmutation of 33P incorporated into bacteriophage S 13 and mechanisms of DNA double helix rupture].

Science.gov (United States)

Apelgot, S

1980-04-01

The experiments show the lethal effect of the beta decay of 33P incorporated in DNA of bacteriophage S 13. The lethal efficiency is high, 0.72 at 0 degrees C and 0.55 at--197 degrees C. The presence of a radical scavenger like AET has no influence. It was found previously that for such phages with single-stranded DNA, the lethal efficiency of 32P decay is unity, and that the lethal event is a DNA single-strand break, owing to the high energy of the nucleogenic 32S atom. As the recoil energy of the 33S atom is too low to account for such a break, it is suggested that the reorganization of the phosphate molecule into sulphate is able to bring about a DNA single-strand break with an efficiency as high as 0.7, at 0 degrees C. A model for the DNA double-strand-break produced by a transmutation processes is suggested.

Human behaviours associated with dominance in elite amateur boxing bouts: A comparison of winners and losers under the Ten Point Must System.

Science.gov (United States)

Dunn, Emily C; Humberstone, Clare E; Iredale, K Fiona; Martin, David T; Blazevich, Anthony J

2017-01-01

Humans commonly ascertain physical dominance through non-lethal fighting by participating in combat sports. However, the behaviours that achieve fight dominance are not fully understood. Amateur boxing competition, which is judged using the subjective "Ten Point Must-System", provides insight into fight dominance behaviours. Notational analysis was performed on 26 elite male competitors in a national boxing championship. Behavioural (guard-drop time; movement style [stepping/bouncing time]; clinch-time; interaction-time) and technical (total punches; punches landed [%Hit]; air punches [%Air]; defence) measures were recorded. Participants reported effort required (0-100%) and perceived effect of fatigue on their own performance (5-point Likert scale) following bouts. Differences between winners and losers, and changes across the duration of the bout were examined. Winners punched more accurately than losers (greater %Hit [33% vs. 23%] and lower %Air [17% vs. 27%]) but total punches, defence and interaction-time were similar. From rounds 1-2, clinch-time and guard drops increased whilst bouncing decreased. Perceived effect of fatigue increased throughout the bout while perceived effort increased only from rounds 2-3. %Hit and movement index together in regression analysis correctly classified 85% of bout outcomes, indicating that judges (subjectively) chose winning (dominant) boxers according to punch accuracy and style, rather than assertiveness (more punches thrown). Boxers appear to use tactical strategies throughout the bout to pace their effort and minimise fatigue (increased guard drops, reduced bouncing), but these did not influence perceived dominance or bout outcome. These results show that judges use several performance indicators not including the total number of successful punches thrown to assess fight dominance and superiority between fighters. These results provide valuable information as to how experienced fight observers subjectively rate superiority

Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities.

Science.gov (United States)

Peters, Diane E; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A; Leppla, Stephen H; Bugge, Thomas H

2014-09-01

We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5-3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. Published by Elsevier Inc.

Data-driven models of dominantly-inherited Alzheimer's disease progression.

Science.gov (United States)

Oxtoby, Neil P; Young, Alexandra L; Cash, David M; Benzinger, Tammie L S; Fagan, Anne M; Morris, John C; Bateman, Randall J; Fox, Nick C; Schott, Jonathan M; Alexander, Daniel C

2018-03-22

Dominantly-inherited Alzheimer's disease is widely hoped to hold the key to developing interventions for sporadic late onset Alzheimer's disease. We use emerging techniques in generative data-driven disease progression modelling to characterize dominantly-inherited Alzheimer's disease progression with unprecedented resolution, and without relying upon familial estimates of years until symptom onset. We retrospectively analysed biomarker data from the sixth data freeze of the Dominantly Inherited Alzheimer Network observational study, including measures of amyloid proteins and neurofibrillary tangles in the brain, regional brain volumes and cortical thicknesses, brain glucose hypometabolism, and cognitive performance from the Mini-Mental State Examination (all adjusted for age, years of education, sex, and head size, as appropriate). Data included 338 participants with known mutation status (211 mutation carriers in three subtypes: 163 PSEN1, 17 PSEN2, and 31 APP) and a baseline visit (age 19-66; up to four visits each, 1.1 ± 1.9 years in duration; spanning 30 years before, to 21 years after, parental age of symptom onset). We used an event-based model to estimate sequences of biomarker changes from baseline data across disease subtypes (mutation groups), and a differential equation model to estimate biomarker trajectories from longitudinal data (up to 66 mutation carriers, all subtypes combined). The two models concur that biomarker abnormality proceeds as follows: amyloid deposition in cortical then subcortical regions (∼24 ± 11 years before onset); phosphorylated tau (17 ± 8 years), tau and amyloid-β changes in cerebrospinal fluid; neurodegeneration first in the putamen and nucleus accumbens (up to 6 ± 2 years); then cognitive decline (7 ± 6 years), cerebral hypometabolism (4 ± 4 years), and further regional neurodegeneration. Our models predicted symptom onset more accurately than predictions that used familial estimates: root mean squared error of 1

PENGARUH PENGGUNAAN LETHAL OVITRAP TERHADAP POPULASI NYAMUK AEDES SP SEBAGAI VEKTOR DEMAM BERDARAH DENGUE

Directory of Open Access Journals (Sweden)

Tri Ramadhani

2013-09-01

Full Text Available ABSTRACT. Field evaluation against lethal ovitrap (LO to control dengue vector Aedes mosquitoes carried intwo endemic areas (Bojongsari and Ledug in Banyumas. Lethal ovitrap made ?with the intent to kill mosquito,because mosquitoes will lay eggs containing ovistrip contact with the insecticide and the relatively short time todie.The aim of research to assess the effect of LO applications with the Aedes of mosquito populations sp. Thisstudy includes a quasi experimental design with pretest-posttest control group without randomization. Researchsites in dengue endemic areas with a total sample of 100 houses in each treatment and control areas. Populationsof Aedes sp measured every week for three weeks prior to the intervention and twelve weeks during theintervention. The mean density of Aedes sp compared before and after intervention and between the treatment andcontrol. Results showed mean mosquito density before and after the intervention in the treatment group of 0.07(p-value 0.044, whereas in the control group by 0037 ( p-value 0341. Use LO made ?with the addition ofinsecticide active cypermetrin on ovistrip impact on the density of Aedes sp in the residential neighborhood.Keywords: lethal ovitrap, DHF, Aedes sp

Organic carbon in sediments of the southwestern margin of India: Influence of productivity and monsoon variability during the Late Quaternary

Digital Repository Service at National Institute of Oceanography (India)

Kessarkar, P; Rao, V.P

, with a zone of green black clayey silts at 200-230 cm interval (~32 14C ka) (Fig. 2). In core 39, silty clays are dominant through out the core. The sediments are moderate brown in colour between the core top and 30 cm (7 ka BP), light olive grey..., with higher proportions of sand around LGM and gradually decreasing proportions in the early Holocene and late Pleistocene sediments can be seen in Fig. 2. Clay content is higher in the early Holocene (11 ka BP - -7 ka BP) than in the late Holocene (up...

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%

A novel plant glutathione S-transferase/peroxidase suppresses Bax lethality in yeast

DEFF Research Database (Denmark)

Kampranis, S C; Damianova, R; Atallah, M

2000-01-01

The mammalian inducer of apoptosis Bax is lethal when expressed in yeast and plant cells. To identify potential inhibitors of Bax in plants we transformed yeast cells expressing Bax with a tomato cDNA library and we selected for cells surviving after the induction of Bax. This genetic screen allows...... for the identification of plant genes, which inhibit either directly or indirectly the lethal phenotype of Bax. Using this method a number of cDNA clones were isolated, the more potent of which encodes a protein homologous to the class theta glutathione S-transferases. This Bax-inhibiting (BI) protein was expressed...... in Escherichia coli and found to possess glutathione S-transferase (GST) and weak glutathione peroxidase (GPX) activity. Expression of Bax in yeast decreases the intracellular levels of total glutathione, causes a substantial reduction of total cellular phospholipids, diminishes the mitochondrial membrane...

Rethinking clinical language mapping approaches: discordant receptive and expressive hemispheric language dominance in epilepsy surgery candidates.

Science.gov (United States)

Gage, Nicole M; Eliashiv, Dawn S; Isenberg, Anna L; Fillmore, Paul T; Kurelowech, Lacey; Quint, Patti J; Chung, Jeffrey M; Otis, Shirley M

2011-06-01

Neuroimaging studies have shed light on cortical language organization, with findings implicating the left and right temporal lobes in speech processing converging to a left-dominant pattern. Findings highlight the fact that the state of theoretical language knowledge is ahead of current clinical language mapping methods, motivating a rethinking of these approaches. The authors used magnetoencephalography and multiple tasks in seven candidates for resective epilepsy surgery to investigate language organization. The authors scanned 12 control subjects to investigate the time course of bilateral receptive speech processes. Laterality indices were calculated for left and right hemisphere late fields ∼150 to 400 milliseconds. The authors report that (1) in healthy adults, speech processes activated superior temporal regions bilaterally converging to a left-dominant pattern, (2) in four of six patients, this was reversed, with bilateral processing converging to a right-dominant pattern, and (3) in three of four of these patients, receptive and expressive language processes were laterally discordant. Results provide evidence that receptive and expressive language may have divergent hemispheric dominance. Right-sided receptive language dominance in epilepsy patients emphasizes the need to assess both receptive and expressive language. Findings indicate that it is critical to use multiple tasks tapping separable aspects of language function to provide sensitive and specific estimates of language localization in surgical patients.

Late Mesozoic basin and range tectonics and related magmatism in Southeast China

Directory of Open Access Journals (Sweden)

Dezi Wang

2012-03-01

Full Text Available During the Late Mesozoic Middle Jurassic–Late Cretaceous, basin and range tectonics and associated magmatism representative of an extensional tectonic setting was widespread in southeastern China as a result of Pacific Plate subduction. Basin tectonics consists of post-orogenic (Type I and intra-continental extensional basins (Type II. Type I basins developed in the piedmont and intraland during the Late Triassic to Early Jurassic, in which coarse-grained terrestrial clastic sediments were deposited. Type II basins formed during intra-continental crustal thinning and were characterized by the development of grabens and half-grabens. Graben basins were mainly generated during the Middle Jurassic and were associated with bimodal volcanism. Sediments in half-grabens are intercalated with rhyolitic tuffs and lavas and are Early Cretaceous in age with a dominance of Late Cretaceous–Paleogene red beds. Ranges are composed of granitoids and bimodal volcanic rocks, A-type granites and dome-type metamorphic core complexes. The authors analyzed lithological, geochemical and geochronological features of the Late Mesozoic igneous rock assemblages and proposed some geodynamical constraints on forming the basin and range tectonics of South China. A comparison of the similarities and differences of basin and range tectonics between the eastern and western shores of the Pacific is made, and the geodynamical evolution model of the Southeast China Block during Late Mesozoic is discussed. Studied results suggest that the basin and range terrane within South China developed on a pre-Mesozoic folded belt was derived from a polyphase tectonic evolution mainly constrained by subduction of the western Pacific Plate since the Late Mesozoic, leading to formation of various magmatism in a back-arc extensional setting. Its geodynamic mechanism can compare with that of basin and range tectonics in the eastern shore of the Pacific. Differences of basin and range

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

Ibsen, Bjørnson and the art of acting

Directory of Open Access Journals (Sweden)

Keld Hyldig

2015-02-01

Full Text Available In this article Henrik Ibsen’s and Bjørnstjerne Bjørnson’s contribution to the development of acting in Norwegian theatre are discussed within the background of Danish romantic acting. In the 1850s and -60s both were active as theatre critics, directors and dramatists. Both had a view on theatre and acting marked by a mixture of romantic and realistic ideas, and both urged for the development of Norwegian acting in continuation of Danish and European traditions. It was, however, Bjørnson, who to begin with, came to be most influential with regard to what direction the acting style, among the Norwegian actors, developed. Through his inspiration and efforts a specific national coloured way of acting developed and came to dominate Norwegian theatre at least until the beginning of the 20th century. The influence from Ibsen – and the development of a Norwegian Ibsen tradition – has first of all come from his contemporary plays. A specific Ibsenian (i.e. psychological realistic acting style developed gradually from the 1880s and onwards, through the actors’ work with the characters in Ibsen’s contemporary plays.

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.)

Galantamine is a novel post-exposure therapeutic against lethal VX challenge

International Nuclear Information System (INIS)

Hilmas, Corey J.; Poole, Melissa J.; Finneran, Kathryn; Clark, Matthew G.; Williams, Patrick T.

2009-01-01

The ability of galantamine hydrobromide (GAL HBr) treatment to antagonize O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX)-induced lethality, impairment of muscle tension, and electroencephalographic (EEG) changes was assessed in guinea pigs. Guinea pigs were challenged with 16.8 μg/kg VX (2LD50). One min after challenge, animals were administered 0.5 mg/kg atropine sulfate (ATR) and 25 mg/kg pyridine-2-aldoxime methochloride (2-PAM). In addition, guinea pigs were given 0, 1, 2, 4, 8 or 10 mg/kg GAL as a post-exposure treatment immediately prior to ATR and 2-PAM. Animals were either monitored for 24-h survival, scheduled for electroencephalography (EEG) recording, or euthanized 60 min later for measurement of indirectly-elicited muscle tension in the hemidiaphragm. Post-exposure GAL therapy produced a dose-dependent increase in survival from lethal VX challenge. Optimal clinical benefits were observed in the presence of 10 mg/kg GAL, which led to 100% survival of VX-challenged guinea pigs. Based on muscle physiology studies, GAL post-exposure treatment protected the guinea pig diaphragm, the major effector muscle of respiration, from fatigue, tetanic fade, and muscular paralysis. Protection against the paralyzing effects of VX was dose-dependent. In EEG studies, GAL did not alter seizure onset for all doses tested. At the highest dose tested (10 mg/kg), GAL decreased seizure duration when administered as a post-exposure treatment 1 min after VX. GAL also reduced the high correlation associated between seizure activity and lethality after 2LD50 VX challenge. GAL may have additional benefits both centrally and peripherally that are unrelated to its established mechanism as a reversible acetylcholinesterase inhibitor (AChEI).

Derangement of cellular plasma membranes due to non-lethal radiation doses

International Nuclear Information System (INIS)

Koeteles, G.J.; Kubasova, T.; Somosy, Z.; Horvath, L.

1983-01-01

Earlier observations in the laboratory on fibroblasts and various blood cells of animal and human origins pointed to alteration of concanavalin A binding sites of plasma membranes as well as to concomitant morphological changes and scanning electron microscopic appearance of cell surfaces following sub-lethal doses of X-, fission neutron and beta irradiations. The effects appeared early and existed temporarily; their intensities and the restitution of membrane function depended on radiation doses, types and conditions of cells. In the present paper further aspects of structural and functional derangements of plasma membranes are introduced which were provoked by X- and tritium beta irradiation in the dose range up to 2.5 Gy and in the concentration range from 3.7 kBq/mL, respectively. The state of membrane structure was followed by bindings of various ligands of different receptor requirements, concanavalin A, cationized ferritin and polio virus. In the case of X-irradiation the binding conditions suggest the shift of overall negative surface charges to less negative ones. It was also found that radiation-induced phenomena appear on the cell surface unevenly. Long- and short-term treatments of cells with 3 H-thymidine and 3 H-water also perturb the plasma membrane; beta irradiation affects it directly. Membrane structure and function are suggested to offer good biological models to study correlation of energy deposition and biological effects, both restricted to domains of nanometre range. The data give evidence for radiation-induced membrane alterations in the sub-lethal or non-lethal ranges which might have consequences in the development of stochastic and non-stochastic effects. (author)

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.

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.

Doctor of Philosophy Thesis in Military Informatics : Lethal Autonomy of Weapons is Designed and/or Recessive

OpenAIRE

Nyagudi, Nyagudi Musandu

2016-01-01

p { margin-bottom: 0.1in; line-height: 120%; } My original contribution to knowledge is : Any weapon that exhibits intended and/or untended lethal autonomy in targeting and interdiction – does so by way of design and/or recessive flaw(s) in its systems of control – any such weapon is capable of war-fighting and other battle-space interaction in a manner that its Human Commander does not anticipate. A lethal autonomous weapons is therefore independently capable of ex...

Piety, Practice, and Politics: Agency and Ritual in the Late Bronze Age Southern Levant

OpenAIRE

DePietro, Dana Douglas

2012-01-01

Striking changes in the archaeological record of the southern Levant during the final years of the Late Bronze Age have long fascinated scholars interested in the region and period. Attempts to explain the emergence of new forms of Canaanite material culture have typically cited external factors such as Egyptian political domination as the driving force behind culture change, relying on theoretical models of acculturation, elite-emulation and center-periphery theory. While these approaches ca...

Reading in Colette: Domination, Resistance, Autonomy

Directory of Open Access Journals (Sweden)

Laurel Cummins

1996-06-01

Full Text Available The act of reading on the part of Colette's characters reveals itself as a dynamic involving domination and resistance. A study of passages from two of her semi-autobiographical works, La Maison de Claudine and Sido , brings to light both a positively connoted model of reading, exemplified by the character 'Colette,' and a negatively connoted model, exemplified by the older sister Juliette. While Juliette approaches texts with no sense of self, and seeks instead to be defined by the texts she reads, 'Colette' remains in relation to texts and to the discourses they contain, and resists them. Gender complicates the process. Both father and mother intervene in 'Colette's' apprenticeship as reader. While the censorship that constitutes the father's intervention proves both debilitating and disempowering, the mother's modeling of reading as dialogue and resistance empowers 'Colette,' both as a reader and a female being.

Relation between trends in late middle age mortality and trends in old age mortality--is there evidence for mortality selection?

NARCIS (Netherlands)

Janssen, F.; Peeters, A.; Mackenbach, J. P.; Kunst, A. E.

2005-01-01

STUDY OBJECTIVE: To test whether mortality selection was a dominant factor in determining trends in old age mortality, by empirically studying the existence of a negative correlation between trends in late middle age mortality and trends in old age mortality among the same cohorts. DESIGN AND

Dominant Species in Subtropical Forests Could Decrease Photosynthetic N Allocation to Carboxylation and Bioenergetics and Enhance Leaf Construction Costs during Forest Succession.

Science.gov (United States)

Xiao, Yihua; Liu, Shirong; Tong, Fuchun; Chen, Bufeng; Kuang, Yuanwen

2018-01-01

It is important to understand how eco-physiological characteristics shift in forests when elucidating the mechanisms underlying species replacement and the process of succession and stabilization. In this study, the dominant species at three typical successional stages (early-, mid-, and late-succession) in the subtropical forests of China were selected. At each stage, we compared the leaf construction costs (CC), payback time (PBT), leaf area based N content ( N A ), maximum CO 2 assimilation rate ( P max ), specific leaf area (SLA), photosynthetic nitrogen use efficiency (PNUE), and leaf N allocated to carboxylation ( N C ), and to bioenergetics ( N B ). The relationships between these leaf functional traits were also determined. The results showed that the early-succession forest is characterized with significantly lower leaf CC, PBT, N A , but higher P max , SLA, PNUE, N C , and N B , in relation to the late-succession forest. From the early- to the late-succession forests, the relationship between P max and leaf CC strengthened, whereas the relationships between N B , N C , PNUE, and leaf CC weakened. Thus, the dominant species are able to decrease the allocation of the photosynthetic N fraction to carboxylation and bioenergetics during forest succession. The shift in these leaf functional traits and their linkages might represent a fundamental physiological mechanism that occurs during forest succession and stabilization.

Alpha-beta T cells provide protection against lethal encephalitis in the murine model of VEEV infection

International Nuclear Information System (INIS)

Paessler, Slobodan; Yun, Nadezhda E.; Judy, Barbara M.; Dziuba, Natallia; Zacks, Michele A.; Grund, Anna H.; Frolov, Ilya; Campbell, Gerald A.; Weaver, Scott C.; Estes, D. Mark

2007-01-01

We evaluated the safety and immunogenicity of a chimeric alphavirus vaccine candidate in mice with selective immunodeficiencies. This vaccine candidate was highly attenuated in mice with deficiencies in the B and T cell compartments, as well as in mice with deficient gamma-interferon responsiveness. However, the level of protection varied among the strains tested. Wild type mice were protected against lethal VEEV challenge. In contrast, alpha/beta (αβ) TCR-deficient mice developed lethal encephalitis following VEEV challenge, while mice deficient in gamma/delta (γδ) T cells were protected. Surprisingly, the vaccine potency was diminished by 50% in animals lacking interferon-gamma receptor alpha chain (R1)-chain and a minority of vaccinated immunoglobulin heavy chain-deficient (μMT) mice survived challenge, which suggests that neutralizing antibody may not be absolutely required for protection. Prolonged replication of encephalitic VEEV in the brain of pre-immunized mice is not lethal and adoptive transfer experiments indicate that CD3 + T cells are required for protection

Combination of opium smoking and hypercholesterolemia augments susceptibility for lethal cardiac arrhythmia and atherogenesis in rabbit.

Science.gov (United States)

Najafipour, Hamid; Joukar, Siyavash

2012-09-01

Opium consumption is increasing in some eastern societies, where it is grown. We investigated the effect of opium smoking on plasma atherogenic index and incidence of lethal cardiac arrhythmia, i.e. ventricular tachycardia (VT) and ventricular fibrillation (VF) in rabbits. Animals were divided into two-, normo- and hyper-cholesterolemic main groups fed with normal or high cholesterol diet prior and during short-term and long-term exposure to opium smoke. Then, isoproterenol (3mg/kg, i.p.) was injected to induce cardiac ischemia and animals were followed for 3h for counting of lethal arrhythmia incidence. Long-term opium smoking significantly increased the plasma atherogenic index. In ischemic hearts, opium smoking along with hypercholesterolemia significantly enhanced the incidence of fatal arrhythmia. This vulnerability was not mediated by changes in QT interval. These data suggest that opium smoking, especially in hypercholesterolemic conditions, can be a predisposing factor for atherogenesis and lethal arrhythmia. Copyright © 2012 Elsevier B.V. All rights reserved.

Molecular and cytogenetic evaluation for potential genotoxicity of hydrocortisone

Directory of Open Access Journals (Sweden)

Maha Aly Fahmy

2015-09-01

Full Text Available Objective: To assess the risk of hydrocortisone sodium succinate through different end points of genotoxicity. Methods: The study examined the induction of chromosomal aberrations in bone marrow cells, morphological sperm abnormalities, the effect on dominant lethal gene and protein synthesis. Hydrocortisone was given intraperitoneally at three dose levels 26, 39 and 52 mg/kg body weight which was equivalent to the therapeutic doses in man. Results: The results showed that single dose treatment with different doses had no effect on chromosomal aberrations. The dose of 52 mg/kg body weight induced significant percentage of chromosomal aberrations in bone marrow cells after repeated treatment for 7 and 14 days. Significant effect of morphological sperm abnormalities was demonstrated only after treatment with the dose of 52 mg/kg body weight. For examining the dominant lethal mutation, male mice were injected with dose of 39 mg/kg body weight for 5 consecutive days. Mating between treated males and virgin untreated females were performed at different time intervals. The results showed that the percentage of fertile mating at 1–7 and 8–14 days reduced to 50% and 60% respectively compared with control group while no effect was recorded at 15–21 days. The percentage of dominant lethal mutation reached 0.32%, 4.4% and 0% in mating intervals respectively indicating pronounced effect of hydrocortisone at the interval 8–14 days which represented by the late spermatids. The results also showed that the repeated treatment with the dose of 52 mg/kg body weight inhibited protein synthesis which contributed to the cytotoxic effect of the drug. Conclusions: It is concluded that long term treatment with large doses of hydrocortisone may have genotoxic effect.

Models and correlations of the DEBRIS Late-Phase Melt Progression Model

International Nuclear Information System (INIS)

Schmidt, R.C.; Gasser, R.D.

1997-09-01

The DEBRIS Late Phase Melt Progression Model is an assembly of models, embodied in a computer code, which is designed to treat late-phase melt progression in dry rubble (or debris) regions that can form as a consequence of a severe core uncover accident in a commercial light water nuclear reactor. The approach is fully two-dimensional, and incorporates a porous medium modeling framework together with conservation and constitutive relationships to simulate the time-dependent evolution of such regions as various physical processes act upon the materials. The objective of the code is to accurately model these processes so that the late-phase melt progression that would occur in different hypothetical severe nuclear reactor accidents can be better understood and characterized. In this report the models and correlations incorporated and used within the current version of DEBRIS are described. These include the global conservation equations solved, heat transfer and fission heating models, melting and refreezing models (including material interactions), liquid and solid relocation models, gas flow and pressure field models, and the temperature and compositionally dependent material properties employed. The specific models described here have been used in the experiment design analysis of the Phebus FPT-4 debris-bed fission-product release experiment. An earlier DEBRIS code version was used to analyze the MP-1 and MP-2 late-phase melt progression experiments conducted at Sandia National Laboratories for the US Nuclear Regulatory Commission

Before the freeze: otoliths from the Eocene of Seymour Island, Antarctica, reveal dominance of gadiform fishes (Teleostei).

Science.gov (United States)

Schwarzhans, Werner; Mörs, Thomas; Engelbrecht, Andrea; Reguero, Marcelo; Kriwet, Jürgen

2017-01-01

The first record of fossil teleostean otoliths from Antarctica is reported. The fossils were obtained from late Early Eocene shell beds of the La Meseta Formation, Seymour Island that represent the last temperate marine climate phase in Antarctica prior to the onset of cooling and subsequent glaciation during the late Eocene. A total of 17 otolith-based teleost taxa are recognized, with 10 being identifiable to species level containing nine new species and one new genus: Argentina antarctica sp. nov., Diaphus? marambionis sp. nov., Macruronus eastmani sp. nov., Coelorinchus balushkini sp. nov., Coelorinchus nordenskjoeldi sp. nov., Palimphemus seymourensis sp. nov., Hoplobrotula? antipoda sp. nov., Notoberyx cionei gen. et sp. nov. and Cepola anderssoni sp. nov. Macruronus eastmani sp. nov. is also known from the late Eocene of Southern Australia, and Tripterophycis immutatus Schwarzhans, widespread in the southern oceans during the Eocene, has been recorded from New Zealand, southern Australia, and now Antarctica. The otolith assemblage shows a typical composition of temperate fishes dominated by gadiforms, very similar at genus and family levels to associations known from middle Eocene strata of New Zealand and the late Eocene of southern Australia, but also to the temperate Northern Hemisphere associations from the Paleocene of Denmark. The Seymour Island fauna bridges a gap in the record of global temperate marine teleost faunas during the early Eocene climate maximum. The dominant gadiforms are interpreted as the main temperate faunal component, as in the Paleocene of Denmark. Here they are represented by the families Moridae, Merlucciidae (Macruroninae), Macrouridae and Gadidae. Nowadays Gadidae are a chiefly Northern Hemisphere temperate family. Moridae, Macruroninae and Macrouridae live today on the lower shelf to deep-water or mesopelagically with Macruroninae being restricted to the Southern Ocean. The extant endemic Antarctic gadiform family

Late calcium EDTA rescues hippocampal CA1 neurons from global ischemia-induced death.

Science.gov (United States)

Calderone, Agata; Jover, Teresa; Mashiko, Toshihiro; Noh, Kyung-min; Tanaka, Hidenobu; Bennett, Michael V L; Zukin, R Suzanne

2004-11-03

Transient global ischemia induces a delayed rise in intracellular Zn2+, which may be mediated via glutamate receptor 2 (GluR2)-lacking AMPA receptors (AMPARs), and selective, delayed death of hippocampal CA1 neurons. The molecular mechanisms underlying Zn2+ toxicity in vivo are not well delineated. Here we show the striking finding that intraventricular injection of the high-affinity Zn2+ chelator calcium EDTA (CaEDTA) at 30 min before ischemia (early CaEDTA) or at 48-60 hr (late CaEDTA), but not 3-6 hr, after ischemia, afforded robust protection of CA1 neurons in approximately 50% (late CaEDTA) to 75% (early CaEDTA) of animals. We also show that Zn2+ acts via temporally distinct mechanisms to promote neuronal death. Early CaEDTA attenuated ischemia-induced GluR2 mRNA and protein downregulation (and, by inference, formation of Zn2+-permeable AMPARs), the delayed rise in Zn2+, and neuronal death. These findings suggest that Zn2+ acts at step(s) upstream from GluR2 gene downregulation and implicate Zn2+ in transcriptional regulation and/or GluR2 mRNA stability. Early CaEDTA also blocked mitochondrial release of cytochrome c and Smac/DIABLO (second mitochondria-derived activator of caspases/direct inhibitor of apoptosis protein-binding protein with low pI), caspase-3 activity (but not procaspase-3 cleavage), p75NTR induction, and DNA fragmentation. These findings indicate that CaEDTA preserves the functional integrity of the mitochondrial outer membrane and arrests the caspase death cascade. Late injection of CaEDTA at a time when GluR2 is downregulated and caspase is activated inhibited the delayed rise in Zn2+, p75NTR induction, DNA fragmentation, and cell death. The finding of neuroprotection by late CaEDTA administration has striking implications for intervention in the delayed neuronal death associated with global ischemia.

"Juntos pero no revueltos": microaggressions and language in the mathematics education of non-dominant Latinas/os

Science.gov (United States)

LópezLeiva, Carlos A.; Khisty, Lena Licón

2014-06-01

In this paper, we discuss the characteristics of microaggressions based on minority language(s) as a form of discriminatory practice against non-dominant students in the mathematics context. Microaggressions are subtle, brief, and commonplace verbal, behavioral, or visual negative slights or insults toward people of color. We extend the concept of microaggression to include discrimination based on a minority language. We draw on our work with Latinas/os in the USA to demonstrate the occurrence of microaggressions in the teaching act. Revealing microaggressions based on language has the potential of creating more equitable learning environments for non-dominant students and can point to possible directions for future research and improvements in the preparation of teachers who serve non-dominant students who speak a language other than the school's official language.

Autonomy and dignity: a discussion on contingency and dominance.

Science.gov (United States)

Van Brussel, Leen

2014-06-01

With dying increasingly becoming a medicalised experience in old age, we are witnessing a shift from concern over death itself to an interest in dying 'well'. Fierce discussions about end-of-life decision making and the permissibility of medical intervention in dying, discursively structured around the notion of a 'good' death, are evidence of this shift. This article focuses on 'autonomy' and 'dignity' as key signifiers in these discussions. Rather than being fully fixed and stable, both signifiers are contingent and carry a variety of meanings within different discursive projects. The article aims to distinguish the varieties of these signifiers by elaborating existing theoretical perspectives on autonomy and dignity, and also, starting from a perspective on mass media as sites of meaning production and contestation, to study the contingency of autonomy and dignity in Belgian newspaper coverage of four prominent euthanasia cases. By means of a discourse-theoretical textual analysis, this study exposes a dominant--yet contested--articulation of rational-personal autonomy and of dignity in external terms as something that can be obtained, retained or lost, rather than in terms of intrinsic human integrity. These logics of representation reflect a more general late modern dominance of liberal autonomy and of dignity as being closely connected to self-identity, but at the same time result in limited visibility of alternative ways of experiencing an autonomous and dignified death.

Test of the acute lethal toxicity of pollutants to marine fish and invertebrates

International Nuclear Information System (INIS)

1989-01-01

This reference method describes the measurement of the acute lethal toxicity of pollutants to marine animals (fish and invertebrates) by a static (non-continuous flow) method. Procedures are given for the determination of the toxicity curve (survival time-concentration relationship) and for the estimation of median lethal concentrations (LC50). The method is suitable for use with fish and macro-invertebrate species. It is not suitable for planktonic organisms nor for determining the toxicity of oil, oil dispersants or other petroleum products. Those methods are described in Reference Methods Nos. 44 and 45, respectively. The test animals are exposed, in groups of approximately ten, to each of several concentrations of the pollutant. The animals are observed, at intervals, for several days, the test solutions being renewed regularly. A record is maintained of the survival times of individual animals exposed to each concentration of pollutant. The medial survival time of each group of animals is determined from a graphical plot of the raw data after a log-probability transformation. Median survival times and their confidence limits are plotted against concentrations of test substance to give a toxicity curve. Additionally, the same experimental data can be used to estimate the median lethal concentration (LC50) of the test substance to the animals after different periods of exposure. 3 refs, 5 figs, 3 tabs

Tumor therapy with a urokinase plasminogen activator-activated anthrax lethal toxin alone and in combination with paclitaxel.

Science.gov (United States)

Wein, Alexander N; Liu, Shihui; Zhang, Yi; McKenzie, Andrew T; Leppla, Stephen H

2013-02-01

PA-U2, an engineered anthrax protective antigen that is activated by urokinase was combined with wildtype lethal factor in the treatment of Colo205 colon adenocarcinoma in vitro and B16-BL6 mouse melanoma in vitro and in vivo. This therapy was also tested in combination with the small molecule paclitaxel, based on prior reports suggesting synergy between ERK1/2 inhibition and chemotherapeutics. Colo205 was sensitive to PA-U2/LF while B16-BL6 was not. For the combination treatment of B16-BL6, paclitaxel showed a dose response in vitro, but cells remained resistant to PA-U2/LF even in the presence of paclitaxel. In vivo, each therapy slowed tumor progression, and an additive effect between the two was observed. Since LF targets tumor vasculature while paclitaxel is an antimitotic, it is possible the agents were acting against different cells in the stroma, precluding a synergistic effect. The engineered anthrax toxin PA-U2/LF warrants further development and testing, possibly in combination with an antiangiogenesis therapy such as sunitinib or sorafinib.

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

INTERACTION ASPECTS OF DOMINANT STYLES: OF TEACHING AND OF AUTHORITY

Directory of Open Access Journals (Sweden)

Cristian PETRE

2014-04-01

Full Text Available Problem Statement. Teaching style is the expression (form of expression of preferred behavioral modalities who return with some regularity in the work of teacher (E.Geissler, Purpose of Study. The intention of this paper is to identify a pattern of expression interact between two dimensions-professional of primary school teachers: the dominant teaching style and the dominant authority type of each teacher. I opted for a classification according to the particular act of communication: emotional-improvising style, emotional-methodical style, rational-improvising style and rational-methodical style. Methods. To identify the dominant teaching style was built a questionnaire consisting of 16 questions. The second questionnaire was proposed for a self-evaluative kind of authority expressed in the daily professional work. To identify the dominant type of authority were updated two classifications: traditional axis authoritarian - democratic - laissez-faire and a classification inspired by John RP French and B. Raven expert authority, rewards, position and personal. In this investigation were involved 30 teachers for primary education. Findings and Results. Exists a moderate correlation between rational-improvising style and authoritarian and position styles of authority. Also, indicates significant statistical connection between rational-improviser teaching style and authoritarian, democratic and expert teacher’s authority. The indexes indicate statistical connections moderate correlation between rational-methodical style and personal authority. The indexes of correlation indicates significant statistical link between emotional-improvisational style teaching styles and reward and expert authority. The indexes indicate statistical connections moderate correlation between emotional-style improvisation and styles of authority laissez-faire, and his model.

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.

Functional interchangeability of late domains, late domain cofactors and ubiquitin in viral budding.

Directory of Open Access Journals (Sweden)

Maria Zhadina

2010-10-01

Full Text Available The membrane scission event that separates nascent enveloped virions from host cell membranes often requires the ESCRT pathway, which can be engaged through the action of peptide motifs, termed late (L- domains, in viral proteins. Viral PTAP and YPDL-like L-domains bind directly to the ESCRT-I and ALIX components of the ESCRT pathway, while PPxY motifs bind Nedd4-like, HECT-domain containing, ubiquitin ligases (e.g. WWP1. It has been unclear precisely how ubiquitin ligase recruitment ultimately leads to particle release. Here, using a lysine-free viral Gag protein derived from the prototypic foamy virus (PFV, where attachment of ubiquitin to Gag can be controlled, we show that several different HECT domains can replace the WWP1 HECT domain in chimeric ubiquitin ligases and drive budding. Moreover, artificial recruitment of isolated HECT domains to Gag is sufficient to stimulate budding. Conversely, the HECT domain becomes dispensable if the other domains of WWP1 are directly fused to an ESCRT-1 protein. In each case where budding is driven by a HECT domain, its catalytic activity is essential, but Gag ubiquitination is dispensable, suggesting that ubiquitin ligation to trans-acting proteins drives budding. Paradoxically, however, we also demonstrate that direct fusion of a ubiquitin moiety to the C-terminus of PFV Gag can also promote budding, suggesting that ubiquitination of Gag can substitute for ubiquitination of trans-acting proteins. Depletion of Tsg101 and ALIX inhibits budding that is dependent on ubiquitin that is fused to Gag, or ligated to trans-acting proteins through the action of a PPxY motif. These studies underscore the flexibility in the ways that the ESCRT pathway can be engaged, and suggest a model in which the identity of the protein to which ubiquitin is attached is not critical for subsequent recruitment of ubiquitin-binding components of the ESCRT pathway and viral budding to proceed.

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...

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

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

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 ...

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.)

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....

Lethal and sublethal effects of pesticides in the management of Polyphagotarsonemus latus (Banks) (Acari: Tarsonemidae) on Capsicum annuum L.

Science.gov (United States)

Breda, Mariana O; Oliveira, José V; Esteves Filho, Alberto B; Barbosa, Douglas Rs; Santos, Andrezo A

2017-10-01

The evaluation of lethal and sublethal effects is of great importance for a complete assessment of the total impact of chemical compounds upon pest populations and the development of management strategies. In this study, we evaluated the lethal and sublethal effects of different synthetic and botanical products on the broad mite Polyphagotarsonemus latus (Banks), a major pest of Capsicum annuum L. and other crops. Abamectin had the highest lethal effect on P. latus, followed by spiromesifen, azadirachtin, neem oil and nitrogen fertiliser + citric acid. The sublethal effects of the products were indicated by the influence on mite population growth, affecting the numbers of females, males, larvae, pupae and eggs. Furthermore, a negative instantaneous rate of increase in P. latus and repellent effects were observed. The lethal and sublethal effects of abamectin, spiromesifen, azadirachtin and neem oil significantly affect P. latus population growth, as well as causing repellence to this mite on C. annuum, and they should be considered in the integrated pest management of this mite. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Dominance behaviour in a non-aggressive flatfish, Senegalese sole (Solea senegalensis and brain mRNA abundance of selected transcripts.

Directory of Open Access Journals (Sweden)

Elvira Fatsini

Full Text Available Dominance is defined as the preferential access to limited resources. The present study aimed to characterise dominance in a non-aggressive flatfish species, the Senegalese sole (Solea senegalensis by 1 identifying dominance categories and associated behaviours and 2 linking dominance categories (dominant and subordinate with the abundance of selected mRNA transcripts in the brain. Early juveniles (n = 74, 37 pairs were subjected to a dyadic dominance test, related to feeding, and once behavioural phenotypes had been described the abundance of ten selected mRNAs related to dominance and aggressiveness was measured in the brain. Late juveniles were subjected to two dyadic dominance tests (n = 34, 17 pairs, related to feeding and territoriality and one group test (n = 24, 4 groups of 6 fish. Sole feeding first were categorized as dominant and sole feeding second or not feeding as subordinate. Three social behaviours (i. "Resting the head" on another fish, ii. "Approaching" another fish, iii. "Swimming above another" fish were associated with dominance of feeding. Two other variables (i. Total time occupying the preferred area during the last 2 hours of the 24 h test, ii. Organisms occupying the preferred area when the test ended were representative of dominance in the place preference test. In all tests, dominant fish compared to subordinate fish displayed a significantly higher number of the behaviours "Rest the head" and "Approaches". Moreover, dominant sole dominated the sand at the end of the test, and in the group test dominated the area close to the feed delivery point before feed was delivered. The mRNA abundance of the selected mRNAs related to neurogenesis (nrd2 and neuroplasticity (c-fos in dominant sole compared to subordinate were significantly different. This is the first study to characterise dominance categories with associated behaviours and mRNA abundance in Senegalese sole and provides tools to study dominance related problems in

Lethal and mutagenic effects of ion beams and γ-rays in Aspergillus oryzae

International Nuclear Information System (INIS)

Toyoshima, Yoshiyuki; Takahashi, Akemi; Tanaka, Hisaki; Watanabe, Jun; Mogi, Yoshinobu; Yamazaki, Tatsuo; Hamada, Ryoko; Iwashita, Kazuhiro; Satoh, Katsuya; Narumi, Issay

2012-01-01

Highlights: ► We investigated the effects of different LET radiation in A. oryzae. ► Both γ-rays and ion beams induced base substitutions, frameshifts, deletions. ► Both γ-rays and ion beams induced genome-wide large-scale mutations in A. oryzae. ► Some differences in the types and frequencies of mutations were found. ► Our results provide new basic insights into the mutation breeding of A. oryzae. - Abstract: Aspergillus oryzae is a fungus that is used widely in traditional Japanese fermentation industries. In this study, the lethal and mutagenic effects of different linear energy transfer (LET) radiation in freeze-dried conidia of A. oryzae were investigated. The lethal effect, which was evaluated by a 90% lethal dose, was dependent on the LET value of the ionizing radiation. The most lethal ionizing radiation among that tested was 12 C 5+ ion beams with an LET of 121 keV/μm. The 12 C 5+ ion beams had a 3.6-times higher lethal effect than low-LET (0.2 keV/μm) γ-rays. The mutagenic effect was evaluated by the frequency of selenate resistant mutants. 12 C 6+ ion beams with an LET of 86 keV/μm were the most effective in inducing selenate resistance. The mutant frequency following exposure to 12 C 6+ ion beams increased with an increase in dose and reached 3.47 × 10 −3 at 700 Gy. In the dose range from 0 to 700 Gy, 12 C 5+ ion beams were the second most effective in inducing selenate resistance, the mutant frequency of which reached a maximum peak (1.67 × 10 −3 ) at 400 Gy. To elucidate the characteristics of mutation induced by ionizing radiation, mutations in the sulphate permease gene (sB) and ATP sulfurylase gene (sC) loci, the loss of function of which results in a selenate resistant phenotype, were compared between 12 C 5+ ion beams and γ-rays. We detected all types of transversions and transitions. For frameshifts, the frequency of a +1 frameshift was the highest in all cases. Although the incidence of deletions >2 bp was generally low

Close Link Between Harmful Cyanobacterial Dominance and Associated Bacterioplankton in a Tropical Eutrophic Reservoir

Directory of Open Access Journals (Sweden)

Iame A. Guedes

2018-03-01

Full Text Available Cyanobacteria tend to become the dominant phytoplankton component in eutrophic freshwater environments during warmer seasons. However, general observations of cyanobacterial adaptive advantages in these circumstances are insufficient to explain the prevalence of one species over another in a bloom period, which may be related to particular strategies and interactions with other components of the plankton community. In this study, we present an integrative view of a mixed cyanobacterial bloom occurring during a warm, rainy period in a tropical hydropower reservoir. We used high-throughput sequencing to follow temporal shifts in the dominance of cyanobacterial genera and shifts in the associated heterotrophic bacteria community. The bloom occurred during late spring-summer and included two distinct periods. The first period corresponded to Microcystis aeruginosa complex (MAC dominance with a contribution from Dolichospermum circinale; this pattern coincided with high water retention time and low transparency. The second period corresponded to Cylindrospermopsis raciborskii and Synechococcus spp. dominance, and the reservoir presented lower water retention time and higher water transparency. The major bacterial phyla were primarily Cyanobacteria and Proteobacteria, followed by Actinobacteria, Bacteroidetes, Verrucomicrobia, and Planctomycetes. Temporal shifts in the dominance of cyanobacterial genera were not only associated with physical features of the water but also with shifts in the associated heterotrophic bacteria. The MAC bloom was associated with a high abundance of Bacteroidetes, particularly Cytophagales. In the second bloom period, Planctomycetes increased in relative abundance, five Planctomycetes OTUs were positively correlated with Synechococcus or C. raciborskii OTUs. Our results suggest specific interactions of the main cyanobacterial genera with certain groups of the heterotrophic bacterial community. Thus, considering biotic

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.

Generalized Power Domination

OpenAIRE

Omerzel, Aleš

2014-01-01

The power domination problem is an optimization problem that has emerged together with the development of the power networks. It is important to control the voltage and current in all the nodes and links in a power network. Measuring devices are expensive, which is why there is a tendency to place a minimum number of devices in a power network so that the network remains fully supervised. The k-power domination is a generalization of the power domination. The thesis represents the rules of th...

Autosomal dominant cutis laxa with progeroid features due to a novel, de novo mutation in ALDH18A1.

Science.gov (United States)

Bhola, Priya T; Hartley, Taila; Bareke, Eric; Boycott, Kym M; Nikkel, Sarah M; Dyment, David A

2017-06-01

De novo dominant mutations in the aldehyde dehydrogenase 18 family member A1 (ALDH18A1) gene have recently been shown to cause autosomal dominant cutis laxa with progeroid features (MIM 616603). To date, all de novo dominant mutations have been found in a single highly conserved amino acid residue at position p.Arg138. We report an 8-year-old male with a clinical diagnosis of autosomal dominant cutis laxa (ADCL) with progeroid features and a novel de novo missense mutation in ALDH18A1 (NM_002860.3: c.377G>A (p.Arg126His)). This is the first report of an individual with ALDH18A1-ADCL due to a substitution at a residue other than p.Arg138. Knowledge of the complete spectrum of dominant-acting mutations that cause this rare syndrome will have implications for molecular diagnosis and genetic counselling of these families.

Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error.

Science.gov (United States)

Shipitsin, M; Small, C; Choudhury, S; Giladi, E; Friedlander, S; Nardone, J; Hussain, S; Hurley, A D; Ernst, C; Huang, Y E; Chang, H; Nifong, T P; Rimm, D L; Dunyak, J; Loda, M; Berman, D M; Blume-Jensen, P

2014-09-09

Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation. Prostatectomy samples from a large patient cohort with long follow-up were blindly assessed by expert pathologists who identified the tissue regions with the highest and lowest Gleason grade from each patient. To simulate biopsy-sampling error, a core from a high- and a low-Gleason area from each patient sample was used to generate a 'high' and a 'low' tumour microarray, respectively. Using a quantitative proteomics approach, we identified from 160 candidates 12 biomarkers that predicted prostate cancer aggressiveness (surgical Gleason and TNM stage) and lethal outcome robustly in both high- and low-Gleason areas. Conversely, a previously reported lethal outcome-predictive marker signature for prostatectomy tissue was unable to perform under circumstances of maximal sampling error. Our results have important implications for cancer biomarker discovery in general and development of a sampling error-resistant clinical biopsy test for prediction of prostate cancer aggressiveness.

Authoritarianism, dominance and assertiveness.

Science.gov (United States)

Ray, J J

1981-08-01

It is shown that there are definitions of the three constructs of authoritarianism, dominance and assertiveness which read very similarly; so much so that no distinction is immediately evident. It is proposed that authoritarianism might be conceived as aggressive dominance and at least some types of assertiveness as nonaggressive dominance. A new scale of Dominance suitable for general population use was produced, and compared with the existing Ray (1976) behavior inventory of authoritarianism. Both scales showed highly significant correlations with peer rated dominance and submission (the latter being negative in sign) but only the authoritarianism scale showed significant correlations with rated aggressiveness and rigidity. It was concluded that the new definitions could be operationalized into valid scales.

Distribution of discontinuous mudstone beds within wave-dominated shallow-marine deposits: Star Point Sandstone and Blackhawk Formation, Eastern Utah, USA

OpenAIRE

Eide, Christian; Buckley, Simon; Howell, John

2017-01-01

Deposits of wave-dominated shorelines are typically considered to act as relatively simple hydrocarbon reservoirs and are commonly modeled as “tanks of sand”. However, important heterogeneities that can act as barriers to fluid flow occur at the parasequence, bedset and bed scales, especially in viscous oil or low permeability oil fields. Heterogeneities at the parasequence and bedset scale have been well-studied, but discontinuous mudstone-beds occurring within the shoreface have received li...

Dominance in domestic dogs

NARCIS (Netherlands)

Borg, Van Der J.A.M.; Schilder, M.B.H.; Vinke, C.M.; Vries, De Han; Petit, Odile

2015-01-01

A dominance hierarchy is an important feature of the social organisation of group living animals. Although formal and/or agonistic dominance has been found in captive wolves and free-ranging dogs, applicability of the dominance concept in domestic dogs is highly debated, and quantitative data are

Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

International Nuclear Information System (INIS)

Peters, Diane E.; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A.; Leppla, Stephen H.; Bugge, Thomas H.

2014-01-01

We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti

Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

Energy Technology Data Exchange (ETDEWEB)

Peters, Diane E. [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Program of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA (United States); Hoover, Benjamin [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Cloud, Loretta Grey [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Liu, Shihui [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Molinolo, Alfredo A. [Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Leppla, Stephen H. [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Bugge, Thomas H., E-mail: thomas.bugge@nih.go [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States)

2014-09-01

We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti

Men's sex-dominance inhibition: do men automatically refrain from sexually dominant behavior?

Science.gov (United States)

Kiefer, Amy K; Sanchez, Diana T

2007-12-01

Men receive conflicting messages about their sexual roles in heterosexual relationships. Men are socialized to initiate and direct sexual activities with women; yet societal norms also proscribe the sexual domination and coercion of women. The authors test these competing hypotheses by assessing whether men inhibit the link between sex and dominance. In Studies 1a and b, using a subliminal priming procedure embedded in a lexical decision task, the authors demonstrate that men automatically suppress the concept of dominance following exposure to subliminal sex primes relative to neutral primes. In Studies 2 and 3, the authors show that men who are less likely to perceive sexual assertiveness as necessary, to refrain from dominant sexual behavior, and who do not invest in masculine gender ideals are more likely to inhibit dominant thoughts following sex primes. Implications for theories of automatic cognitive networks and gender-based sexual roles are discussed.

1H NMR metabolomics of earthworm exposure to sub-lethal concentrations of phenanthrene in soil

International Nuclear Information System (INIS)

Brown, Sarah A.E.; McKelvie, Jennifer R.; Simpson, Andre J.; Simpson, Myrna J.

2010-01-01

1 H NMR metabolomics was used to monitor earthworm responses to sub-lethal (50-1500 mg/kg) phenanthrene exposure in soil. Total phenanthrene was analyzed via soxhlet extraction, bioavailable phenanthrene was estimated by hydroxypropyl-β-cyclodextrin (HPCD) and 1-butanol extractions and sorption to soil was assessed by batch equilibration. Bioavailable phenanthrene (HPCD-extracted) comprised ∼65-97% of total phenanthrene added to the soil. Principal component analysis (PCA) showed differences in responses between exposed earthworms and controls after 48 h exposure. The metabolites that varied with exposure included amino acids (isoleucine, alanine and glutamine) and maltose. PLS models indicated that earthworm response is positively correlated to both total phenanthrene concentration and bioavailable (HPCD-extracted) phenanthrene in a freshly spiked, unaged soil. These results show that metabolomics is a powerful, direct technique that may be used to monitor contaminant bioavailability and toxicity of sub-lethal concentrations of contaminants in the environment. These initial findings warrant further metabolomic studies with aged contaminated soils. - 1 H NMR metabolomics is used to directly monitor metabolic responses of Eisenia fetida after 48 h of exposure to sub-lethal concentrations of phenanthrene in soil.

Total well dominated trees

DEFF Research Database (Denmark)

Finbow, Arthur; Frendrup, Allan; Vestergaard, Preben D.

cardinality then G is a total well dominated graph. In this paper we study composition and decomposition of total well dominated trees. By a reversible process we prove that any total well dominated tree can both be reduced to and constructed from a family of three small trees....

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

Real or symbolic domination: New revision of La Domination masculine

Directory of Open Access Journals (Sweden)

Tassadit Yacine

2017-07-01

Full Text Available This paper does a rereading of Pierre Bourdieu’s Masculine Domination (1998, from the context in which it was developed. Thus, we rely on the work carried out during the 50s in Algeria (Sociologie de l'Algérie, 1958, Esquisse d'une théorie de la pratique, 1972 and Le Sens pratique, 1980 and later in France, to show that Masculine Domination was not born spontaneously, but as a result of a long decantation enriched by field experiences and the theoretical advances of the author’s concepts. If it is true that the situation of the women described in Sociologie de l'Algérie is the result of empirical research, it is less so for Masculine Domination, whose analysis retakes the concepts forged by the social anthropologist, such as habitus and symbolic domination. In this way, this article proposes a rereading of this work through the analysis of the work that preceded it in the field.

When Suicide Kills: An Empirical Analysis of the Lethality of Suicide Terrorism

Directory of Open Access Journals (Sweden)

Burcu Pinar Alakoc

2017-12-01

Full Text Available Why are some suicide terrorist attacks deadlier than others? Suicide bombers, unlike stationary bombs, are self-guided human weapons; they can deliver and detonate explosives at a specific time and place with precision. Coding and analyzing new data on over four hundred suicide terrorist incidents from all around the world between 1998 and 2015, this paper argues that the number of fatalities resulting from suicide attacks is a function of strategic choices made by the perpetrators, such as where to attack and whom to target. Results of this analysis show that suicide attacks that seize targets of opportunity are the most lethal. Specifically, suicide attacks that target civilians in enclosed and easily accessible places, and that are undertaken by multiple perpetrators result in the highest numbers of fatalities. Understanding these strategic tactical attributes of suicide terrorism is fundamental to devising effective counterterrorism strategies that aim at hardening soft targets and minimizing the lethal impact of these attacks.

Points of Influence for Lethal Means Counseling and Safe Gun Storage Practices.

Science.gov (United States)

Runyan, Carol W; Brooks-Russell, Ashley; Betz, Marian E

2018-06-07

Counseling about reducing access to lethal means of suicide, especially firearms, is a recommended practice in emergency departments (EDs) but does not occur routinely. Understanding influencers of decisions makers in health care (ED nurse leaders, mental health providers) and temporary firearm storage (law enforcement and gun retailers) could enhance practice. We surveyed these 4 groups in the 8-state region of the Mountain West. For ED nurse leaders (n = 190), hospital legal, risk management, and quality improvement representatives, and the ED nursing director were most often cited as influential, whereas mental health providers (n = 67) cited their own team. Law enforcement officials (n = 448) identified the overall community and leaders of mental health or general health organizations as influential. Firearm retailers (n = 95) cited local law enforcement and national firearm organizations. Advocacy from influential groups may encourage efforts to provide lethal means counseling and temporary off-site storage of firearms for suicide prevention.

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

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)

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.

Late Wisconsinan Glacial Geomorphology of the Kent Interlobate Complex, Ohio, USA

Directory of Open Access Journals (Sweden)

João Bessa Santos

2012-06-01

Full Text Available The northern sector of the Kent Interlobate Complex, created by twomajor ice lobes of the Laurentide Ice Sheet during late Wisconsinan times, dominates the glacial landscape of northeast Ohio. The geomorphology of this impressive complex reveals the presence of large hummocks, kettle lakes and substantial esker chains. The esker chains,usually smaller than 1.3 km long, run parallel to the interlobate complex geographic orientation of northeast-southwest. Gravel pits present on large hummocks display bedded and sorted sedimentary units of gravel, sand and gravel and climbing ripple laminated sand with folds, which demonstrate that the northern sector of the interlobate complex is primarily a glaciofluvial feature. Topping these hummocks is a massive clast-supported diamicton interpreted to be a debris flow. These geomorphic and sedimentary characteristics seem to indicate that hummocks present in the interlobate area are in fact kames and that the entire northern sector of the interlobate complex is a product of late Wisconsinan time transgressive ice stagnation that occurred between two major ice lobes.

The Genetics of Hybrid Male Sterility Between the Allopatric Species Pair Drosophila persimilis and D. pseudoobscura bogotana: Dominant Sterility Alleles in Collinear Autosomal Regions

OpenAIRE

Chang, Audrey S.; Noor, Mohamed A. F.

2007-01-01

F1 hybrid male sterility is thought to result from interactions between loci on the X chromosome and dominant-acting loci on the autosomes. While X-linked loci that contribute to hybrid male sterility have been precisely localized in many animal taxa, their dominant autosomal interactors have been more difficult to localize precisely and/or have been shown to be of relatively smaller effect. Here, we identified and mapped at least four dominant autosomal factors contributing to hybrid male st...

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

Late Pleistocene sequence architecture on the geostrophic current-dominated southwest margin of the Ulleung Basin, East Sea

Science.gov (United States)

Choi, Dong-Lim; Shin, Dong-Hyeok; Kum, Byung-Cheol; Jang, Seok; Cho, Jin-Hyung; Jou, Hyeong-Tae; Jang, Nam-Do

2018-06-01

High-resolution multichannel seismic data were collected to identify depositional sequences on the southwestern shelf of the Ulleung Basin, where a unidirectional ocean current is dominant at water depths exceeding 130 m. Four aggradational stratigraphic sequences with a 100,000-year cycle were recognized since marine isotope stage (MIS) 10. These sequences consist only of lowstand systems tracts (LSTs) and falling-stage systems tracts (FSSTs). Prograding wedge-shaped deposits are present in the LSTs near the shelf break. Oblique progradational clinoforms of forced regressive deposits are present in the FSSTs on the outer continental shelf. Each FSST has non-uniform forced regressional stratal geometries, reflecting that the origins of sediments in each depositional sequence changed when sea level was falling. Slump deposits are characteristically developed in the upper layer of the FSSTs, and this was used as evidence to distinguish the sequence boundaries. The subsidence rates around the shelf break reached as much as 0.6 mm/year since MIS 10, which contributed to the well-preserved depositional sequence. During the Quaternary sea-level change, the water depth in the Korea Strait declined and the intensity of the Tsushima Current flowing near the bottom of the inner continental shelf increased. This resulted in greater erosion of sediments that were delivered to the outer continental shelf, which was the main cause of sediment deposition on the deep, low-angled outer shelf. Therefore, a depositional sequence formation model that consists of only FSSTs and LSTs, excluding highstand systems tracts (HSTs) and transgressive systems tracts (TSTs), best explains the depositional sequence beneath this shelf margin dominated by a geostrophic current.

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

Brazilian Credit Union Member Groups: Borrower-dominated, Saver-dominated or Neutral Behavior?

Directory of Open Access Journals (Sweden)

Valéria Gama Fully Bressan

2013-01-01

Full Text Available Theoretical models concerning Credit Unions (CUs suggest that the type of CU domination determines the way it allocates the monetary value it generates. A borrower- (saver- dominated CU benefits borrower (saver members at the expenses of saver (borrower members, and a neutral CU equally benefits its member groups.This paper applies direct measure of monetary benefits to each member group (Patin & McNiel, 1991a to testfor the existence of dominated behavior in Brazilian CUs, and is the first to apply panel data regressions to identify the determinants of CUs behavior. We use a unique panel data with 40,664 observations taken from 533 CUs affiliated with the largest Brazilian cooperative network. Results indicate Brazilian CUs are dominated by borrowers, but behave close to neutrality. Panel regression estimates show that common or multiple bond type,size and overdue loans of a CU have no effect on its behavior, the greater the total amount of loans over social capital and adjusted equity over total assets are the more likely a CU is borrower dominated, and the greater the age and current operational expenses over total asset of a CU are the more likely a CU is saver dominated.

Evidence of the Zn vacancy acting as the dominant acceptor in n-type ZnO.

Science.gov (United States)

Tuomisto, F; Ranki, V; Saarinen, K; Look, D C

2003-11-14

We have used positron annihilation spectroscopy to determine the nature and the concentrations of the open volume defects in as-grown and electron irradiated (E(el)=2 MeV, fluence 6 x 10(17) cm(-2)) ZnO samples. The Zn vacancies are identified at concentrations of [V(Zn)] approximately 2 x 10(15) cm(-3) in the as-grown material and [V(Zn)] approximately 2 x 10(16) cm(-3) in the irradiated ZnO. These concentrations are in very good agreement with the total acceptor density determined by temperature dependent Hall experiments. Thus, the Zn vacancies are dominant acceptors in both as-grown and irradiated ZnO.

Evidence of the Zn vacancy acting as the dominant acceptor in n-type ZnO

International Nuclear Information System (INIS)

Tuomisto, F.; Ranki, V.; Saarinen, K.; Look, D.C.

2003-01-01

We have used positron annihilation spectroscopy to determine the nature and the concentrations of the open volume defects in as-grown and electron irradiated (E el =2 MeV, fluence 6x10 17 cm -2 ) ZnO samples. The Zn vacancies are identified at concentrations of [V Zn ]≅2x10 15 cm -3 in the as-grown material and [V Zn ]≅2x10 16 cm -3 in the irradiated ZnO. These concentrations are in very good agreement with the total acceptor density determined by temperature dependent Hall experiments. Thus, the Zn vacancies are dominant acceptors in both as-grown and irradiated ZnO

Lethal Means Counseling for Parents of Youth Seeking Emergency Care for Suicidality

Directory of Open Access Journals (Sweden)

Carol W. Runyan, MPH, PhD

2016-01-01

Full Text Available Introduction: A youth’s emergency department (ED visit for suicidal behaviors or ideation provides an opportunity to counsel families about securing medications and firearms (i.e., lethal means counseling. Methods: In this quality improvement project drawing on the Counseling on Access to Lethal Means (CALM model, we trained 16 psychiatric emergency clinicians to provide lethal means counseling with parents of patients under age 18 receiving care for suicidality and discharged home from a large children’s hospital. Through chart reviews and follow-up interviews of parents who received the counseling, we examined what parents recalled, their reactions to the counseling session, and actions taken after discharge. Results: Between March and July 2014, staff counseled 209 of the 236 (89% parents of eligible patients. We conducted follow-up interviews with 114 parents, or 55% of those receiving the intervention; 48% of those eligible. Parents had favorable impressions of the counseling and good recall of the main messages. Among the parents contacted at follow up, 76% reported all medications in the home were locked as compared to fewer than 10% at the time of the visit. All who had indicated there were guns in the home at the time of the visit reported at follow up that all were currently locked, compared to 67% reporting this at the time of the visit. Conclusion: Though a small project in just one hospital, our findings demonstrate the feasibility of adding a counseling protocol to the discharge process within a pediatric psychiatric emergency service. Our positive findings suggest that further study, including a randomized control trial in more facilities, is warranted.

Speaker-sensitive emotion recognition via ranking: Studies on acted and spontaneous speech☆

Science.gov (United States)

Cao, Houwei; Verma, Ragini; Nenkova, Ani

2015-01-01

We introduce a ranking approach for emotion recognition which naturally incorporates information about the general expressivity of speakers. We demonstrate that our approach leads to substantial gains in accuracy compared to conventional approaches. We train ranking SVMs for individual emotions, treating the data from each speaker as a separate query, and combine the predictions from all rankers to perform multi-class prediction. The ranking method provides two natural benefits. It captures speaker specific information even in speaker-independent training/testing conditions. It also incorporates the intuition that each utterance can express a mix of possible emotion and that considering the degree to which each emotion is expressed can be productively exploited to identify the dominant emotion. We compare the performance of the rankers and their combination to standard SVM classification approaches on two publicly available datasets of acted emotional speech, Berlin and LDC, as well as on spontaneous emotional data from the FAU Aibo dataset. On acted data, ranking approaches exhibit significantly better performance compared to SVM classification both in distinguishing a specific emotion from all others and in multi-class prediction. On the spontaneous data, which contains mostly neutral utterances with a relatively small portion of less intense emotional utterances, ranking-based classifiers again achieve much higher precision in identifying emotional utterances than conventional SVM classifiers. In addition, we discuss the complementarity of conventional SVM and ranking-based classifiers. On all three datasets we find dramatically higher accuracy for the test items on whose prediction the two methods agree compared to the accuracy of individual methods. Furthermore on the spontaneous data the ranking and standard classification are complementary and we obtain marked improvement when we combine the two classifiers by late-stage fusion.

hERG trafficking inhibition in drug-induced lethal cardiac arrhythmia.

Science.gov (United States)

Nogawa, Hisashi; Kawai, Tomoyuki

2014-10-15

Acquired long QT syndrome induced by non-cardiovascular drugs can cause lethal cardiac arrhythmia called torsades de points and is a significant problem in drug development. The prolongation of QT interval and cardiac action potential duration are mainly due to reduced physiological function of the rapidly activating voltage-dependent potassium channels encoded by human ether-a-go-go-related gene (hERG). Structurally diverse groups of drugs are known to directly inhibit hERG channel conductance. Therefore, the ability of acute hERG inhibition is routinely assessed at the preclinical stages in pharmaceutical testing. Recent findings indicated that chronic treatment with various drugs not only inhibits hERG channels but also decreases hERG channel expression in the plasma membrane of cardiomyocytes, which has become another concern in safety pharmacology. The mechanisms involve the disruption of hERG trafficking to the surface membrane or the acceleration of hERG protein degradation. From this perspective, we present a brief overview of mechanisms of drug-induced trafficking inhibition and pathological regulation. Understanding of drug-induced hERG trafficking inhibition may provide new strategies for predicting drug-induced QT prolongation and lethal cardiac arrhythmia in pharmaceutical drug development. Copyright © 2014 Elsevier B.V. All rights reserved.

Lateness to School Remediation Game

Science.gov (United States)

Ugwuegbulam, Charles N.; Ibrahim, Haj. Naheed

2015-01-01

Primary and secondary school in Nigeria encourage punctuality to school yet a good number of the learners came late to school. This is especially true in the case of day students. Learners who come late to school are usually punished in one way or the other yet the lateness to school phenomenon still persist. Lateness to school behaviour affects…

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...

Perfect secure domination in graphs

Directory of Open Access Journals (Sweden)

S.V. Divya Rashmi

2017-07-01

Full Text Available Let $G=(V,E$ be a graph. A subset $S$ of $V$ is a dominating set of $G$ if every vertex in $Vsetminus  S$ is adjacent to a vertex in $S.$ A dominating set $S$ is called a secure dominating set if for each $vin Vsetminus S$ there exists $uin S$ such that $v$ is adjacent to $u$ and $S_1=(Ssetminus{u}cup {v}$ is a dominating set. If further the vertex $uin S$ is unique, then $S$ is called a perfect secure dominating set. The minimum cardinality of a perfect secure dominating set of $G$ is called the perfect  secure domination number of $G$ and is denoted by $gamma_{ps}(G.$ In this paper we initiate a study of this parameter and present several basic results.

Trace fossils and sedimentary facies from a Late Cambrian‐Early Ordovician tide‐dominated shelf (Santa Rosita Formation, northwest Argentina): Implications for ichnofacies models of shallow marine successions

Science.gov (United States)

Mángano, M. Gabriela; Buatois, Luis A.; Aceñolaza, Guillermo F.

1996-01-01

The Santa Rosita Formation is one the most widely distributed lower Paleozoic units of northwest Argentina. At the Quebrada del Salto Alto section, east of Purmamarca, Jujuy Province, it is represented by four sedimentary facies: thick‐bedded planar cross‐stratified quartzose sandstones (A), thin‐bedded planar cross‐stratified quartzose sandstones and mudstones (B), wave‐rippled sandstones and bioturbated mudstones (C), and black and greenish gray shales (D). Paleocurrent data, sandstone architecture, and sedimentary structures from faciès A and B indicate bipolar/bimodal paleoflows, suggesting the action of tidal currents. The succession is interpreted as that of a tide‐dominated shelf, with only secondary influence of wave processes. Trace fossils are restricted to facies B and C.The Cruziana ichnocoenosis is preserved on the soles of thin‐bedded planar cross‐stratified quartzose sandstones (faciès B). This ichnocoenosis consists of Conostichus isp., Cruziana omanica, C. semiplicata, C. cf. tortworthi, Cruziana isp. Helminthopsis abeli, Monomorphichnus bilinearis, M. multilineatus, Palaeophycus tubularis, Rusophycus carbonarias, R. latus, and R. isp. The occurrence of Cruziana semiplicata, C. omanica, C. cf. tortworthi, and Rusophycus latus supports a Late Cambrian‐Tremadoc age. Slabbing of Cruziana shows complex interactions between biologic and sedimentologic processes, and suggests a predominance of exhumed traces, washed out and recast by tractive sand deposition. Sandstone soles are densely packed with biogenic structures and exhibit distinctive clusters of Rusophycus isp. that most likely represent trilobite nesting burrows. The Cruziana ichnocoenosis records the resident fauna of a protected, lower intertidal to subtidal interbar setting.The Skolithos ichnocoenosis is represented by high to low density vertical burrows of Skolithos linearis, which extend downwards to the quartzose sandstone soles of faciès B and