Visual abnormalities associated with enhanced optic nerve myelination.

PubMed

Yu, Minzhong; Narayanan, S Priyadarshini; Wang, Feng; Morse, Emily; Macklin, Wendy B; Peachey, Neal S

2011-02-16

Expression of the constitutively active serine/threonine kinase Akt in oligodendrocytes results in enhanced myelination in the CNS. Here, we have examined the effects of this Akt overexpression on optic nerve structure and on optic nerve function, assessed using the visual evoked potential (VEP). Transgenic mice have been generated with the Plp promoter driving expression of a modified form of Akt, in which aspartic acids are substituted for Thr308 and Ser473. These Plp-Akt-DD (Akt-DD) mice, and littermate controls, were studied at different ages. Optic nerves were examined anatomically at 2 and 6 months of age. At 2 months of age, optic nerves were substantially thicker in Akt-DD mice, reflecting an increase in myelination of optic nerve axons. By electron microscopy, myelin thickness was increased in Akt-DD optic nerve, with extended paranodal domains having excess paranodal loops, and the density of nodes of Ranvier was reduced, relative to control mice. We recorded VEPs in response to strobe flash ganzfeld stimuli presented after overnight dark- and light-adapted conditions at ages ranging from 1 to 10 months. It was possible to record a clear VEP from Akt-DD mice at all ages examined. At 1 month of age, VEP implicit times were somewhat shorter in Akt-DD transgenic mice than in control animals. Beyond 6months of age, VEP latencies were consistently delayed in Akt-DD transgenic mice. These abnormalities did not reflect an alteration in retinal function as there were no significant differences between ERGs obtained from control or Akt-DD transgenic mice. In young mice, the somewhat faster responses may reflect improved transmission due to increased myelination of optic nerve axons. In older mice, where the Akt-DD optic nerve is markedly thicker than control, it is remarkable that optic nerves continue to function. Copyright © 2010 Elsevier B.V. All rights reserved.

Susceptibility to deltamethrin of wild and domestic populations of Triatoma infestans of the Gran Chaco and the Inter-Andean Valleys of Bolivia.

PubMed

Gomez, Marinely Bustamante; D'Avila, Grasielle Caldas Pessoa; Orellana, Ana Lineth Garcia; Cortez, Mirko Rojas; Rosa, Aline Cristine Luiz; Noireau, François; Diotaiuti, Liléia Gonçalves

2014-11-14

The persistence of Triatoma infestans and the continuous transmission of Trypanosoma cruzi in the Inter-Andean Valleys and in the Gran Chaco of Bolivia are of great significance. Coincidentally, it is in these regions the reach of the vector control strategies is limited, and reports of T. infestans resistance to insecticides, including in wild populations, have been issued. This study aims to characterize the susceptibility to deltamethrin of wild and domestic populations of T. infestans from Bolivia, in order to better understand the extent of this relevant problem. Susceptibility to deltamethrin was assessed in nine, wild and domestic, populations of T. infestans from the Gran Chaco and the Inter-Andean Valleys of Bolivia. Serial dilutions of deltamethrin in acetone (0.2 μL) were topically applied in first instar nymphs (F1, five days old, fasting, weight 1.2 ± 0.2 mg). Dose response results were analyzed with PROBIT version 2, determining the lethal doses, slope and resistance ratios (RR). Qualitative tests were also performed. Three wild T. infestans dark morph samples of Chaco from the Santa Cruz Department were susceptible to deltamethrin with RR50 of <2, and 100% mortality to the diagnostic dose (DD); however, two domestic populations from the same region were less susceptible than the susceptibility reference lineage (RR50 of 4.21 and 5.04 respectively and 93% DD). The domestic population of Villa Montes from the Chaco of the Tarija Department presented high levels of resistance (RR50 of 129.12 and 0% DD). Moreover, the domestic populations from the Valleys of the Cochabamba Department presented resistance (RR50 of 8.49 and 62% DD), the wild populations were less susceptible than SRL and T. infestans dark morph populations (RR50 < 5). The elimination of T. infestans with pyrethroid insecticides in Brazil, Uruguay, Chile, and its drastic reduction in large parts of Paraguay and Argentina, clearly indicates that pyrethroid resistance was very uncommon in non-Andean regions. The pyrethroid susceptibility of non-Andean T. infestans dark morph population, and the resistance towards it, of Andean T. infestans wild and domestic populations, indicates that the Andean populations from Bolivia are less susceptible.

Light exposure influences the diurnal oscillation of gut microbiota in mice.

PubMed

Wu, Guangyan; Tang, Wenli; He, Yan; Hu, Jingjuan; Gong, Shenhai; He, Zhanke; Wei, Guoquan; Lv, Liyi; Jiang, Yong; Zhou, Hongwei; Chen, Peng

2018-06-18

The gut microbiota exhibit diurnal compositional and functional oscillations that influence the host homeostasis. However, the upstream factors that affect the microbial oscillations remain elusive. Here, we focused on the potential impact of light exposure, the main factor that affects the host circadian oscillation, on the diurnal oscillations of intestinal microflora to explore the upstream factor that governs the fluctuations of the gut microbes. The gut microbiota of the mice that were underwent regular light/dark (LD) cycles exhibited a robust rhythm at both compositional and functional level, in all parts of the intestine. Comparably, constant darkness (Dark-Dark, DD) led to the loss of the rhythmic oscillations in almost all parts of the intestine. Additionally, the abundance of Clostridia in DD conditions was dramatically enhanced in the small intestine. Our data indicated light exposure is the upstream factor that governs the regular diurnal fluctuations of gut microbiota in vivo. Copyright © 2018 Elsevier Inc. All rights reserved.

Circadian intraocular pressure rhythms in athletic horses under different lighting regime.

PubMed

Bertolucci, Cristiano; Giudice, Elisabetta; Fazio, Francesco; Piccione, Giuseppe

2009-02-01

The present study was undertaken to investigate the existence of intraocular pressure (IOP) rhythms in athletic thoroughbred horses maintained under a 24 h cycle of light and darkness (LD) or under constant light (LL) or constant dark (DD) conditions. We identified an IOP circadian rhythm that is entrained to the 24 h LD cycle. IOP was low during the dark phase and high during the light phase, with a peak at the end of the light phase (ZT10). The circadian rhythm of IOP persisted in DD (with a peak at CT9.5), demonstrating an endogenous component in IOP rhythm. As previously shown in other mammalian species, horse IOP circadian rhythmicity was abolished in LL. Because tonometry is performed in horses for the diagnosis of ophthalmologic diseases, such as glaucoma or anterior uveitis, the daily variation in IOP must be taken into account in clinical practice to properly time tests and to interpret clinical findings.

Sleep-like behavior and 24-h rhythm disruption in the Tc1 mouse model of Down syndrome.

PubMed

Heise, I; Fisher, S P; Banks, G T; Wells, S; Peirson, S N; Foster, R G; Nolan, P M

2015-02-01

Down syndrome is a common disorder associated with intellectual disability in humans. Among a variety of severe health problems, patients with Down syndrome exhibit disrupted sleep and abnormal 24-h rest/activity patterns. The transchromosomic mouse model of Down syndrome, Tc1, is a trans-species mouse model for Down syndrome, carrying most of human chromosome 21 in addition to the normal complement of mouse chromosomes and expresses many of the phenotypes characteristic of Down syndrome. To date, however, sleep and circadian rhythms have not been characterized in Tc1 mice. Using both circadian wheel-running analysis and video-based sleep scoring, we showed that these mice exhibited fragmented patterns of sleep-like behaviour during the light phase of a 12:12-h light/dark (LD) cycle with an extended period of continuous wakefulness at the beginning of the dark phase. Moreover, an acute light pulse during night-time was less effective in inducing sleep-like behaviour in Tc1 animals than in wild-type controls. In wheel-running analysis, free running in constant light (LL) or constant darkness (DD) showed no changes in the circadian period of Tc1 animals although they did express subtle behavioural differences including a reduction in total distance travelled on the wheel and differences in the acrophase of activity in LD and in DD. Our data confirm that Tc1 mice express sleep-related phenotypes that are comparable with those seen in Down syndrome patients with moderate disruptions in rest/activity patterns and hyperactive episodes, while circadian period under constant lighting conditions is essentially unaffected. © 2015 Medical Research Council. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

Melatonin secretion in the Mashona mole-rat, Cryptomys darlingi--influence of light on rhythmicity.

PubMed

Vasicek, Caroline A; Malpaux, Benoît; Fleming, Patricia A; Bennett, Nigel C

2005-01-17

The hormone melatonin is synthesised and secreted from the pineal gland in darkness and triggers the daily and seasonal timing of various physiological and behavioural processes. The Mashona mole-rat, Cryptomys darlingi, lives in subterranean burrows that are completely sealed and is therefore rarely, if ever, exposed to light under natural conditions. Hence, this species is of particular interest for studies on rhythms of melatonin secretion. We investigated how plasma melatonin concentrations of the Mashona mole-rat responded to exposure to a long-term standard photoperiod of 12 h light, 12 h dark (12:12 LD), constant light (LL) and constant dark (DD). In addition, we examined whether plasma melatonin concentration was coupled to locomotor activity. Mashona mole-rats displayed rhythms of plasma melatonin concentration that appeared entrained to the standard LD photoperiod, suggesting that the mole-rat is capable of perceiving and entraining to this photic zeitgeber. Furthermore, under chronic constant lighting conditions (DD, LL), circadian rhythms in plasma melatonin concentration were observed, suggesting the possible existence of an endogenous rhythm. Light suppressed melatonin secretion, but constant light did not abolish the rhythm of plasma melatonin concentration. Between active and non-active animals, no difference in plasma melatonin concentration was found for any of the sequential photoperiods (LD1 DD, LD2, LL), tentatively suggesting that the rhythm of melatonin secretion is uncoupled from that of locomotor activity.

Light deprivation damages monoamine neurons and produces a depressive behavioral phenotype in rats

PubMed Central

Gonzalez, M. M. C.; Aston-Jones, G.

2008-01-01

Light is an important environmental factor for regulation of mood. There is a high frequency of seasonal affective disorder in high latitudes where light exposure is limited, and bright light therapy is a successful antidepressant treatment. We recently showed that rats kept for 6 weeks in constant darkness (DD) have anatomical and behavioral features similar to depressed patients, including dysregulation of circadian sleep–waking rhythms and impairment of the noradrenergic (NA)-locus coeruleus (LC) system. Here, we analyzed the cell viability of neural systems related to the pathophysiology of depression after DD, including NA-LC, serotoninergic-raphe nuclei and dopaminergic-ventral tegmental area neurons, and evaluated the depressive behavioral profile of light-deprived rats. We found increased apoptosis in the three aminergic systems analyzed when compared with animals maintained for 6 weeks in 12:12 light-dark conditions. The most apoptosis was observed in NA-LC neurons, associated with a significant decrease in the number of cortical NA boutons. Behaviorally, DD induced a depression-like condition as measured by increased immobility in a forced swim test (FST). DD did not appear to be stressful (no effect on adrenal or body weights) but may have sensitized responses to subsequent stressors (increased fecal number during the FST). We also found that the antidepressant desipramine decreases these neural and behavioral effects of light deprivation. These findings indicate that DD induces neural damage in monoamine brain systems and this damage is associated with a depressive behavioral phenotype. Our results suggest a mechanism whereby prolonged limited light intensity could negatively impact mood. PMID:18347342

An Examination of the Dirty Dozen Measure of Psychopathy: A Cautionary Tale about the Costs of Brief Measures

ERIC Educational Resources Information Center

Miller, Joshua D.; Few, Lauren R.; Seibert, L. Alana; Watts, Ashley; Zeichner, Amos; Lynam, Donald R.

2012-01-01

Given substantial interest in the traits conceived of as part of the "Dark Triad"--psychopathy, narcissism, and Machiavellianism--assessment of these traits is of great importance. The Dirty Dozen (DD; Jonason & Webster, 2010) is a brief measure of the Dark Triad constructs that uses 4 items to assess each of these constructs. In the present…

[Light pollution increases morbidity and mortality rate from different causes in male rats].

PubMed

Bukalev, A V; Vinogradova, I A; Zabezhinskiĭ, M A; Semenchenko, A V; Anisimov, V N

2012-01-01

The influence of different light regimes (constant light--LL; constant darkness--DD; standard light regime--LD, 12 hours light 12 hours darkness; natural lightening of the North-West of Russia--NL) on the dynamics of life's morbidity rate, spontaneous tumorigenesis and frequency of some kinds of non-tumor pathology revealed at the post-mortem examination of male rats was studied. It was found out that the maintenance of animals at LL and NL conditions led to the increase of the number of infectious diseases, substantially faster development of spontaneous tumors and the increase of non-tumor diseases in comparison with the animals kept at LD (standard light) regime. Light deprivation (DD) led to substantial reduction of development of new growth, of non-tumor and infectious diseases in comparison with the similar parameters in standard light regime.

Care of adults with developmental disabilities: Effects of a continuing education course for primary care providers.

PubMed

Balogh, Robert; Wood, Jessica; Lunsky, Yona; Isaacs, Barry; Ouellette-Kuntz, Hélène; Sullivan, William

2015-07-01

To evaluate the effects of an interdisciplinary, guideline-based continuing education course on measures related to the care of adults with developmental disabilities (DD). Before-and-after study with a control group. Ontario. Forty-seven primary care providers (physicians, registered nurses, and nurse practitioners). Participants either only received reference material about primary care of people with DD (control group) or participated in a continuing education course on primary care of people with DD in addition to receiving the reference material (intervention group). Participants reported on 5 key measures related to care of adults with DD: frequency of using guidelines, frequency of performing periodic health examinations, frequency of assessing patients who present with behaviour changes, level of comfort while caring for adults with DD, and knowledge of primary care related to adults with DD. Over time, the intervention group showed significant increases in 4 of the 5 key measures of care compared with the control group: the frequency of guideline use (P < .001), frequency of assessment of patients' behaviour change (P = .03), comfort level in caring for people with DD (P = .01), and knowledge of primary care related to adults with DD (P = .01). A continuing education course on primary care of adults with DD is a useful interdisciplinary model to train health professionals who provide primary care services to these patients.

Behavioral and molecular analyses suggest that circadian output is disrupted by disconnected mutants in D. melanogaster.

PubMed Central

Hardin, P E; Hall, J C; Rosbash, M

1992-01-01

Mutations in the disconnected (disco) gene act to disrupt neural cell patterning in the Drosophila visual system. These mutations also affect adult locomotor activity rhythms, as disco flies are arrhythmic under conditions of constant darkness (DD). To determine the state of the circadian pacemaker in disco mutants, we constructed with pers double mutants (a short period allele of the period gene) and assayed their behavioral rhythms in light-dark cycles (LD), and their biochemical rhythms of period gene expression under both LD and DD conditions. The results demonstrate that disco flies are rhythmic, indicating that they have an active circadian pacemaker that can be entrained by light. They also suggest that disco mutants block or interfere with elements of the circadian system located between the central pacemaker and its outputs that mediate overt rhythms. Images PMID:1740100

Suppressing the Neurospora crassa circadian clock while maintaining light responsiveness in continuous stirred tank reactors

PubMed Central

Cockrell, Allison L.; Pirlo, Russell K.; Babson, David M.; Cusick, Kathleen D.; Soto, Carissa M.; Petersen, Emily R.; Davis, Miah J.; Hong, Christian I.; Lee, Kwangwon; Fitzgerald, Lisa A.; Biffinger, Justin C.

2015-01-01

Neurospora crassa has been utilized as a model organism for studying biological, regulatory, and circadian rhythms for over 50 years. These circadian cycles are driven at the molecular level by gene transcription events to prepare for environmental changes. N. crassa is typically found on woody biomass and is commonly studied on agar-containing medium which mimics its natural environment. We report a novel method for disrupting circadian gene transcription while maintaining light responsiveness in N. crassa when held in a steady metabolic state using bioreactors. The arrhythmic transcription of core circadian genes and downstream clock-controlled genes was observed in constant darkness (DD) as determined by reverse transcription-quantitative PCR (RT-qPCR). Nearly all core circadian clock genes were up-regulated upon exposure to light during 11hr light/dark cycle experiments under identical conditions. Our results demonstrate that the natural timing of the robust circadian clock in N. crassa can be disrupted in the dark when maintained in a consistent metabolic state. Thus, these data lead to a path for the production of industrial scale enzymes in the model system, N. crassa, by removing the endogenous negative feedback regulation by the circadian oscillator. PMID:26031221

Time management in a co-housed social rodent species (Arvicanthis niloticus).

PubMed

Castillo-Ruiz, Alexandra; Indic, Premananda; Schwartz, William J

2018-01-19

Sociality has beneficial effects on fitness, and timing the activities of animals may be critical. Social cues could influence daily rhythmic activities via direct effects on the circadian clock or on processes that bypass it (masking), but these possibilities remain incompletely addressed. We investigated the effects of social cues on the circadian body temperature (Tb) rhythms in pairs of co-housed and isolated grass rats, Arvicanthis niloticus (a social species), in constant darkness (DD). Cohabitation did not induce synchronization of circadian Tb rhythms. However, socio-sexual history did affect circadian properties: accelerating the clock in sexually experienced males and females in DD and advancing rhythm phase in the females in a light-dark cycle. To address whether synchronization occurs at an ultradian scale, we analyzed Tb and activity rhythms in pairs of co-housed sisters or couples in DD. Regardless of pair type, co-housing doubled the percentage of time individuals were simultaneously active without increasing individual activity levels, suggesting that activity bouts were synchronized by redistribution over 24 h. Together, our laboratory findings show that social cues affect individual "time allocation" budgets via mechanisms at multiple levels of biological organization. We speculate that in natural settings these effects could be adaptive, especially for group-living animals.

Image analysis of single event transient effects on charge coupled devices irradiated by protons

NASA Astrophysics Data System (ADS)

Wang, Zujun; Xue, Yuanyuan; Liu, Jing; He, Baoping; Yao, Zhibin; Ma, Wuying

2016-10-01

The experiments of single event transient (SET) effects on charge coupled devices (CCDs) irradiated by protons are presented. The radiation experiments have been carried out at the accelerator protons with the energy of 200 MeV and 60 MeV.The incident angles of the protons are at 30°and 90° to the plane of the CCDs to obtain the images induced by the perpendicularity and incline incident angles. The experimental results show that the typical characteristics of the SET effects on a CCD induced by protons are the generation of a large number of dark signal spikes (hot pixels) which are randomly distributed in the "pepper" images. The characteristics of SET effects are investigated by observing the same imaging area at different time during proton radiation to verify the transient effects. The experiment results also show that the number of dark signal spikes increases with increasing integration time during proton radiation. The CCDs were tested at on-line and off-line to distinguish the radiation damage induced by the SET effects or DD effects. The mechanisms of the dark signal spike generation induced by the SET effects and the DD effects are demonstrated respectively.

[Effects of a short-term diet of precooked corn flour on the vaginal cycle, in rats placed in various conditions of environmental illumination].

PubMed

Lopez de Onate, R; Giammanco, S; Carollo, F; Ernandes, M; Paderni, M A

1989-03-01

The aim of this research is to study the effects of a diet almost devoid of tryptophan, which is given by a feeding with precooked yellow corn meal (corn mush), on the alterations of the estrous cycle of animals in several conditions of environmental lighting. Indeed, it is known that cerebral serotonin influences the releasing of LH and consequently the ovulation. The different types of environmental lighting are: 1) Natural (alternating Day-Night = L/D). 2) Continuous dark (D/D). 3) Continuous light by sodium steams (L/L sodium). 4) Continuous light by fluorescent neon tubes (L/L neon). The muricide behaviour is studied by comparison rat-mouse. The feeding with precooked yellow corn meal (diet lacking of tryptophan) unchains in the 100% of the observations the CEA (Constant Estrous Anovulatory), and significantly shrinks the estral cycle in the female Wistar Rat in several conditions of environmental lighting.

Postnatal light alters hypothalamic-pituitary-adrenal axis function and induces a depressive-like phenotype in adult mice.

PubMed

Coleman, Georgia; Gigg, John; Canal, Maria Mercè

2016-11-01

The postnatal light environment that a mouse experiences during the critical first three postnatal weeks has long-term effects on both its circadian rhythm output and clock gene expression. Furthermore, data from our lab suggest that postnatal light may also impact the hypothalamic-pituitary-adrenal (HPA) axis, which is a key regulator of stress. To test the effect of postnatal light exposure on adult stress responses and circadian rhythmicity, we raised mice under either 24-h light-dark cycles (LD), constant light (LL) or constant dark (DD) during the first three postnatal weeks. After weaning we then exposed all animals to LD cycles (basal conditions), followed by LL (stressed conditions) environments. We examined brain neuropeptide and glucocorticoid receptor (GR) expression, plasma corticosterone concentration rhythm and body temperature rhythm, together with depression- and anxiety-related behaviour. Results showed that LL- and DD-raised mice exhibited decreased GR expression in the hippocampus, increased plasma corticosterone concentration at the onset of the dark phase and a depressive phenotype when exposed to LD cycles later in life. Furthermore, LL-raised mice showed increased corticotrophin-releasing hormone mRNA expression in the paraventricular nucleus of the hypothalamus. When exposed to LL as adults, LL-raised mice showed a significant circadian rhythm of plasma corticosterone concentration, together with a shorter period and stronger circadian rhythm of body temperature compared to DD-raised mice. Taken together, these data suggest that altered postnatal light environments have long-term effects on the HPA axis and the circadian system, which can lead to altered stress responses and a depressive phenotype in adulthood. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Differential regulation of mammalian Period genes and circadian rhythmicity by cryptochromes 1 and 2

PubMed Central

Vitaterna, Martha Hotz; Selby, Christopher P.; Todo, Takeshi; Niwa, Hitoshi; Thompson, Carol; Fruechte, Ethan M.; Hitomi, Kenichi; Thresher, Randy J.; Ishikawa, Tomoko; Miyazaki, Junichi; Takahashi, Joseph S.; Sancar, Aziz

1999-01-01

Cryptochromes regulate the circadian clock in animals and plants. Humans and mice have two cryptochrome (Cry) genes. A previous study showed that mice lacking the Cry2 gene had reduced sensitivity to acute light induction of the circadian gene mPer1 in the suprachiasmatic nucleus (SCN) and had an intrinsic period 1 hr longer than normal. In this study, Cry1−/− and Cry1−/−Cry2−/− mice were generated and their circadian clocks were analyzed at behavioral and molecular levels. Behaviorally, the Cry1−/− mice had a circadian period 1 hr shorter than wild type and the Cry1−/−Cry2−/− mice were arrhythmic in constant darkness (DD). Biochemically, acute light induction of mPer1 mRNA in the SCN was blunted in Cry1−/− and abolished in Cry1−/−Cry2−/− mice. In contrast, the acute light induction of mPer2 in the SCN was intact in Cry1−/− and Cry1−/−Cry2−/− animals. Importantly, in double mutants, mPer1 expression was constitutively elevated and no rhythmicity was detected in either 12-hr light/12-hr dark or DD, whereas mPer2 expression appeared rhythmic in 12-hr light/12-hr dark, but nonrhythmic in DD with intermediate levels. These results demonstrate that Cry1 and Cry2 are required for the normal expression of circadian behavioral rhythms, as well as circadian rhythms of mPer1 and mPer2 in the SCN. The differential regulation of mPer1 and mPer2 by light in Cry double mutants reveals a surprising complexity in the role of cryptochromes in mammals. PMID:10518585

Proposed low-energy absolute calibration of nuclear recoils in a dual-phase noble element TPC using D-D neutron scattering kinematics

NASA Astrophysics Data System (ADS)

Verbus, J. R.; Rhyne, C. A.; Malling, D. C.; Genecov, M.; Ghosh, S.; Moskowitz, A. G.; Chan, S.; Chapman, J. J.; de Viveiros, L.; Faham, C. H.; Fiorucci, S.; Huang, D. Q.; Pangilinan, M.; Taylor, W. C.; Gaitskell, R. J.

2017-04-01

We propose a new technique for the calibration of nuclear recoils in large noble element dual-phase time projection chambers used to search for WIMP dark matter in the local galactic halo. This technique provides an in situ measurement of the low-energy nuclear recoil response of the target media using the measured scattering angle between multiple neutron interactions within the detector volume. The low-energy reach and reduced systematics of this calibration have particular significance for the low-mass WIMP sensitivity of several leading dark matter experiments. Multiple strategies for improving this calibration technique are discussed, including the creation of a new type of quasi-monoenergetic neutron source with a minimum possible peak energy of 272 keV. We report results from a time-of-flight-based measurement of the neutron energy spectrum produced by an Adelphi Technology, Inc. DD108 neutron generator, confirming its suitability for the proposed nuclear recoil calibration.

Strong resetting of the mammalian clock by constant light followed by constant darkness

PubMed Central

Chen, Rongmin; Seo, Dong-oh; Bell, Elijah; von Gall, Charlotte; Lee, Choogon

2008-01-01

The mammalian molecular circadian clock in the suprachiasmatic nuclei (SCN) regulates locomotor activity rhythms as well as clocks in peripheral tissues (Reppert and Weaver, 2002; Ko and Takahashi, 2006). Constant light (LL) can induce behavioral and physiological arrhythmicity, by desynchronizing clock cells in the SCN (Ohta et al., 2005). We examined how the disordered clock cells resynchronize by probing the molecular clock and measuring behavior in mice transferred from LL to constant darkness (DD). The circadian locomotor activity rhythms disrupted in LL become robustly rhythmic again from the beginning of DD, and the starting phase of the rhythm in DD is specific, not random, suggesting that the desynchronized clock cells are quickly reset in an unconventional manner by the L:D transition. By measuring mPERIOD protein rhythms, we showed that the SCN and peripheral tissue clocks quickly become rhythmic again in phase with the behavioral rhythms. We propose that this resetting mechanism may be different from conventional phase shifting, which involves light-induction of Period genes (Albrecht et al., 1997; Shearman et al., 1997; Shigeyoshi et al., 1997). Using our functional insights, we could shift the circadian phase of locomotor activity rhythms by 12 hours using a 15-hour LL treatment: essentially producing phase reversal by a single light pulse, a feat that has not been reported previously in wild-type mice and that has potential clinical utility. PMID:19005049

Extremely high energy hadron and gamma-ray families(3). Core structure of the halo of superfamily

NASA Technical Reports Server (NTRS)

Yamashita, S.; Ohsawa, A.; Chinellato, J. A.; Shibuya, E. H.

1985-01-01

The study of the core structure seen in the halo of Mini-Andromeda 3(M.A.3), which was observed in the Chacaltaya emulsion chamber, is presented. On the assumption that lateral distribution of darkness of the core is exponential type, i.e., D=D0exp(-R/r0), subtraction of D from halo darkness is performed until the cores are gone. The same quantity on cores obtained by this way are summarized. The analysis is preliminary and is going to be developed.

Circadian rhythms in heart rate, motility, and body temperature of wild-type C57 and eNOS knock-out mice under light-dark, free-run, and after time zone transition.

PubMed

Arraj, M; Lemmer, B

2006-01-01

The nitric oxide (NO) system is involved in the regulation of the cardiovascular system in controlling central and peripheral vascular tone and cardiac functions. It was the aim of this study to investigate in wild-type C57BL/6 and endothelial nitric oxide synthase (eNOS) knock-out mice (eNOS-/-) the contribution of NO on the circadian rhythms in heart rate (HR), motility (motor activity [MA]), and body temperature (BT) under various environmental conditions. Experiments were performed in 12:12 h of a light:dark cycle (LD), under free-run in total darkness (DD), and after a phase delay shift of the LD cycle by -6 h (i.e., under simulation of a westward time zone transition). All parameters were monitored by radiotelemetry in freely moving mice. In LD, no significant differences in the rhythms of HR and MA were observed between the two strains of mice. BT, however, was significantly lower during the light phase in eNOS-/- mice, resulting in a significantly greater amplitude. The period of the free-running rhythm in DD was slightly shorter for all variables, though not significant. In general, rhythmicity was greater in eNOS-/- than in C57 mice both in LD and DD. After a delay shift of the LD cycle, HR and BT were resynchronized to the new LD schedule within 5-6 days, and resynchronization of MA occurred within 2-3 days. The results in telemetrically instrumented mice show that complete knock-out of the endothelial NO system--though expressed in the suprachiasmatic nuclei and in peripheral tissues--did not affect the circadian organization of heart rate and motility. The circadian regulation of the body temperature was slightly affected in eNOS-/- mice.

Steep discounting of delayed monetary and food rewards in obesity: a meta-analysis.

PubMed

Amlung, M; Petker, T; Jackson, J; Balodis, I; MacKillop, J

2016-08-01

An increasing number of studies have investigated delay discounting (DD) in relation to obesity, but with mixed findings. This meta-analysis synthesized the literature on the relationship between monetary and food DD and obesity, with three objectives: (1) to characterize the relationship between DD and obesity in both case-control comparisons and continuous designs; (2) to examine potential moderators, including case-control v. continuous design, money v. food rewards, sample sex distribution, and sample age (18 years); and (3) to evaluate publication bias. From 134 candidate articles, 39 independent investigations yielded 29 case-control and 30 continuous comparisons (total n = 10 278). Random-effects meta-analysis was conducted using Cohen's d as the effect size. Publication bias was evaluated using fail-safe N, Begg-Mazumdar and Egger tests, meta-regression of publication year and effect size, and imputation of missing studies. The primary analysis revealed a medium effect size across studies that was highly statistically significant (d = 0.43, p < 10-14). None of the moderators examined yielded statistically significant differences, although notably larger effect sizes were found for studies with case-control designs, food rewards and child/adolescent samples. Limited evidence of publication bias was present, although the Begg-Mazumdar test and meta-regression suggested a slightly diminishing effect size over time. Steep DD of food and money appears to be a robust feature of obesity that is relatively consistent across the DD assessment methodologies and study designs examined. These findings are discussed in the context of research on DD in drug addiction, the neural bases of DD in obesity, and potential clinical applications.

Circadian disruption induced by light-at-night accelerates aging and promotes tumorigenesis in rats

PubMed Central

Vinogradova, Irina A.; Anisimov, Vladimir N.; Bukalev, Andrey V.; Semenchenko, Anna V.; Zabezhinski, Mark A.

2009-01-01

We evaluated the effect of various light/dark regimens on the survival, life span and tumorigenesis in rats. Two hundred eight male and 203 females LIO rats were subdivided into 4 groups and kept at various light/dark regimens: standard 12:12 light/dark (LD); natural lighting of the North-West of Russia (NL); constant light (LL), and constant darkness (DD) since the age of 25 days until natural death. We found that exposure to NL and LL regimens accelerated development of metabolic syndrome and spontaneous tumorigenesis, shortened life span both in male and females rats as compared to the standard LD regimen. We conclude that circadian disruption induced by light-at-night accelerates aging and promotes tumorigenesis in rats. This observation supports the conclusion of the International Agency Research on Cancer that shift-work that involves circadian disruption is probably carcinogenic to humans. PMID:20157558

A randomized trial to evaluate the effect of a trace mineral premix on the incidence of active digital dermatitis lesions in cattle.

PubMed

Gomez, A; Bernardoni, N; Rieman, J; Dusick, A; Hartshorn, R; Read, D H; Socha, M T; Cook, N B; Döpfer, D

2014-10-01

A balanced, parallel-group, single-blinded randomized efficacy study divided into 2 periods was conducted to evaluate the effect of a premix containing higher than typically recommended levels of organic trace minerals and iodine (HOTMI) in reducing the incidence of active digital dermatitis (DD) lesions acquired naturally and induced by an experimental infection challenge model. For the natural exposure phase of the study, 120 healthy Holstein steers 5 to 7 mo of age without signs of hoof disease were randomized into 2 groups of 60 animals. The control group was fed a standard trace mineral supplement and the treatment group was fed the HOTMI premix, both for a period of 60 d. On d 60, 15 steers free of macroscopic DD lesions were randomly selected from each group for the challenge phase and transported to an experimental facility, where they were acclimated and then challenged within a DD infection model. The same diet group allocation was maintained during the 60 d of the challenge phase. The primary outcome measured was the development of an active DD lesion greater than 20mm in diameter across its largest dimension. No lesions were identified during the natural exposure phase. During the challenge phase, 55% (11/20) and 30% (6/20) of feet were diagnosed with an active DD lesion in the control and treatment groups, respectively. Diagnosis of DD was confirmed by histopathologic demonstration of invasive Treponema spp. within eroded and hyperplastic epidermis and ulcerated papillary dermis. All DD confirmed lesions had dark-field microscopic features compatible with DD and were positive for Treponema spp. by PCR. As a secondary outcome, the average DD lesion size observed in all feet was also evaluated. Overall mean (standard deviation) lesion size was 17.1 (2.36) mm and 11.1 (3.33) mm for the control and treatment groups, respectively, with this difference being driven by acute DD lesions >20mm. A trend existed for the HOTMI premix to reduce the total DD infection rate and the average size of the experimentally induced lesions. Further research is needed to validate the effect of this intervention strategy in the field and to generate prevention and control measures aimed at optimizing claw health based on nutritional programs. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

77 FR 71174 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-29

...-0039. Title; Associated Form; and OMB Number: Continued Health Care Benefit Program, DD Form 2837; OMB... order to be eligible for health care coverage under CHCBP, an individual must first enroll in CHCBP. DD...

Developmental Dyscalculia and Automatic Magnitudes Processing: Investigating Interference Effects between Area and Perimeter.

PubMed

Eidlin-Levy, Hili; Rubinsten, Orly

2017-01-01

The relationship between numbers and other magnitudes has been extensively investigated in the scientific literature. Here, the objectives were to examine whether two continuous magnitudes, area and perimeter, are automatically processed and whether adults with developmental dyscalculia (DD) are deficient in their ability to automatically process one or both of these magnitudes. Fifty-seven students (30 with DD and 27 with typical development) performed a novel Stroop-like task requiring estimation of one aspect (area or perimeter) while ignoring the other. In order to track possible changes in automaticity due to practice, we measured performance after initial and continuous exposure to stimuli. Similar to previous findings, current results show a significant group × congruency interaction, evident beyond exposure level or magnitude type. That is, the DD group systematically showed larger Stroop effects. However, analysis of each exposure period showed that during initial exposure to stimuli the DD group showed larger Stroop effects in the perimeter and not in the area task. In contrast, during continuous exposure to stimuli no triple interaction was evident. It is concluded that both magnitudes are automatically processed. Nevertheless, individuals with DD are deficient in inhibiting irrelevant magnitude information in general and, specifically, struggle to inhibit salient area information after initial exposure to a perimeter comparison task. Accordingly, the findings support the assumption that DD involves a deficiency in multiple cognitive components, which include domain-specific and domain-general cognitive functions.

Developmental Dyscalculia and Automatic Magnitudes Processing: Investigating Interference Effects between Area and Perimeter

PubMed Central

Eidlin-Levy, Hili; Rubinsten, Orly

2017-01-01

The relationship between numbers and other magnitudes has been extensively investigated in the scientific literature. Here, the objectives were to examine whether two continuous magnitudes, area and perimeter, are automatically processed and whether adults with developmental dyscalculia (DD) are deficient in their ability to automatically process one or both of these magnitudes. Fifty-seven students (30 with DD and 27 with typical development) performed a novel Stroop-like task requiring estimation of one aspect (area or perimeter) while ignoring the other. In order to track possible changes in automaticity due to practice, we measured performance after initial and continuous exposure to stimuli. Similar to previous findings, current results show a significant group × congruency interaction, evident beyond exposure level or magnitude type. That is, the DD group systematically showed larger Stroop effects. However, analysis of each exposure period showed that during initial exposure to stimuli the DD group showed larger Stroop effects in the perimeter and not in the area task. In contrast, during continuous exposure to stimuli no triple interaction was evident. It is concluded that both magnitudes are automatically processed. Nevertheless, individuals with DD are deficient in inhibiting irrelevant magnitude information in general and, specifically, struggle to inhibit salient area information after initial exposure to a perimeter comparison task. Accordingly, the findings support the assumption that DD involves a deficiency in multiple cognitive components, which include domain-specific and domain-general cognitive functions. PMID:29312066

32 CFR Appendix E to Part 286 - DD Form 2564, “Annual Report Freedom of Information Act”

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 2 2013-07-01 2013-07-01 false DD Form 2564, âAnnual Report Freedom of Information Actâ E Appendix E to Part 286 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) FREEDOM OF INFORMATION ACT PROGRAM DOD FREEDOM OF INFORMATION ACT PROGRAM...

32 CFR Appendix E to Part 286 - DD Form 2564, “Annual Report Freedom of Information Act”

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 2 2012-07-01 2012-07-01 false DD Form 2564, âAnnual Report Freedom of Information Actâ E Appendix E to Part 286 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) FREEDOM OF INFORMATION ACT PROGRAM DOD FREEDOM OF INFORMATION ACT PROGRAM...

32 CFR Appendix E to Part 286 - DD Form 2564, “Annual Report Freedom of Information Act”

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 2 2010-07-01 2010-07-01 false DD Form 2564, âAnnual Report Freedom of Information Actâ E Appendix E to Part 286 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) FREEDOM OF INFORMATION ACT PROGRAM DOD FREEDOM OF INFORMATION ACT PROGRAM...

32 CFR Appendix E to Part 286 - DD Form 2564, “Annual Report Freedom of Information Act”

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 2 2011-07-01 2011-07-01 false DD Form 2564, âAnnual Report Freedom of Information Actâ E Appendix E to Part 286 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) FREEDOM OF INFORMATION ACT PROGRAM DOD FREEDOM OF INFORMATION ACT PROGRAM...

32 CFR Appendix E to Part 286 - DD Form 2564, “Annual Report Freedom of Information Act”

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 2 2014-07-01 2014-07-01 false DD Form 2564, âAnnual Report Freedom of Information Actâ E Appendix E to Part 286 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) FREEDOM OF INFORMATION ACT PROGRAM DOD FREEDOM OF INFORMATION ACT PROGRAM...

76 FR 82003 - Submission for Review: DD 1918 Establishment Information Form, DD 1919 Wage Data Collection Form...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-29

... 1919 Wage Data Collection Form, DD 1919C Wage Data Collection Continuation Form AGENCY: U.S. Office of Personnel Management. ACTION: 30-Day Notice and request for comments. SUMMARY: The U.S. Office of Personnel... the Paperwork Reduction Act of 1995 (Pub. L. 104-13, 44 U.S.C. chapter 35) as amended by the Clinger...

Circadian Clocks for All Meal-Times: Anticipation of 2 Daily Meals in Rats

PubMed Central

Mistlberger, Ralph E.; Kent, Brianne A.; Chan, Sofina; Patton, Danica F.; Weinberg, Alexander; Parfyonov, Maksim

2012-01-01

Anticipation of a daily meal in rats has been conceptualized as a rest-activity rhythm driven by a food-entrained circadian oscillator separate from the pacemaker generating light-dark (LD) entrained rhythms. Rats can also anticipate two daily mealtimes, but whether this involves independently entrained oscillators, one ‘continuously consulted’ clock, cue-dependent non-circadian interval timing or a combination of processes, is unclear. Rats received two daily meals, beginning 3-h (meal 1) and 13-h (meal 2) after lights-on (LD 14∶10). Anticipatory wheel running began 68±8 min prior to meal 1 and 101±9 min prior to meal 2 but neither the duration nor the variability of anticipation bout lengths exhibited the scalar property, a hallmark of interval timing. Meal omission tests in LD and constant dark (DD) did not alter the timing of either bout of anticipation, and anticipation of meal 2 was not altered by a 3-h advance of meal 1. Food anticipatory running in this 2-meal protocol thus does not exhibit properties of interval timing despite the availability of external time cues in LD. Across all days, the two bouts of anticipation were uncorrelated, a result more consistent with two independently entrained oscillators than a single consulted clock. Similar results were obtained for meals scheduled 3-h and 10-h after lights-on, and for a food-bin measure of anticipation. Most rats that showed weak or no anticipation to one or both meals exhibited elevated activity at mealtime during 1 or 2 day food deprivation tests in DD, suggesting covert operation of circadian timing in the absence of anticipatory behavior. A control experiment confirmed that daytime feeding did not shift LD-entrained rhythms, ruling out displaced nocturnal activity as an explanation for daytime activity. The results favor a multiple oscillator basis for 2-meal anticipatory rhythms and provide no evidence for involvement of cue-dependent interval timing. PMID:22355393

Atomistic tight-binding theory of excitonic splitting energies in CdX(X = Se, S and Te)/ZnS core/shell nanocrystals

NASA Astrophysics Data System (ADS)

Sukkabot, Worasak; Pinsook, Udomsilp

2017-01-01

Using the atomistic tight-binding theory (TB) and a configuration interaction description (CI), we numerically compute the excitonic splitting of CdX(X = Se, S and Te)/ZnS core/shell nanocrystals with the objective to explain how types of the core materials and growth shell thickness can provide the detailed manipulation of the dark-dark (DD), dark-bright (DB) and bright-bright (BB) excitonic splitting, beneficial for the active application of quantum information. To analyze the splitting of the excitonic states, the optical band gaps, ground-state wave function overlaps and atomistic electron-hole interactions tend to be numerically demonstrated. Based on the atomistic computations, the single-particle and excitonic gaps are mainly reduced with the increasing ZnS shell thickness owing to the quantum confinement. In the range of the higher to lower energies, the order of the single-particle gaps is CdSe/ZnS, CdS/ZnS and CdTe/ZnS core/shell nanocrystals, while one of the excitonic gaps is CdS/ZnS, CdSe/ZnS and CdTe/ZnS core/shell nanocrystals because of the atomistic electron-hole interaction. The strongest electron-hole interactions are mainly observed in CdSe/ZnS core/shell nanocrystals. In addition, the computational results underline that the energies of the dark-dark (DD), dark-bright (DB) and bright-bright (BB) excitonic splitting are generally reduced with the increasing ZnS growth shell thickness as described by the trend of the electron-hole exchange interaction. The high-to-low splitting of the excitonic states is demonstrated in CdSe/ZnS, CdTe/ZnS and CdS/ZnS core/shell nanocrystals because of the fashion in the electron-hole exchange interaction and overlaps of the electron-hole wave functions. As the resulting calculations, it is expected that CdS/ZnS core/shell nanocrystals are the best candidates to be the source of entangled photons. Finally, the comprehensive information on the excitonic splitting can enable the use of suitable core/shell nanocrystals for the entangled photons in the application of quantum information.

Light-Regulated Thyroid Hormone Signaling Is Required for Rod Photoreceptor Development in the Mouse Retina.

PubMed

Sawant, Onkar; Horton, Amanda M; Shukla, Meenal; Rayborn, Mary E; Peachey, Neal S; Hollyfield, Joe G; Rao, Sujata

2015-12-01

Ambient light is both a stimulus for visual function and a regulator of photoreceptor physiology. However, it is not known if light can regulate any aspect of photoreceptor development. The purpose of this study was to investigate whether ambient light is required for the development of mouse rod photoreceptors. Newborn mouse pups (C57BL/6) were reared in either cyclic light (LD) or constant dark (DD). Pups were collected at postnatal day (P)5, P10, P17, or P24. We performed retinal morphometric and cell death analysis at P5, P10, and P17. Rhodopsin expression was assessed using immunofluorescence, Western blot, and quantitative RT-PCR analysis. Electroretinograms were performed at P17 and P24. Radioimmunoassay and ELISA were used to follow changes in thyroid hormone levels in the serum and vitreous. In the DD pups, the outer nuclear layer was significantly thinner at P10 and there were higher numbers of apoptotic cells at P5 compared to the LD pups. Rhodopsin expression was lower at P10 and P17 in DD pups. Electroretinogram a-waves were reduced in amplitude at P17 in the DD pups. The DD animals had lower levels of circulating thyroid hormones at P10. Light-mediated changes in thyroid hormones occur as early as P5, as we detected lower levels of total triiodothyronine in the vitreous from the DD animals. Drug-induced developmental hypothyroidism resulted in lower rhodopsin expression at P10. Our data demonstrate that light exposure during postnatal development is required for rod photoreceptor development and that this effect could be mediated by thyroid hormone signaling.

TA-03-0035 Press Building – D&D

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

Hasenack, Marvin Leroy

The Press Building was constructed in 1954 with 15,073 ft 2 of floor space. It was built to house a 5000 ton double action Lake Erie hydraulic press and a uranium casting area. Missions included uranium activities associated with the Nuclear Weapons and Rover Rocket programs. At the end of the Rover program, the building continued to support various uranium materials science projects until the building was placed into a cold and dark status in 2013 and then was demolished in 2017. The building interior, the press, and associated systems were radiological contaminated and disposed of as low level waste.more » The demolition of this building opened up valuable real estate in the TA-3 area for the future construction of an ~11,000 Sq. Ft. Biosafety Level 2 laboratory and office building. This building will support the ongoing Bioscience Division mission at the laboratory.« less

32 CFR Appendix C to Part 286 - DD Form 2086, “Record of Freedom of Information (FOI) Processing Cost”

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 2 2010-07-01 2010-07-01 false DD Form 2086, âRecord of Freedom of Information (FOI) Processing Costâ C Appendix C to Part 286 National Defense Department of Defense (Continued... INFORMATION ACT PROGRAM REGULATION Pt. 286, App. C Appendix C to Part 286—DD Form 2086, “Record of Freedom of...

Effects on development, growth responses and thyroid-hormone systems in eyed-eggs and yolk-sac larvae of Atlantic salmon (Salmo salar) continuously exposed to 3,3',4,4'-tetrachlorobiphenyl (PCB-77).

PubMed

Arukwe, Augustine; Olufsen, Marianne; Cicero, Nicola; Hansen, Marianne D

2014-01-01

Thyroid hormones (triiodothyronine, T3; and thyroxine, T4) play significant roles in development, metamorphosis, metabolism, homeostasis, cellular proliferation, and differentiation, for which the effects are mediated through thyroid hormone receptors (TRα and TRβ). Similarly, the insulin-like growth factor (IGF) is involved in growth and development through regulation of somatic growth. This study was designed to examine the effects of the dioxin-like 3,3',4,4'-tetrachlorobiphenyl (PCB-77) on responses related to growth and thyroid hormone system in eyed eggs and yolk-sac larvae of Atlantic salmon. Salmon eggs were continuously exposed to two waterborne concentrations of PCB-77 (1 or 10 ng/L) over a period of 50 d covering hatching and through yolk-sac absorption stages. Sampling was performed regularly throughout the exposure period and at different time intervals. Gene expression patterns were performed on whole-body homogenate at age 500, 548, 632, 674, and 716 dd (dd: day degrees) using quantitative polymerase chain reaction (PCR). Total T3 (TT3) and total T4 (TT4) were measured using radioimmunoassay (RIA). Data showed that 10 ng PCB-77 increased dioiodinase 2 (Dio2) at 500 dd and both PCB-77 concentrations decreased dio2 expression at 548 dd. PCB-77 elevated cellular TT3 at 500 dd and was lowered at 548 dd only at 10 ng. Otherwise, time-related reduction was not affected by PCB-77 exposure as observed for the rest of the exposure period. For TT4, 1 ng PCB-77 produced a rise at 500 dd, and an apparent concentration decrease at 548 dd, before a total inhibition at 632 dd. The IGF-1 and IGF-1R were variably affected by PCB-77. For IGF-2, PCB-77 produced a concentration-dependent increase at 548 dd, and thereafter an elevation (1 ng) and fall (10 ng) at 632 dd. TRβ mRNA demonstrated PCB-77 related increases during the exposure period, and this effect returned to control levels at 716 dd. For TRα, a rise was noted only after exposure to 10 ng PCB-77 at 500 dd. Overall, the present study demonstrates some possible growth and developmental consequences following exposure to PCB-77 during early life stages of Atlantic salmon.

All genes encoding enzymes participating in melatonin biosynthesis in the chicken pineal gland are transcribed rhythmically.

PubMed

Adamska, I; Marhelava, K; Walkiewicz, D; Kedzierska, U; Markowska, M; Majewski, P M

2016-08-01

Our recent research on the pineal gland of young chickens confirmed that three genes encoding enzymes involved in pineal melatonin biosynthesis, tryptophan hydroxylase 1 (Tph1), arylalkylamine-N-acetyltransferase (Aanat) and acetylserotonin O-methyltransferase (Asmt), are transcribed rhythmically under light:dark (L:D) 12:12 conditions in vivo. Additionally, in the pineal gland of maturing chickens, the dopa decarboxylase (Ddc) gene is transcribed rhythmically at a specific stage of the developmental process. Therefore, the aim of the present study was to verify whether all of these genes are transcribed rhythmically in vivo under constant darkness (D:D) and in pinealocyte cultures under both L:D and D:D. Experiments were performed on chickens maintained under L:D 12:12 conditions. Chickens at 15 days of age were divided into two groups; chickens from the first group remained under the same conditions, whereas those from the second group were kept in darkness. Subsequently, 16-day-old animals were sacrificed every 2 hours over a 24-h period. For the in vitro experiments, 16-day-old chickens were sacrificed at ZT 6, and their pineal glands were isolated. Pineal cultures were maintained for up to two days in L:D conditions. Then, the pinealocyte cultures were divided into two groups: the first remained under L:D conditions, whereas the second was transferred to D:D conditions. Pinealocytes were subsequently collected every 2 hours over a 24-h period. Transcription was evaluated using the RT-qPCR method, and the rhythm percentage was calculated through Cosinor analysis. The mRNA levels of all genes examined were rhythmic under all conditions. Moreover, in silico analysis of the promoters of all of the genes examined revealed the presence of enhancer box sequences in all of the promoters as well as DBP/E4BP4 binding elements in the promoters of Tph1 and Asmt. This suggests that these genes may all be regulated transcriptionally by the molecular clock mechanism and may be considered clock as controlled genes.

The clock gene cycle plays an important role in the circadian clock of the cricket Gryllus bimaculatus.

PubMed

Uryu, Outa; Karpova, Svetlana G; Tomioka, Kenji

2013-07-01

To dissect the molecular oscillatory mechanism of the circadian clock in the cricket Gryllus bimaculatus, we have cloned a cDNA of the clock gene cycle (Gb'cyc) and analyzed its structure and function. Gb'cyc contains four functional domains, i.e. bHLH, PAS-A, PAS-B and BCTR domains, and is expressed rhythmically in light dark cycles, peaking at mid night. The RNA interference (RNAi) of Clock (Gb'Clk) and period (Gb'per) reduced the Gb'cyc mRNA levels and abolished the rhythmic expression, suggesting that the rhythmic expression of Gb'cyc is regulated by a mechanism including Gb'Clk and Gb'per. These features are more similar to those of mammalian orthologue of cyc (Bmal1) than those of Drosophila cyc. A single treatment with double-stranded RNA (dsRNA) of Gb'cyc effectively knocked down the Gb'cyc mRNA level and abolished its rhythmic expression. The cyc RNAi failed to disrupt the locomotor rhythm, but lengthened its free-running period in constant darkness (DD). It is thus likely that Gb'cyc is involved in the circadian clock machinery of the cricket. The cyc RNAi crickets showed a rhythmic expression of Gb'per and timeless (Gb'tim) in the optic lobe in DD, explaining the persistence of the locomotor rhythm. Surprisingly, cyc RNAi revealed a rhythmic expression of Gb'Clk in DD which is otherwise rather constitutively expressed in the optic lobe. These facts suggest that the cricket might have a unique clock oscillatory mechanism in which both Gb'cyc and Gb'Clk are rhythmically controlled and that under abundant expression of Gb'cyc the rhythmic expression of Gb'Clk may be concealed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Twilight and photoperiod affect behavioral entrainment in the house mouse (Mus musculus).

PubMed

Comas, M; Hut, R A

2009-10-01

The effect of twilight transitions on entrainment of C57BL/6JOlaHsd mice (Mus musculus) was studied using light-dark cycles of different photoperiods (6, 12, and 18 h) and twilight transitions of different durations (0, 1, and 2 h). Phase angle differences of the onset, center of gravity, and offset of activity, activity duration (alpha), as well as free-running period (tau) in continuous darkness were analyzed. The main finding was that for all conditions the onset of activity was close to dusk or lights-off except for the short photoperiod with 2 h of twilight where activity onset was on average 5.3 (SEM 1.07) h after lights-off. This finding contrasts with the results of Boulos and Macchi for Syrian hamsters where a 5.9-h earlier activity onset was observed when similar photoperiod and twilight conditions are compared with a rectangular LD cycle. The authors suggest the opposite effects of 2 h of twilight in the 2 species may be related to their different free-running periods under DD conditions following entrainment to short photoperiod with 2-h twilight conditions. Since the authors observed larger variation in phase angle of entrainment in longer twilight conditions, twilight does not necessarily form a stronger zeitgeber.

32 CFR 728.33 - Nonavailability statement (DD 1251).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 5 2012-07-01 2012-07-01 false Nonavailability statement (DD 1251). 728.33 Section 728.33 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL MEDICAL AND DENTAL CARE FOR ELIGIBLE PERSONS AT NAVY MEDICAL DEPARTMENT FACILITIES Retired Members and...

The Epidemiology of Chronic Major Depressive Disorder and Dysthymic Disorder: Results from the National Epidemiologic Survey on Alcohol and Related Conditions

PubMed Central

Blanco, Carlos; Okuda, Mayumi; Markowitz, John C.; Liu, Shang-Min; Grant, Bridget F.; Hasin, Deborah S.

2011-01-01

Objective To examine the prevalence of chronic major depressive disorder (CMDD) and dysthymic disorder (DD), their sociodemographic correlates, patterns of 12-month and lifetime psychiatric comorbidity, lifetime risk factors, psychosocial functioning, and mental health service utilization. Method Face-to-face interviews were conducted in the 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions (n = 43,093). Results The 12-month and lifetime prevalence were greater for CMDD (1.5% and 3.1%) than for DD (0.5% and 0.9%). Individuals with CMDD and DD shared most sociodemographic correlates and lifetime risk factors for MDD. Individuals with CMDD and DD had almost identically high rates of Axis I and Axis II comorbid disorders. However, individuals with CMDD received higher rates of all treatment modalities than individuals with DD. Conclusion Individuals with CMDD and DD share many sociodemographic correlates, comorbidity patterns, risk factors, and course. Individuals with chronic depressive disorders, especially those with DD, continue to face substantial unmet treatment needs. PMID:21190638

Differential Sensitivity to Ethanol-Induced Circadian Rhythm Disruption in Adolescent and Adult Mice

PubMed Central

Ruby, Christina L.; Palmer, Kaitlyn N.; Zhang, Jiawen; Risinger, Megan O.; Butkowski, Melissa A.; Swartzwelder, H. Scott

2016-01-01

Background Growing evidence supports a central role for the circadian system in alcohol use disorders, but few studies have examined this relationship during adolescence. In mammals, circadian rhythms are regulated by the suprachiasmatic nucleus (SCN), a biological clock whose timing is synchronized (reset) to the environment primarily by light (photic) input. Alcohol (ethanol) disrupts circadian timing in part by attenuating photic phase-resetting responses in adult rodents. However, circadian rhythms change throughout life and it is not yet known whether ethanol has similar effects on circadian regulation during adolescence. Methods General circadian locomotor activity was monitored in male C57BL6/J mice beginning in adolescence (P27) or adulthood (P61) in a 12 h light, 12 h dark photocycle for ~2 weeks to establish baseline circadian activity measures. On the day of the experiment, mice received an acute injection of ethanol (1.5 g/kg, i.p.) or equal volume saline 15 min prior to a 30-min light pulse at Zeitgeber Time 14 (2 h into the dark phase), then were released into constant darkness (DD) for ~2 weeks to assess phase-resetting responses. Control mice of each age group received injections but no light pulse prior to DD. Results While adults showed the expected decrease in photic phase-delays induced by acute ethanol, this effect was absent in adolescent mice. Adolescents also showed baseline differences in circadian rhythmicity compared to adults, including advanced photocycle entrainment, larger photic phase-delays, a shorter free-running (endogenous) circadian period, and greater circadian rhythm amplitude. Conclusions Collectively, our results indicate that adolescent mice are less sensitive to the effect of ethanol on circadian photic phase-resetting and that their daily activity rhythms are markedly different than those of adults. PMID:27997028

Is the sex communication of two pyralid moths, Plodia interpunctella and Ephestia kuehniella, under circadian clock regulation?

PubMed

Závodská, Radka; Fexová, Silvie; von Wowern, Germund; Han, Gui-Biao; Dolezel, David; Sauman, Ivo

2012-06-01

Females of the Indian meal moth, Plodia interpunctella, and females of the Mediterranean flour month, Ephestia kuehniella (both Lepidoptera: Pyralidae), exhibit daily rhythms in calling behavior. The peak in P. interpunctella calling occurs at dusk, whereas E. kuehniella calls preferentially at dawn. This behavior turned arrhythmic in P. interpunctella females in constant darkness (DD) and remained arrhythmic in constant light (LL), whereas E. kuehniella females showed a persistent rhythm in DD and suppression of the behavior in LL, indicating regulation by a circadian clock mechanism. The rhythm of male locomotor activity corresponded well with the sexual activity of females, reaching the peak at dusk in P. interpunctella and at dawn in E. kuehniella. An immunohistochemical study of the pheromone biosynthesis activating neuropeptide, corazonin, and pigment dispersing factor revealed distinct sets of neurons in the brain-subesophageal complex and in the neurohemal organs of the 2 species.

Neonatal Alcohol Exposure Permanently Disrupts the Circadian Properties and Photic Entrainment of the Activity Rhythm in Adult Rats

PubMed Central

Allen, Gregg C.; West, James R.; Chen, Wei-Jung A.; Earnest, David J.

2009-01-01

Background Alcohol exposure during the period of rapid brain development produces structural damage in different brain regions, including the suprachiasmatic nucleus (SCN), that may have permanent neurobehavioral consequences. Thus, this study examined the long-term effects of neonatal alcohol exposure on circadian behavioral activity in adult rats. Methods Artificially reared Sprague-Dawley rat pups were exposed to alcohol (EtOH; 4.5 g/kg/day) or isocaloric milk formula (gastrostomy control; GC) on postnatal days 4–9. At 2 months of age, rats from the EtOH, GC, and suckle control (SC) groups were housed individually, and properties of the circadian rhythm in wheel-running behavior were continuously analyzed during exposure to a 12-hr light:12-hr dark photoperiod (LD 12:12) or constant darkness (DD). Results Neonatal alcohol exposure had distinctive effects on the rhythmic properties and quantitative parameters of adult wheel-running behavior. EtOH-treated animals were distinguished by unstable and altered entrainment to LD 12:12 such that their daily onsets of activity were highly variable and occurred at earlier times relative to control animals. In DD, circadian regulation of wheel-running behavior was altered by neonatal alcohol exposure such that the free-running period of the activity rhythm was shorter in EtOH-exposed rats than in control animals. Total amount of daily wheel-running activity in EtOH-treated rats was greater than that observed in the SC group. In addition, the circadian activity patterns of EtOH-exposed rats were fragmented such that the duration of the active phase and the number of activity bouts per day were increased. Conclusions These data indicate that neonatal alcohol exposure produces permanent changes in the circadian regulation of the rat activity rhythm and its entrainment to LD cycles. These long-term alterations in circadian behavior, along with the developmental alcohol-induced changes in SCN endogenous rhythmicity, may have important implications in clinical sleep-wake disturbances observed in neonates, children, and adults exposed to alcohol in utero. PMID:16269914

D-D Neutron Generator Calibrations and Hardware in the LUX-ZEPLIN Dark Matter Search Experiment

NASA Astrophysics Data System (ADS)

Taylor, Will; Lux-Zeplin Collaboration

2016-03-01

The LUX-ZEPLIN (LZ) dark matter search experiment will be a two-phase liquid/gas xenon time projection chamber with 7 tonnes of active liquid xenon (LXe) located at the 4850 ft level of the Sanford Underground Research Facility in Lead, SD. LZ will utilize an in-situ, absolute calibration of nuclear recoils (NR) in LXe using mono-energetic 2.45 MeV neutrons produced by a D-D neutron generator. This technique was used in the LUX detector to measured the NR charge yield in LXe (Qy) to 0.7 keV recoil energy and the NR light yield in LXe (Ly) to recoil energies of 1.1 keV - both of which were the lowest energy measurements achieved in the field. These absolute, ultra-low energy calibrations of the NR signal yields in LXe provide clear measurements of the detector response used for the WIMP search analysis. The improvements made for LZ will include shorter neutron pulse times, multiple neutron conduit configurations, and lower energy neutrons. The upgrades allow for even lower energy measurements of the nuclear recoil response in LXe and an independent measurement of Ly, as well as providing less uncertainty in energy reconstruction. In addition to discussing the physics of the neutron calibrations, I will describe the hardware systems used to implement them.

The transcription factor DBP affects circadian sleep consolidation and rhythmic EEG activity.

PubMed

Franken, P; Lopez-Molina, L; Marcacci, L; Schibler, U; Tafti, M

2000-01-15

Albumin D-binding protein (DBP) is a PAR leucine zipper transcription factor that is expressed according to a robust circadian rhythm in the suprachiasmatic nuclei, harboring the circadian master clock, and in most peripheral tissues. Mice lacking DBP display a shorter circadian period in locomotor activity and are less active. Thus, although DBP is not essential for circadian rhythm generation, it does modulate important clock outputs. We studied the role of DBP in the circadian and homeostatic aspects of sleep regulation by comparing DBP deficient mice (dbp-/-) with their isogenic controls (dbp+/+) under light-dark (LD) and constant-dark (DD) baseline conditions, as well as after sleep loss. Whereas total sleep duration was similar in both genotypes, the amplitude of the circadian modulation of sleep time, as well as the consolidation of sleep episodes, was reduced in dbp-/- under both LD and DD conditions. Quantitative EEG analysis demonstrated a marked reduction in the amplitude of the sleep-wake-dependent changes in slow-wave sleep delta power and an increase in hippocampal theta peak frequency in dbp-/- mice. The sleep deprivation-induced compensatory rebound of EEG delta power was similar in both genotypes. In contrast, the rebound in paradoxical sleep was significant in dbp+/+ mice only. It is concluded that the transcriptional regulatory protein DBP modulates circadian and homeostatic aspects of sleep regulation.

Patterns of activity expressed by juvenile horseshoe crabs.

PubMed

Dubofsky, E A; Simpson, S D; Chabot, Christopher C; Watson, Winsor H

2013-09-01

Adult American horseshoe crabs, Limulus polyphemus, possess endogenous circadian and circatidal clocks controlling visual sensitivity and locomotion, respectively. The goal of this study was to determine the types of activity rhythms expressed by juvenile horseshoe crabs (n = 24) when exposed to a 14:10 light/dark cycle (LD) for 10 days, followed by 10 days of constant darkness (DD). Horseshoe crab activity was recorded with a digital time-lapse video system that used an infrared-sensitive camera so animals could be monitored at night. In LD, 15 animals expressed daily patterns of activity, 6 displayed a circatidal pattern, and the remaining 3 were arrhythmic. Of the 15 animals with daily patterns of locomotion, 7 had a significant preference (P < 0.05) for diurnal activity and 3 for nocturnal activity; the remainder did not express a significant preference for day or night activity. In DD, 13 horseshoe crabs expressed circatidal rhythms and 8 maintained a pattern of about 24 h. Although these results suggest the presence of a circadian clock influencing circatidal patterns of locomotion, these apparent circadian rhythms may actually represent the expression of just one of the two bouts of activity driven by the putative circalunidian clocks that control their tidal rhythms. Overall, these results indicate that, like adults, juvenile horseshoe crabs express both daily and tidal patterns of activity and that at least one, and maybe both, of these patterns is driven by endogenous clocks.

Bovine digital dermatitis: Current concepts from laboratory to farm.

PubMed

Evans, N J; Murray, R D; Carter, S D

2016-05-01

Bovine digital dermatitis (DD) is a severe infectious disease causing lameness in dairy cattle worldwide and is an important ruminant welfare problem that has considerable economic issues. Bovine DD is endemic in many regions worldwide and it is important to understand this major disease so that effective control strategies can be identified. There is substantial evidence that specific treponeme phylotypes play an important causative role in bovine DD. This review considers current research, including DD Treponema spp. investigations, associated DD pathobiology, and current and potential treatment and control options. Epidemiological data, alongside new microbiological data, help delineate important transmission routes and reservoirs of infection that allow effective interventions to be identified. Better on-farm housing hygiene, pasture access, routine footbathing and claw trimming with disinfected equipment need to be implemented to significantly reduce the incidence of DD. There is a paucity of peer reviewed research into both commonly used and novel treatments. In vitro antimicrobial susceptibility studies of DD treponemes and effective treatment of human treponematoses clearly indicate that antibiotics frequently selected for DD treatments are not the most efficacious. Whilst there are understandable concerns over milk withdrawal times in dairy cattle, more needs to be done to identify, license and implement more appropriate antibiotic treatments, since continued overuse of less efficacious antibiotics, applied incorrectly, will lead to increased disease recurrence and transmission. More research is needed into methods of preventing DD that circumvent the use of antibiotics, including vaccination and transmission blocking studies, to reduce or hopefully eradicate DD in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

Selection and characterization of a mutant of feline immunodeficiency virus resistant to 2',3'-dideoxycytidine.

PubMed Central

Medlin, H K; Zhu, Y Q; Remington, K M; Phillips, T R; North, T W

1996-01-01

We have selected and plaque purified a mutant of feline immunodeficiency virus (FIV) that is resistant to 2',3'-dideoxycytidine (ddC). This mutant was selected in cultured cells in the continuous presence of 25 microM ddC. The mutant, designated DCR-5c, was fourfold resistant to ddC, threefold resistant to 2',3'-dideoxyinosine, and more than fourfold resistant to phosphonoformic acid. DCR-5c displayed little or no resistance to (-)-beta-2',3'-dideoxy-3'-thiacytidine, 3'-azido-3'-deoxythymidine, or 9-(2-phosphonylmethoxyethyl) adenine. Reverse transcriptase purified from DCR-5c was less susceptible to inhibition by ddCTP, phosphonoformic acid, ddATP, or azido-dTTP than the wild-type FIV reverse transcriptase. Sequence analysis of DCR-5c revealed a single base change (G to C at nucleotide 2342) in the reverse transcriptase-encoding region of FIV. This mutation results in substitution of His for Asp at codon 3 of FIV reverse transcriptase. The role of this mutation in ddC resistance was confirmed by site-directed mutagenesis. PMID:8849258

Physiological and Biochemical Mechanisms of Lifespan Regulation in Rats Kept Under Various Light Conditions.

PubMed

Khizhkin, Evgeniy A; Ilukha, Victor A; Vinogradova, Irina A; Uzenbaeva, Lyudmila B; Ilyina, Tatiana N; Yunash, Victoria D; Morozov, Artem V; Anisimov, Vladimir N

2017-01-01

The present study was aimed to identify how age-related changes in some physiological and biochemical systems are related to changes in the life span of rats with long-term pineal gland hypo- and hyperfunction induced by constant light and constant darkness, respectively. At the age of 25 days the rats were randomly divided into 3 groups: standard light/dark regimen (LD), constant light (LL) and constant darkness (DD). Age-related Antioxidant System (AOS) changes in liver tissues, alteration of immunoreactivity in blood smears were investigated, pubescence and lifespan of the animals were determined. Modification of the level of melatonin synthesis induced by constant light results in interrelated rearrangements in the functioning of the investigated physiological systems. Elevated activity of the antioxidant system extends the lifespan, while at the same time slowing down pubescence and altering the morpho-functional properties of leukocytes in blood. The absence of light/dark alternation (constant light and constant darkness) affects only those physiological indices that follow the organism's circadian rhythms (Activity of Antioxidant Enzymes (AOE), levels of individual immune system cell types), whereas changes in the parameters not governed by circadian fluctuations (vitamin concentrations, pubescence, and aging) depend on the level of melatonin produced by the pineal gland.

Modelling crystal plasticity by 3D dislocation dynamics and the finite element method: The Discrete-Continuous Model revisited

NASA Astrophysics Data System (ADS)

Vattré, A.; Devincre, B.; Feyel, F.; Gatti, R.; Groh, S.; Jamond, O.; Roos, A.

2014-02-01

A unified model coupling 3D dislocation dynamics (DD) simulations with the finite element (FE) method is revisited. The so-called Discrete-Continuous Model (DCM) aims to predict plastic flow at the (sub-)micron length scale of materials with complex boundary conditions. The evolution of the dislocation microstructure and the short-range dislocation-dislocation interactions are calculated with a DD code. The long-range mechanical fields due to the dislocations are calculated by a FE code, taking into account the boundary conditions. The coupling procedure is based on eigenstrain theory, and the precise manner in which the plastic slip, i.e. the dislocation glide as calculated by the DD code, is transferred to the integration points of the FE mesh is described in full detail. Several test cases are presented, and the DCM is applied to plastic flow in a single-crystal Nickel-based superalloy.

Impaired Statistical Learning in Developmental Dyslexia

PubMed Central

Thiessen, Erik D.; Holt, Lori L.

2015-01-01

Purpose Developmental dyslexia (DD) is commonly thought to arise from phonological impairments. However, an emerging perspective is that a more general procedural learning deficit, not specific to phonological processing, may underlie DD. The current study examined if individuals with DD are capable of extracting statistical regularities across sequences of passively experienced speech and nonspeech sounds. Such statistical learning is believed to be domain-general, to draw upon procedural learning systems, and to relate to language outcomes. Method DD and control groups were familiarized with a continuous stream of syllables or sine-wave tones, the ordering of which was defined by high or low transitional probabilities across adjacent stimulus pairs. Participants subsequently judged two 3-stimulus test items with either high or low statistical coherence as being the most similar to the sounds heard during familiarization. Results As with control participants, the DD group was sensitive to the transitional probability structure of the familiarization materials as evidenced by above-chance performance. However, the performance of participants with DD was significantly poorer than controls across linguistic and nonlinguistic stimuli. In addition, reading-related measures were significantly correlated with statistical learning performance of both speech and nonspeech material. Conclusion Results are discussed in light of procedural learning impairments among participants with DD. PMID:25860795

The Role of Beta-Adrenergic Receptors in the Regulation of Circadian Intraocular Pressure Rhythm in Mice.

PubMed

Tsuchiya, Shunsuke; Higashide, Tomomi; Toida, Kazunori; Sugiyama, Kazuhisa

2017-07-01

To investigate whether the elimination of β1- and β2-adrenergic receptors alters the diurnal intraocular pressure (IOP) rhythm in mice. β1-/β2-adrenergic receptor double-knockout and C57BL/6J mice were anesthetized intraperitoneally, with their IOPs measured via microneedle method. After entrainment to a 12-h light-dark (LD) cycle (light phase 6:00-18:00), IOPs were measured every 3 h from 9:00 to 24:00 (group 1, β1-/β2-adrenergic receptor double-knockout mice, n = 11; C57BL/6J, n = 15). The IOP measurements at 15:00 and 24:00 under a 12-h LD cycle and in the constant darkness (1 day and 8 days after exposure to darkness, respectively) were performed in another group of β1-/β2-adrenergic receptor double-knockout mice (group 2, n = 12). IOP variance throughout the day and mean IOP differences among time points were evaluated using a linear mixed model. β1-/β2-adrenergic receptor double-knockout and C57BL/6J mice showed biphasic IOP curves, low during the light phase and high during the dark phase; the fluctuation was significant (P < 0.001). The peak IOP (18.7 ± 1.4 mmHg) occurred at 24:00 and the trough IOP (13.5 ± 1.5 mmHg) occurred at 15:00 in β1-/β2-adrenergic receptor double-knockout mice group. IOP curves of β1-/β2-adrenergic receptor double-knockout and C57BL/6J were nearly parallel, and the IOPs of β1-/β2-adrenergic receptor double-knockout mice were significantly higher than those of C57BL/6J mice (P < 0.001). Under constant dark (DD) conditions, IOP at 24:00 (18.1 ± 1.5 mmHg) was significantly higher than that at 15:00 (13.3 ± 1.2 mmHg) (P < 0.001). The transition from the LD cycle to DD environment produced no significant change in IOP (P = 0.728). Elimination of both β1- and β2-adrenergic receptors did not disturb the biphasic diurnal IOP rhythm in mice.

Genomic profiling of dedifferentiated liposarcoma compared to matched well-differentiated liposarcoma reveals higher genomic complexity and a common origin

PubMed Central

Beird, Hannah C.; Wu, Chia-Chin; Ingram, Davis R.; Wang, Wei-Lien; Alimohamed, Asrar; Gumbs, Curtis; Little, Latasha; Song, Xingzhi; Feig, Barry W.; Roland, Christina L.; Zhang, Jianhua; Benjamin, Robert S.; Hwu, Patrick; Lazar, Alexander J.; Futreal, P. Andrew; Somaiah, Neeta

2018-01-01

Well-differentiated (WD) liposarcoma is a low-grade mesenchymal tumor with features of mature adipocytes and high propensity for local recurrence. Often, WD patients present with or later progress to a higher-grade nonlipogenic form known as dedifferentiated (DD) liposarcoma. These DD tumors behave more aggressively and can metastasize. Both WD and DD liposarcomas harbor neochromosomes formed from amplifications and rearrangements of Chr 12q that encode oncogenes (MDM2, CDK4, and YEATS2) and adipocytic differentiation factors (HMGA2 and CPM). However, genomic changes associated with progression from WD to DD have not been well-defined. Therefore, we selected patients with matched WD and DD tumors for extensive genomic profiling in order to understand their clonal relationships and to delineate any defining alterations for each entity. Exome and transcriptomic sequencing was performed for 17 patients with both WD and DD diagnoses. Somatic point and copy-number alterations were integrated with transcriptional analyses to determine subtype-associated genomic features and pathways. The results were, on average, that only 8.3% of somatic mutations in WD liposarcoma were shared with their cognate DD component. DD tumors had higher numbers of somatic copy-number losses, amplifications involving Chr 12q, and fusion transcripts than WD tumors. HMGA2 and CPM rearrangements occur more frequently in DD components. The shared somatic mutations indicate a clonal origin for matched WD and DD tumors and show early divergence with ongoing genomic instability due to continual generation and selection of neochromosomes. Stochastic generation and subsequent expression of fusion transcripts from the neochromosome that involve adipogenesis genes such as HMGA2 and CPM may influence the differentiation state of the subsequent tumor. PMID:29610390

Isolation of genes negatively or positively co-expressed with human recombination activating gene 1 (RAG1) by differential display PCR (DD RT-PCR).

PubMed

Verkoczy, L K; Berinstein, N L

1998-10-01

Differential display PCR (DD RT-PCR) has been extensively used for analysis of differential gene expression, but continues to be hampered by technical limitations that impair its effectiveness. In order to isolate novel genes co-expressing with human RAG1, we have developed an effective, multi-tiered screening/purification approach which effectively complements the standard DD RT-PCR methodology. In 'primary' screens, standard DD RT-PCR was used, detecting 22 reproducible differentially expressed amplicons between clonally related cell variants with differential constitutive expression of RAG mRNAs. 'Secondary' screens used differential display (DD) amplicons as probes in low and high stringency northern blotting. Eight of 22 independent DD amplicons detected nine independent differentially expressed transcripts. 'Tertiary' screens used reconfirmed amplicons as probes in northern analysis of multiple RAG-and RAG+sources. Reconfirmed DD amplicons detected six independent RAG co-expressing transcripts. All DD amplicons reconfirmed by northern blot were a heterogeneous mixture of cDNAs, necessitating further purification to isolate single cDNAs prior to subcloning and sequencing. To effectively select the appropriate cDNAs from DD amplicons, we excised and eluted the cDNA(s) directly from regions of prior northern blots in which differentially expressed transcripts were detected. Sequences of six purified cDNA clones specifically detecting RAG co-expressing transcripts included matches to portions of the human RAG2 and BSAP regions and to four novel partial cDNAs (three with homologies to human ESTs). Overall, our results also suggest that even when using clonally related variants from the same cell line in addition to all appropriate internal controls previously reported, further screening and purification steps are still required in order to efficiently and specifically isolate differentially expressed genes by DD RT-PCR.

Egg hatching response to a range of ultraviolet-B (UV-B) radiation doses for four predatory mites and the herbivorous spider mite Tetranychus urticae.

PubMed

Koveos, Dimitrios S; Suzuki, Takeshi; Terzidou, Anastasia; Kokkari, Anastasia; Floros, George; Damos, Petros; Kouloussis, Nikos A

2017-01-01

Egg hatchability of four predatory mites-Phytoseiulus persimilis Athias-Henriot, Iphiseius [Amblyseius] degenerans Berlese, Amblyseius swirskii Athias-Henriot, and Euseius finlandicus Oudemans (Acari: Phytoseiidae)-and the spider mite Tetranychus urticae Koch (Acari: Tetranychidae) was determined under various UV-B doses either in constant darkness (DD) or with simultaneous irradiation using white light. Under UV-B irradiation and DD or simultaneous irradiation with white light, the predator's eggs hatched in significantly lower percentages than in the control non-exposed eggs, which indicates deleterious effects of UV-B on embryonic development. In addition, higher hatchability percentages were observed under UV-B irradiation and DD in eggs of the predatory mites than in eggs of T. urticae. This might be caused by a higher involvement of an antioxidant system, shield effects by pigments or a mere shorter duration of embryonic development in predatory mites than in T. urticae, thus avoiding accumulative effects of UV-B. Although no eggs of T. urticae hatched under UV-B irradiation and DD, variable hatchability percentages were observed under simultaneous irradiation with white light, which suggests the involvement of a photoreactivation system that reduces UV-B damages. Under the same doses with simultaneous irradiation with white light, eggs of T. urticae displayed higher photoreactivation and were more tolerant to UV-B than eggs of the predatory mites. Among predators variation regarding the tolerance to UV-B effects was observed, with eggs of P. persimilis and I. degenerans being more tolerant to UV-B radiation than eggs of A. swirskii and E. finlandicus.

Constant light during lactation programs circadian and metabolic systems.

PubMed

Madahi, Palma-Gómez; Ivan, Osnaya; Adriana, Balderas; Diana, Ortega; Carolina, Escobar

2018-04-24

Exposure to light at night is a disruptive condition for the adult circadian system, leading to arrhythmicity in nocturnal rodents. Circadian disruption is a risk factor for developing physiological and behavioral alterations, including weight gain and metabolic disease. During early stages of development, the circadian system undergoes a critical period of adjustment, and it is especially vulnerable to altered lighting conditions that may program its function, leading to long-term effects. We hypothesized that during lactation a disrupted light-dark cycle due to light at night may disrupt the circadian system and in the long term induce metabolic disorders. Here we explored in pups, short- and long-term effects of constant light (LL) during lactation. In the short term, LL caused a loss of rhythmicity and a reduction in the immunopositive cells of VIP, AVP, and PER1 in the suprachiasmatic nucleus (SCN). In the short term, the affection on the circadian clock in the pups resulted in body weight gain, loss of daily rhythms in general activity, plasma glucose and triglycerides (TG). Importantly, the DD conditions during development also induced altered daily rhythms in general activity and in the SCN. Exposure to LD conditions after lactation did not restore rhythmicity in the SCN, and the number of immunopositve cells to VIP, AVP, and PER1 remained reduced. In the long term, daily rhythmicity in general activity was restored; however, daily rhythms in glucose and TG remained disrupted, and daily mean levels of TG were significantly increased. Present results point out the programming role played by the LD cycle during early development in the function of the circadian system and on metabolism. This study points out the risk represented by exposure to an altered light-dark cycle during early stages of development. AVP: arginine vasopressin peptide; CRY: cryptochrome; DD: constant darkness; DM: dorsomedial; LD: light-dark cycle; LL: constant light; NICUs: neonatal intensive care units; P: postnatal days; PER: period; S.E.M.: standard error of the mean; SCN: suprachiasmatic nucleus; TG: triglycerides; VIP: vasointestinal peptide; VL: ventrolateral; ZT: zeitgeber time.

A tightly-coupled domain-decomposition approach for highly nonlinear stochastic multiphysics systems

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

Taverniers, Søren; Tartakovsky, Daniel M., E-mail: dmt@ucsd.edu

2017-02-01

Multiphysics simulations often involve nonlinear components that are driven by internally generated or externally imposed random fluctuations. When used with a domain-decomposition (DD) algorithm, such components have to be coupled in a way that both accurately propagates the noise between the subdomains and lends itself to a stable and cost-effective temporal integration. We develop a conservative DD approach in which tight coupling is obtained by using a Jacobian-free Newton–Krylov (JfNK) method with a generalized minimum residual iterative linear solver. This strategy is tested on a coupled nonlinear diffusion system forced by a truncated Gaussian noise at the boundary. Enforcement ofmore » path-wise continuity of the state variable and its flux, as opposed to continuity in the mean, at interfaces between subdomains enables the DD algorithm to correctly propagate boundary fluctuations throughout the computational domain. Reliance on a single Newton iteration (explicit coupling), rather than on the fully converged JfNK (implicit) coupling, may increase the solution error by an order of magnitude. Increase in communication frequency between the DD components reduces the explicit coupling's error, but makes it less efficient than the implicit coupling at comparable error levels for all noise strengths considered. Finally, the DD algorithm with the implicit JfNK coupling resolves temporally-correlated fluctuations of the boundary noise when the correlation time of the latter exceeds some multiple of an appropriately defined characteristic diffusion time.« less

The bZIP transcription factor HY5 interacts with the promoter of the monoterpene synthase gene QH6 in modulating its rhythmic expression.

PubMed

Zhou, Fei; Sun, Tian-Hu; Zhao, Lei; Pan, Xi-Wu; Lu, Shan

2015-01-01

The Artemisia annua L. β-pinene synthase QH6 was previously determined to be circadian-regulated at the transcriptional level, showing a rhythmic fluctuation of steady-state transcript abundances. Here we isolated both the genomic sequence and upstream promoter region of QH6. Different regulatory elements, such as G-box (TGACACGTGGCA, -421 bp from the translation initiation site) which might have effects on rhythmic gene expression, were found. Using the yeast one-hybrid and electrophoretic mobility shift assay (EMSA), we confirmed that the bZIP transcription factor HY5 binds to this motif of QH6. Studies with promoter truncations before and after this motif suggested that this G-box was important for the diurnal fluctuation of the transgenic β-glucuronidase gene (GUS) transcript abundance in Arabidopsis thaliana. GUS gene driven by the promoter region immediately after G-box showed an arrhythmic expression in both light/dark (LD) and constant dark (DD) conditions, whereas the control with G-box retained its fluctuation in both LD and DD. We further transformed A. thaliana with the luciferase gene (LUC) driven by an 1400 bp fragment upstream QH6 with its G-box intact or mutated, respectively. The luciferase activity assay showed that a peak in the early morning disappeared in the mutant. Gene expression analysis also demonstrated that the rhythmic expression of LUC was abolished in the hy5-1 mutant.

Drug and alcohol use among patients with schizophrenia and related psychoses: levels and consequences.

PubMed

Margolese, Howard C; Malchy, Leslie; Negrete, Juan Carlos; Tempier, Raymond; Gill, Kathryn

2004-04-01

Patients with schizophrenia and related psychoses frequently use, abuse and become dependent on psychoactive substances. Local surveys indicate differences in both types and patterns of substances used. A cross-sectional survey was conducted to document abuse in 207 successive outpatients presenting to a psychiatric continuing care facility in a large Canadian city. Nicotine, alcohol and cannabis were the most frequently abused substances in the cohort. Excluding nicotine, 44.9% met criteria for lifetime and 14.0% for current abuse/dependence. Cocaine, heroin, hallucinogen, amphetamine, and inhalant use were rarely reported. Patients with current substance abuse/dependence and a psychotic disorder (dual diagnosis, DD) had significantly higher Positive and Negative Symptom Scale (PANSS) positive scores than lifetime-DD or those with a single diagnosis (SD). Significantly more current-DD (69.0%) patients were depressed (HAM-D score > or =12) compared to SD (45.6%). Furthermore, current-DD (27.6%) patients were more likely than SD (4.5%) to be medication non-compliant. Patients with current-DD were more likely to smoke cigarettes (88.9%) compared to those with SD (49.6%) and they had significantly longer histories of cigarette smoking (19.1 for DD vs. 11.5 years for SD). The smoking behavior of the DD population is discussed in terms of enhanced risk for alcohol abuse, as well as effects on antipsychotic blood levels and metabolism.

The effects of feedback lighting on the circadian rhythm of locomotor activity and the reproductive maturation of the male Djungarian hamster (Phodopus sungorus)

NASA Technical Reports Server (NTRS)

Ferraro, J. S.

1988-01-01

The non-parametric model of entrainment suggests that brief pulses of light, delivered between dusk and dawn can simulate the phasing effects of full photoperiods or even constant light (LL). Feedback lighting (LDFB) is a lighting condition where individual animals, otherwise in constant darkness (DD), are exposed to light in response to a monitored behavior. The specific purpose of this type of illumination is to expose the circadian cycle to light only during the subjective night. LDFB has been used to support this hypothesis in several species of nocturnal rodents and one species of diurnal primate by producing similar free-running periods in LDFB as in LL. This lighting condition has also been used to test the hypothesis that exposing the subjective night to even short duration light pulses will maintain reproductive function in long day breeders. In the Syrian hamster (Mesocricetus auratus), however, LDFB is not as photostimulatory as LL despite extensive light exposure during the subjective night. In the experiments presented here, a group of immature male Djungarian hamsters (Phodopus sungorus) were placed in individual light-tight sound attenuated chambers where they had free access to food, water and an activity wheel. The animals were exposed to one of four lighting conditions [DD, LL, LDFB or a neighbor control of feedback lighting (LDFB NC)] for approximately 30 days shortly after weaning. LDFB NC is a lighting condition where a neighbor control hamster receives the identical lighting regime as a paired animal exposing itself to LDFB, yet the neighbor has no control over it. A fifth group was exposed to a light-dark cycle of 16 hours of light and 8 hours of dark (LD16:8). This group was housed in cages in a colony room and did not have access to a running wheel. The free-running periods of the locomotor activity rhythms for hamsters exposed to LDFB and LL were not similar, unlike the results for rats, Syrian hamsters, mice, monkeys and even mature Djungarian hamsters. Immature hamsters exposed to DD and LDFB NC developed more slowly than animals exposed to LL or LD16:8, while hamsters in LDFB developed at an intermediate rate. Thus, it appears that LDFB, although capable of inducing reproductive function in immature Djungarian hamsters, is not as photostimulatory as may have been expected from current photoperiodic models, despite substantial light exposure during the subjective night. Furthermore, this data may suggest that the circadian system of 18-48 day old Djungarian hamsters are still undergoing organizational maturation.

Novel mutation in the human immunodeficiency virus type 1 reverse transcriptase gene that encodes cross-resistance to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine.

PubMed Central

Gu, Z; Gao, Q; Li, X; Parniak, M A; Wainberg, M A

1992-01-01

We have used the technique of in vitro selection to generate variants of human immunodeficiency virus type 1 (HIV-1) that are resistant to 2',3'-dideoxyinosine (ddI) and cross-resistant to 2',3'-dideoxycytidine (ddC). The complete reverse transcriptase (RT)-coding regions, plus portions of flanking sequences, of viruses possessing a ddI-resistant phenotype were cloned and sequenced by polymerase chain reaction (PCR)-based methods. We observed that several of these viruses possessed mutations at amino acid sites 184 (Met-->Val; ATG-->GTG) and 294 (Pro-->Ser; CCA-->TCA). These mutations were introduced in the pol gene of infectious, cloned HXB2-D DNA by site-directed mutagenesis. Viral replication assays confirmed the importance of site 184 with regard to resistance to ddI. The recombinant viruses thus generated displayed more than fivefold-greater resistance to ddI than parental HXB2-D did. Moreover, more than fivefold-greater resistance to ddC was also documented; however, the recombinant viruses continued to be inhibited by zidovudine (AZT). No resistance to ddI, ddC, or AZT was introduced by inclusion of mutation site 294 in the pol gene of HXB2-D. PCR analysis performed on viral samples obtained from patients receiving long-term ddI therapy confirmed the presence of mutation site 184 in five of seven cases tested. In three of these five positive cases, the wild-type codon was also detected, indicating that mixtures of viral quasispecies were apparently present. Viruses possessing a ddI resistance phenotype were isolated from both subjects whose viruses contained only the mutated rather than wild-type codon at position 184 as well as from a third individual, whose viruses appeared to be mostly of the mutated variety. Images PMID:1279198

Longitudinal Brain Development of Numerical Skills in Typically Developing Children and Children with Developmental Dyscalculia.

PubMed

McCaskey, Ursina; von Aster, Michael; Maurer, Urs; Martin, Ernst; O'Gorman Tuura, Ruth; Kucian, Karin

2017-01-01

Developmental dyscalculia (DD) is a learning disability affecting the acquisition of numerical-arithmetical skills. Studies report persistent deficits in number processing and aberrant functional activation of the fronto-parietal numerical network in DD. However, the neural development of numerical abilities has been scarcely investigated. The present paper provides a first attempt to investigate behavioral and neural trajectories of numerical abilities longitudinally in typically developing (TD) and DD children. During a study period of 4 years, 28 children (8-11 years) were evaluated twice by means of neuropsychological tests and a numerical order fMRI paradigm. Over time, TD children improved in numerical abilities and showed a consistent and well-developed fronto-parietal network. In contrast, DD children revealed persistent deficits in number processing and arithmetic. Brain imaging results of the DD group showed an age-related activation increase in parietal regions (intraparietal sulcus), pointing to a delayed development of number processing areas. Besides, an activation increase in frontal areas was observed over time, indicating the use of compensatory mechanisms. In conclusion, results suggest a continuation in neural development of number representation in DD, whereas the neural network for simple ordinal number estimation seems to be stable or show only subtle changes in TD children over time.

Longitudinal Brain Development of Numerical Skills in Typically Developing Children and Children with Developmental Dyscalculia

PubMed Central

McCaskey, Ursina; von Aster, Michael; Maurer, Urs; Martin, Ernst; O'Gorman Tuura, Ruth; Kucian, Karin

2018-01-01

Developmental dyscalculia (DD) is a learning disability affecting the acquisition of numerical-arithmetical skills. Studies report persistent deficits in number processing and aberrant functional activation of the fronto-parietal numerical network in DD. However, the neural development of numerical abilities has been scarcely investigated. The present paper provides a first attempt to investigate behavioral and neural trajectories of numerical abilities longitudinally in typically developing (TD) and DD children. During a study period of 4 years, 28 children (8–11 years) were evaluated twice by means of neuropsychological tests and a numerical order fMRI paradigm. Over time, TD children improved in numerical abilities and showed a consistent and well-developed fronto-parietal network. In contrast, DD children revealed persistent deficits in number processing and arithmetic. Brain imaging results of the DD group showed an age-related activation increase in parietal regions (intraparietal sulcus), pointing to a delayed development of number processing areas. Besides, an activation increase in frontal areas was observed over time, indicating the use of compensatory mechanisms. In conclusion, results suggest a continuation in neural development of number representation in DD, whereas the neural network for simple ordinal number estimation seems to be stable or show only subtle changes in TD children over time. PMID:29354041

Existence of a photoinducible phase for ovarian development and photoperiod-related alteration of clock gene expression in a damselfish.

PubMed

Takeuchi, Yuki; Hada, Noriko; Imamura, Satoshi; Hur, Sung-Pyo; Bouchekioua, Selma; Takemura, Akihiro

2015-10-01

The sapphire devil, Chrysiptera cyanea, is a reef-associated damselfish and their ovarian development can be induced by a long photoperiod. In this study, we demonstrated the existence of a photoinducible phase for the photoperiodic ovarian development in the sapphire devil. Induction of ovarian development under night-interruption light schedules and Nanda-Hamner cycles revealed that the photoinducible phase appeared in a circadian manner between ZT12 and ZT13. To characterize the effect of photoperiod on clock gene expression in the brain of this species, we determined the expression levels of the sdPer1, sdPer2, sdCry1, and sdCry2 clock genes under constant light and dark conditions (LL and DD) and photoperiodic (short and long photoperiods). The expression of sdPer1 exhibited clear circadian oscillation under both LL and DD conditions, while sdPer2 and sdCry1 expression levels were lower under DD than under LL conditions and sdCry2 expression was lower under LL than under DD conditions. These results suggest a key role for sdPer1 in circadian clock cycling and that sdPer2, sdCry1, and sdCry2 are light-responsive clock genes in the sapphire devil. After 1 week under a long photoperiod, we observed photoperiod-related changes in sdPer1, sdPer2, and sdCry2 expression, but not in sdCry1 expression. These results suggest that the expression patterns of some clock genes exhibit seasonal variation according to seasonal changes in day length and that such seasonal alteration of clock gene expression may contribute to seasonal recognition by the sapphire devil. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of Metal-Organic Frameworks for the Removal of Toxic Industrial Chemicals

DTIC Science & Technology

2008-06-01

ECBC ID# 085-07), more commonly known as Cu-BTC or HKUST - 1 , has the empirical formula CuO 4C 6H 2. The sample is a dark blue/purple powder. 2.2...0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing...FORM TO THE ABOVE ADDRESS. 1 . REPORT DATE (DD-MM-YYYY) 2. REPORT TYPE 3. DATES COVERED (From - To) XX-06-2008 Final Nov 2007 - Jan 2008 4. TITLE AND

Improving time-delay cosmography with spatially resolved kinematics

NASA Astrophysics Data System (ADS)

Shajib, Anowar J.; Treu, Tommaso; Agnello, Adriano

2018-01-01

Strongly gravitational lensed quasars can be used to measure the so-called time-delay distance DΔt, and thus the Hubble constant H0 and other cosmological parameters. Stellar kinematics of the deflector galaxy play an essential role in this measurement by: (i) helping break the mass-sheet degeneracy; (ii) determining in principle the angular diameter distance Dd to the deflector and thus further improving the cosmological constraints. In this paper we simulate observations of lensed quasars with integral field spectrographs and show that spatially resolved kinematics of the deflector enables further progress by helping break the mass-anisotropy degeneracy. Furthermore, we use our simulations to obtain realistic error estimates with current/upcoming instruments like OSIRIS on Keck and NIRSPEC on the James Webb Space Telescope for both distances (typically ∼6 per cent on DΔt and ∼10 per cent on Dd). We use the error estimates to compute cosmological forecasts for the sample of nine lenses that currently have well-measured time delays and deep Hubble Space Telescope images and for a sample of 40 lenses that is projected to be available in a few years through follow-up of candidates found in ongoing wide field surveys. We find that H0 can be measured with 2 per cent (1 per cent) precision from nine (40) lenses in a flat Λcold dark matter cosmology. We study several other cosmological models beyond the flat Λcold dark matter model and find that time-delay lenses with spatially resolved kinematics can greatly improve the precision of the cosmological parameters measured by cosmic microwave background data.

Genome-wide profiling of diel and circadian gene expression in the malaria vector Anopheles gambiae.

PubMed

Rund, Samuel S C; Hou, Tim Y; Ward, Sarah M; Collins, Frank H; Duffield, Giles E

2011-08-09

Anopheles gambiae, the primary African vector of malaria parasites, exhibits numerous rhythmic behaviors including flight activity, swarming, mating, host seeking, egg laying, and sugar feeding. However, little work has been performed to elucidate the molecular basis for these daily rhythms. To study how gene expression is regulated globally by diel and circadian mechanisms, we have undertaken a DNA microarray analysis of An. gambiae under light/dark cycle (LD) and constant dark (DD) conditions. Adult mated, non-blood-fed female mosquitoes were collected every 4 h for 48 h, and samples were processed with DNA microarrays. Using a cosine wave-fitting algorithm, we identified 1,293 and 600 rhythmic genes with a period length of 20-28 h in the head and body, respectively, under LD conditions, representing 9.7 and 4.5% of the An. gambiae gene set. A majority of these genes was specific to heads or bodies. Examination of mosquitoes under DD conditions revealed that rhythmic programming of the transcriptome is dependent on an interaction between the endogenous clock and extrinsic regulation by the LD cycle. A subset of genes, including the canonical clock components, was expressed rhythmically under both environmental conditions. A majority of genes had peak expression clustered around the day/night transitions, anticipating dawn and dusk. Genes cover diverse biological processes such as transcription/translation, metabolism, detoxification, olfaction, vision, cuticle regulation, and immunity, and include rate-limiting steps in the pathways. This study highlights the fundamental roles that both the circadian clock and light play in the physiology of this important insect vector and suggests targets for intervention.

Openness and avoidance--a longitudinal study of fathers of children with intellectual disability.

PubMed

Boström, P K; Broberg, M

2014-09-01

Fathers' interactions with children who have intellectual disabilities (ID) or developmental delays (DD) have increased over the past few decades and may be expected to continue to increase as maternal and paternal roles, along with other gender roles, become more equal. The aim of the present study was to explore fathers' experiences of parenthood in relation to a child with ID/DD from the initial discovery of the disability to 5 years later. Fathers' experiences of parenting children with ID/DD were explored in a longitudinal framework. Seven Swedish fathers of young children with ID/DD participated in a series of semi-structured interviews from 2005 to 2010, and their accounts were subjected to interpretative phenomenological analysis. The analysis revealed three themes: (1) An interrupted path - no longer taking things for granted, which describes the fathers' reactions to their children's diagnosis; (2) Being a good father, which describes the fathers' overall perceptions of their parenting of a child with ID/DD; and (3) Dealing with the unexpected, which describes fathers' individual ways of integrating, managing, and living with the knowledge of their child's disability over the 5 years during which fathers were interviewed. Fathers' individual paths need to be taken into consideration when offering psychological support to families of children with ID/DD. © 2013 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Examining educational attainment, prepregnancy smoking rate, and delay discounting as predictors of spontaneous quitting among pregnant smokers.

PubMed

White, Thomas J; Redner, Ryan; Skelly, Joan M; Higgins, Stephen T

2014-10-01

We investigated three potential predictors (educational attainment, prepregnancy smoking rate, and delay discounting [DD]) of spontaneous quitting among pregnant smokers. These predictors were examined alone and in combination with other potential predictors using study-intake assessments from controlled clinical trials examining the efficacy of financial incentives for smoking cessation and relapse prevention. Data from 349 pregnant women (231 continuing smokers and 118 spontaneous quitters) recruited from the greater Burlington, VT, area contributed to this secondary analysis, including psychiatric/sociodemographic characteristics, smoking characteristics, and performance on a computerized DD task. Educational attainment, smoking rate, and DD values were each significant predictors of spontaneous quitting in univariate analyses. A model examining those three predictors together retained educational attainment as a main effect and revealed a significant interaction of DD and smoking rate (i.e., DD was a significant predictor at lower but not higher smoking rates). A final model considering all potential predictors, included education, the interaction of DD and smoking rate, and five additional predictors (i.e., stress ratings, the belief that smoking during pregnancy will "greatly harm my baby," age of smoking initiation, marital status, and prior quit attempts during pregnancy). The study presented here contributes new knowledge on predictors of spontaneous quitting among pregnant smokers with substantive practical implications for reducing smoking during pregnancy. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Sequential chemotherapy with dose-dense docetaxel, cisplatin, folinic acid and 5-fluorouracil (TCF-dd) followed by combination of oxaliplatin, folinic acid, 5-fluorouracil and irinotecan (COFFI) in metastatic gastric cancer: results of a phase II trial.

PubMed

Dalla Chiesa, Matteo; Tomasello, Gianluca; Buti, Sebastiano; Rovere, Rodrigo Kraft; Brighenti, Matteo; Lazzarelli, Silvia; Donati, Gianvito; Passalacqua, Rodolfo

2011-01-01

To evaluate a new strategy of two sequential, intensified chemotherapy regimens in metastatic gastric cancer. Chemo-naïve patients with metastatic gastric cancer were enrolled to receive 4 cycles of TCF-dd (docetaxel initially 85 mg/m(2) and cisplatin initially 75 mg/m(2) on day 1 [later modified due to toxicity: 70 and 60 mg/m(2) respectively], l-folinic acid 100 mg/m(2) on days 1 and 2, 5-fluorouracil 400 mg/m(2) bolus and then 600 mg/m(2) as a 22 h continuous infusion on day 1 and 2, every 14 days). Subsequently, patients with CR, PR or SD received 4 cycles of COFFI (oxaliplatin 85 mg/m(2), irinotecan 140 mg/m(2), l-folinic acid 200 mg/m(2), 5-fluorouracil bolus 400 mg/m(2) on day 1 followed by 2,400 mg/m(2) as a 48 h continuous infusion, every 14 days). In both regimens pegfilgrastim 6 mg subcutaneously on day 3 was included. Forty consecutive patients were enrolled. TCF-dd regimen achieved an ORR of 55% (95% CI, 40-70). Twenty-three patients proceeded to COFFI. After this regimen the ORR was then increased to 60% (95% CI, 45-75). Among the 21 patients treated with TCF-dd after the protocol amendments, main grade 3-4 toxicities were: neutropenia (29%), thrombocytopenia (19%), asthenia (24%) and diarrhea (14%). COFFI caused grade 3-4 neutropenia (all not febrile) and diarrhea in 35% and 17% of patients respectively. A sequential strategy with TCF-dd followed by COFFI is very active and may be of special interest in selected patients.

National study of public spending for mental retardation and developmental disabilities.

PubMed

Braddock, D; Hemp, R; Fujiura, G

1987-09-01

Results of a nationwide study of public mental retardation/developmental disabilities (MR/DD) spending in the states during Fiscal Years 1977 through 1986 were summarized. Trends identified included: (a) continuing growth in spending for community services, (b) contraction of total spending for institutional operations, and (c) predominance of ICF/MR support in large (16+ beds) congregate care settings. Periodic replication of the study was recommended as was additional research to identify the political and economic determinants of state MR/DD spending.

Influence of the Diadinoxanthin Pool Size on Photoprotection in the Marine Planktonic Diatom Phaeodactylum tricornutum1

PubMed Central

Lavaud, Johann; Rousseau, Bernard; van Gorkom, Hans J.; Etienne, Anne-Lise

2002-01-01

The pool size of the xanthophyll cycle pigment diadinoxanthin (DD) in the diatom Phaeodactylum tricornutum depends on illumination conditions during culture. Intermittent light caused a doubling of the DD pool without significant change in other pigment contents and photosynthetic parameters, including the photosystem II (PSII) antenna size. On exposure to high-light intensity, extensive de-epoxidation of DD to diatoxanthin (DT) rapidly caused a very strong quenching of the maximum chlorophyll fluorescence yield (Fm, PSII reaction centers closed), which was fully reversed in the dark. The non-photochemical quenching of the minimum fluorescence yield (Fo, PSII centers open) decreased the quantum efficiency of PSII proportionally. For both Fm and Fo, the non-photochemical quenching expressed as F/F′ − 1 (with F′ the quenched level) was proportional to the DT concentration. However, the quenching of Fo relative to that of Fm was much stronger than random quenching in a homogeneous antenna could explain, showing that the rate of photochemical excitation trapping was limited by energy transfer to the reaction center rather than by charge separation. The cells can increase not only the amount of DT they can produce, but also its efficiency in competing with the PSII reaction center for excitation. The combined effect allowed intermittent light grown cells to down-regulate PSII by 90% and virtually eliminated photoinhibition by saturating light. The unusually rapid and effective photoprotection by the xanthophyll cycle in diatoms may help to explain their dominance in turbulent waters. PMID:12114593

Mouse genotypes drive the liver and adrenal gland clocks

NASA Astrophysics Data System (ADS)

Košir, Rok; Prosenc Zmrzljak, Uršula; Korenčič, Anja; Juvan, Peter; Ačimovič, Jure; Rozman, Damjana

2016-08-01

Circadian rhythms regulate a plethora of physiological processes. Perturbations of the rhythm can result in pathologies which are frequently studied in inbred mouse strains. We show that the genotype of mouse lines defines the circadian gene expression patterns. Expression of majority of core clock and output metabolic genes are phase delayed in the C56BL/6J line compared to 129S2 in the adrenal glands and the liver. Circadian amplitudes are generally higher in the 129S2 line. Experiments in dark - dark (DD) and light - dark conditions (LD), exome sequencing and data mining proposed that mouse lines differ in single nucleotide variants in the binding regions of clock related transcription factors in open chromatin regions. A possible mechanisms of differential circadian expression could be the entrainment and transmission of the light signal to peripheral organs. This is supported by the genotype effect in adrenal glands that is largest under LD, and by the high number of single nucleotide variants in the Receptor, Kinase and G-protein coupled receptor Panther molecular function categories. Different phenotypes of the two mouse lines and changed amino acid sequence of the Period 2 protein possibly contribute further to the observed differences in circadian gene expression.

Continuous cultivation approach for fermentative succinic acid production from crude glycerol by Basfia succiniciproducens DD1.

PubMed

Scholten, Edzard; Renz, Torsten; Thomas, Jochen

2009-12-01

A continuous cultivation process for the fermentative production of succinic acid from glycerol with the recently isolated bacterium Basfia succiniciproducens DD1 was developed. Crude glycerol (5.1 g l(-1)) was used as C-source and NH(4)OH as N-source and pH-control agent. The problem of wall growth was solved by transfers of the cultivation broth into an empty identical fermentor. The resulting continuous cultivation process was maintained for more than 80 days. Glycerol-limited steady states were established for dilution rates between 0.004 and 0.018 h(-1). Higher dilution rates resulted in glycerol accumulation. Succinic acid concentrations, productivities, yields and specific productivities increased with increasing dilution rates: at 0.018 h(-1) the highest values were 5.21 g l(-1), 0.094 g l(-1) h(-1), 1.02 g g(-1) and 0.375 g g(-1) h(-1), respectively.

32 CFR 310.7 - Information requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

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32 CFR 310.7 - Information requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

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32 CFR 310.7 - Information requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 2 2011-07-01 2011-07-01 false Information requirements. 310.7 Section 310.7 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) PRIVACY... § 310.6(d)(7) are assigned Report Control Symbol DD-DA&M(A)1379. ...

32 CFR 310.7 - Information requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

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32 CFR 310.7 - Information requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

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Oxidative stress and toxicity induced by the nucleoside reverse transcriptase inhibitor (NRTI)--2',3'-dideoxycytidine (ddC): relevance to HIV-dementia.

PubMed

Opii, Wycliffe O; Sultana, Rukhsana; Abdul, Hafiz Mohmmad; Ansari, Mubeen Ahmad; Nath, Avindra; Butterfield, D Allan

2007-03-01

Human immunodeficiency virus dementia (HIVD) is the most common form of dementia occurring among young adults. In HIVD, neuronal cell loss occurs in the absence of neuronal infection. With the advent of highly active anti-retroviral therapy (HAART), the incidence of HIVD has drastically reduced, though prevalence of milder forms of HIVD continues to rise. Though these agents have been used successfully in suppressing viral production, they have also been associated with a number of side effects. Here we examine the possible role of NRTIs, in particular 2',3'-dideoxycytidine (ddC), in the neuropathology of HIVD. Synaptosomes and isolated mitochondria treated and incubated for 6 h with CSF-achievable concentrations of ddC, i.e., 6-11 ng/ml, were found to show a significant increase in oxidative stress with 40 nM ddC as measured by protein carbonyls and 3-nitrotyrosine (3NT), effects that were not observed in the more tolerable NRTI, 3TC. Protection against protein oxidation induced by ddC was observed when brain mitochondria were isolated from gerbils 1 h after injection i.p. with the brain accessible antioxidant and glutathione mimetic, tricyclodecan-9-yl-xanthogenate (D609). In addition, there is a significant reduction in the levels of anti-apoptotic protein Bcl-2 and a significant increase in cytochrome c release and also a significant increase in the expression of pro-apoptotic protein caspase-3 after mitochondria were treated with 40 nM ddC. The results reported here show that ddC at 40 nM can induce oxidative stress, cause the release of cytochrome c, and in addition, reduce the levels of anti-apoptotic proteins, increase the levels of pro-apoptotic proteins, thereby increasing the possibility for induction of apoptosis. These findings are consistent with the notion of a possible role of the NRTIs, and in particular, ddC, in the mechanisms involved in HIVD.

Frontoparietal function in young people with dysthymic disorder (DSM-5: Persistent depressive disorder) during spatial working memory.

PubMed

Vilgis, Veronika; Chen, Jian; Silk, Timothy J; Cunnington, Ross; Vance, Alasdair

2014-05-01

Dysthymic disorder (DD) is a depressive disorder characterised by persistent low and/or irritable mood and has been identified as a major risk factor for developing major depressive disorder (MDD). MDD and DD have been associated with executive function difficulties of working memory and attention. Little is known about how executive function networks in the brain are affected in children and adolescents with MDD and even less in DD. This study used fMRI and two spatial working memory paradigms to investigate associated brain function in young people with DD and an age-, gender- and IQ- matched typically developing group. Nineteen male patients with DD (mean age 11.2±1.5 years) diagnosed according to DSM-IV criteria and 16 typically developing boys (mean age 10.5±1.1 years) performed a mental rotation and a delay-match to sample (DMTS) task while undergoing fMRI. All participants were medication-naïve at the time of testing. Compared to typically developing young people, the DD group showed less activation in left frontal regions including left ventro- and dorsolateral prefrontal cortices (PFC) during mental rotation. Medial frontal regions including dorsomedial PFC, anterior cingulate cortex and frontal pole also showed relatively reduced activation. During the DMTS task patients showed significantly more activation in the right precuneus and posterior cingulate cortex. This was a cross-sectional study with a small sample limiting the generalizability of the results. The results complement previous findings in adults with MDD that have shown differential activation of left PFC regions during working memory tasks. Additionally, altered function of cortical midline structures in young patients with DD was identified. This supports findings in children, adolescents and adults with MDD suggesting that the pathophysiology of depressive disorders extends to DD as a risk factor for MDD and exhibits continuity over the lifespan. Copyright © 2014 Elsevier B.V. All rights reserved.

The effects of deep-level defects on the electrical properties of Cd0.9Zn0.1Te crystals

NASA Astrophysics Data System (ADS)

Wang, Pengfei; Nan, Ruihua; Jian, Zengyun

2017-06-01

The deep-level defects of CdZnTe (CZT) crystals grown by the modified vertical Bridgman (MVB) method act as trapping centers or recombination centers in the band gap, which have significant effects on its electrical properties. The resistivity and electron mobility-lifetime product of high resistivity Cd0.9Zn0.1Te wafer marked CZT1 and low resistivity Cd0.9Zn0.1Te wafer marked CZT2 were tested respectively. Their deep-level defects were identified by thermally stimulated current (TSC) spectroscopy and thermoelectric effect spectroscopy (TEES) respectively. Then the trap-related parameters were characterized by the simultaneous multiple peak analysis (SIMPA) method. The deep donor level ({E}{{DD}}) dominating dark current was calculated by the relationship between dark current and temperature. The Fermi-level was characterized by current-voltage measurements of temperature dependence. The width of the band gap was characterized by ultraviolet-visible-infrared transmittance spectroscopy. The results show the traps concentration and capture cross section of CZT1 are lower than CZT2, so its electron mobility-lifetime product is greater than CZT2. The Fermi-level of CZT1 is closer to the middle gap than CZT2. The degree of Fermi-level pinned by {E}{{DD}} of CZT1 is larger than CZT2. It can be concluded that the resistivity of CZT crystals increases as the degree of Fermi-level pinned near the middle gap by the deep donor level enlarges. Project supported by the National Natural Science Foundation of China (No. 51502234) and the Scientific Research Plan Projects of Shaanxi Provincial Department of Education of China (No. 15JS040).

The Circadian Clock Gene Csnk1e Regulates Rapid Eye Movement Sleep Amount, and Nonrapid Eye Movement Sleep Architecture in Mice

PubMed Central

Zhou, Lili; Bryant, Camron D.; Loudon, Andrew; Palmer, Abraham A.; Vitaterna, Martha Hotz; Turek, Fred W.

2014-01-01

Study Objectives: Efforts to identify the genetic basis of mammalian sleep have included quantitative trait locus (QTL) mapping and gene targeting of known core circadian clock genes. We combined three different genetic approaches to identify and test a positional candidate sleep gene — the circadian gene casein kinase 1 epsilon (Csnk1e), which is located in a QTL we identified for rapid eye movement (REM) sleep on chromosome 15. Measurements and Results: Using electroencephalographic (EEG) and electromyographic (EMG) recordings, baseline sleep was examined in a 12-h light:12-h dark (LD 12:12) cycle in mice of seven genotypes, including Csnk1etau/tau and Csnk1e-/- mutant mice, Csnk1eB6.D2 and Csnk1eD2.B6 congenic mice, and their respective wild-type littermate control mice. Additionally, Csnk1etau/tau and wild-type mice were examined in constant darkness (DD). Csnk1etau/tau mutant mice and both Csnk1eB6.D2 and Csnk1eD2.B6 congenic mice showed significantly higher proportion of sleep time spent in REM sleep during the dark period than wild-type controls — the original phenotype for which the QTL on chromosome 15 was identified. This phenotype persisted in Csnk1etau/tau mice while under free-running DD conditions. Other sleep phenotypes observed in Csnk1etau/tau mice and congenics included a decreased number of bouts of nonrapid eye movement (NREM) sleep and an increased average NREM sleep bout duration. Conclusions: These results demonstrate a role for Csnk1e in regulating not only the timing of sleep, but also the REM sleep amount and NREM sleep architecture, and support Csnk1e as a causal gene in the sleep QTL on chromosome 15. Citation: Zhou L; Bryant CD; Loudon A; Palmer AA; Vitaterna MH; Turek FW. The circadian clock gene Csnk1e regulates rapid eye movement sleep amount, and nonrapid eye movement sleep architecture in mice. SLEEP 2014;37(4):785-793. PMID:24744456

Horizontal angular VOR, nystagmus dumping, and sensation duration in spacelab SLS-1 crewmembers

NASA Technical Reports Server (NTRS)

Oman, C. M.; Balkwill, M. D.; Young, L. R. (Principal Investigator)

1993-01-01

In 1G, the apparent time constant (Td) of postrotatory SPV decay with the head tilted face down is 55% of that with head erect (Te). This phenomenon is called "nystagmus dumping" and has been attributed to G effects on VOR velocity storage. Similarly, postrotatory sensation duration with head tilted (Dd) is 32% of that when head erect (De). In parabolic flight, Te and De are 70% of 1-G values, but a pitch back dumping movement produces no further change. Te, Td, and Dd have not previously been measured in orbital flight. VOR and sensation duration was tested in 4 crewmembers in 4 preflight, 1 inflight (days 4 or 5) and 4 post flight sessions. Bitemporal EOG was recorded with eyes open in darkness. Instructions were to "gaze straight ahead," and indicate when "rotation sensation disappears or becomes ambiguous". Subjects were rotated CW and CCW head erect for 1 min at 120 degrees/s, stopped, and EOG was recorded for another 1 min. This procedure was then used to study dumping, except that immediately after chair stop, subjects pitched their head forward 90 degrees. SPV was calculated using order statistic filtering, and dropouts removed using an iterative model fitting method. Te and Td were determined by logarithmic linear regression of mean SPV for each subject. In orbit, 90 degrees pitch movement produced rapid subjective dumping, but not nystagmus dumping. Dd was noticeably shorter ("almost instantaneous") compared to preflight Dd. Te and Td in orbit were similar to preflight Te for 3/4 subjects (rather than to preflight Td as expected). No consistent VOR gain changes were seen in orbit. Although Te is known to decrease acutely in parabolic flight, a longer time constant was measured in 3/4 subjects after 4-5 days adaptation to weightlessness, suggesting a return of angular velocity storage.

Cyclic Colour Change in the Bearded Dragon Pogona vitticeps under Different Photoperiods

PubMed Central

Fan, Marie; Stuart-Fox, Devi; Cadena, Viviana

2014-01-01

The ability to change colour rapidly is widespread among ectotherms and has various functions including camouflage, communication and thermoregulation. The process of colour change can occur as an aperiodic event or be rhythmic, induced by cyclic environmental factors or regulated by internal oscillators. Despite the importance of colour change in reptile ecology, few studies have investigated the occurrence of a circadian rhythm in lizard pigmentation. Additionally, although colour change also entails changes in near-infrared reflectance, which may affect thermoregulation, little research has examined this part of the spectrum. We tested whether the bearded dragon lizard, Pogona vitticeps, displays an endogenous circadian rhythm in pigmentation changes that could be entrained by light/dark (LD) cycles and how light affected the relative change in reflectance in both ultraviolet-visible and near-infrared spectra. We subjected 11 lizards to four photoperiodic regimens: LD 12∶12; LD 6∶18; LD 18∶6 and DD; and measured their dorsal skin reflectance at 3-hour intervals for 72 hours after a habituation period. A proportion of lizards displayed a significant rhythm under constant darkness, with maximum reflectance occurring in the subjective night. This endogenous rhythm synchronised to the different artificial LD cycles, with maximum reflectance occurring during dark phases, but did not vary in amplitude. In addition, the total ultraviolet-visible reflectance in relation to the total near-infrared reflectance was significantly higher during dark phases than during light phases. We conclude that P. vitticeps exhibits a circadian pigmentation rhythm of constant amplitude, regulated by internal oscillators and that can be entrained by light/dark cycles. PMID:25354192

Cyclic colour change in the bearded dragon Pogona vitticeps under different photoperiods.

PubMed

Fan, Marie; Stuart-Fox, Devi; Cadena, Viviana

2014-01-01

The ability to change colour rapidly is widespread among ectotherms and has various functions including camouflage, communication and thermoregulation. The process of colour change can occur as an aperiodic event or be rhythmic, induced by cyclic environmental factors or regulated by internal oscillators. Despite the importance of colour change in reptile ecology, few studies have investigated the occurrence of a circadian rhythm in lizard pigmentation. Additionally, although colour change also entails changes in near-infrared reflectance, which may affect thermoregulation, little research has examined this part of the spectrum. We tested whether the bearded dragon lizard, Pogona vitticeps, displays an endogenous circadian rhythm in pigmentation changes that could be entrained by light/dark (LD) cycles and how light affected the relative change in reflectance in both ultraviolet-visible and near-infrared spectra. We subjected 11 lizards to four photoperiodic regimens: LD 12:12; LD 6:18; LD 18:6 and DD; and measured their dorsal skin reflectance at 3-hour intervals for 72 hours after a habituation period. A proportion of lizards displayed a significant rhythm under constant darkness, with maximum reflectance occurring in the subjective night. This endogenous rhythm synchronised to the different artificial LD cycles, with maximum reflectance occurring during dark phases, but did not vary in amplitude. In addition, the total ultraviolet-visible reflectance in relation to the total near-infrared reflectance was significantly higher during dark phases than during light phases. We conclude that P. vitticeps exhibits a circadian pigmentation rhythm of constant amplitude, regulated by internal oscillators and that can be entrained by light/dark cycles.

Search for {eta}-mesic helium using WASA-at-COSY

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

Moskal, P.; Institut fuer Kernphysik and Juelich Center for Hadron Physics, Forschungszentrum Juelich, Juelich

2010-08-05

The installation of the WASA detector at the cooler synchrotron COSY opened the possibility to search for {eta}-mesic helium with high statistics and high acceptance. A search for the {sup 4}He--{eta} bound state is conducted via an exclusive measurement of the excitation function for the dd{yields}{sup 3}Hep{pi}{sup -} reaction varying continuously the beam momentum around the threshold for the dd{yields}{sup 4}He{eta} reaction. Ramping of the beam momentum and taking advantage of the large acceptance of the WASA detector allows to minimize systematical uncertainities.

32 CFR 285.5 - Information requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

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32 CFR 216.6 - Information requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

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32 CFR 295.8 - Annual report.

Code of Federal Regulations, 2012 CFR

2012-07-01

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32 CFR 295.8 - Annual report.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 2 2010-07-01 2010-07-01 false Annual report. 295.8 Section 295.8 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) FREEDOM OF... report. The FOIA Annual Report, assigned Report Control System DD-PA (A) 1365, will be prepared by the...

32 CFR 285.5 - Information requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 2 2014-07-01 2014-07-01 false Information requirements. 285.5 Section 285.5 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) FREEDOM... requirements. Reporting requirements are in DoD 32 CFR part 286 and have been assigned Report Control Symbol DD...

32 CFR 295.8 - Annual report.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 2 2013-07-01 2013-07-01 false Annual report. 295.8 Section 295.8 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) FREEDOM OF... report. The FOIA Annual Report, assigned Report Control System DD-PA (A) 1365, will be prepared by the...

32 CFR 295.8 - Annual report.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 2 2011-07-01 2011-07-01 false Annual report. 295.8 Section 295.8 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) FREEDOM OF... report. The FOIA Annual Report, assigned Report Control System DD-PA (A) 1365, will be prepared by the...

32 CFR 295.8 - Annual report.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 2 2014-07-01 2014-07-01 false Annual report. 295.8 Section 295.8 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) FREEDOM OF... report. The FOIA Annual Report, assigned Report Control System DD-PA (A) 1365, will be prepared by the...

A study of intrinsic statistical variation for low-energy nuclear recoils in liquid xenon detector for dark matter searches

NASA Astrophysics Data System (ADS)

Wang, Lu; Wei, Wenzhao; Mei, Dongming; Cubed Collaboration

2015-10-01

Noble liquid xenon experiments, such as XENON100, LUX, XENON 1-Ton, and LZ are large dark matter experiments directly searches for weakly interacting massive particles (WIMPs). One of the most important features is to discriminate nuclear recoils from electronic recoils. Detector response is generally calibrated with different radioactive sources including 83mKr, tritiated methane, 241AmBe, 252Cf, and DD-neutrons. The electronic recoil and nuclear recoil bands have been determined by these calibrations. However, the width of nuclear recoil band needs to be fully understood. We derive a theoretical model to understand the correlation of the width of nuclear recoil band and intrinsic statistical variation. In addition, we conduct experiments to validate the theoretical model. In this paper, we present the study of intrinsic statistical variation contributing to the width of nuclear recoil band. DE-FG02-10ER46709 and the state of South Dakota.

A hybrid-drive nonisobaric-ignition scheme for inertial confinement fusion

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

He, X. T., E-mail: xthe@iapcm.ac.cn; Center for Applied Physics and Technology, HEDPS, Peking University, Beijing 100871; IFSA Collaborative Innovation Center of MoE, Shanghai Jiao-Tong University, Shanghai 200240

A new hybrid-drive (HD) nonisobaric ignition scheme of inertial confinement fusion (ICF) is proposed, in which a HD pressure to drive implosion dynamics increases via increasing density rather than temperature in the conventional indirect drive (ID) and direct drive (DD) approaches. In this HD (combination of ID and DD) scheme, an assembled target of a spherical hohlraum and a layered deuterium-tritium capsule inside is used. The ID lasers first drive the shock to perform a spherical symmetry implosion and produce a large-scale corona plasma. Then, the DD lasers, whose critical surface in ID corona plasma is far from the radiationmore » ablation front, drive a supersonic electron thermal wave, which slows down to a high-pressure electron compression wave, like a snowplow, piling up the corona plasma into high density and forming a HD pressurized plateau with a large width. The HD pressure is several times the conventional ID and DD ablation pressure and launches an enhanced precursor shock and a continuous compression wave, which give rise to the HD capsule implosion dynamics in a large implosion velocity. The hydrodynamic instabilities at imploding capsule interfaces are suppressed, and the continuous HD compression wave provides main pdV work large enough to hotspot, resulting in the HD nonisobaric ignition. The ignition condition and target design based on this scheme are given theoretically and by numerical simulations. It shows that the novel scheme can significantly suppress implosion asymmetry and hydrodynamic instabilities of current isobaric hotspot ignition design, and a high-gain ICF is promising.« less

Adolescents with Developmental Dyscalculia Do Not Have a Generalized Magnitude Deficit - Processing of Discrete and Continuous Magnitudes.

PubMed

McCaskey, Ursina; von Aster, Michael; O'Gorman Tuura, Ruth; Kucian, Karin

2017-01-01

The link between number and space has been discussed in the literature for some time, resulting in the theory that number, space and time might be part of a generalized magnitude system. To date, several behavioral and neuroimaging findings support the notion of a generalized magnitude system, although contradictory results showing a partial overlap or separate magnitude systems are also found. The possible existence of a generalized magnitude processing area leads to the question how individuals with developmental dyscalculia (DD), known for deficits in numerical-arithmetical abilities, process magnitudes. By means of neuropsychological tests and functional magnetic resonance imaging (fMRI) we aimed to examine the relationship between number and space in typical and atypical development. Participants were 16 adolescents with DD (14.1 years) and 14 typically developing (TD) peers (13.8 years). In the fMRI paradigm participants had to perform discrete (arrays of dots) and continuous magnitude (angles) comparisons as well as a mental rotation task. In the neuropsychological tests, adolescents with dyscalculia performed significantly worse in numerical and complex visuo-spatial tasks. However, they showed similar results to TD peers when making discrete and continuous magnitude decisions during the neuropsychological tests and the fMRI paradigm. A conjunction analysis of the fMRI data revealed commonly activated higher order visual (inferior and middle occipital gyrus) and parietal (inferior and superior parietal lobe) magnitude areas for the discrete and continuous magnitude tasks. Moreover, no differences were found when contrasting both magnitude processing conditions, favoring the possibility of a generalized magnitude system. Group comparisons further revealed that dyscalculic subjects showed increased activation in domain general regions, whilst TD peers activate domain specific areas to a greater extent. In conclusion, our results point to the existence of a generalized magnitude system in the occipito-parietal stream in typical development. The detailed investigation of spatial and numerical magnitude abilities in DD reveals that the deficits in number processing and arithmetic cannot be explained with a general magnitude deficiency. Our results further indicate that multiple neuro-cognitive components might contribute to the explanation of DD.

Adolescents with Developmental Dyscalculia Do Not Have a Generalized Magnitude Deficit – Processing of Discrete and Continuous Magnitudes

PubMed Central

McCaskey, Ursina; von Aster, Michael; O’Gorman Tuura, Ruth; Kucian, Karin

2017-01-01

The link between number and space has been discussed in the literature for some time, resulting in the theory that number, space and time might be part of a generalized magnitude system. To date, several behavioral and neuroimaging findings support the notion of a generalized magnitude system, although contradictory results showing a partial overlap or separate magnitude systems are also found. The possible existence of a generalized magnitude processing area leads to the question how individuals with developmental dyscalculia (DD), known for deficits in numerical-arithmetical abilities, process magnitudes. By means of neuropsychological tests and functional magnetic resonance imaging (fMRI) we aimed to examine the relationship between number and space in typical and atypical development. Participants were 16 adolescents with DD (14.1 years) and 14 typically developing (TD) peers (13.8 years). In the fMRI paradigm participants had to perform discrete (arrays of dots) and continuous magnitude (angles) comparisons as well as a mental rotation task. In the neuropsychological tests, adolescents with dyscalculia performed significantly worse in numerical and complex visuo-spatial tasks. However, they showed similar results to TD peers when making discrete and continuous magnitude decisions during the neuropsychological tests and the fMRI paradigm. A conjunction analysis of the fMRI data revealed commonly activated higher order visual (inferior and middle occipital gyrus) and parietal (inferior and superior parietal lobe) magnitude areas for the discrete and continuous magnitude tasks. Moreover, no differences were found when contrasting both magnitude processing conditions, favoring the possibility of a generalized magnitude system. Group comparisons further revealed that dyscalculic subjects showed increased activation in domain general regions, whilst TD peers activate domain specific areas to a greater extent. In conclusion, our results point to the existence of a generalized magnitude system in the occipito-parietal stream in typical development. The detailed investigation of spatial and numerical magnitude abilities in DD reveals that the deficits in number processing and arithmetic cannot be explained with a general magnitude deficiency. Our results further indicate that multiple neuro-cognitive components might contribute to the explanation of DD. PMID:28373834

Light Evokes Rapid Circadian Network Oscillator Desynchrony Followed by Gradual Phase Retuning of Synchrony

PubMed Central

Roberts, Logan; Leise, Tanya L.; Noguchi, Takako; Galschiodt, Alexis M.; Houl, Jerry H.; Welsh, David K.; Holmes, Todd C.

2015-01-01

Summary Background Circadian neural circuits generate near 24 hr physiological rhythms that can be entrained by light to coordinate animal physiology with daily solar cycles. To examine how a circadian circuit reorganizes its activity in response to light, we imaged period (per) clock gene cycling for up to 6 days at single neuron resolution in whole brain explant cultures prepared from per-luciferase transgenic flies. We compared cultures subjected to a phase-advancing light pulse (LP) to cultures maintained in darkness (DD). Results In DD, individual neuronal oscillators in all circadian subgroups are initially well synchronized, then show monotonic decrease in oscillator rhythm amplitude and synchrony with time. The s-LNvs and LNds exhibit this decrease at a slower relative rate. In contrast, the LP evokes a rapid loss of oscillator synchrony between and within most circadian neuronal subgroups followed by gradual phase retuning of whole circuit oscillator synchrony. The LNds maintain high rhythmic amplitude and synchrony following the LP along with the most rapid coherent phase advance. Immunocytochemical analysis of PER show these dynamics in DD and LP are recapitulated in vivo. Anatomically distinct circadian neuronal subgroups vary in their response to the LP, showing differences in the degree and kinetics of their loss, recovery and/or strengthening of synchrony and rhythmicity. Conclusions Transient desynchrony appears to be an integral feature of light response of the Drosophila multicellular circadian clock. Individual oscillators in different neuronal subgroups of the circadian circuit show distinct kinetic signatures of light response and phase retuning. PMID:25754644

Using Simulation to Determine a Strategy for Positively Tracking a Cruise Missile by CMMCA

DTIC Science & Technology

1990-03-01

ANPOS/SS(6),ATC/SS(7),ATAS/ SS(8),ABANGLE/SS(9),CBANGLE/DD(1),CEVEL/ DD(2),CNVEL/DD(3),CTCC/DD(4),AEVEL/ DD(5), ANVEL /DD(6),ATCC RECORD,TNOW,MINUTES,20...ABANGLE),(SS(9),CBANGLE), & (DD(1),CEVEL),(DD(2),CNVEL).(DD(3),CTCC), & (DD(4),AEVEL),(DD(5), ANVEL ),(DD(6).ATCC) GOTO(l,2,3,4,5,6) ,I 1IF (XX(14) *EQ. 1...ABANGLE),(SS(9),CBANGLE), & (DD(l),CEVEL),(DD(2),CNVEL),(DD(3),CTCG), & (DD(4),AEVEL),(DD(5), ANVEL ),CDD(6),ATCC) REAL COSD EXTERNAL COSD REAL SIND

Activity, sleep and ambient light have a different impact on circadian blood pressure, heart rate and body temperature rhythms.

PubMed

Gubin, D G; Weinert, D; Rybina, S V; Danilova, L A; Solovieva, S V; Durov, A M; Prokopiev, N Y; Ushakov, P A

2017-01-01

The aim of the present study was to investigate the impact of endogenous and exogenous factors for the expression of the daily rhythms of body temperature (BT), blood pressure (BP) and heart rate (HR). One hundred and seventy-three young adults (YA), 17-24 years old (y.o.), of both genders were studied under a modified constant-routine (CR) protocol for 26 h. Participants were assigned randomly to groups with different lighting regimens: CR-LD, n = 77, lights (>400 l×) on from 09:00 to 17:00 h and off (<10 l×) from 17:00 to 09:00 next morning; CR-LL, n = 81, lights on (>400 l×) during the whole experimental session; CR-DD, n = 15, constant dim light (<10 l×) during the whole experiment. Systolic (SBP) and diastolic (DBP) BP, HR and BT were measured every 2 h. For comparison, the results of the former studies performed under conditions of regular life with an activity period from 07:00 to 23:00 h and sleep from 23:00 till 07:00 h (Control) were reanalyzed. Seven-day Ambulatory Blood Pressure Monitoring (ABPM) records from 27 YA (16-38 y.o.) and BT self-measurement data from 70 YA (17-30 y.o.) taken on ≥ 3 successive days at 08:00, 11:00, 14:00, 17:00, 20:00, 23:00 and 03:00 were available. The obtained daily patterns were different between Control and CR-DD groups, due to effects of activity, sleep and light. The comparison of Control and CR-LD groups allowed the effects of sleep and activity to be estimated since the lighting conditions were similar. The activity level substantially elevated SBP, but not DBP. Sleep, on the other hand, lowered the nighttime DBP, but has no effect on SBP. HR was affected both by activity and sleep. In accordance with previous studies, these results confirm that the steep BP increase in the morning is not driven by the circadian clock, but rather by sympathoadrenal factors related to awakening and corresponding anticipatory mechanisms. The effect on BT was not significant. To investigate the impact of light during the former dark time and darkness during the former light time, the CR-LL and CR-DD groups were each compared with the CR-LD group. Light delayed the evening decrease of BT, most likely via a suppression of the melatonin rise. Besides, it had a prominent arousal effect on SBP both in the former light and dark phases, a moderate effect on DBP and no effect on HR. Darkness induced decline in BT. BP values were decreased during the former light time. No effects on HR were found. Altogether, the results of the present paper show that BT, BP and HR are affected by exogenous factors differently. Moreover, the effect was gender-specific. Especially, the response of BT and BP to ambient light was evident only in females. We suppose that the distinct, gender-specific responses of SBP, DBP and HR to activity, sleep and ambient light do reflect fundamental differences in the circadian control of various cardiovascular functions. Furthermore, the presented data are important for the elaboration of updated reference standards, the interpretation of rhythm disorders and for personalized chronotherapeutic approaches to prevent adverse cardiovascular events more effectively.

Caring for children with intellectual and developmental disabilities: virtual patient instruction improves students' knowledge and comfort level.

PubMed

Sanders, Carla L; Kleinert, Harold L; Free, Teresa; Slusher, Ida; Clevenger, Kim; Johnson, Stephanie; Boyd, Sara E

2007-12-01

Nurses play a vital role in providing health care to children with developmental disability (DD) throughout the United States. Unfortunately, most nurses continue to report that they receive little or no clinical education in the area of DDs. In response to this need, a core development team consisting of nurse practitioners and nursing faculty from three universities, one physician assistant faculty, parents of children with DD, and educational specialists developed two multimedia (virtual patient) pediatric instructional modules in CD-ROM format--one involving a child with Down syndrome, and the other involving an infant born at 26 weeks' gestation. Participants were required to make clinical decisions throughout the cases. The modules on CD were piloted with nursing students from three universities. Results of the effectiveness study demonstrated significant gains in knowledge and comfort level regarding the care of children with DD.

Circadian Clock Protein Content and Daily Rhythm of Locomotor Activity Are Altered after Chronic Exposure to Lead in Rat

PubMed Central

Sabbar, Mariam; Dkhissi-Benyahya, Ouria; Benazzouz, Abdelhamid; Lakhdar-Ghazal, Nouria

2017-01-01

Lead exposure has been reported to produce many clinical features, including parkinsonism. However, its consequences on the circadian rhythms are still unknown. Here we aimed to examine the circadian rhythms of locomotor activity following lead intoxication and investigate the mechanisms by which lead may induce alterations of circadian rhythms in rats. Male Wistar rats were injected with lead or sodium acetate (10 mg/kg/day, i.p.) during 4 weeks. Both groups were tested in the “open field” to quantify the exploratory activity and in the rotarod to evaluate motor coordination. Then, animals were submitted to continuous 24 h recordings of locomotor activity under 14/10 Light/dark (14/10 LD) cycle and in complete darkness (DD). At the end of experiments, the clock proteins BMAL1, PER1-2, and CRY1-2 were assayed in the suprachiasmatic nucleus (SCN) using immunohistochemistry. We showed that lead significantly reduced the number of crossing in the open field, impaired motor coordination and altered the daily locomotor activity rhythm. When the LD cycle was advanced by 6 h, both groups adjusted their daily locomotor activity to the new LD cycle with high onset variability in lead-intoxicated rats compared to controls. Lead also led to a decrease in the number of immunoreactive cells (ir-) of BMAL1, PER1, and PER2 without affecting the number of ir-CRY1 and ir-CRY2 cells in the SCN. Our data provide strong evidence that lead intoxication disturbs the rhythm of locomotor activity and alters clock proteins expression in the SCN. They contribute to the understanding of the mechanism by which lead induce circadian rhythms disturbances. PMID:28970786

32 CFR 634.21 - Department of Defense Form 2220.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 4 2014-07-01 2013-07-01 true Department of Defense Form 2220. 634.21 Section 634.21 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW... Department of Defense Form 2220. (a) Use. DD Form 2220 will be used to identify registered POVs on Army, Navy...

32 CFR 634.21 - Department of Defense Form 2220.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 4 2012-07-01 2011-07-01 true Department of Defense Form 2220. 634.21 Section 634.21 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW... Department of Defense Form 2220. (a) Use. DD Form 2220 will be used to identify registered POVs on Army, Navy...

32 CFR 634.21 - Department of Defense Form 2220.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 4 2013-07-01 2013-07-01 false Department of Defense Form 2220. 634.21 Section 634.21 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW... Department of Defense Form 2220. (a) Use. DD Form 2220 will be used to identify registered POVs on Army, Navy...

32 CFR 634.21 - Department of Defense Form 2220.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Department of Defense Form 2220. 634.21 Section 634.21 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW... Department of Defense Form 2220. (a) Use. DD Form 2220 will be used to identify registered POVs on Army, Navy...

32 CFR 634.21 - Department of Defense Form 2220.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 4 2011-07-01 2011-07-01 false Department of Defense Form 2220. 634.21 Section 634.21 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW... Department of Defense Form 2220. (a) Use. DD Form 2220 will be used to identify registered POVs on Army, Navy...

Phosphatidylazidothymidine and phosphatidyl-ddC: assessment of uptake in mouse lymphoid tissues and antiviral activities in human immunodeficiency virus-infected cells and in Rauscher leukemia virus-infected mice.

PubMed Central

Hostetler, K Y; Richman, D D; Sridhar, C N; Felgner, P L; Felgner, J; Ricci, J; Gardner, M F; Selleseth, D W; Ellis, M N

1994-01-01

During the early stages of human immunodeficiency virus (HIV) infection, although symptoms are absent and viral replication in peripheral blood mononuclear cells is low, substantial levels of HIV replication can be documented in lymphoid tissue [G. Pantaleo, C. Graziosi, J.F. Demarest, L. Butini, M. Montroni, C.H. Fox, J.M. Orenstein, D.P. Kotler, and A.S. Fauci, Nature (London) 362:355-358, 1993, and J. Embretsen, M. Zupancic, J.L. Ribas, A. Burke, P. Racz, K. Tenner-Tacz, and A.T. Haase, Nature (London) 362:359-362, 1993]. This observation suggests that earlier treatment of HIV infection may be indicated and that strategies for enhancing drug targeting to the lymphoid tissue reservoris of HIV infection may be beneficial. To address this issue, we synthesized dioleoylphosphatidyl-ddC (DOP-ddC) and dipalmitoylphosphatidyl-3'-azido-3'-deoxythymidine (DPP-AZT), phospholipid prodrugs which form lipid bilayers and which are readily incorporated into liposomes. The anti-HIV activity of DOP-ddC was similar to that of ddC in HIV type 1-infected HT4-6C cells, but DPP-AZT was considerably less active than AZT in HT4-6C cells. Liposomes containing DOP-[3H]ddC or DPP-[3H]AZT administered intraperitoneally to mice produced greater levels of total radioactivity over time in plasma, spleen, and lymphoid tissue relative to the results with [3H]ddC and [3H]AZT, respectively. DPP-AZT administered intraperitoneally in liposomes as a single daily dose to mice infected with Rauscher leukemia virus prevented increased spleen weight and reverse transcriptase levels in serum with a dose-response roughly comparable to that of AZT given continuously in the drinking water. DOP-ddC, DPP-AZT, and lipid conjugates of other antiretroviral nucleosides may provide higher levels of drug over time in plasma and in lymph nodes and spleen, important reservoirs of HIV infection, and may represent an interesting alternative approach to antiviral nucleoside treatment of AIDS. PMID:7695264

How robust is the pre-1931 National Climatic Data Center—climate divisional dataset? Examples from Georgia and Louisiana

NASA Astrophysics Data System (ADS)

Allard, Jason; Thompson, Clint; Keim, Barry D.

2015-04-01

The National Climatic Data Center's climate divisional dataset (CDD) is commonly used in climate change analyses. This dataset is a spatially continuous dataset for the conterminous USA from 1895 to the present. The CDD since 1931 is computed by averaging all available representative cooperative weather station data into a single monthly value for each of the 344 climate divisions of the conterminous USA, while pre-1931 data for climate divisions are derived from statewide averages using regression equations. This study examines the veracity of these pre-1931 data. All available Cooperative Observer Program (COOP) stations within each climate division in Georgia and Louisiana were averaged into a single monthly value for each month and each climate division from 1897 to 1930 to generate a divisional dataset (COOP DD), using similar methods to those used by the National Climatic Data Center to generate the post-1931 CDD. The reliability of the official CDD—derived from statewide averages—to produce temperature and precipitation means and trends prior to 1931 are then evaluated by comparing that dataset with the COOP DD with difference-of-means tests, correlations, and linear regression techniques. The CDD and the COOP DD are also compared to a divisional dataset derived from the United States Historical Climatology Network (USHCN) data (USHCN DD), with difference of means and correlation techniques, to demonstrate potential impacts of inhomogeneities within the CDD and the COOP DD. The statistical results, taken as a whole, not only indicate broad similarities between the CDD and COOP DD but also show that the CDD does not adequately portray pre-1931 temperature and precipitation in certain climate divisions within Georgia and Louisiana. In comparison with the USHCN DD, both the CDD and the COOP DD appear to be subject to biases that probably result from changing stations within climate divisions. As such, the CDD should be used judiciously for long-term studies of climate change, and past studies using the CDD should be evaluated in the context of these new findings.

Kinetic Study of Yellow Fever 17DD Viral Infection in Gallus gallus domesticus Embryos

PubMed Central

Manso, Pedro Paulo de Abreu; E. P. Dias de Oliveira, Bárbara Cristina; Carvalho de Sequeira, Patrícia; Rodrigues Maia de Souza, Yuli; dos Santos Ferro, Jessica Maria; da Silva, Igor José; Gonçalves Caputo, Luzia Fátima; Tavares Guedes, Priscila; Araujo Cunha dos Santos, Alexandre; da Silva Freire, Marcos; Bonaldo, Myrna Cristina; Pelajo Machado, Marcelo

2016-01-01

Yellow fever continues to be an important epidemiological problem in Africa and South America even though the disease can be controlled by vaccination. The vaccine has been produced since 1937 and is based on YFV 17DD chicken embryo infection. However, little is known about the histopathological background of virus infection and replication in this model. Here we show by morphological and molecular methods (brightfield and confocal microscopies, immunofluorescence, nested-PCR and sequencing) the kinetics of YFV 17DD infection in chicken embryos with 9 days of development, encompassing 24 to 96 hours post infection. Our principal findings indicate that the main cells involved in virus production are myoblasts with a mesenchymal shape, which also are the first cells to express virus proteins in Gallus gallus embryos at 48 hours after infection. At 72 hours post infection, we observed an increase of infected cells in embryos. Many sites are thus affected in the infection sequence, especially the skeletal muscle. We were also able to confirm an increase of nervous system infection at 96 hours post infection. Our data contribute to the comprehension of the pathogenesis of YF 17DD virus infection in Gallus gallus embryos. PMID:27158977

Determining the scale of designer drugs (DD) abuse and risk to public health in Poland through an epidemiological study in adolescents.

PubMed

Biliński, Przemysław; Kapka-Skrzypczak, Lucyna; Jabłoński, Piotr

2012-01-01

Since 2008, it has been recognised by most health authorities worldwide that the abuse of newly-emerging psychoactive drugs, ('designer drugs'/'legal highs'; DD), in youth is a rapidly increasing problem, especially in the EU, threatening to offset gains made in tackling established and illegal drugs which they are intended to mimic; DD diversity is continually increasing to circumvent laws. The aim of the study was to determine the scale of DD abuse/availability amongst Polish youth. The surveyed test population was randomly selected from a representative group of adolescents attending high schools, secondary schools and universities throughout Poland. Questionnaires were completed by 14,511 subjects (10,083 school pupils and 4,428 students). Few persons from each group admitted using DDs; 453 school pupils (4.49%) vs. 81 students (1.83%). More males (4.74%) took DDs than females (2.77%). The tendency to take DDs in the company of friends was high in both DD-taking groups (>80%). DDs were consumed mostly in open spaces (34.15%), discos/pubs (21.13%) and boarding school/friend's house (20.57). Most frequently, DDs came from shops (57.68%), friends (31.46%) or dealers (10.11%). Ensuing symptoms included; happy/euphoric mood (58.80%), talkativeness (42.51%) and hallucinations (22.85%). Over 74% of DD-takers in both groups experienced adverse reactions, and those requiring help sought it from: friends/colleagues (6.74%), doctors (5.06%), and hospitals (4.87%), but most rarely from parents/guardians (2.62%). Urgent action is being taken, especially in youth education, to prevent DDs becoming the serious menace seen with conventional drugs.

The Redundancy of Peptidoglycan Carboxypeptidases Ensures Robust Cell Shape Maintenance in Escherichia coli

PubMed Central

Peters, Katharina; Kannan, Suresh; Rao, Vincenzo A.; Biboy, Jacob; Vollmer, Daniela; Erickson, Stephen W.; Lewis, Richard J.

2016-01-01

ABSTRACT Peptidoglycan (PG) is an essential structural component of the bacterial cell wall and maintains the integrity and shape of the cell by forming a continuous layer around the cytoplasmic membrane. The thin PG layer of Escherichia coli resides in the periplasm, a unique compartment whose composition and pH can vary depending on the local environment of the cell. Hence, the growth of the PG layer must be sufficiently robust to allow cell growth and division under different conditions. We have analyzed the PG composition of 28 mutants lacking multiple PG enzymes (penicillin-binding proteins [PBPs]) after growth in acidic or near-neutral-pH media. Statistical analysis of the muropeptide profiles identified dd-carboxypeptidases (DD-CPases) that were more active in cells grown at acidic pH. In particular, the absence of the DD-CPase PBP6b caused a significant increase in the pentapeptide content of PG as well as morphological defects when the cells were grown at acidic pH. Other DD-CPases (PBP4, PBP4b, PBP5, PBP6a, PBP7, and AmpH) and the PG synthase PBP1B made a smaller or null contribution to the pentapeptide-trimming activity at acidic pH. We solved the crystal structure of PBP6b and also demonstrated that the enzyme is more stable and has a lower Km at acidic pH, explaining why PBP6b is more active at low pH. Hence, PBP6b is a specialized DD-CPase that contributes to cell shape maintenance at low pH, and E. coli appears to utilize redundant DD-CPases for normal growth under different conditions. PMID:27329754

Effect of continuous theta burst stimulation of the right dorsolateral prefrontal cortex on cerebral blood flow changes during decision making.

PubMed

Cho, Sang Soo; Pellecchia, Giovanna; Ko, Ji Hyun; Ray, Nicola; Obeso, Ignacio; Houle, Sylvain; Strafella, Antonio P

2012-04-01

Decision making is a cognitive function relaying on a complex neural network. In particular, the right dorsolateral prefrontal cortex (DLPFC) plays a key role within this network. We used positron emission tomography (PET) combined with continuous theta burst transcranial magnetic stimulation (cTBS) to investigate neuronal and behavioral changes in normal volunteers while performing a delay discounting (DD) task. We aimed to test whether stimulation of right DLPFC would modify the activation pattern of the neural circuit underlying decision making during the DD task and influence discounting behavior. We found that cTBS of the right DLPFC influenced decision making by reducing impulsivity and inducing participants to favor large but delayed rewards instead of immediate but small rewards. Stimulation also affected activation in several prefrontal areas associated with DD. In particular, we observed a reduced regional cerebral blood flow (rCBF) in the ipsilateral DLPFC (BA 46) extending into the rostral part of the prefrontal cortex (BA 10) as well as a disrupted relationship between impulsivity (k-value) and rCBF in these and other prefrontal areas. These findings suggest that transcranial magnetic stimulation of the DLPFC influences the neural network underlying impulsive decision making behavior. Copyright © 2012 Elsevier Inc. All rights reserved.

Six-year follow-up of the treatment of patients with dissociative disorders study.

PubMed

Myrick, Amie C; Webermann, Aliya R; Loewenstein, Richard J; Lanius, Ruth; Putnam, Frank W; Brand, Bethany L

2017-01-01

Objective : Literature on the treatment of dissociative disorders (DDs) suggests that these individuals require long-term and specialized treatment to achieve stabilization and functionality. There is considerable empirical support for specialized phasic, dissociation-focused treatment in reducing a myriad of psychological symptoms and self-harm in this population. However, until recently, there has been a paucity of longitudinal treatment research on DD patients. Method : In the present six-year follow-up study, 61 therapists who participated in the initial phase of the Treatment of Patients with Dissociative Disorders (TOP DD) study answered questionnaires about their study patient's stressors, quality of life, global functioning, victimization, and safety. These results provided a view of patients' progress six years since the beginning of the TOP DD study. Results : Longitudinal analyses demonstrated patients had significantly fewer stressors ( Χ 2 (6) = 18.76, p  < .01, canonical r  = .48, N  = 76), instances of sexual revictimization ( X 2 (1) = 107.05, p  < .001) and psychiatric hospitalizations ( t (54) = 2.57, p  < .05, Cohen's d  = .43), as well as higher global functioning ( Χ 2 (2) = 59.27, p  < .001, canonical r  = .65, N  = 111). Conclusions : These findings continue to support the initial results of the TOP DD study that, despite marked initial difficulties and functional impairment, DD patients benefit from specialized treatment.

Continuity of drunk and drugged driving behaviors four years post-college.

PubMed

Caldeira, Kimberly M; Arria, Amelia M; Allen, Hannah K; Bugbee, Brittany A; Vincent, Kathryn B; O'Grady, Kevin E

2017-11-01

Driving under the influence of alcohol is a leading cause of injury and premature death among young adults, and college-educated individuals are at particularly high risk. Less is known about driving under the influence of other drugs, which is on the rise. This study describes prospective seven-year trends in alcohol and other drug (AOD)-involved driving among a young-adult sample beginning with their second year of college (i.e., Years 2-8), and documents the extent of continuity in such behaviors across time. Originally recruited as incoming first-year students at one large public university, participants (n=1194) were interviewed annually about how frequently they drove while drunk/intoxicated (DWI), after drinking any alcohol (DAD), and/or while under the influence of other drugs (DD). Follow-up rates were high (>75% annually). Among participants with access to drive a car, annual prevalence peaked in Year 4 (modal age 21) for both DWI (24.3% wt ) and DD (19.1% wt ) and declined significantly thereafter through Year 8 (both ps<0.05). DAD was far more prevalent than DWI or DD, increasing from 40.5% wt in Year 2 to 66.9% wt in Year 5, and plateauing thereafter. Among marijuana-using participants, likelihood of DD was consistently greater than the likelihood of DWI among Heavy Episodic and Light-to-Moderate drinkers, and it declined significantly during Years 5-8 (p<0.05). Post-college declines in heavy drinking and DWI prevalence were encouraging but did not necessarily translate to reductions in likelihood of engaging in DWI, depending on drinking pattern. College-educated individuals represent an important target for AOD-involved driving prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

Time processing in dyscalculia.

PubMed

Cappelletti, Marinella; Freeman, Elliot D; Butterworth, Brian L

2011-01-01

To test whether atypical number development may affect other types of quantity processing, we investigated temporal discrimination in adults with developmental dyscalculia (DD). This also allowed us to test whether number and time may be sub-served by a common quantity system or decision mechanisms: if they do, both should be impaired in dyscalculia, but if number and time are distinct they should dissociate. Participants judged which of two successively presented horizontal lines was longer in duration, the first line being preceded by either a small or a large number prime ("1" or "9") or by a neutral symbol ("#"), or in a third task participants decided which of two Arabic numbers (either "1," "5," "9") lasted longer. Results showed that (i) DD's temporal discriminability was normal as long as numbers were not part of the experimental design, even as task-irrelevant stimuli; however (ii) task-irrelevant numbers dramatically disrupted DD's temporal discriminability the more their salience increased, though the actual magnitude of the numbers had no effect; in contrast (iii) controls' time perception was robust to the presence of numbers but modulated by numerical quantity: therefore small number primes or numerical stimuli seemed to make durations appear shorter than veridical, but longer for larger numerical prime or numerical stimuli. This study is the first to show spared temporal discrimination - a dimension of continuous quantity - in a population with a congenital number impairment. Our data reinforce the idea of a partially shared quantity system across numerical and temporal dimensions, which supports both dissociations and interactions among dimensions; however, they suggest that impaired number in DD is unlikely to originate from systems initially dedicated to continuous quantity processing like time.

Nocturnal illumination maintains reproductive function and simulates the period-lengthening effect of constant light in the mature male Djungarian hamster (Phodopus sungorus)

NASA Technical Reports Server (NTRS)

Ferraro, J. S.

1990-01-01

Mature male Djungarian hamsters (Phodopus sungorus) were placed in individual light-tight, sound attenuated chambers and exposed to one of four lighting conditions for a duration of approximately seven weeks. The four lighting conditions were: constant light (LL); constant dark (DD); feedback lighting (LDFB; a condition that illuminates the cage in response to locomotor activity); or a feedback lighting neighbor control (LDFB NC; the animal receives the same light pattern as a paired animal in feedback lighting, but has no control over it). Exposure of hamsters to LL or LDFB produced significantly and similarly longer free-running periods of the locomotor activity rhythm than exposure of animals to DD. Hamsters exposed to LDFB NC did not free-run or entrain, but rather displayed "relative coordination". The paired testes and sex accessory glands weights suggest that in the Djungarian hamster, LL and LDFB exposed animals maintained reproductive function, whereas DD exposed animals did not. Animals exposed to LDFB NC had intermediate paired testes weights. Since several previous studies have demonstrated that short pulses of light, which are coincident with the subjective night, are photostimulatory, it is not surprising that LDFB maintained reproductive function in the mature Djungarian hamster. Feedback lighting, however, has been shown to be an insufficient stimulus to maintain reproductive function of mature male and female Syrian hamsters, and to the reproductive maturation of immature Djungarian hamsters. The results suggest that there may be slight, but significant differences in the way these two species interpret photoperiod, as well as a developmental change in the photoperiodic response of Djungarian hamsters.

Effects of abnormal light-rearing conditions on retinal physiology in larvae zebrafish.

PubMed

Saszik, S; Bilotta, J

1999-11-01

Anatomic studies have found that zebrafish retinal neurons develop in a sequential fashion. In addition, exposure to abnormal light-rearing conditions produces deficits in visual behavior of larvae zebrafish, even though there appears to be little effect of the light-rearing conditions on the gross morphology of the retina. The purpose of this study was to assess the effects of abnormal light-rearing conditions on larvae zebrafish retinal physiology. Larvae zebrafish (Danio rerio) were exposed to constant light (LL), constant dark (DD), or normal cyclic light (LD) from fertilization to 6 days postfertilization (dpf). After 6 days, the animals were placed into normal cyclic light and tested at 6 to 8, 13 to 15, and 21 to 24 dpf. Electroretinogram (ERG) responses to visual stimuli, consisting of various wavelengths and irradiances, were recorded. Comparisons were made across the three age groups and the three light-rearing conditions. Deficits from the light-rearing conditions were seen immediately after exposure (6 8 dpf). The LL-condition subjects showed the greatest deficit in the UV and short-wavelength areas and the DD-condition subjects showed a slight deficit across the entire spectrum. At 13 to 15 dpf, the LL and DD groups showed an increase in sensitivity and by 21 to 24 dpf, the groups no longer differed from controls. Abnormal lighting environments can adversely influence the physiological development of the larvae zebrafish retina. The pattern of damage that was seen in zebrafish is similar to that found in other vertebrates, including higher vertebrates. However, unlike higher vertebrates, the zebrafish appears to be capable of regeneration. This suggests that the zebrafish would be a viable model for light environment effects and neural regeneration.

32 CFR 65.8 - Reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... assigned Report Control Symbols DD-P&R(AR)1221, DD-P&R(Q)2077, DD-RA(M)1147, DD-RA(D)1148, DD-RA(D)2170, DD-RA(M)2171, DD-RA(D)2302, and DD-RA(M)2303 in accordance with the requirements of DoD 8910.1-M...

Activation of a non-cAMP/PKA signaling pathway downstream of the PTH/PTHrP receptor is essential for a sustained hypophosphatemic response to PTH infusion in male mice.

PubMed

Guo, Jun; Song, Lige; Liu, Minlin; Segawa, Hiroko; Miyamoto, Ken-Ichi; Bringhurst, F Richard; Kronenberg, Henry M; Jüppner, Harald

2013-05-01

PTH increases urinary Pi excretion by reducing expression of two renal cotransporters [NaPi-IIa (Npt2a) and NaPi-IIc (Npt2c)]. In contrast to acute transporter regulation that is cAMP/protein kinase A dependent, long-term effects require phospholipase C (PLC) signaling by the PTH/PTHrP receptor (PPR). To determine whether the latter pathway regulates Pi through Npt2a and/or Npt2c, wild-type mice (Wt) and animals expressing a mutant PPR incapable of PLC activation (DD) were tested in the absence of one (Npt2a(-/-) or Npt2c(-/-)) or both phosphate transporters (2a/2c-dko). PTH infusion for 8 days caused a rapid and persistent decrease in serum Pi in Wt mice, whereas serum Pi in DD mice fell only transiently for the first 2 days. Consistent with these findings, fractional Pi excretion index was increased initially in both animals, but this increase persisted only when the PPR Wt was present. The hypophosphatemic response to PTH infusion was impaired only slightly in PPR Wt/Npt2c(-/-) or DD/Npt2c(-/-) mice. Despite lower baselines, PTH infusion in PPR Wt/Npt2a(-/-) mice decreased serum Pi further, an effect that was attenuated in DD/Npt2a(-/-) mice. Continuous PTH had no effect on serum Pi in 2a/2c-dko mice. PTH administration increased serum 1,25 dihydroxyvitamin D3 levels in Wt and DD mice and increased levels above the elevated baseline with ablation of either but not of both transporters. Continuous PTH elevated serum fibroblast growth factor 23 and blood Ca(2+) equivalently in all groups of mice. Our data indicate that PLC signaling at the PPR contributes to the long-term effect of PTH on Pi homeostasis but not to the regulation of 1,25 dihydroxyvitamin D3, fibroblast growth factor 23, or blood Ca(2+).

12 CFR 230.10 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 3 2010-01-01 2010-01-01 false [Reserved] 230.10 Section 230.10 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM TRUTH IN SAVINGS (REGULATION DD) § 230.10 [Reserved] ...

Effect of 2',3'-dideoxythymidine-5'-triphosphate on HeLa cell in vitro DNA synthesis: evidence that DNA polymerase alpha is the only polymerase required for cellular DNA replication.

PubMed Central

Waqar, M A; Evans, M J; Huberman, J A

1978-01-01

We have studied the effects of the nucleotide analogue, 2',3'-dideoxythymidine-5'-triphosphate (ddTTP) on replicative DNA synthesis in HeLa cell lysates. As previously demonstrated (1), such lysates carry out extensive DNA synthesis in vitro, at rates and in a fashion similar to in vivo DNA replication. We report here that all aspects of DNA synthesis in such lysates (total dNTP incorporation, elongation of continuous nascent strands, and the initiation, elongation, and joining of Okazaki pieces) are only slightly inhibited by concentrations of ddTTP as high as 100-500 micrometer when the dTTP concentration is maintained at 10 micrometer. This finding is consistent with the report by Edenberg, Anderson, and DePamphilis (2) that all aspects of replicative in vitro simian virus 40 DNA synthesis are also resistant to ddTTP. We also find, in agreement with Edenberg, Anderson, and DePamphilis (2), that DNA synthesis catalyzed by DNA polymerases beta or gamma is easily inhibited by ddTTP, while synthesis catalyzed by DNA polymerase alpha is very resistant. These observations suggest that DNA polymerase alpha may be the only DNA polymerase required for all aspects of cellular DNA synthesis. PMID:673840

Frequency steps and compositions determine properties of nee- dling sensation during electroacupuncture.

PubMed

Xuan, Chen; Xiaoran, Ye; Suying, Ge; Zhifang, Yao; Xiaoqing, Huang

2015-04-01

To investigate the relationship of electro-parameters and the electroacupuncture sensation (EAS), which is thought to be an important factor for optimal treatment. The frequency steps and compositions of three frequently used electrical stimulations were set when the switch of the electroacupuncture apparatus was turned to the second or third grade of the dense-disperse frequency wave (DD2 and DD3, respectively) or the second grade of the continuous wave (C2). Three groups of patients according to the three electroacupuncture stimulations were divided again into three sub-groups according to the stimulated acupoints: the face acupoint Quanliao (SI 18), the upper-limb acupoint Quchi (LI 11) and the back acupoint Dachangshu (BL 25). The EAS values were measured every 5 min during 30 min electroacupuncture treatments using a visual analogue scale. The frequency compositions of the three electroacupuncture stimulations were 3.3 and 33 Hz, 12.5 and 66.7 Hz, and 3.3 and 3.3 Hz; each frequency step was 30, 54 and 0 Hz, respectively. In each sub-group of the C2 group, the EAS values from 10 to 30 min were significantly weaker than at 0 min. The sensation fluctuations in the DD2 and DD3 groups were different during the 30 min. The greater the frequency step of the electroacupuncture stimulation, the longer the needling sensation lasted. The electroacupuncture stimulations of the DD3 group were unsuitable for the facial acupoint because of its painful and uncomfortable EAS, but more suitable for the back acupoint.

32 CFR 253.6 - Procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... continuation of assignment is not clearly consistent with the national interest. (d) Completed security forms (DD Form 398, Personnel Security Questionnaire (BI/SBI), or 398-2, Personnel Security Questionnaire (National Agency Check)) shall be forwarded to the Defense Industrial Security Clearance Office (DISCO...

Early development of circadian rhythmicity in the suprachiamatic nuclei and pineal gland of teleost, flounder (Paralichthys olivaeus), embryos.

PubMed

Mogi, Makoto; Uji, Susumu; Yokoi, Hayato; Suzuki, Tohru

2015-08-01

Circadian rhythms enable organisms to coordinate multiple physiological processes and behaviors with the earth's rotation. In mammals, the suprachiasmatic nuclei (SCN), the sole master circadian pacemaker, has entrainment mechanisms that set the circadian rhythm to a 24-h cycle with photic signals from retina. In contrast, the zebrafish SCN is not a circadian pacemaker, instead the pineal gland (PG) houses the major circadian oscillator. The SCN of flounder larvae, unlike that of zebrafish, however, expresses per2 with a rhythmicity of daytime/ON and nighttime/OFF. Here, we examined whether the rhythm of per2 expression in the flounder SCN represents the molecular clock. We also examined early development of the circadian rhythmicity in the SCN and PG. Our three major findings were as follows. First, rhythmic per2 expression in the SCN was maintained under 24 h dark (DD) conditions, indicating that a molecular clock exists in the flounder SCN. Second, onset of circadian rhythmicity in the SCN preceded that in the PG. Third, both 24 h light (LL) and DD conditions deeply affected the development of circadian rhythmicity in the SCN and PG. This is the first report dealing with the early development of circadian rhythmicity in the SCN in fish. © 2015 Japanese Society of Developmental Biologists.

Delay of behavioral estrus in hamsters and phenobarbital.

PubMed

Alleva, J J

1989-01-01

The onset of behavioral estrus was used as a phase marker of the hamster timing system in SLD 16:8 (dark 20:00-04:00). TZ was injected between 11:00 of cycle day 3 and noon of cycle day 4 when onset of estrus was determined. At no time did injection of TZ cause a phase advance in SLD 16:8. Small delays of estrus resulted from 11:00-16:00 injections but marked delays began with the 17:00 injection. Phenobarbital was injected between noon and 19:30 on cycle day 3. Injections between noon and 16:00 had no effect but all later injections beginning at 17:00 delayed estrus, the 17:30 injection causing the greatest delay. Diazepam also markedly delayed estrus when tested at 17:30. These results with three drugs support results with light pulses that 18:00 in SLD 16:8 marks the same phase of the 24-h hamster timing system as the onset of wheel running does in DD, LL, and WLD. These findings with three GABA potentiators extend to SLD previous evidence based on the onset of wheel running in DD, LL and WLD that GABA may be involved in hamster timekeeping and its responses to light and drugs.

48 CFR 53.303-DD-254 - Department of Defense DD Form 254, Contract Security Classification Specification.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Department of Defense DD Form 254, Contract Security Classification Specification. 53.303-DD-254 Section 53.303-DD-254 Federal... Illustrations of Forms 53.303-DD-254 Department of Defense DD Form 254, Contract Security Classification...

48 CFR 53.303-DD-254 - Department of Defense DD Form 254, Contract Security Classification Specification.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Department of Defense DD Form 254, Contract Security Classification Specification. 53.303-DD-254 Section 53.303-DD-254 Federal... Illustrations of Forms 53.303-DD-254 Department of Defense DD Form 254, Contract Security Classification...

48 CFR 53.303-DD-254 - Department of Defense DD Form 254, Contract Security Classification Specification.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Department of Defense DD Form 254, Contract Security Classification Specification. 53.303-DD-254 Section 53.303-DD-254 Federal... Illustrations of Forms 53.303-DD-254 Department of Defense DD Form 254, Contract Security Classification...

48 CFR 53.303-DD-441 - Department of Defense DD Form 441, Security Agreement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Department of Defense DD Form 441, Security Agreement. 53.303-DD-441 Section 53.303-DD-441 Federal Acquisition Regulations...-DD-441 Department of Defense DD Form 441, Security Agreement. EC01MY91.163 EC01MY91.164 ...

48 CFR 53.303-DD-441 - Department of Defense DD Form 441, Security Agreement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Department of Defense DD Form 441, Security Agreement. 53.303-DD-441 Section 53.303-DD-441 Federal Acquisition Regulations...-DD-441 Department of Defense DD Form 441, Security Agreement. EC01MY91.163 EC01MY91.164 ...

48 CFR 53.303-DD-441 - Department of Defense DD Form 441, Security Agreement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Department of Defense DD Form 441, Security Agreement. 53.303-DD-441 Section 53.303-DD-441 Federal Acquisition Regulations...-DD-441 Department of Defense DD Form 441, Security Agreement. EC01MY91.163 EC01MY91.164 ...

48 CFR 53.303-DD-254 - Department of Defense DD Form 254, Contract Security Classification Specification.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Department of Defense DD Form 254, Contract Security Classification Specification. 53.303-DD-254 Section 53.303-DD-254 Federal... Illustrations of Forms 53.303-DD-254 Department of Defense DD Form 254, Contract Security Classification...

48 CFR 53.303-DD-254 - Department of Defense DD Form 254, Contract Security Classification Specification.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 2 2012-10-01 2012-10-01 false Department of Defense DD Form 254, Contract Security Classification Specification. 53.303-DD-254 Section 53.303-DD-254 Federal... Illustrations of Forms 53.303-DD-254 Department of Defense DD Form 254, Contract Security Classification...

48 CFR 53.303-DD-441 - Department of Defense DD Form 441, Security Agreement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 2 2012-10-01 2012-10-01 false Department of Defense DD Form 441, Security Agreement. 53.303-DD-441 Section 53.303-DD-441 Federal Acquisition Regulations...-DD-441 Department of Defense DD Form 441, Security Agreement. EC01MY91.163 EC01MY91.164 ...

48 CFR 53.303-DD-441 - Department of Defense DD Form 441, Security Agreement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Department of Defense DD Form 441, Security Agreement. 53.303-DD-441 Section 53.303-DD-441 Federal Acquisition Regulations...-DD-441 Department of Defense DD Form 441, Security Agreement. EC01MY91.163 EC01MY91.164 ...

32 CFR 199.20 - Continued Health Care Benefit Program (CHCBP).

Code of Federal Regulations, 2011 CFR

2011-07-01

... attained the age of 21 if not in school or age 23 if enrolled in a full time course of study at an... Privilege Card”; (iii) A front and back copy of a DD Form 1173, “Uniformed Services Identification and...

Genetic requirements for sensitivity of bacteriophage t7 to dideoxythymidine.

PubMed

Tran, Ngoc Q; Tabor, Stanley; Richardson, Charles C

2014-08-01

We previously reported that the presence of dideoxythymidine (ddT) in the growth medium selectively inhibits the ability of bacteriophage T7 to infect Escherichia coli by inhibiting phage DNA synthese (N. Q. Tran, L. F. Rezende, U. Qimron, C. C. Richardson, and S. Tabor, Proc. Natl. Acad. Sci. U. S. A. 105:9373-9378, 2008, doi:10.1073/pnas.0804164105). In the presence of T7 gene 1.7 protein, ddT is taken up into the E. coli cell and converted to ddTTP. ddTTP is incorporated into DNA as ddTMP by the T7 DNA polymerase, resulting in chain termination. We have identified the pathway by which exogenous ddT is converted to ddTTP. The pathway consists of ddT transport by host nucleoside permeases and phosphorylation to ddTMP by the host thymidine kinase. T7 gene 1.7 protein phosphorylates ddTMP and ddTDP, resulting in ddTTP. A 74-residue peptide of the gene 1.7 protein confers ddT sensitivity to the same extent as the 196-residue wild-type gene 1.7 protein. We also show that cleavage of thymidine to thymine and deoxyribose-1-phosphate by the host thymidine phosphorylase greatly increases the sensitivity of phage T7 to ddT. Finally, a mutation in T7 DNA polymerase that leads to discrimination against the incorporation of ddTMP eliminates ddT sensitivity. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Genetic Requirements for Sensitivity of Bacteriophage T7 to Dideoxythymidine

PubMed Central

Tran, Ngoc Q.; Tabor, Stanley

2014-01-01

We previously reported that the presence of dideoxythymidine (ddT) in the growth medium selectively inhibits the ability of bacteriophage T7 to infect Escherichia coli by inhibiting phage DNA synthese (N. Q. Tran, L. F. Rezende, U. Qimron, C. C. Richardson, and S. Tabor, Proc. Natl. Acad. Sci. U. S. A. 105:9373–9378, 2008, doi:10.1073/pnas.0804164105). In the presence of T7 gene 1.7 protein, ddT is taken up into the E. coli cell and converted to ddTTP. ddTTP is incorporated into DNA as ddTMP by the T7 DNA polymerase, resulting in chain termination. We have identified the pathway by which exogenous ddT is converted to ddTTP. The pathway consists of ddT transport by host nucleoside permeases and phosphorylation to ddTMP by the host thymidine kinase. T7 gene 1.7 protein phosphorylates ddTMP and ddTDP, resulting in ddTTP. A 74-residue peptide of the gene 1.7 protein confers ddT sensitivity to the same extent as the 196-residue wild-type gene 1.7 protein. We also show that cleavage of thymidine to thymine and deoxyribose-1-phosphate by the host thymidine phosphorylase greatly increases the sensitivity of phage T7 to ddT. Finally, a mutation in T7 DNA polymerase that leads to discrimination against the incorporation of ddTMP eliminates ddT sensitivity. PMID:24858186

12 CFR 230.3 - General disclosure requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 230.3 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM TRUTH IN SAVINGS (REGULATION DD) § 230.3 General disclosure requirements. (a) Form. Depository... the consumer and the depository institution. Disclosures may be made in languages other than English...

Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay

PubMed Central

Lee, Li-Ching; Crum, Rosa M.; Zimmerman, Andrew W.; Hertz-Picciotto, Irva

2014-01-01

OBJECTIVE: To examine associations between prenatal use of selective serotonin reuptake inhibitors (SSRIs) and the odds of autism spectrum disorders (ASDs) and other developmental delays (DDs). METHODS: A total of 966 mother-child pairs were evaluated (492 ASD, 154 DD, 320 typical development [TD]) from the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, a population-based case-control study. Standardized measures confirmed developmental status. Interviews with biological mothers ascertained prenatal SSRI use, maternal mental health history, and sociodemographic information. RESULTS: Overall, prevalence of prenatal SSRI exposure was lowest in TD children (3.4%) but did not differ significantly from ASD (5.9%) or DD (5.2%) children. Among boys, prenatal SSRI exposure was nearly 3 times as likely in children with ASD relative to TD (adjusted odds ratio [OR]: 2.91; 95% confidence interval [CI]: 1.07–7.93); the strongest association occurred with first-trimester exposure (OR: 3.22; 95% CI: 1.17–8.84). Exposure was also elevated among boys with DD (OR: 3.39; 95% CI: 0.98–11.75) and was strongest in the third trimester (OR: 4.98; 95% CI: 1.20–20.62). Findings were similar among mothers with an anxiety or mood disorder history. CONCLUSIONS: In boys, prenatal exposure to SSRIs may increase susceptibility to ASD or DD. Findings from published studies on SSRIs and ASD continues to be inconsistent. Potential recall bias and residual confounding by indication are concerns. Larger samples are needed to replicate DD results. Because maternal depression itself carries risks for the fetus, the benefits of prenatal SSRI use should be carefully weighed against potential harms. PMID:24733881

A comparison of pregnancy outcomes in Ghanaian women with varying dietary diversity: a prospective cohort study protocol

PubMed Central

Saaka, Mahama; Siassi, Fereydoun; Qorbani, Mostafa; Yavari, Parvaneh; Danquah, Ina; Sotoudeh, Gity

2016-01-01

Introduction Poor dietary intake during pregnancy can have negative repercussions on the mother and fetus. This study therefore aims to explore the dietary diversity (DD) of pregnant women and its associations with pregnancy outcomes among women in Northern Ghana. The main outcome variables to be measured are gestational weight gain and birth weight. Methods and analysis A prospective cohort study design will be used and 600 pregnant women in their first trimester will be systematically recruited at health facilities and followed until delivery. In three follow-up visits after recruitment, information on sociodemographic and general characteristics, physical activity (International Physical Activity Questionnaire (IPAQ) short form, dietary intake (24-hour food recall), anthropometry and pregnancy outcomes will be collected. DD will be measured three times using the minimum DD-women (MDD-W) indicator and the mean of the three values overall will be used to determine low (<5 food groups) and high (≥5 food groups) DD. Data will be analysed using SPSS. Comparisons between groups (categorical data) will be made using the χ2 test for proportions, and t-tests and ANOVA will be performed on continuous variables. Regression analysis will be used to identify independent outcome predictors while controlling for possible confounding factors. The results may help to identify differences in DD between healthy and unhealthy pregnancy outcomes. Ethics and dissemination The study protocol has been approved by the ethics committee of Tehran University of Medical Sciences and the ethical review committee of the Tamale Teaching Hospital. Written informed consent will be obtained from all subjects. The results will be published in due course. PMID:27655259

PHOTOMETRIC STUDY OF THE VERY SHORT PERIOD SHALLOW CONTACT BINARY DD COMAE BERENICES

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

Zhu, L.; Qian, S.-B.; Mikulasek, Z.

2010-07-15

The first photometric solutions of the very short period (VSP) close binary DD Comae Berenices (P = 0fd26920811) based on our new complete (IR){sub C} light curves are derived by the 2003 version Wilson-Van Hamme code. They show that the system belongs to shallow contact W-type W UMa systems with a degree of overcontact of 8.7%. The observed light curve distortions are explained by employing the spots model due to the late-type nature of both components. We have collected all available photometric data about the system with emphasis on the individual observational data, which we treated simultaneously using our ownmore » method based on the usage of computed model light curves as templates. We recalculated published times of light minimum and added new ones of our own to construct an O - C diagram that spans over 70 years. Using a least squares method orthogonal quadratic model function, we found that the orbital period of DD Com is continuously increasing with P-dot =0.00401(22) s yr{sup -1}. The period increase may be caused by the mass transfer from the less-massive component to the more-massive one. With the period increase, the binary is evolving from the present shallow contact phase to the broken stage predicted by the thermal relaxation oscillation (TRO) theory. Compared with other VSP systems, DD Com is a rare system that lies on the expanding phase of the TRO cycle. Until now, only four such systems including DD Com are found in this stage. Thus, this target is another good observational proof of the TRO theory in a very short period region.« less

PAM50 gene signatures and breast cancer prognosis with adjuvant anthracycline- and taxane-based chemotherapy: correlative analysis of C9741 (Alliance)

PubMed Central

Liu, Minetta C; Pitcher, Brandelyn N; Mardis, Elaine R; Davies, Sherri R; Friedman, Paula N; Snider, Jacqueline E; Vickery, Tammi L; Reed, Jerry P; DeSchryver, Katherine; Singh, Baljit; Gradishar, William J; Perez, Edith A; Martino, Silvana; Citron, Marc L; Norton, Larry; Winer, Eric P; Hudis, Clifford A; Carey, Lisa A; Bernard, Philip S; Nielsen, Torsten O; Perou, Charles M; Ellis, Matthew J; Barry, William T

2016-01-01

PAM50 intrinsic breast cancer subtypes are prognostic independent of standard clinicopathologic factors. CALGB 9741 demonstrated improved recurrence-free (RFS) and overall survival (OS) with 2-weekly dose-dense (DD) versus 3-weekly therapy. A significant interaction between intrinsic subtypes and DD-therapy benefit was hypothesized. Suitable tumor samples were available from 1,471 (73%) of 2,005 subjects. Multiplexed gene-expression profiling generated the PAM50 subtype call, proliferation score, and risk of recurrence score (ROR-PT) for the evaluable subset of 1,311 treated patients. The interaction between DD-therapy benefit and intrinsic subtype was tested in a Cox proportional hazards model using two-sided alpha=0.05. Additional multivariable Cox models evaluated the proliferation and ROR-PT scores as continuous measures with selected clinical covariates. Improved outcomes for DD therapy in the evaluable subset mirrored results from the complete data set (RFS; hazard ratio=1.20; 95% confidence interval=0.99–1.44) with 12.3-year median follow-up. Intrinsic subtypes were prognostic of RFS (P<0.0001) irrespective of treatment assignment. No subtype-specific treatment effect on RFS was identified (interaction P=0.44). Proliferation and ROR-PT scores were prognostic for RFS (both P<0.0001), but no association with treatment benefit was seen (P=0.14 and 0.59, respectively). Results were similar for OS. The prognostic value of PAM50 intrinsic subtype was greater than estrogen receptor/HER2 immunohistochemistry classification. PAM50 gene signatures were highly prognostic but did not predict for improved outcomes with DD anthracycline- and taxane-based therapy. Clinical validation studies will assess the ability of PAM50 and other gene signatures to stratify patients and individualize treatment based on expected risks of distant recurrence. PMID:28691057

Trends in dual diagnosis of severe mental illness and substance use disorders, 1996-2010, Israel.

PubMed

Ponizovsky, Alexander M; Rosca, Paola; Haklai, Ziona; Goldberger, Nehama

2015-03-01

(1) To examine the trends in the incidence of dual diagnosis (DD) of severe mental illness and substance-related disorders among inpatients in Israel, and (2) the demographic and clinical correlates of DD patients. Using data from the National Psychiatric Case Register, we identified 56,774 inpatients aged 15-64 whose first psychiatric hospitalization occurred between 1996 and 2010. We compared the characteristics of inpatients having DD with drugs, alcohol or drug/alcohol abuse with those with mental disorder only. Over the period, DD with drugs decreased from 8.2% in 1996 to 6% in 2010; DD with alcohol increased from 3% to 4% and DD with drugs/alcohol from 2% to 4%. DD with drugs was highest, whereas DD with alcohol was lowest for the youngest age- group in 1996 but increased to the same as other age-groups in 2006-2010. Male gender, a previous suicide attempt, compulsory hospitalizations and marital status were positive predictors for all DD. Immigrant status was a positive predictor of DD with alcohol, but the opposite for DD with drugs; being Jewish and psychotic diagnosis was a positive predictor of DD with drugs, but negative for DD with alcohol. Over the study period, DD with drugs has decreased among young patients, although it is still higher than among older groups. However, DD with alcohol or drugs/alcohol has increased in the younger group. The clinical-demographic profile of DD patients was similar to that from the relevant literature, except for immigrant status that was negatively associated with DD with drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Platelet-derived growth factor-DD targeting arrests pathological angiogenesis by modulating glycogen synthase kinase-3beta phosphorylation.

PubMed

Kumar, Anil; Hou, Xu; Lee, Chunsik; Li, Yang; Maminishkis, Arvydas; Tang, Zhongshu; Zhang, Fan; Langer, Harald F; Arjunan, Pachiappan; Dong, Lijin; Wu, Zhijian; Zhu, Linda Y; Wang, Lianchun; Min, Wang; Colosi, Peter; Chavakis, Triantafyllos; Li, Xuri

2010-05-14

Platelet-derived growth factor-DD (PDGF-DD) is a recently discovered member of the PDGF family. The role of PDGF-DD in pathological angiogenesis and the underlying cellular and molecular mechanisms remain largely unexplored. In this study, using different animal models, we showed that PDGF-DD expression was up-regulated during pathological angiogenesis, and inhibition of PDGF-DD suppressed both choroidal and retinal neovascularization. We also demonstrated a novel mechanism mediating the function of PDGF-DD. PDGF-DD induced glycogen synthase kinase-3beta (GSK3beta) Ser(9) phosphorylation and Tyr(216) dephosphorylation in vitro and in vivo, leading to increased cell survival. Consistently, GSK3beta activity was required for the antiangiogenic effect of PDGF-DD targeting. Moreover, PDGF-DD regulated the expression of GSK3beta and many other genes important for angiogenesis and apoptosis. Thus, we identified PDGF-DD as an important target gene for antiangiogenic therapy due to its pleiotropic effects on vascular and non-vascular cells. PDGF-DD inhibition may offer new therapeutic options to treat neovascular diseases.

How dark chocolate is processed

USDA-ARS?s Scientific Manuscript database

This month’s column will continue the theme of “How Is It Processed?” The column will focus on dark chocolate. The botanical name for the cacao tree is Theobroma cacao, which literally means “food of the Gods.” Dark chocolate is both delicious and nutritious. Production of dark chocolate will be des...

32 CFR 65.8 - Reporting requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 1 2012-07-01 2012-07-01 false Reporting requirements. 65.8 Section 65.8 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN... assigned Report Control Symbols DD-P&R(AR)1221, DD-P&R(Q)2077, DD-RA(M)1147, DD-RA(D)1148, DD-RA(D)2170, DD...

48 CFR 53.204-1 - Safeguarding classified information within industry (DD Form 254, DD Form 441).

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Safeguarding classified information within industry (DD Form 254, DD Form 441). 53.204-1 Section 53.204-1 Federal Acquisition....204-1 Safeguarding classified information within industry (DD Form 254, DD Form 441). The following...

48 CFR 53.204-1 - Safeguarding classified information within industry (DD Form 254, DD Form 441).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Safeguarding classified information within industry (DD Form 254, DD Form 441). 53.204-1 Section 53.204-1 Federal Acquisition....204-1 Safeguarding classified information within industry (DD Form 254, DD Form 441). The following...

48 CFR 53.204-1 - Safeguarding classified information within industry (DD Form 254, DD Form 441).

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 2 2012-10-01 2012-10-01 false Safeguarding classified information within industry (DD Form 254, DD Form 441). 53.204-1 Section 53.204-1 Federal Acquisition....204-1 Safeguarding classified information within industry (DD Form 254, DD Form 441). The following...

48 CFR 53.204-1 - Safeguarding classified information within industry (DD Form 254, DD Form 441).

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Safeguarding classified information within industry (DD Form 254, DD Form 441). 53.204-1 Section 53.204-1 Federal Acquisition....204-1 Safeguarding classified information within industry (DD Form 254, DD Form 441). The following...

48 CFR 53.204-1 - Safeguarding classified information within industry (DD Form 254, DD Form 441).

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Safeguarding classified information within industry (DD Form 254, DD Form 441). 53.204-1 Section 53.204-1 Federal Acquisition....204-1 Safeguarding classified information within industry (DD Form 254, DD Form 441). The following...

Basic numerical processing, calculation, and working memory in children with dyscalculia and/or ADHD symptoms.

PubMed

Kuhn, Jörg-Tobias; Ise, Elena; Raddatz, Julia; Schwenk, Christin; Dobel, Christian

2016-09-01

Deficits in basic numerical skills, calculation, and working memory have been found in children with developmental dyscalculia (DD) as well as children with attention-deficit/hyperactivity disorder (ADHD). This paper investigates cognitive profiles of children with DD and/or ADHD symptoms (AS) in a double dissociation design to obtain a better understanding of the comorbidity of DD and ADHD. Children with DD-only (N = 33), AS-only (N = 16), comorbid DD+AS (N = 20), and typically developing controls (TD, N = 40) were assessed on measures of basic numerical processing, calculation, working memory, processing speed, and neurocognitive measures of attention. Children with DD (DD, DD+AS) showed deficits in all basic numerical skills, calculation, working memory, and sustained attention. Children with AS (AS, DD+AS) displayed more selective difficulties in dot enumeration, subtraction, verbal working memory, and processing speed. Also, they generally performed more poorly in neurocognitive measures of attention, especially alertness. Children with DD+AS mostly showed an additive combination of the deficits associated with DD-only and A_Sonly, except for subtraction tasks, in which they were less impaired than expected. DD and AS appear to be related to largely distinct patterns of cognitive deficits, which are present in combination in children with DD+AS.

Physicochemical, mechanical and thermal properties of chitosan films with and without sorbitol.

PubMed

Liu, Mei; Zhou, Yibin; Zhang, Yang; Yu, Chen; Cao, Shengnan

2014-09-01

The effect of sorbitol on the physicochemical, mechanical and thermal properties of chitosan films with different degrees of deacetylation (DD; i.e., DD85% and DD95%) was investigated. The thickness, moisture content (MC), water solubility (WS) and water-vapor permeability (WVP) of the films were evaluated. Sorbitol addition reduced MC, increased WS and significantly (p<0.01) reduced WVP of both film types. DD95% films had lower MC and WVP, and higher WS than DD85% films. Static (thermomechanical analysis) and dynamic (dynamic mechanical analysis) tests indicated that sorbitol increased the strain and decreased stress for both DD films, but DD95% could sustain higher strain and DD85% could sustain higher stress. Thermogravimetrics analysis and differential scanning calorimetry showed that sorbitol elicited a lower degradation temperature for both films, and that DD95% films exhibited higher thermal stability than DD85% films. Copyright © 2014 Elsevier B.V. All rights reserved.

Synergistic dark and photo-fermentation continuous system for hydrogen production from molasses by Clostridium acetobutylicum ATCC 824 and Rhodobacter capsulatus DSM 1710.

PubMed

Morsy, Fatthy Mohamed

2017-04-01

This study investigated synergistic dark and photo-fermentation using continuous fermentation system (CFS). The system relies on connecting several fermenters from bottom of one to top culture level of the next in a manner that allows for delaying movement of the substrate and thus for its full consumption. While H 2 was collected, CFS allowed for moving liquid byproducts toward the outlet and hence continuous productivity. CFS could be efficiently used for: (1) Continuous dark and photo-fermentation H 2 production by Clostridium acetobutylicum and Rhodobacter capsulatus producing 5.65moleH 2 mole -1 hexose; (2) Continuous dark-fermentation synergistic H 2 , acetone, butanol and ethanol (ABE) production by C. acetobutylicum which produced per mole hexose, 2.43mol H 2 along with 73.08g ABE (3) Continuous H 2 and methane production by C. acetobutylicum and bacterial sludge producing, per mole hexose, 1.64mol pure H 2 and 2.56mol CH 4 mixed with 0.37mol H 2 ·The hydraulic retention time (HRT) for whole system was short where organic acids produced in dark-fermentation in first fermenter were synergistically utilized for H 2 production by R. capsulatus in subsequent fermenters. CFS is suitable for fast-digestible sugars but not lignocelluloses or other hard-digestible organics, requiring prolonged HRT, unless such polymeric organics were hydrolyzed prior to fermentation. Copyright © 2017 Elsevier B.V. All rights reserved.

ddPCRclust - An R package and Shiny app for automated analysis of multiplexed ddPCR data.

PubMed

Brink, Benedikt G; Meskas, Justin; Brinkman, Ryan R

2018-03-09

Droplet digital PCR (ddPCR) is an emerging technology for quantifying DNA. By partitioning the target DNA into ∼20000 droplets, each serving as its own PCR reaction compartment, a very high sensitivity of DNA quantification can be achieved. However, manual analysis of the data is time consuming and algorithms for automated analysis of non-orthogonal, multiplexed ddPCR data are unavailable, presenting a major bottleneck for the advancement of ddPCR transitioning from low-throughput to high- throughput. ddPCRclust is an R package for automated analysis of data from Bio-Rad's droplet digital PCR systems (QX100 and QX200). It can automatically analyse and visualise multiplexed ddPCR experiments with up to four targets per reaction. Results are on par with manual analysis, but only take minutes to compute instead of hours. The accompanying Shiny app ddPCRvis provides easy access to the functionalities of ddPCRclust through a web-browser based GUI. R package: https://github.com/bgbrink/ddPCRclust; Interface: https://github.com/bgbrink/ddPCRvis/; Web: https://bibiserv.cebitec.uni-bielefeld.de/ddPCRvis/. bbrink@cebitec.uni-bielefeld.de.

Roles of the C-terminal domains of human dihydrodiol dehydrogenase isoforms in the binding of substrates and modulators: probing with chimaeric enzymes.

PubMed Central

Matsuura, K; Hara, A; Deyashiki, Y; Iwasa, H; Kume, T; Ishikura, S; Shiraishi, H; Katagiri, Y

1998-01-01

Human liver dihydrodiol dehydrogenase (DD; EC 1.3.1.20) exists in isoforms (DD1, DD2 and DD4) composed of 323 amino acids. DD1 and DD2 share 98% amino acid sequence identity, but show lower identities (approx. 83%) with DD4, in which a marked difference is seen in the C-terminal ten amino acids. DD4 exhibits unique catalytic properties, such as the ability to oxidize both (R)- and (S)-alicyclic alcohols equally, high dehydrogenase activity for bile acids, potent inhibition by steroidal anti-inflammatory drugs and activation by sulphobromophthalein and clofibric acid derivatives. In this study, we have prepared chimaeric enzymes, in which we exchanged the C-terminal 39 residues between the two enzymes. Compared with DD1, CDD1-4 (DD1 with the C-terminal sequence of DD4) had increased kcat/Km values for 3alpha-hydroxy-5beta-androstanes and bile acids of 3-9-fold and decreased values for the other substrates by 5-100-fold. It also became highly sensitive to DD4 inhibitors such as phenolphthalein and hexoestrol. Another chimaeric enzyme, CDD4-1 (DD4 with the C-terminal sequence of DD1), showed the same (S)-stereospecificity for the alicyclic alcohols as DD1, had decreased kcat/Km values for bile acids with 7beta- or 12alpha-hydroxy groups by more than 120-fold and was resistant to inhibition by betamethasone. In addition, the activation effects of sulphobromophthalein and bezafibrate decreased or disappeared for CDD4-1. The recombinant DD4 with the His314-->Pro (the corresponding residue of DD1) mutation showed intermediate changes in the properties between those of wild-type DD4 and CDD4-1. The results indicate that the binding of substrates, inhibitors and activators to the enzymes is controlled by residues in their C-terminal domains; multiple residues co-ordinately act as determinants for substrate specificity and inhibitor sensitivity. PMID:9820821

32 CFR 750.6 - Claims: Presentment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 5 2013-07-01 2013-07-01 false Claims: Presentment. 750.6 Section 750.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY CLAIMS GENERAL CLAIMS REGULATIONS... Claims Act shall be submitted on DD Form 1842. 2 The claim and all other papers requiring the signature...

32 CFR 750.6 - Claims: Presentment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Claims: Presentment. 750.6 Section 750.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY CLAIMS GENERAL CLAIMS REGULATIONS... Claims Act shall be submitted on DD Form 1842. 2 The claim and all other papers requiring the signature...

32 CFR 750.6 - Claims: Presentment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 5 2011-07-01 2011-07-01 false Claims: Presentment. 750.6 Section 750.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY CLAIMS GENERAL CLAIMS REGULATIONS... Claims Act shall be submitted on DD Form 1842. 2 The claim and all other papers requiring the signature...

32 CFR 750.6 - Claims: Presentment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 5 2012-07-01 2012-07-01 false Claims: Presentment. 750.6 Section 750.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY CLAIMS GENERAL CLAIMS REGULATIONS... Claims Act shall be submitted on DD Form 1842. 2 The claim and all other papers requiring the signature...

32 CFR 855.8 - Application procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 6 2013-07-01 2013-07-01 false Application procedures. 855.8 Section 855.8 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE AIRCRAFT CIVIL AIRCRAFT USE.... To allow time for processing, the application (DD Forms 2400, 2401, and 2402) and a self-addressed...

32 CFR 855.8 - Application procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 6 2012-07-01 2012-07-01 false Application procedures. 855.8 Section 855.8 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE AIRCRAFT CIVIL AIRCRAFT USE.... To allow time for processing, the application (DD Forms 2400, 2401, and 2402) and a self-addressed...

32 CFR 855.8 - Application procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 6 2014-07-01 2014-07-01 false Application procedures. 855.8 Section 855.8 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE AIRCRAFT CIVIL AIRCRAFT USE.... To allow time for processing, the application (DD Forms 2400, 2401, and 2402) and a self-addressed...

32 CFR 855.8 - Application procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 6 2011-07-01 2011-07-01 false Application procedures. 855.8 Section 855.8 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE AIRCRAFT CIVIL AIRCRAFT USE.... To allow time for processing, the application (DD Forms 2400, 2401, and 2402) and a self-addressed...

Interpretation of Overall Colonic Transit in Defecation Disorders in Males and Females

PubMed Central

Shin, Andrea; Camilleri, Michael; Nadeau, Ashley; Nullens, Sara; Rhee, Jong Chul; Jeong, In Du; Burton, Duane D.

2013-01-01

Background There is little information regarding gender-specific measurements of colonic transit and anorectal function in patients with defecation disorders (DD). Aim To compare overall colonic transit by gender in DD. Methods In 407 patients with constipation due to DD diagnosed by a single gastroenterologist (1994– 2012), DD was characterized by anorectal manometry, balloon expulsion test, and colonic transit by scintigraphy. The primary endpoint was overall colonic transit (geometric center, GC) at 24hours (GC24). Effects of gender in DD on colonic transit, and comparison with transit in 208 healthy controls were assessed by Mann-Whitney rank sum test. Secondary endpoints were maximum anal resting (ARP) and squeeze (ASP) pressures. We also tested association of the physiological endpoints among DD females by pregnancy history and among DD patients by colectomy history. Results The DD patients were 67 males (M) and 340 females (F). Significant differences by gender in DD patients were observed in GC24 (median: M: 2.2; F: 1.8; p=0.01), ARP (median: M: 87.8mmHg; F: 82.4mmHg; p=0.04), and ASP (median: M: 182.4mmHg; F: 128.7mmHg; p<0.001). GC24 was slower in DD compared to same gender healthy controls. GC24 did not differ among DD females by pregnancy history. Anorectal functions and upper GI transit did not differ among DD patients by colectomy history. Conclusions Patients with DD have slower colonic transit compared to gender-matched controls. Among DD patients, males have higher ARP and ASP, and females have slower colonic transit. Although the clinical significance of these differences may be unclear, findings suggest that interpretation of these tests in suspected DD should be based on same gender control data. PMID:23406422

Direct measurements of the non-DD cross section {sigma}{sub {psi}}{sub (3770){yields}}{sub non-DD} at E{sub cm}=3.773 GeV and the branching fraction for {psi}(3770){yields}non-DD

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

Ablikim, M.; Bai, J. Z.; Cai, X.

2007-12-15

By analyzing the data collected at the center-of-mass energy E{sub cm}=3.773 GeV and below the DD meson pair production threshold with the BES-II detector at the BEPC Collider, we directly measured the observed non-DD cross section of {psi}(3770) decay to be {sigma}{sub {psi}}{sub (3770){yields}}{sub non-DD}{sup obs}=(0.95{+-}0.35{+-}0.29) nb at E{sub cm}=3.773 GeV, and the branching fraction BF[{psi}(3770){yields}non-DD]=(13.4{+-}5.0{+-}3.6)% for inclusive non-DD decay of {psi}(3770). We also determined the cross section for DD meson pair production to be {sigma}{sub DD}{sup obs}=(6.12{+-}0.37{+-}0.23) nb at E{sub cm}=3.773 GeV.

2,3 Butanediol production in an obligate photoautotrophic cyanobacterium in dark conditions via diverse sugar consumption.

PubMed

McEwen, Jordan T; Kanno, Masahiro; Atsumi, Shota

2016-07-01

Cyanobacteria are under investigation as a means to utilize light energy to directly recycle CO2 into chemical compounds currently derived from petroleum. Any large-scale photosynthetic production scheme must rely on natural sunlight for energy, thereby limiting production time to only lighted hours during the day. Here, an obligate photoautotrophic cyanobacterium was engineered for enhanced production of 2,3-butanediol (23BD) in continuous light, 12h:12h light-dark diurnal, and continuous dark conditions via supplementation with glucose or xylose. This study achieved 23BD production under diurnal conditions comparable to production under continuous light conditions. The maximum 23BD titer was 3.0gL(-1) in 10d. Also achieving chemical production under dark conditions, this work enhances the feasibility of using cyanobacteria as industrial chemical-producing microbes. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

[Effect of light regimens on the age dynamics of estrous function and serum prolactin level in rats].

PubMed

Vinogradova, I A; Chernova, I V

2006-01-01

The effect of different light regimens (standard 12 h. light : 12 h. darkness LD; 24-hour constant light LL, light deprivation DD, natural light regimen of the North-West of Russia NL) on the age dynamics of estrous function and on the serum prolactin in female LIO rats has been studied for two years. The rats were maintained at the one of above-mentioned regimes from the age of 25 days. The cytological monitoring of the estrous cycle was conducted every three months. The level of prolactin was studied at the age of 6, 12, 18 and 24 months. It has been found out that the regimen of constant light (LL) and the spring-summer period lead to earlier maturation, premature age-related changes of the rats' estrous cycle and to the increase of the level of serum prolactin in comparison with those in rats kept at the LD regimen. Light deprivation (DD) leads to the opposite changes. It has been noted that the exposure to constant light during the whole year is accompanied by more expressed and earlier developed age-related changes of estrous cycle in comparison with the natural light of the North-West of Russia with its peculiar year photoperiodicity (short day in autumn-winter period and white nights in spring-summer period).

Compressed 3D and 2D digital images versus standard 3D slide film for the evaluation of glaucomatous optic nerve features.

PubMed

Sandhu, Simrenjeet; Rudnisky, Chris; Arora, Sourabh; Kassam, Faazil; Douglas, Gordon; Edwards, Marianne C; Verstraten, Karin; Wong, Beatrice; Damji, Karim F

2018-03-01

Clinicians can feel confident compressed three-dimensional digital (3DD) and two-dimensional digital (2DD) imaging evaluating important features of glaucomatous disc damage is comparable to the previous gold standard of stereoscopic slide film photography, supporting the use of digital imaging for teleglaucoma applications. To compare the sensitivity and specificity of 3DD and 2DD photography with stereo slide film in detecting glaucomatous optic nerve head features. This prospective, multireader validation study imaged and compressed glaucomatous, suspicious or normal optic nerves using a ratio of 16:1 into 3DD and 2DD (1024×1280 pixels) and compared both to stereo slide film. The primary outcome was vertical cup-to-disc ratio (VCDR) and secondary outcomes, including disc haemorrhage and notching, were also evaluated. Each format was graded randomly by four glaucoma specialists. A protocol was implemented for harmonising data including consensus-based interpretation as needed. There were 192 eyes imaged with each format. The mean VCDR for slide, 3DD and 2DD was 0.59±0.20, 0.60±0.18 and 0.62±0.17, respectively. The agreement of VCDR for 3DD versus film was κ=0.781 and for 2DD versus film was κ=0.69. Sensitivity (95.2%), specificity (95.2%) and area under the curve (AUC; 0.953) of 3DD imaging to detect notching were better (p=0.03) than for 2DD (90.5%; 88.6%; AUC=0.895). Similarly, sensitivity (77.8%), specificity (98.9%) and AUC (0.883) of 3DD to detect disc haemorrhage were better (p=0.049) than for 2DD (44.4%; 99.5%; AUC=0.72). There was no difference between 3DD and 2DD imaging in detecting disc tilt (p=0.7), peripapillary atrophy (p=0.16), grey crescent (p=0.1) or pallor (p=0.43), although 3D detected sloping better (p=0.013). Both 3DD and 2DD imaging demonstrates excellent reproducibility in comparison to stereo slide film with experts evaluating VCDR, notching and disc haemorrhage. 3DD in this study was slightly more accurate than 2DD for evaluating disc haemorrhage, notching and sloping. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Danish Centre for Strategic Research in Type 2 Diabetes (DD2) study: expected outcome from the DD2 project and two intervention studies

PubMed Central

Beck-Nielsen, Henning; Solomon, Thomas PJ; Lauridsen, Jørgen; Karstoft, Kristian; Pedersen, Bente K; Johnsen, Søren P; Nielsen, Jens Steen; Kryger, Tine Bjerregaard; Sortsø, Camilla; Vaag, Allan

2012-01-01

The overall aim of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) is to near-normalize metabolic control in newly diagnosed patients with type 2 diabetes (T2D) using an individualized treatment approach. We hypothesize that this will not only prevent complications and improve quality of life for T2D patients but also result in increased cost efficiency compared with current treatment modalities. This paper provides an overview of the expected outcomes from DD2, focusing on the two main intervention studies. The main data for the DD2 project are collected during patient enrollment and stored using the individual civil registration number. This enables subsequent linking to other national databases where supplemental data can be obtained. All data will be used for designing treatment guidelines and continuously monitoring the development of diabetic complications, thereby obtaining knowledge about predictors for the long-term outcome and identifying targets for new interventions. Further data are being collected from two intervention studies. The aim of the first intervention study is to improve T2D treatment using an individualized treatment modality optimizing medication according to individual metabolic responses and phenotypic characteristics. The aim of the second intervention study is to develop an evidence-based training protocol to be implemented as a treatment modality for T2D and used for initiating lifelong changes in physical activity levels in patients with T2D. An initial pilot study evaluating an interval-based walking protocol is ongoing, and preliminary results indicate that this protocol is an optimal “free-living” training intervention. An initial health-economic analysis will also be performed as a basis for analysis of the data collected during the project. A cost-benefit analysis of the two intervention studies will be conducted. The DD2 project is expected to lead to improved treatment modalities and increased knowledge about existing treatment guidelines, and will also provide a solid base for health-economic decision-making. PMID:23071408

Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation: a study in 203 Indian patients.

PubMed

Boggula, Vijay R; Shukla, Anju; Danda, Sumita; Hariharan, Sankar V; Nampoothiri, Sheela; Kumar, Rashmi; Phadke, Shubha R

2014-01-01

Developmental delay (DD)/mental retardation also described as intellectual disability (ID), is seen in 1-3 per cent of general population. Diagnosis continues to be a challenge at clinical level. With the advancement of new molecular cytogenetic techniques such as cytogenetic microarray (CMA), multiplex ligation-dependent probe amplification (MLPA) techniques, many microdeletion/microduplication syndromes with DD/ID are now delineated. MLPA technique can probe 40-50 genomic regions in a single reaction and is being used for evaluation of cases with DD/ID. In this study we evaluated the clinical utility of MLPA techniques with different probe sets to identify the aetiology of unexplained mental retardation in patients with ID/DD. A total of 203 randomly selected DD/ID cases with/without malformations were studied. MLPA probe sets for subtelomeric regions (P070/P036) and common microdeletions/microduplications (P245-A2) and X-chromosome (P106) were used. Positive cases with MLPA technique were confirmed using either fluorescence in situ hybridization (FISH) or follow up confirmatory MLPA probe sets. The overall detection rate was found to be 9.3 per cent (19 out of 203). The detection rates were 6.9 and 7.4 per cent for common microdeletion/microduplication and subtelomeric probe sets, respectively. No abnormality was detected with probe set for X-linked ID. The subtelomeric abnormalities detected included deletions of 1p36.33, 4p, 5p, 9p, 9q, 13q telomeric regions and duplication of 9pter. The deletions/duplications detected in non telomeric regions include regions for Prader Willi/Angelman regions, Williams syndrome, Smith Magenis syndrome and Velocardiofacial syndrome. Our results show that the use of P245-A2 and P070/P036-E1 probes gives good diagnostic yield. Though MLPA cannot probe the whole genome like cytogenetic microarray, due to its ease and relative low cost it is an important technique for evaluation of cases with DD/ID.

The diatom Phaeodactylum tricornutum adjusts nonphotochemical fluorescence quenching capacity in response to dynamic light via fine-tuned Lhcx and xanthophyll cycle pigment synthesis.

PubMed

Lepetit, Bernard; Gélin, Gautier; Lepetit, Mariana; Sturm, Sabine; Vugrinec, Sascha; Rogato, Alessandra; Kroth, Peter G; Falciatore, Angela; Lavaud, Johann

2017-04-01

Diatoms contain a highly flexible capacity to dissipate excessively absorbed light by nonphotochemical fluorescence quenching (NPQ) based on the light-induced conversion of diadinoxanthin (Dd) into diatoxanthin (Dt) and the presence of Lhcx proteins. Their NPQ fine regulation on the molecular level upon a shift to dynamic light conditions is unknown. We investigated the regulation of Dd + Dt amount, Lhcx gene and protein synthesis and NPQ capacity in the diatom Phaeodactylum tricornutum after a change from continuous low light to 3 d of sine (SL) or fluctuating (FL) light conditions. Four P. tricornutum strains with different NPQ capacities due to different expression of Lhcx1 were included. All strains responded to dynamic light comparably, independently of initial NPQ capacity. During SL, NPQ capacity was strongly enhanced due to a gradual increase of Lhcx2 and Dd + Dt amount. During FL, cells enhanced their NPQ capacity on the first day due to increased Dd + Dt, Lhcx2 and Lhcx3; already by the second day light acclimation was accomplished. While quenching efficiency of Dt was strongly lowered during SL conditions, it remained high throughout the whole FL exposure. Our results highlight a more balanced and cost-effective photoacclimation strategy of P. tricornutum under FL than under SL conditions. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Effect of light-dark cycles on hydrogen and poly-β-hydroxybutyrate production by a photoheterotrophic culture and Rhodobacter capsulatus using a dark fermentation effluent as substrate.

PubMed

Montiel Corona, Virginia; Le Borgne, Sylvie; Revah, Sergio; Morales, Marcia

2017-02-01

A Rhodobacter capsulatus strain and a photoheterotrophic culture (IZT) were cultivated to produce hydrogen under different light-dark cycles. A dark fermentation effluent (DFE) was used as substrate. It was found that IZT culture had an average cumulative hydrogen production (Paccum H 2 ) of 1300±43mLH 2 L -1 under continuous illumination and light-dark cycles of 30 or 60min. In contrast, R. capsulatus reduced its Paccum H 2 by 20% under 30:30min light-dark cycles, but tripled its poly-β-hydroxybutyrate (PHB) content (308±2mgPHB gdw -1 ) compared to continuous illumination. The highest PHB content by IZT culture was 178±10mgPHB gdw -1 under 15:15min light-dark cycles. PCR-DGGE analysis revealed that the IZT culture was mainly composed of Rhodopseudomonas palustris identified with high nucleotide similarity (99%). The evaluated cultures might be used for hydrogen and PHB production. They might provide energy savings by using light-dark cycles and DFE valorization. Copyright © 2016 Elsevier Ltd. All rights reserved.

77 FR 58109 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-19

... Regulation Supplement (DFARS) part 245, Government Property, and the following related clauses and forms: DD Form 1149, Requisition and Invoice/Shipping Document; DD Form 1348-1A, DoD Single Line item Release/Receipt Document; DD Form 1639, Scrap Warranty; DD Form 1640, Request for Plant Clearance; DD Form 1641...

77 FR 6094 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-07

... Acquisition Regulation Supplement (DFARS) part 245, Government Property; DD Form 1149, Requisition and Invoice/Shipping Document; DD Form 1348-1A, DoD Single Line item Release/Receipt Document; DD Form 1637, Notice of Acceptance of Inventory Schedules; DD Form 1639, Scrap Warranty; DD Form 1640, Request for Plant Clearance...

40 CFR Table 2 to Subpart Dd of... - Applicability of Paragraphs in Subpart A of This Part 63-General Provisions to Subpart DD

Code of Federal Regulations, 2010 CFR

2010-07-01

... A of This Part 63-General Provisions to Subpart DD 2 Table 2 to Subpart DD of Part 63 Protection of... Hazardous Air Pollutants from Off-Site Waste and Recovery Operations Pt. 63, Subpt. DD, Table 2 Table 2 to Subpart DD of Part 63—Applicability of Paragraphs in Subpart A of This Part 63—General Provisions to...

Definitive Results of a Phase III Adjuvant Trial Comparing Three Chemotherapy Regimens in Women With Operable, Node-Positive Breast Cancer: The NSABP B-38 Trial

PubMed Central

Swain, Sandra M.; Tang, Gong; Geyer, Charles E.; Rastogi, Priya; Atkins, James N.; Donnellan, Paul P.; Fehrenbacher, Louis; Azar, Catherine A.; Robidoux, André; Polikoff, Jonathan A.; Brufsky, Adam M.; Biggs, David D.; Levine, Edward A.; Zapas, John L.; Provencher, Louise; Northfelt, Donald W.; Paik, Soonmyung; Costantino, Joseph P.; Mamounas, Eleftherios P.; Wolmark, Norman

2013-01-01

Purpose Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer. This trial (NSABP B-38; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer) asked whether the incorporation of a fourth drug could improve outcomes relative to two standard regimens and provided a direct comparison of those two regimens. Patients and Methods We randomly assigned 4,894 women with node-positive early-stage breast cancer to six cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC), four cycles of dose-dense (DD) doxorubicin and cyclophosphamide followed by four cycles of DD paclitaxel (P; DD AC→P), or DD AC→P with four cycles of gemcitabine (G) added to the DD paclitaxel (DD AC→PG). Primary granulocyte colony-stimulating factor support was required; erythropoiesis-stimulating agents (ESAs) were used at the investigator's discretion. Results There were no significant differences in 5-year disease-free survival (DFS) between DD AC→PG and DD AC→P (80.6% v 82.2%; HR, 1.07; P = .41), between DD AC→PG and TAC (80.6% v 80.1%; HR, 0.93; P = .39), in 5-year overall survival (OS) between DD AC→PG and DD AC→P (90.8% v 89.1%; HR, 0.85; P = .13), between DD AC→PG and TAC (90.8% v 89.6%; HR, 0.86; P = .17), or between DD AC→P versus TAC for DFS (HR, 0.87; P = .07) and OS (HR, 1.01; P = .96). Grade 3 to 4 toxicities for TAC, DD AC→P, and DD AC→PG, respectively, were febrile neutropenia (9%, 3%, 3%; P < .001), sensory neuropathy (< 1%, 7%, 6%; P < .001), and diarrhea (7%, 2%, 2%; P < .001). Exploratory analyses for ESAs showed no association with DFS events (HR, 1.02; P = .95). Conclusion Adding G to DD AC→P did not improve outcomes. No significant differences in efficacy were identified between DD AC→P and TAC, although toxicity profiles differed. PMID:23940225

Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial.

PubMed

Swain, Sandra M; Tang, Gong; Geyer, Charles E; Rastogi, Priya; Atkins, James N; Donnellan, Paul P; Fehrenbacher, Louis; Azar, Catherine A; Robidoux, André; Polikoff, Jonathan A; Brufsky, Adam M; Biggs, David D; Levine, Edward A; Zapas, John L; Provencher, Louise; Northfelt, Donald W; Paik, Soonmyung; Costantino, Joseph P; Mamounas, Eleftherios P; Wolmark, Norman

2013-09-10

Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer. This trial (NSABP B-38; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer) asked whether the incorporation of a fourth drug could improve outcomes relative to two standard regimens and provided a direct comparison of those two regimens. We randomly assigned 4,894 women with node-positive early-stage breast cancer to six cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC), four cycles of dose-dense (DD) doxorubicin and cyclophosphamide followed by four cycles of DD paclitaxel (P; DD AC→P), or DD AC→P with four cycles of gemcitabine (G) added to the DD paclitaxel (DD AC→PG). Primary granulocyte colony-stimulating factor support was required; erythropoiesis-stimulating agents (ESAs) were used at the investigator's discretion. There were no significant differences in 5-year disease-free survival (DFS) between DD AC→PG and DD AC→P (80.6% v 82.2%; HR, 1.07; P = .41), between DD AC→PG and TAC (80.6% v 80.1%; HR, 0.93; P = .39), in 5-year overall survival (OS) between DD AC→PG and DD AC→P (90.8% v 89.1%; HR, 0.85; P = .13), between DD AC→PG and TAC (90.8% v 89.6%; HR, 0.86; P = .17), or between DD AC→P versus TAC for DFS (HR, 0.87; P = .07) and OS (HR, 1.01; P = .96). Grade 3 to 4 toxicities for TAC, DD AC→P, and DD AC→PG, respectively, were febrile neutropenia (9%, 3%, 3%; P < .001), sensory neuropathy (< 1%, 7%, 6%; P < .001), and diarrhea (7%, 2%, 2%; P < .001). Exploratory analyses for ESAs showed no association with DFS events (HR, 1.02; P = .95). Adding G to DD AC→P did not improve outcomes. No significant differences in efficacy were identified between DD AC→P and TAC, although toxicity profiles differed.

Season-dependent effects of photoperiod and temperature on circadian rhythm of arylalkylamine N-acetyltransferase2 gene expression in pineal organ of an air-breathing catfish, Clarias gariepinus.

PubMed

Singh, Kshetrimayum Manisana; Saha, Saurav; Gupta, Braj Bansh Prasad

2017-08-01

Arylalkylamine N-acetyltransferase (AANAT) activity, aanat gene expression and melatonin production have been reported to exhibit prominent circadian rhythm in the pineal organ of most species of fish. Three types of aanat genes are expressed in fish, but the fish pineal organ predominantly expresses aanat2 gene. Increase and decrease in daylength is invariably associated with increase and decrease in temperature, respectively. But so far no attempt has been made to delineate the role of photoperiod and temperature in regulation of the circadian rhythm of aanat2 gene expression in the pineal organ of any fish with special reference to seasons. Therefore, we studied effects of various lighting regimes (12L-12D, 16L-8D, 8L-16D, LL and DD) at a constant temperature (25°C) and effects of different temperatures (15°, 25° and 35°C) under a common photoperiod 12L-12D on circadian rhythm of aanat2 gene expression in the pineal organ of Clarias gariepinus during summer and winter seasons. Aanat2 gene expression in fish pineal organ was studied by measuring aanat2 mRNA levels using Real-Time PCR. Our findings indicate that the pineal organ of C. gariepinus exhibits a prominent circadian rhythm of aanat2 gene expression irrespective of photoperiods, temperatures and seasons, and the circadian rhythm of aanat2 gene expression responds differently to different photoperiods and temperatures in a season-dependent manner. Existence of circadian rhythm of aanat2 gene expression in pineal organs maintained in vitro under 12L-12D and DD conditions as well as a free running rhythm of the gene expression in pineal organ of the fish maintained under LL and DD conditions suggest that the fish pineal organ possesses an endogenous circadian oscillator, which is entrained by light-dark cycle. Copyright © 2017 Elsevier B.V. All rights reserved.

A feasibility study of a deuterium-deuterium neutron generator-based boron neutron capture therapy system for treatment of brain tumors.

PubMed

Hsieh, Mindy; Liu, Yingzi; Mostafaei, Farshad; Poulson, Jean M; Nie, Linda H

2017-02-01

Boron neutron capture therapy (BNCT) is a binary treatment modality that uses high LET particles to achieve tumor cell killing. Deuterium-deuterium (DD) compact neutron generators have advantages over nuclear reactors and large accelerators as the BNCT neutron source, such as their compact size, low cost, and relatively easy installation. The purpose of this study is to design a beam shaping assembly (BSA) for a DD neutron generator and assess the potential of a DD-based BNCT system using Monte Carlo (MC) simulations. The MC model consisted of a head phantom, a DD neutron source, and a BSA. The head phantom had tally cylinders along the centerline for computing neutron and photon fluences and calculating the dose as a function of depth. The head phantom was placed at 4 cm from the BSA. The neutron source was modeled to resemble the source of our current DD neutron generator. A BSA was designed to moderate and shape the 2.45-MeV DD neutrons to the epithermal (0.5 eV to 10 keV) range. The BSA had multiple components, including moderator, reflector, collimator, and filter. Various materials and configurations were tested for each component. Each BSA layout was assessed in terms of the in-air and in-phantom parameters. The maximum brain dose was limited to 12.5 Gray-Equivalent (Gy-Eq) and the skin dose to 18 Gy-Eq. The optimized BSA configuration included 30 cm of lead for reflector, 45 cm of LiF, and 10 cm of MgF 2 for moderator, 10 cm of lead for collimator, and 0.1 mm of cadmium for thermal neutron filter. Epithermal flux at the beam aperture was 1.0 × 10 5  n epi /cm 2 -s; thermal-to-epithermal neutron ratio was 0.05; fast neutron dose per epithermal was 5.5 × 10 -13  Gy-cm 2 /φ epi , and photon dose per epithermal was 2.4 × 10 -13  Gy-cm 2 /φ epi . The AD, AR, and the advantage depth dose rate were 12.1 cm, 3.7, and 3.2 × 10 -3  cGy-Eq/min, respectively. The maximum skin dose was 0.56 Gy-Eq. The DD neutron yield that is needed to irradiate in reasonable time was 4.9 × 10 13  n/s. Results demonstrated that a DD-based BNCT system could be designed to produce neutron beams that have acceptable in-air and in-phantom characteristics. The parameter values were comparable to those of existing BNCT facilities. Continuing efforts are ongoing to improve the DD neutron yield. © 2016 American Association of Physicists in Medicine.

Dancing in the dark: darkness as a signal in plants.

PubMed

Seluzicki, Adam; Burko, Yogev; Chory, Joanne

2017-11-01

Daily cycles of light and dark provide an organizing principle and temporal constraints under which life on Earth evolved. While light is often the focus of plant studies, it is only half the story. Plants continuously adjust to their surroundings, taking both dawn and dusk as cues to organize their growth, development and metabolism to appropriate times of day. In this review, we examine the effects of darkness on plant physiology and growth. We describe the similarities and differences between seedlings grown in the dark versus those grown in light-dark cycles, and the evolution of etiolated growth. We discuss the integration of the circadian clock into other processes, looking carefully at the points of contact between clock genes and growth-promoting gene-regulatory networks in temporal gating of growth. We also examine daily starch accumulation and degradation, and the possible contribution of dark-specific metabolic controls in regulating energy and growth. Examining these studies together reveals a complex and continuous balancing act, with many signals, dark included, contributing information and guiding the plant through its life cycle. The extraordinary interconnection between light and dark is manifest during cycles of day and night and during seedling emergence above versus below the soil surface. © 2017 John Wiley & Sons Ltd.

Patients with IgA nephropathy exhibit high systemic PDGF-DD levels.

PubMed

Boor, Peter; Eitner, Frank; Cohen, Clemens D; Lindenmeyer, Maja T; Mertens, Peter R; Ostendorf, Tammo; Floege, Jürgen

2009-09-01

Platelet-derived growth factor (PDGF) is a central mediator of mesangioproliferative glomerulonephritis (GN). In experimental mesangioproliferative GN, PDGF-DD serum levels, unlike PDGF-BB, increased up to 1000-fold. We assessed disease activity in 72 patients with GN, established a novel PDGF-D ELISA and then determined their PDGF-DD levels. In parallel, we studied renal PDGF-DD mRNA expression by RT-PCR. PDGF-DD serum levels in patients with IgA nephropathy (IgAN) were significantly higher (1.67 +/- 0.45 ng/ml) and in patients with lupus nephritis significantly lower (0.66 +/- 0.86 ng/ml) compared to healthy controls (1.17 +/- 0.46 ng/ml), while patients with focal segmental glomerulosclerosis, membranous GN and ANCA-positive vasculitis did not differ from controls. The subgroup of IgAN patients with elevated PDGF-DD levels (27% of samples) did not differ in their clinical features from those with normal PDGF-DD levels. In IgAN patients with repetitive PDGF-DD determinations, most exhibited only minor fluctuations of serum levels over time. Intrarenal PDGF-DD mRNA expression did not differ between controls and patients, suggesting an extrarenal source of the elevated PDGF-DD in IgAN. Serum PDGF-DD levels were specifically elevated in patients with IgAN, in particular in those with early disease, i.e. preserved renal function. Our data support the rationale for anti-PDGF-DD therapy in mesangioproliferative GN.

Studies of Phlebotomine Sand Flies.

DTIC Science & Technology

1981-05-01

20, It different from Report) IS. SUPPLEMENTARY NOTES 9’. KEY WOFDS (Continue an teers*e aide it necessa y mid identify by block number) Lutzomyia ...illustrations and a description of a new species. Other new Lutzomyia sand flies were discovered in Mexico and Ecuador. A species group of Lutzomyia ...egg structure of some Lutzomyia D IN J OBSOLETE Continued-- / ’DD , j. 1473 EtnT oN OFNvS = LT Unclaggi;fi;R~d y - SECURITY CLASSIFICA rIOm OF THIS

Behavioral Strategies for Enhancing Productivity

DTIC Science & Technology

1980-07-01

goals -and measured achievement, making comparisons across people , (continue-d on rpxrpr~p) DD Rm CO EITIONO I0 NOV 641 0IS )SOLtTE 7 UNCLASSIFIED...FOR ENH-ANqCING PRODUCTIVITYJehia et0 -- --- 6.PERFORMING ORG. REPORT NUMBER GS-2 7 . AT"O (0)CONTRACT OR GRANT NUMUER(s) CC ~ ! Gary Latham L. L...identity by block number) C.2 ’ 7 A three stage process is proposed for enhancing productivity through the utilization of human resources. The stages

Contractile Ring-independent Localization of DdINCENP, a Protein Important for Spindle Stability and CytokinesisD⃞V⃞

PubMed Central

Chen, Qian; Li, Hui; De Lozanne, Arturo

2006-01-01

Dictyostelium DdINCENP is a chromosomal passenger protein associated with centromeres, the spindle midzone, and poles during mitosis and the cleavage furrow during cytokinesis. Disruption of the single DdINCENP gene revealed important roles for this protein in mitosis and cytokinesis. DdINCENP null cells lack a robust spindle midzone and are hypersensitive to microtubule-depolymerizing drugs, suggesting that their spindles may not be stable. Furthermore DdCP224, a protein homologous to the microtubule-stabilizing protein TOGp/XMAP215, was absent from the spindle midzone of DdINCENP null cells. Overexpression of DdCP224 rescued the weak spindle midzone defect of DdINCENP null cells. Although not required for the localization of the myosin II contractile ring and subsequent formation of a cleavage furrow, DdINCENP is important for the abscission of daughter cells at the end of cytokinesis. Finally, we show that the localization of DdINCENP at the cleavage furrow is modulated by myosin II but it occurs by a mechanism different from that controlling the formation of the contractile ring. PMID:16339076

Effects of environmental lighting and tryptophan devoid diet on the rat vaginal cycle.

PubMed

Giammanco, S; Ernandes, M; La Guardia, M

1997-09-01

Cerebral serotonin level influences luteinizing hormone release and, consequently, ovulation. The present study evaluated the effects of precooked maize meal (polenta), a diet almost devoid of tryptophan the serotonin precursor on the alterations of the estrus cycle as measured by vaginal smears analysis in Wistar rats. Several conditions of environmental lighting were used in order to modify ovarian cycle: 1) natural alternating light/dark cycle; 2) continuous darkness; 3) continuous light by sodium steams: 4) continuous light by fluorescent neon tubes. Rats bred in continuous lighting showed estrus-proestrus rate significantly greater than rats bred in normal lighting or in continuous darkness. The feeding with precooked maize meal suppressed persistent estrus in rats bred in continuous lighting, and significantly cut down the estrus-proestrus frequency in any condition of environmental lighting. Our results lead to hypothesize that polenta diet, for its low tryptophan content, cutting down both tryptophan plasma content and serotonin neuronal synthesis, promotes luteinizing hormone peak.

Angiotensin converting enzyme genotype and chronic allograft nephropathy in protocol biopsies.

PubMed

Hueso, Miguel; Alía, Pedro; Moreso, Francesc; Beltrán-Sastre, Violeta; Riera, Luis; González, Carlota; Navarro, Miguel Angel; Grinyó, Josep Maria; Navarro, Estanis; Serón, Daniel

2004-08-01

Genotype DD of the angiotensin-converting enzyme (ACE) is not associated with an increased incidence of native renal diseases, although it could modulate progression to renal failure in patients who already display chronic lesions. Because its role in renal allograft degeneration is not well characterized, whether ACE genotype was associated with the prevalence of chronic allograft nephropathy (CAN) was studied, in a group of protocol biopsies from 180 patients, or with the incidence of CAN in 152 patients with at least two sequential biopsies. As a control group, ACE genotype was also studied in 41 donors and 72 healthy subjects. For analyzing the influence of ACE genotype in graft survival, patients were grouped into six categories (II-normal biopsy, ID-normal, DD-normal, II-CAN, ID-CAN and DD-CAN). Finally, relative renal ACE mRNA levels were measured in 67 cases by real-time PCR using the delta threshold cycle method. ACE-DD genotype was more frequent in patients who received a transplant than in control subjects (43.3% versus 30.1%, P = 0.026), but prevalence (DD = 42.7% versus non-DD = 42.2%) or incidence (DD = 24.6% versus non-DD = 29.9%) of CAN was not different regarding recipient ACE genotype. Furthermore, patients with the ACE-DD genotype and CAN had the poorest graft survival (II-normal = 100%, ID-normal = 91%, DD-normal = 84%, II-CAN = 100%, ID-CAN = 66%, and DD-CAN = 36%; P = 0.034) and higher ACE mRNA levels than non-DD and CAN (DD = -3.36 +/- 2.35 versus non-DD = -5.65 +/- 1.72-fold in ACE copies; P = 0.012). It is concluded that ACE-DD genotype is not associated with an increased prevalence or incidence of CAN but is actually associated with higher ACE mRNA levels and poorer graft survival in patients who already display CAN.

The Shift of ERG B-Wave Induced by Hours' Dark Exposure in Rodents.

PubMed

Li, Dake; Fang, Qi; Yu, Hongbo

2016-01-01

Dark adaptation can induce a rapid functional shift in the retina, and after that, the retinal function is believed to remain stable during the continuous dark exposure. However, we found that electroretinograms (ERG) b-waves gradually shifted during 24 hours' dark exposure in rodents. Detailed experiments were designed to explore this non-classical dark adaptation. In vivo ERG recording in adult and developing rodents after light manipulations. We revealed a five-fold decrease in ERG b-waves in adult rats that were dark exposed for 24 hours. The ERG b-waves significantly increased within the first hour's dark exposure, but after that decreased continuously and finally attained steady state after 1 day's dark exposure. After 3 repetitive, 10 minutes' light exposure, the dark exposed rats fully recovered. This recovery effect was eye-specific, and light exposure to one eye could not restore the ERGs in the non-exposed eye. The prolonged dark exposure-induced functional shift was also reflected in the down-regulation on the amplitude of intensity-ERG response curve, but the dynamic range of the responsive light intensity remained largely stable. Furthermore, the ERG b-wave shifts occurred in and beyond classical critical period, and in both rats and mice. Importantly, when ERG b-wave greatly shifted, the amplitude of ERG a-wave did not change significantly after the prolonged dark exposure. This rapid age-independent ERG change demonstrates a generally existing functional shift in the retina, which is at the entry level of visual system.

PHYSICS OF OUR DAYS: Dark energy: myths and reality

NASA Astrophysics Data System (ADS)

Lukash, V. N.; Rubakov, V. A.

2008-03-01

We discuss the questions related to dark energy in the Universe. We note that in spite of the effect of dark energy, large-scale structure is still being generated in the Universe and this will continue for about ten billion years. We also comment on some statements in the paper "Dark energy and universal antigravitation" by A D Chernin, Physics Uspekhi 51 (3) (2008).

Large Enhancement of the Sagnac Effect Based on Nonlinearly Induced Nonreciprocity.

DTIC Science & Technology

1983-05-30

Og4 ,, % 20. ABSTRACT (Continue on reverse side It ne c,&aty and Identify by block number) LL On Back -°. La . -k. DD 1JAN73 1473 EDITION OF ’NOV6S...be published. 8. L. A. Hackel, R. P. Hackel, and S. Ezekiel, Metrologia 13, 141 (1977). Ř. .4

32 CFR 728.13 - Application for care.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Duty § 728.13 Application for care. Possession of an ID card (a green colored DD 2 (with letter suffix... 32 National Defense 5 2010-07-01 2010-07-01 false Application for care. 728.13 Section 728.13 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL MEDICAL AND DENTAL CARE...

32 CFR 842.24 - Filing a claim.

Code of Federal Regulations, 2010 CFR

2010-07-01

... properly completed AF Form 180, DD Form 1842 or other written and signed demand for a specified sum of money. (b) Amending a claim. A claimant may amend a claim at any time prior to the expiration of the... Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE CLAIMS AND LITIGATION ADMINISTRATIVE...

Multiscale Modeling of Structurally-Graded Materials Using Discrete Dislocation Plasticity Models and Continuum Crystal Plasticity Models

NASA Technical Reports Server (NTRS)

Saether, Erik; Hochhalter, Jacob D.; Glaessgen, Edward H.

2012-01-01

A multiscale modeling methodology that combines the predictive capability of discrete dislocation plasticity and the computational efficiency of continuum crystal plasticity is developed. Single crystal configurations of different grain sizes modeled with periodic boundary conditions are analyzed using discrete dislocation plasticity (DD) to obtain grain size-dependent stress-strain predictions. These relationships are mapped into crystal plasticity parameters to develop a multiscale DD/CP model for continuum level simulations. A polycrystal model of a structurally-graded microstructure is developed, analyzed and used as a benchmark for comparison between the multiscale DD/CP model and the DD predictions. The multiscale DD/CP model follows the DD predictions closely up to an initial peak stress and then follows a strain hardening path that is parallel but somewhat offset from the DD predictions. The difference is believed to be from a combination of the strain rate in the DD simulation and the inability of the DD/CP model to represent non-monotonic material response.

Zidovudine (AZT) versus AZT plus didanosine (ddI) versus AZT plus zalcitabine (ddC) in HIV infected adults.

PubMed

Darbyshire, J; Foulkes, M; Peto, R; Duncan, W; Babiker, A; Collins, R; Hughes, M; Peto, T; Walker, A

2000-01-01

Zidovudine (AZT) monotherapy was the first antiretroviral drug to be tested widely. The next two drugs to be developed were didanosine (ddI) and zalcitabine (ddC). To assess the effects of zidovudine (AZT), zidovudine plus didanosine (ddI) and zidovudine plus zalcitabine (ddC) on HIV disease progression and survival. Investigators and pharmaceutical companies were contacted, and MEDLINE searches were supplemented by searching conference abstracts. Randomised controlled trials comparing any two of AZT plus ddI, AZT plus ddC or AZT alone in participants with or without AIDS which collected information on deaths and new AIDS events. Individual patient data with, wherever possible, follow-up obtained beyond that previously published were obtained and checked for internal consistency and consistency with any published reports; any apparent discrepancies were resolved with the trialists. Time to death and to disease progression (defined as a new AIDS-defining event or prior death) were analysed on an intention to treat basis, stratified to avoid direct comparisons between participants in different trials. Six trials were included in the meta-analysis. During a median follow-up of 29 months, 2904 individuals progressed, of whom 1850 died. The addition of ddI to AZT delayed both progression (RR 0.74; 95% CI 0.67 to 0.82, P<0.0001) and death (RR 0.72; 95% CI 0.64 to 0.82, P<0.0001). Likewise, the addition of ddC to AZT also delayed progression (RR 0. 86; 95% CI 0.78 to 0.94, P=0.001) and death (RR 0.87; 95% CI 0.77 to 0.98, P=0.02). After 3 years the estimated percentages alive and without a new AIDS event were 53% for AZT+ddI, 49% for AZT+ddC and 44% for AZT alone; the percentages alive were 68%, 63% and 59% respectively. Five of the six trials involved randomised comparisons of AZT+ddI versus AZT+ddC: in these, the AZT+ddI regimen had greater effects on disease progression (P=0.004) and death (P=0.009). The use of ddI and, to a lesser extent, ddC delayed both HIV disease progression and death, at least when added to AZT.

Continuous Flavor Symmetries and the Stability of Asymmetric Dark Matter

DOE PAGES

Bishara, Fady; Zupan, Jure

2015-01-19

Generically, the asymmetric interactions in asymmetric dark matter (ADM) models could lead to decaying DM. We show that, for ADM that carries nonzero baryon number, continuous flavor symmetries that generate the flavor structure in the quark sector also imply a looser lower bound on the mass scale of the asymmetric mediators between the dark and visible sectors. Furthermore, the mediators for B = 2 ADM that can produce a signal in the future indirect dark matter searches can thus also be searched for at the LHC. For two examples of the mediator models, with either the MFV or Froggatt-Nielsen flavormore » breaking pattern, we derive the FCNC constraints and discuss the search strategies at the LHC.« less

Continuous Flavor Symmetries and the Stability of Asymmetric Dark Matter

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

Bishara, Fady; Zupan, Jure

Generically, the asymmetric interactions in asymmetric dark matter (ADM) models could lead to decaying DM. We show that, for ADM that carries nonzero baryon number, continuous flavor symmetries that generate the flavor structure in the quark sector also imply a looser lower bound on the mass scale of the asymmetric mediators between the dark and visible sectors. Furthermore, the mediators for B = 2 ADM that can produce a signal in the future indirect dark matter searches can thus also be searched for at the LHC. For two examples of the mediator models, with either the MFV or Froggatt-Nielsen flavormore » breaking pattern, we derive the FCNC constraints and discuss the search strategies at the LHC.« less

Delusional disorder and schizophrenia: a comparative study across multiple domains.

PubMed

Peralta, V; Cuesta, M J

2016-10-01

Delusional disorder (DD) is an under-researched condition and its relationship to schizophrenia (SZ) controversial. This study aimed to further characterize DD and to examine multi-domain evidence for the distinction between DD and SZ. Using univariate analyses we examined 146 subjects with DD, 114 subjects with paranoid SZ and 244 subjects with non-paranoid SZ on 52 characteristics from several domains including demographics, risk factors, premorbid features, illness characteristics, index episode features, delusional-related features, response to treatment and outcome. In a further step, we searched for independent associations of the examined characteristics with DD v. SZ. Univariate analyses showed that DD differed from either form of SZ in 40 characteristics, the pattern of findings indicated that paranoid SZ was much more similar to non-paranoid SZ than DD. Relative to subjects with SZ, those with DD were more likely to have drug abuse before illness onset, better premorbid sexual adjustment, later age at illness onset, higher levels of affective symptoms and lack of insight, poorer response to antipsychotic medication, better functioning in the domains of personal care, paid work and social functioning; last, subjects with DD had fewer but more severe delusions and higher ratings of conviction of delusional experience than those with SZ. Predominance of jealousy and somatic delusions was confined to subjects with DD. DD and SZ represent two distinct classes of disorders, the differential features of DD being of nosological, aetiological and therapeutic relevance.

The e{sup +}e{sup -}{yields}J/{psi}DD-bar, J/{psi}DD-bar* reactions with dynamically generated resonances

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

Gamermann, D.; Oset, E.

2008-08-31

In two recent reactions by Belle producing DD-bar and DD-bar* meson pairs, peaks above threshold have been measured in the differential cross sections, possibly indicating new resonances in these channels. We want to study such reactions from the point of view that the D meson pairs are produced from already known or predicted resonances below threshold. Our study shows that the peak in the DD-bar* production is not likely to be caused by the X(3872) resonance, but the peak seen in DD-bar invariant mass can be well described if the DD-bar pair comes from the already predicted scalar X(3700) resonance.

75 FR 68333 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; DFARS...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-05

... Supplement (DFARS) Appendix F, Material Inspection and Receiving Report; DD Form 250, DD Form 250c, DD form... Report; and DD Forms 250, 250c, and 250-1. The clause at DFARS 252.246-7000 is used in contracts that... the Government a material inspection and receiving report (DD Form 250) in a manner and to the extent...

Effects of the finite size of the ion (dd{mu}){sup +} on the energy levels of the molecules (dd{mu})e and (dd{mu})dee

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

Harston, M.R.; Hara, S.; Kino, Y.

1997-10-01

The energy shift due to the finite size of the pseudonucleus (dd{mu}){sub 11}{sup +} in the molecules (dd{mu}){sub 11}e and (dd{mu}){sub 11}dee, the subscripts indicating the first excited state with total angular momentum of one unit, is of importance in the theoretical estimation of the rate of d-d fusion catalyzed by negative muons. The energy shift in the molecule (dd{mu}){sub 11}e is calculated using perturbation theory up to second order. The finite-size shift is found to be 1.46 meV. This is significantly larger than the value of 0.7 meV for this energy shift calculated by Bakalov [Muon Catalyzed Fusion {boldmore » 3}, 321 (1988)] by a method similar to the present method; recently found excellent agreement of theory with experimental results for the formation rate of the molecule (dd{mu}){sub 11}dee was based on Bakalov{close_quote}s value with some modifications. The results of a direct calculation of the finite-size energy shifts in (dd{mu}){sub 11}dee using first-order perturbation theory are presented. The contribution from the quadrupole component of the (dd{mu}){sub 11} charge distribution, which is not taken into account in the conventional scaling procedure based on the finite-size energy shifts of (dd{mu}){sub 11}e, is found to be of the order of 1 meV and to depend on the angular-momentum states of (dd{mu}){sub 11}dee. Sources of uncertainty in the current theoretical estimates are also discussed. {copyright} {ital 1997} {ital The American Physical Society}« less

Ecological and social patterns of child dietary diversity in India: a population-based study.

PubMed

Gausman, Jewel; Perkins, Jessica M; Lee, Hwa-Young; Mejia-Guevara, Ivan; Nam, You-Seon; Lee, Jong-Koo; Oh, Juhwan; Subramanian, S V

2018-02-13

Dietary diversity (DD) measures dietary variation in children. Factors at the child, community, and state levels may be associated with poor child nutritional outcomes. However, few studies have examined the role of macro-level factors on child DD. This study seeks to 1) describe the distribution of child DD in India, 2) examine the variation in DD attributable to the child, community and state levels, and 3) explore the relationship between community socioeconomic context and child DD. Using nationally representative data from children aged 6-23 months in India, multilevel models were used to determine the associations between child DD and individual- and community-level factors. There was substantial variation in child DD score across demographic and socioeconomic characteristics. In an age and sex-only adjusted regression model, the largest portion of variation in child DD was attributable to the child level (75%) while the portions of variance attributable to the community-level and state level were similar to each other (15% and 11%). Including individual-level socioeconomic factors explained 35.6 percent of the total variation attributed to child DD at the community level and 24.8 percent of the total variation attributed to child DD at the state level. Finally, measures of community disadvantage were associated with child DD in when added to the fully adjusted model. This study suggests that both individual and contextual factors are associated with child DD. These results suggest that a population-based approach combined with a targeted intervention for at-risk children may be needed to improve child DD in India. Copyright © 2018 Elsevier Inc. All rights reserved.

The in vitro and in vivo evaluation of ddC as a topical antiviral for ocular adenovirus infections.

PubMed

Romanowski, Eric G; Yates, Kathleen A; Gordon, Y Jerold

2009-11-01

To evaluate the antiviral activity of 2', 3'-dideoxycytidine (ddC) in vitro against a panel of ocular adenovirus serotypes and in vivo in the ocular Ad5/NZW rabbit replication model. In vitro, the 50% inhibitory concentrations (IC(50)) of ddC and cidofovir were determined using standard plaque-reduction assays. In vivo, 40 rabbits were topically inoculated in both eyes with Ad5 after corneal scarification. On day 1, the rabbits were equally divided into four topical treatment groups: 3% ddC; 2% ddC; 0.5% cidofovir; and saline. ddC and saline eyes were treated four times daily for 7 days, and cidofovir-treated eyes were treated twice daily for 7 days. Eyes were cultured for virus a multiple times over 2 weeks. The in vitro IC(50) for ddC ranged from 0.18 to 1.85 microg/mL, whereas those for cidofovir ranged from 0.018 to 5.47 microg/mL. ddC was more potent than cidofovir for seven of nine serotypes. In vivo, 3% ddC, 2% ddC, and 0.5% cidofovir significantly reduced the number of Ad5-positive cultures per total (days 1-14), mean Ad5 ocular titer (days 1-5), and duration of shedding (among other outcome measures) compared with the saline control. The 3% and 2% ddC treatments were significantly more efficacious than the 0.5% cidofovir treatment in the parameters listed above. ddC demonstrated potent antiadenovirus activity in vitro and in vivo. Systemic safety studies after topical ocular administration are needed to evaluate ddC as a topical antiviral treatment for adenoviral ocular infections in the target population.

Altered Microbiomes in Bovine Digital Dermatitis Lesions, and the Gut as a Pathogen Reservoir

PubMed Central

Zinicola, Martin; Lima, Fabio; Lima, Svetlana; Machado, Vinicius; Gomez, Marilia; Döpfer, Dörte; Guard, Charles; Bicalho, Rodrigo

2015-01-01

Bovine digital dermatitis (DD) is the most important infectious disease associated with lameness in cattle worldwide. Since the disease was first described in 1974, a series of Treponema species concurrent with other microbes have been identified in DD lesions, suggesting a polymicrobial etiology. However, the pathogenesis of DD and the source of the causative microbes remain unclear. Here we characterized the microbiomes of healthy skin and skin lesions in dairy cows affected with different stages of DD and investigated the gut microbiome as a potential reservoir for microbes associated with this disease. Discriminant analysis revealed that the microbiomes of healthy skin, active DD lesions (ulcerative and chronic ulcerative) and inactive DD lesions (healing and chronic proliferative) are completely distinct. Treponema denticola, Treponema maltophilum, Treponema medium, Treponema putidum, Treponema phagedenis and Treponema paraluiscuniculi were all found to be present in greater relative abundance in active DD lesions when compared with healthy skin and inactive DD lesions, and these same Treponema species were nearly ubiquitously present in rumen and fecal microbiomes. The relative abundance of Candidatus Amoebophilus asiaticus, a bacterium not previously reported in DD lesions, was increased in both active and inactive lesions when compared with healthy skin. In conclusion, our data support the concept that DD is a polymicrobial disease, with active DD lesions having a markedly distinct microbiome dominated by T. denticola, T. maltophilum, T. medium, T. putidum, T. phagedenis and T. paraluiscuniculi. Furthermore, these Treponema species are nearly ubiquitously found in rumen and fecal microbiomes, suggesting that the gut is an important reservoir of microbes involved in DD pathogenesis. Additionally, the bacterium Candidatus Amoebophilus asiaticus was highly abundant in active and inactive DD lesions. PMID:25781328

Diaper Dermatitis in Infants Admitted to Social Pediatrics Health Center: Role of Socio-demographic Factors and Infant Care.

PubMed

Kayaoglu, Semra; Kivanc-Altunay, Ilknur; Sarikaya, Sezgi

2015-10-01

To determine infant diaper dermatitis (DD) at pediatrics health center; its relation to socio-demographic factors and infant care. The study included 113 infants aged 0-24 mo. Data on infants' age, sex, weight, mothers' education, nutrition, diaper change frequency, cleaning methods and prophylactic cream use were recorded. Infants with minimum one time rash, were accepted to have DD. Seventy six (67.3 %) infants had DD [32 girls (42.1 %), 44 boys (57 %), mean age: 6.5 mo]. Infants with DD had significantly higher age than those without (p 0.001). DD frequency in infants ≥4.5 mo-old was 5.8(2.4-13.7) times more than in infants ≤4.5 mo. Cleaning material types did not affect DD frequency. No significant difference was observed in DD with diaper change of ≤3 times and ≥4 times. Significant difference in DD increase was observed with supplementary food intake vs. without it (p 0.000). DD frequency in infants with supplementary food intake was 6.4 times (2.4-17.1) more than in those without it. Human milk intake was statistically significant in causing less occurrence of DD as shown in univariate model (p < 0.05). Rash incidence was significantly lower with cream use compared to without its use (p < 0.001). DD prevalence was decreased 0.203 (0.087-0.477) times by cream usage. Age, supplementary food intake and lack of cream use seem to be accountable for DD whereas human milk intake lessened the occurrence of DD. Mothers should be informed on dermatitis care and encouraged for breastfeeding.

Characterization of Calmodulin–Fas Death Domain Interaction: An Integrated Experimental and Computational Study

PubMed Central

2015-01-01

The Fas death receptor-activated death-inducing signaling complex (DISC) regulates apoptosis in many normal and cancer cells. Qualitative biochemical experiments demonstrate that calmodulin (CaM) binds to the death domain of Fas. The interaction between CaM and Fas regulates Fas-mediated DISC formation. A quantitative understanding of the interaction between CaM and Fas is important for the optimal design of antagonists for CaM or Fas to regulate the CaM–Fas interaction, thus modulating Fas-mediated DISC formation and apoptosis. The V254N mutation of the Fas death domain (Fas DD) is analogous to an identified mutant allele of Fas in lpr-cg mice that have a deficiency in Fas-mediated apoptosis. In this study, the interactions of CaM with the Fas DD wild type (Fas DD WT) and with the Fas DD V254N mutant were characterized using isothermal titration calorimetry (ITC), circular dichroism spectroscopy (CD), and molecular dynamics (MD) simulations. ITC results reveal an endothermic binding characteristic and an entropy-driven interaction of CaM with Fas DD WT or with Fas DD V254N. The Fas DD V254N mutation decreased the association constant (Ka) for CaM–Fas DD binding from (1.79 ± 0.20) × 106 to (0.88 ± 0.14) × 106 M–1 and slightly increased a standard state Gibbs free energy (ΔG°) for CaM–Fas DD binding from −8.87 ± 0.07 to −8.43 ± 0.10 kcal/mol. CD secondary structure analysis and MD simulation results did not show significant secondary structural changes of the Fas DD caused by the V254N mutation. The conformational and dynamical motion analyses, the analyses of hydrogen bond formation within the CaM binding region, the contact numbers of each residue, and the electrostatic potential for the CaM binding region based on MD simulations demonstrated changes caused by the Fas DD V254N mutation. These changes caused by the Fas DD V254N mutation could affect the van der Waals interactions and electrostatic interactions between CaM and Fas DD, thereby affecting CaM–Fas DD interactions. Results from this study characterize CaM–Fas DD interactions in a quantitative way, providing structural and thermodynamic evidence of the role of the Fas DD V254N mutation in the CaM–Fas DD interaction. Furthermore, the results could help to identify novel strategies for regulating CaM–Fas DD interactions and Fas DD conformation and thus to modulate Fas-mediated DISC formation and thus Fas-mediated apoptosis. PMID:24702583

Prevalence of digital dermatitis in young stock in Alberta, Canada, using pen walks.

PubMed

Jacobs, C; Orsel, K; Barkema, H W

2017-11-01

Digital dermatitis (DD), an infectious bacterial foot lesion prevalent in dairy cattle worldwide, reduces both animal welfare and production. This disease was recently identified in replacement dairy heifers, with implications including increased risk of DD and decreased milk production in first lactation, poor reproductive performance, and altered hoof conformation. Therefore, a simple and effective method is needed to identify DD in young stock and to determine risk factors for DD in this group so that effective control strategies can be implemented. The objectives of this study were to (1) determine prevalence of DD in young stock (based on pen walks); and (2) identify potential risk factors for DD in young stock. A cross-sectional study was conducted on 28 dairy farms in Alberta, Canada; pen walks were used to identify DD (present/absent) on the hind feet of group-housed, young dairy stock. A subset of 583 young stock on 5 farms were selected for chute inspection of feet to determine the accuracy of pen walks for DD detection. Pen walks as a means of identifying DD lesions on the hind feet in young stock had sensitivity and specificity at the animal level of 65 and 98%, with positive and negative predictive values of 94 and 83%, respectively, at a prevalence of 37%. At the foot level, pen walks had sensitivity and specificity of 62 and 98%, respectively, with positive and negative predictive values of 92 and 88%, respectively, at a prevalence of 26%. Pen walks identified DD in 79 [2.9%; 95% confidence interval (95% CI): 2.3-3.6%] of 2,815 young stock on 11 (39%; 95% CI: 22-59%) of 28 farms, with all 79 DD-positive young stock ≥309 d of age. Apparent within-herd prevalence estimates ranged from 0 to 9.3%, with a mean of 1.4%. True within-herd prevalence of DD in young stock, calculated using the sensitivity and specificity of the pen walks, ranged from 0 to 12.6%, with a mean of 1.4%. On the 11 DD-positive farms, the proportion of young stock >12 mo of age with DD lesions was 9.9% (95% CI: 7.8-12.0%). Multilevel logistic regression was used to assess associations with potential risk factors for DD lesions, including age, leg cleanliness, and lactating herd DD prevalence. Presence of DD in young stock increased as their age increased and was associated with increased prevalence of DD in the lactating herd. Pen walks can be used to identify specific young stock with DD or groups where management practices can be implemented to prevent disease proliferation and transmission. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Evidence for a functional link between Dd-STATa and Dd-PIAS, a Dictyostelium PIAS homologue.

PubMed

Kawata, Takefumi; Hirano, Tatsunori; Ogasawara, Shun; Aoshima, Ryota; Yachi, Ayako

2011-09-01

Several mammalian protein families inhibit the activity of signal transducer and activator of transcription (STAT) proteins. The protein inhibitor of activated STAT (PIAS) was initially identified through its ability to interact with human STAT proteins. We isolated a gene (pisA) encoding a Dictyostelium orthologue of PIAS, Dd-PIAS, which possesses almost all the representative motifs and domains of mammalian PIAS proteins. A Dd-PIAS null mutant strain displays a normal terminal morphology but with accelerated development once cells are aggregated. In contrast, Dd-PIAS overexpressor strains demonstrate delayed aggregation, almost no slug phototaxis, impaired slug motility, and a prolonged slug migration period. This strain is a near phenocopy of the Dd-STATa null mutant, although it eventually forms a fruiting body, albeit inefficiently. The expression of several Dd-STATa-activated genes is upregulated in the Dd-PIAS null mutant and there is ectopic expression of pstAB makers. The concentration of a PIAS-green fluorescent protein (GFP) fusion protein, expressed under the PIAS promoter, is greatest in the pstO cells and gradually decreases with proximity to the tip of the slug and culminant: a pattern diametrically opposite to that of Dd-STATa. Our results suggest a functional interrelationship between Dd-PIAS and Dd-STATa that influences gene expression and development. © 2011 The Authors. Development, Growth & Differentiation © 2011 Japanese Society of Developmental Biologists.

Comorbidity in Dupuytren disease.

PubMed

Degreef, I

2016-09-01

In this report, a possible association between Dupuytren's disease (DD) and other health problems was investigated. The health problems included in this study are : cardiac ischemia, hypertension, hyper-lipidemia, diabetes mellitus, epilepsy, gout, rheumatoid arthritis, malignancy, asthma and COPD. The data of 725 patients with DD were collected from -Intego, a database including all morbidity presented to the General Practitioners (GPs) in Flanders. The control group of 2900 age and sex matched non-DD patients was selected from the same database. A possible influence of severity of DD was evaluated by comparing the data of 333 patients operated for DD with the group of Integopatients with DD. This study showed a significant association of every single studied health condition with DD. Comparison of the -operated group with the group from Intego with DD, demonstrated only some significant associations, a difference which may be explained by the difference in data collection.

Differential phosphorylation of azidothymidine, dideoxycytidine, and dideoxyinosine in resting and activated peripheral blood mononuclear cells.

PubMed Central

Gao, W Y; Shirasaka, T; Johns, D G; Broder, S; Mitsuya, H

1993-01-01

The antiviral activity of azidothymidine (AZT), dideoxycytidine (ddC), and dideoxyinosine (ddI) against HIV-1 was comparatively evaluated in PHA-stimulated PBM. The mean drug concentration which yielded 50% p24 Gag negative cultures were substantially different: 0.06, 0.2, and 6 microM for AZT, ddC, and ddI, respectively. We found that AZT was preferentially phosphorylated to its triphosphate (TP) form in PHA-PBM rather than unstimulated, resting PBM (R-PBM), producing 10- to 17-fold higher ratios of AZTTP/dTTP in PHA-PBM than in R-PBM. The phosphorylation of ddC and ddI to their TP forms was, however, much less efficient in PHA-PBM, resulting in approximately 5-fold and approximately 15-fold lower ratios of ddCTP/dCTP and ddATP/dATP, respectively, in PHA-PBM than in R-PBM. The comparative order of PHA-induced increase in cellular enzyme activities examined was: thymidine kinase > uridine kinase > deoxycytidine kinase > adenosine kinase > 5'-nucleotidase. We conclude that AZT, ddC, and ddI exert disproportionate antiviral effects depending on the activation state of the target cells, i.e., ddI and ddC exert antiviral activity more favorably in resting cells than in activated cells, while AZT preferentially protects activated cells against HIV infection. Considering that HIV-1 proviral DNA synthesis in resting lymphocytes is reportedly initiated at levels comparable with those of activated lymphocytes, the current data should have practical relevance in the design of anti-HIV chemotherapy, particularly combination chemotherapy. PMID:8387546

Thrombin-activable fibrinolysis inhibitor attenuates (DD)E-mediated stimulation of plasminogen activation by reducing the affinity of (DD)E for tissue plasminogen activator. A potential mechanism for enhancing the fibrin specificity of tissue plasminogen activator.

PubMed

Stewart, R J; Fredenburgh, J C; Rischke, J A; Bajzar, L; Weitz, J I

2000-11-24

A complex of d-dimer noncovalently associated with fragment E ((DD)E), a degradation product of cross-linked fibrin that binds tissue plasminogen activator (t-PA) and plasminogen (Pg) with affinities similar to those of fibrin, compromises the fibrin specificity of t-PA by stimulating systemic Pg activation. In this study, we examined the effect of thrombin-activable fibrinolysis inhibitor (TAFI), a latent carboxypeptidase B (CPB)-like enzyme, on the stimulatory activity of (DD)E. Incubation of (DD)E with activated TAFI (TAFIa) or CPB (a) produces a 96% reduction in the capacity of (DD)E to stimulate t-PA-mediated activation of Glu- or Lys-Pg by reducing k(cat) and increasing K(m) for the reaction; (b) induces the release of 8 mol of lysine/mol of (DD)E, although most of the stimulatory activity is lost after release of only 4 mol of lysine/mol (DD)E; and (c) reduces the affinity of (DD)E for Glu-Pg, Lys-Pg, and t-PA by 2-, 4-, and 160-fold, respectively. Because TAFIa- or CPB-exposed (DD)E produces little stimulation of Glu-Pg activation by t-PA, (DD)E is not degraded into fragment E and d-dimer, the latter of which has been reported to impair fibrin polymerization. These data suggest a novel role for TAFIa. By attenuating systemic Pg activation by (DD)E, TAFIa renders t-PA more fibrin-specific.

The Shift of ERG B-Wave Induced by Hours' Dark Exposure in Rodents

PubMed Central

Li, Dake; Fang, Qi; Yu, Hongbo

2016-01-01

Purpose Dark adaptation can induce a rapid functional shift in the retina, and after that, the retinal function is believed to remain stable during the continuous dark exposure. However, we found that electroretinograms (ERG) b-waves gradually shifted during 24 hours’ dark exposure in rodents. Detailed experiments were designed to explore this non-classical dark adaptation. Methods In vivo ERG recording in adult and developing rodents after light manipulations. Results We revealed a five-fold decrease in ERG b-waves in adult rats that were dark exposed for 24 hours. The ERG b-waves significantly increased within the first hour’s dark exposure, but after that decreased continuously and finally attained steady state after 1 day’s dark exposure. After 3 repetitive, 10 minutes’ light exposure, the dark exposed rats fully recovered. This recovery effect was eye-specific, and light exposure to one eye could not restore the ERGs in the non-exposed eye. The prolonged dark exposure-induced functional shift was also reflected in the down-regulation on the amplitude of intensity-ERG response curve, but the dynamic range of the responsive light intensity remained largely stable. Furthermore, the ERG b-wave shifts occurred in and beyond classical critical period, and in both rats and mice. Importantly, when ERG b-wave greatly shifted, the amplitude of ERG a-wave did not change significantly after the prolonged dark exposure. Conclusions This rapid age-independent ERG change demonstrates a generally existing functional shift in the retina, which is at the entry level of visual system. PMID:27517462

Inhibitory ability of children with developmental dyscalculia.

PubMed

Zhang, Huaiying; Wu, Hanrong

2011-02-01

Inhibitory ability of children with developmental dyscalculia (DD) was investigated to explore the cognitive mechanism underlying DD. According to the definition of developmental dyscalculia, 19 children with DD-only and 10 children with DD&RD (DD combined with reading disability) were selected step by step, children in two control groups were matched with children in case groups by gender and age, and the match ratio was 1:1. Psychological testing software named DMDX was used to measure inhibitory ability of the subjects. The differences of reaction time in number Stroop tasks and differences of accuracy in incongruent condition of color-word Stroop tasks and object inhibition tasks between DD-only children and their controls reached significant levels (P<0.05), and the differences of reaction time in number Stroop tasks between dyscalculic and normal children did not disappear after controlling the non-executive components. The difference of accuracy in color-word incongruent tasks between children with DD&RD and normal children reached significant levels (P<0.05). Children with DD-only confronted with general inhibitory deficits, while children with DD&RD confronted with word inhibitory deficits only.

Evidence that the Dictyostelium Dd-STATa protein is a repressor that regulates commitment to stalk cell differentiation and is also required for efficient chemotaxis.

PubMed

Mohanty, S; Jermyn, K A; Early, A; Kawata, T; Aubry, L; Ceccarelli, A; Schaap, P; Williams, J G; Firtel, R A

1999-08-01

Dd-STATa is a structural and functional homologue of the metazoan STAT (Signal Transducer and Activator of Transcription) proteins. We show that Dd-STATa null cells exhibit several distinct developmental phenotypes. The aggregation of Dd-STATa null cells is delayed and they chemotax slowly to a cyclic AMP source, suggesting a role for Dd-STATa in these early processes. In Dd-STATa null strains, slug-like structures are formed but they have an aberrant pattern of gene expression. In such slugs, ecmB/lacZ, a marker that is normally specific for cells on the stalk cell differentiation pathway, is expressed throughout the prestalk region. Stalk cell differentiation in Dictyostelium has been proposed to be under negative control, mediated by repressor elements present in the promoters of stalk cell-specific genes. Dd-STATa binds these repressor elements in vitro and the ectopic expression of ecmB/lacZ in the null strain provides in vivo evidence that Dd-STATa is the repressor protein that regulates commitment to stalk cell differentiation. Dd-STATa null cells display aberrant behavior in a monolayer assay wherein stalk cell differentiation is induced using the stalk cell morphogen DIF. The ecmB gene, a general marker for stalk cell differentiation, is greatly overinduced by DIF in Dd-STATa null cells. Also, Dd-STATa null cells are hypersensitive to DIF for expression of ST/lacZ, a marker for the earliest stages in the differentiation of one of the stalk cell sub-types. We suggest that both these manifestations of DIF hypersensitivity in the null strain result from the balance between activation and repression of the promoter elements being tipped in favor of activation when the repressor is absent. Paradoxically, although Dd-STATa null cells are hypersensitive to the inducing effects of DIF and readily form stalk cells in monolayer assay, the Dd-STATa null cells show little or no terminal stalk cell differentiation within the slug. Dd-STATa null slugs remain developmentally arrested for several days before forming very small spore masses supported by a column of apparently undifferentiated cells. Thus, complete stalk cell differentiation appears to require at least two events: a commitment step, whereby the repression exerted by Dd-STATa is lifted, and a second step that is blocked in a Dd-STATa null organism. This latter step may involve extracellular cAMP, a known repressor of stalk cell differentiation, because Dd-STATa null cells are abnormally sensitive to the inhibitory effects of extracellular cyclic AMP.

Dideoxynucleoside resistance emerges with prolonged zidovudine monotherapy. The RV43 Study Group.

PubMed Central

Mayers, D L; Japour, A J; Arduino, J M; Hammer, S M; Reichman, R; Wagner, K F; Chung, R; Lane, J; Crumpacker, C S; McLeod, G X

1994-01-01

Human immunodeficiency virus type 1 (HIV-1) isolates resistant to zidovudine (ZDV) have previously been demonstrated to exhibit in vitro cross-resistance to other similar dideoxynucleoside agents which contain a 3'-azido group. However, cross-resistance to didanosine (ddI) or dideoxycytidine (ddC) has been less well documented. ZDV, ddI, and ddC susceptibility data have been collected from clinical HIV-1 isolates obtained by five clinical centers and their respective retrovirology laboratories. All subjects were treated only with ZDV. Clinical HIV-1 isolates were isolated, amplified, and assayed for drug susceptibility in standardized cultures of phytohemagglutinin-stimulated donor peripheral blood mononuclear cells obtained from healthy seronegative donors. All five cohorts showed a correlation between decreased in vitro susceptibility to ZDV and decreased susceptibility to ddI and ddC. For each 10-fold decrease in ZDV susceptibility, an average corresponding decrease of 2.2-fold in ddI susceptibility was observed (129 isolates studied; P < 0.001, Fisher's test of combined significance). Similarly, susceptibility to ddC decreased 2.0-fold for each 10-fold decrease in ZDV susceptibility (82 isolates studied; P < 0.001, Fisher's test of combined significance). These data indicate that a correlation exists between HIV-1 susceptibilities to ZDV and ddI or ddC for clinical HIV-1 isolates. PMID:8192457

The uPA/uPAR system regulates the bioavailability of PDGF-DD: implications for tumour growth.

PubMed

Ehnman, M; Li, H; Fredriksson, L; Pietras, K; Eriksson, U

2009-01-29

Members of the platelet-derived growth factor (PDGF) family are mitogens for cells of mesenchymal origin and have important functions during embryonic development, blood vessel maturation, fibrotic diseases and cancer. In contrast to the two classical PDGFs, the novel and less well-characterized members, PDGF-CC and PDGF-DD, are latent factors that need to be processed extracellularly by activating proteases, before they can mediate PDGF receptor activation. Here, we elucidate the structural requirements for urokinase plasminogen activator (uPA)-mediated activation of PDGF-DD, as well as the intricate interplay with uPA receptor (uPAR) signalling. Furthermore, we show that activated PDGF-DD, in comparison to latent, more potently transforms NIH/3T3 cells in vitro. Conversely, xenograft studies in nude mice demonstrate that cells expressing latent PDGF-DD are more tumorigenic than those expressing activated PDGF-DD. These findings imply that a fine-tuned proteolytic activation, in the local milieu, controls PDGF-DD bioavailability. Moreover, we suggest that proteolytic activation of PDGF-DD reveals a retention motif mediating interactions with pericellular components. Our proposed mechanism, where uPA not only generates active PDGF-DD, but also regulates its spatial distribution, provides novel insights into the biological function of PDGF-DD.

Personality in male patients with substance use disorder and/or severe mental illness.

PubMed

Fernández-Mondragón, Susana; Adan, Ana

2015-08-30

Dual diagnosis (DD) is the coexistence of a substance use disorder (SUD) and severe mental illness (SMI). The aim of this study is to determine for the first time if a specific personality pattern exists for DD patients compared to those who only have SUD or SMI. The sample was composed of 102 male, 34 patients in each group (DD, SUD and SMI). DD and SMI groups included 20 schizophrenic and 14 depressed patients respectively. Cloninger's TCI-R was administered together with a structured interview of sociodemographic and clinical characteristics. All the temperament dimensions and Self-directedness provided differences among groups. The DD and SUD showed significant higher scores in Novelty Seeking regarding SMI, whereas for Harm Avoidance the SUD subjects scored lower with respect to the DD and SMI group. Persistence was significant lower for the DD and SMI groups compared to the SUD patients. The DD obtained low significant scores in Reward Dependence in relation to the SUD and Self-directedness in relation to the SUD and SMI. Our data highlight the presence of a different personality profiles among DD, SUD and SMI disorders. Taking into account the patients' personality can benefit the clinical course and minimize the DD impact. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Rejuvenating direct modulation and direct detection for modern optical communications

NASA Astrophysics Data System (ADS)

Che, Di; Li, An; Chen, Xi; Hu, Qian; Shieh, William

2018-02-01

High-speed transoceanic optical fiber transmission using direct modulation (DM) and direct detection (DD) was one of the most stirring breakthroughs for telecommunication in 1990s, which drove the internet as a global phenomenon. However, the later evolution of optical coherent communications in 2000s gradually took over the long-haul applications, due to its superior optical spectral efficiency. Nowadays, DM-DD systems are dominant mainly in cost- and power-sensitive short-reach applications, because of its natural characteristics-the simplicity. This paper reviews the recent advances of DM-DD transceivers from both hardware and signal processing perspectives. It introduces a variety of modified DM and/or DD systems for 3 application scenarios: very-short-reach interconnect with little fiber channel impact; single or a few spans of fiber transmission up to several hundred km; and distance beyond the 2nd scenario. Besides the DM-DD and multi-dimension DM-DD with polarization diversity, this paper focuses on how to rejuvenate traditional DM and DD technologies in order to bridge the transmission application gap between DM-DD and coherent transceivers, using technologies such as dispersion compensation, signal field recovery from the intensity-only DD receiver, and complex direct modulation with coherent detection. More than 30 years since the birth, DM and DD still hold indispensable roles in modern optical communications.

Cellular traditional Chinese medicine on photobiomodulation

NASA Astrophysics Data System (ADS)

Liu, Timon Cheng-Yi; Cheng, Lei; Liu, Jiang; Wang, Shuang-Xi; Xu, Xiao-Yang; Deng, Xiao-Yuan; Liu, Song-Hao

2006-09-01

Although yin-yang is one of the basic models of traditional Chinese medicine (TCM) for TCM objects such as whole body, five zangs or six fus, they are widely used to discuss cellular processes in papers of famous journals such as Cell, Nature, or Science. In this paper, the concept of the degree of difficulty (DD) of a process was introduced to redefine yin and yang and extend the TCM yin-yang model to the DD yin-yang model so that we have the DD yin-yang inter-transformation, the DD yin-yang antagonism, the DD yin-yang interdependence and the DD yin ping yang mi, which and photobiomodulation (PBM) on cells are supported by each other. It was shown that healthy cells are in the DD yin ping yang mi so that there is no PBM, and there is PBM on non-healthy cells until the cells become healthy so that PBM can be called a cellular rehabilitation. The DD yin-yang inter-transformation holds for our biological information model of PBM. The DD yin-yang antagonism and the DD yin-yang interdependence also hold for a series of experimental studies such as the stimulation of DNA synthesis in HeLa cells after simultaneous irradiation with narrow-band red light and a wide-band cold light, or consecutive irradiation with blue and red light.

Effect of indinavir used alone or in double or triple combination with AZT and ddC on human immune functions.

PubMed

Mattioli, Benedetta; Giordani, Luciana; Quaranta, Maria Giovanna; Viora, Marina

2004-03-19

Indinavir (IDV) is a potent and selective human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) widely used in antiretroviral therapy, but its effects on the immune system are relatively unknown. In this study we have investigated the in vitro effect of IDV on normal human peripheral blood mononuclear cells (PBMC). We used the drug alone or in double and triple combination with AZT and ddC to assess whether IDV interferes with the previously observed immunomodulatory effects induced by AZT and ddC. We found that proliferative response, induction of immunoglobulins (Ig) production and cytokine production was not modulated by IDV. More importantly, IDV used in double or triple combination with AZT and ddC, does not further strenghten the inhibition of proliferative response induced by AZT and is able to abrogate the inhibitory effect induced by ddC on proliferative response. Similarly, IDV/AZT, IDV/ddC and IDV/AZT/ddC combinations does not strenghten the modulation of TNF-alpha, IFN-gamma and IL-4 induced by AZT, ddC and AZT/ddC. On the other hand, IDV neutralizes the up-regulating effects of AZT on IL-2 production while the up-regulating effects of ddC on IL-2 production is not affected. These data suggest that IDV used in combination with AZT and ddC did not add any further immunotoxicity.

Improving Environmental Model Calibration and Prediction

DTIC Science & Technology

2011-01-18

REPORT Final Report - Improving Environmental Model Calibration and Prediction 14. ABSTRACT 16. SECURITY CLASSIFICATION OF: First, we have continued to...develop tools for efficient global optimization of environmental models. Our algorithms are hybrid algorithms that combine evolutionary strategies...toward practical hybrid optimization tools for environmental models. 1. REPORT DATE (DD-MM-YYYY) 4. TITLE AND SUBTITLE 18-01-2011 13

The gastrointestinal tract as a potential infection reservoir of digital dermatitis-associated treponemes in beef cattle and sheep.

PubMed

Sullivan, L E; Carter, S D; Duncan, J S; Grove-White, D H; Angell, J W; Evans, N J

2015-11-01

Digital dermatitis (DD) is an important cause of lameness in dairy cattle worldwide. It has now been reported in beef cattle and also sheep (contagious ovine digital dermatitis [CODD]). Three Treponema phylogroups are consistently isolated from lesions, Treponema medium-like, Treponema phagedenis-like, and Treponema pedis. The gastrointestinal (GI) tract and feces are suggested sites of treponemal infection in dairy cattle; however, isolation of DD-associated treponemes from these areas has previously failed. This study surveyed gingival tissues, rectal tissues, and feces of beef cattle and sheep for the molecular presence (PCR) and isolation of the three cultivable DD-treponeme phylogroups. Of the sheep gingival (n = 40) and rectal (n = 40) tissues, 1/40 gingival tissues was positive for DD-associated treponemes (T. pedis), as were 3/40 rectal tissues (one containing T. medium-like and two containing T. pedis). No DD-associated treponeme DNA was amplified from beef cattle rectal tissues (n = 40); however, 4/40 beef gingival tissues were positive for DD-associated treponemes (all containing T. phagedenis-like). A T. phagedenis-like DD-associated treponeme was isolated from the rectal tissue of a CODD symptomatic sheep. Beef cattle (n = 41) and sheep (n = 79) feces failed to amplify DD-associated Treponema DNA. Twenty-two treponemes were isolated from sheep feces; however, upon phylogenetic analysis, these clustered with the considered nonpathogenic treponemes. This study detected DD-associated treponemes in the GI tract tissues of sheep and beef cattle and successfully isolated a DD-associated treponeme from ruminant rectal tissue. This gives evidence that the GI tract is an important infection reservoir of DD-associated treponemes in multiple DD-infected species. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The Gastrointestinal Tract as a Potential Infection Reservoir of Digital Dermatitis-Associated Treponemes in Beef Cattle and Sheep

PubMed Central

Carter, S. D.; Duncan, J. S.; Grove-White, D. H.; Angell, J. W.; Evans, N. J.

2015-01-01

Digital dermatitis (DD) is an important cause of lameness in dairy cattle worldwide. It has now been reported in beef cattle and also sheep (contagious ovine digital dermatitis [CODD]). Three Treponema phylogroups are consistently isolated from lesions, Treponema medium-like, Treponema phagedenis-like, and Treponema pedis. The gastrointestinal (GI) tract and feces are suggested sites of treponemal infection in dairy cattle; however, isolation of DD-associated treponemes from these areas has previously failed. This study surveyed gingival tissues, rectal tissues, and feces of beef cattle and sheep for the molecular presence (PCR) and isolation of the three cultivable DD-treponeme phylogroups. Of the sheep gingival (n = 40) and rectal (n = 40) tissues, 1/40 gingival tissues was positive for DD-associated treponemes (T. pedis), as were 3/40 rectal tissues (one containing T. medium-like and two containing T. pedis). No DD-associated treponeme DNA was amplified from beef cattle rectal tissues (n = 40); however, 4/40 beef gingival tissues were positive for DD-associated treponemes (all containing T. phagedenis-like). A T. phagedenis-like DD-associated treponeme was isolated from the rectal tissue of a CODD symptomatic sheep. Beef cattle (n = 41) and sheep (n = 79) feces failed to amplify DD-associated Treponema DNA. Twenty-two treponemes were isolated from sheep feces; however, upon phylogenetic analysis, these clustered with the considered nonpathogenic treponemes. This study detected DD-associated treponemes in the GI tract tissues of sheep and beef cattle and successfully isolated a DD-associated treponeme from ruminant rectal tissue. This gives evidence that the GI tract is an important infection reservoir of DD-associated treponemes in multiple DD-infected species. PMID:26276110

Modeling Emerging Solar Cell Materials and Devices

NASA Astrophysics Data System (ADS)

Thongprong, Non

Organic photovoltaics (OPVs) and perovskite solar cells are emerging classes of solar cell that are promising for clean energy alternatives to fossil fuels. Understanding fundamental physics of these materials is crucial for improving their energy conversion efficiencies and promoting them to practical applications. Current density-voltage (JV) curves; which are important indicators of OPV efficiency, have direct connections to many fundamental properties of solar cells. They can be described by the Shockley diode equation, resulting in fitting parameters; series and parallel resistance (Rs and Rp), diode saturation current ( J0) and ideality factor (n). However, the Shockley equation was developed specifically for inorganic p-n junction diodes, so it lacks physical meanings when it is applied to OPVs. Hence, the puRposes of this work are to understand the fundamental physics of OPVs and to develop new diode equations in the same form as the Shockley equation that are based on OPV physics. We develop a numerical drift-diffusion simulation model to study bilayer OPVs, which will be called the drift-diffusion for bilayer interface (DD-BI) model. The model solves Poisson, drift-diffusion and current-continuity equations self-consistently for charge densities and potential profiles of a bilayer device with an organic heterojunction interface described by the GWWF model. We also derive new diode equations that have JV curves consistent with the DD-BI model and thus will be called self-consistent diode (SCD) equations. Using the DD-BI and the SCD model allows us to understand working principles of bilayer OPVs and physical definitions of the Shockley parameters. Due to low carrier mobilities in OPVs, space charge accumulation is common especially near the interface and electrodes. Hence, quasi-Fermi levels (i.e. chemical potentials), which depend on charge densities, are modified around the interface, resulting in a splitting of quasi-Fermi levels that works as a driving potential for the heterojunction diode. This brings about the meaning of R s as the resistance that gives rise to the diode voltage equal to the interface quasi-Fermi level splitting instead of the voltage between the electrodes. Quasi-Fermi levels that drop near the electrodes because of unmatched electrode work functions or due to charge injection can also increase Rs. Furthermore, we are able to study dissociation and recombination rates of bound charge pairs across the interface (i.e. polaron pairs or PPs) and arrive at the physical meaning of Rp as recombination resistance of PPs. In the dark, PP density is very low, so Rp is possibly caused by a tunneling leakage current at the interface. Ideality factors are parameters that depend on the split of quasi-Fermi levels and the ratio of recombination rate to recombination rate at equilibrium. Even though they are related to trap characteristics as normally understood, their relations are complicated and careful inte Rpretations of fitted ideality factors are needed. Our models are successfully applied to actual devices, and useful physics can be deduced, for example differences between the Shockley parameters under dark and illumination conditions. Another puRpose of this thesis is to study electronic properties of CsSnBr3 perovskite and processes of growing the perovskite film using an epitaxy technique. Calculation results using density functional theory reveal that a CsSnBr3 film that is grown on a NaCl(100) substrate can undergo a phase transition to CsSn 2Br5, which is a wide-bandgap semiconductor material. Actual mechanisms of the transition and the interface between CsSnBr3 and CsSn2Br5are interesting for future studies.

Visual deprivation alters dendritic bundle architecture in layer 4 of rat visual cortex.

PubMed

Gabbott, P L; Stewart, M G

2012-04-05

The effect of visual deprivation followed by light exposure on the tangential organisation of dendritic bundles passing through layer 4 of the rat visual cortex was studied quantitatively in the light microscope. Four groups of animals were investigated: (I) rats reared in an environment illuminated normally--group 52 dL; (II) rats reared in the dark until 21 days postnatum (DPN) and subsequently light exposed for 31 days-group 21/31; (III) rats dark reared until 52 DPN and then subsequently light exposed for 3 days--group 3 dL; and (IV) rats totally dark reared until 52 DPN--group 52 DPN. Each group contained five animals. Semithin 0.5-1-μm thick resin-embedded sections were collected from tangential sampling levels through the middle of layer 4 in area 17 and stained with Toluidine Blue. These sections were used to quantitatively analyse the composition and distribution of dendritic clusters in the tangential plane. The key result of this study indicates a significant reduction in the mean number of medium- and small-sized dendritic profiles (diameter less than 2 μm) contributing to clusters in layer 4 of groups 3 dL and 52 dD compared with group 21/31. No differences were detected in the mean number of large-sized dendritic profiles composing a bundle in these experimental groups. Moreover, the mean number of clusters and their tangential distribution in layer 4 did not vary significantly between all four groups. Finally, the clustering parameters were not significantly different between groups 21/31 and the normally reared group 52 dL. This study demonstrates, for the first time, that extended periods of dark rearing followed by light exposure can alter the morphological composition of dendritic bundles in thalamorecipient layer 4 of rat visual cortex. Because these changes occur in the primary region of thalamocortical input, they may underlie specific alterations in the processing of visual information both cortically and subcortically during periods of dark rearing and light exposure. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Associations between biosecurity practices and bovine digital dermatitis in Danish dairy herds.

PubMed

Oliveira, Victor H S; Sørensen, Jan T; Thomsen, Peter T

2017-10-01

The relationship between biosecurity and digital dermatitis (DD) was evaluated in 8,269 cows from a convenience sample of 39 freestall dairy herds. The hypothesis was that poor implementation of biosecurity was associated with higher within-herd prevalence of DD. All lactating cows were scored as negative or positive for DD at the hind legs during milking in the milking parlor. Information about biosecurity was obtained through questionnaires addressed to farmers, on-farm observations, and information from the Danish Cattle Database (www.seges.dk). These assessment tools covered potential infection sources of DD pathogens to susceptible cows (e.g., via animals, humans, manure, vehicles, equipment, and facilities). External and internal biosecurity measures were explanatory variables in 2 separate logistic regression models, whereas within-herd DD prevalence was the outcome. Overall DD prevalence among cows and herds were 24 and 97%, respectively; the within-herd DD prevalence ranged from 0 to 56%. Poor external biosecurity measures associated with higher prevalence of DD were recent animal purchase, access to pasture, lack of boots available for visitors, farm staff working at other dairy farms as well, hoof trimming without a professional attending, and animal transporters having access to cattle area. For internal biosecurity, higher DD prevalence were associated with infrequent hoof bathing, manure scraping less than 8 times a day, manure removal direction from cows to heifers, animal pens' exit without water hoses, manure-handling vehicle used in other activities, and water troughs contaminated with manure. These findings showed that improvements on biosecurity may be beneficial for controlling DD in dairy herds. The study is relevant for farmers facing problems with DD, as well as hoof trimmers, advisors, and veterinarians, who can use the results for optimized recommendations regarding biosecurity in relation to DD. Furthermore, our results might be considered by future studies investigating DD pathogen reservoirs and transmission routes. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Evidence that noncoding RNA dutA is a multicopy suppressor of Dictyostelium discoideum STAT protein Dd-STATa.

PubMed

Shimada, Nao; Kawata, Takefumi

2007-06-01

Dd-STATa, a Dictyostelium discoideum homologue of metazoan STAT transcription factors, is necessary for culmination. We created a mutant strain with partial Dd-STATa activity and used it to screen for unlinked suppressor genes. We screened approximately 450,000 clones from a slug-stage cDNA library for their ability to rescue the culmination defect when overexpressed. There were 12 multicopy suppressors of Dd-STATa, of which 4 encoded segments of a known noncoding RNA, dutA. Expression of dutA is specific to the pstA zone, the region where Dd-STATa is activated. In suppressed strains the expression patterns of several putative Dd-STATa target genes become similar to the wild-type strain. In addition, the amount of the tyrosine-phosphorylated form of Dd-STATa is significantly increased in the suppressed strain. These results indicate that partial copies of dutA may act upstream of Dd-STATa to regulate tyrosine phosphorylation by an unknown mechanism.

Evidence that Noncoding RNA dutA Is a Multicopy Suppressor of Dictyostelium discoideum STAT Protein Dd-STATa▿

PubMed Central

Shimada, Nao; Kawata, Takefumi

2007-01-01

Dd-STATa, a Dictyostelium discoideum homologue of metazoan STAT transcription factors, is necessary for culmination. We created a mutant strain with partial Dd-STATa activity and used it to screen for unlinked suppressor genes. We screened approximately 450,000 clones from a slug-stage cDNA library for their ability to rescue the culmination defect when overexpressed. There were 12 multicopy suppressors of Dd-STATa, of which 4 encoded segments of a known noncoding RNA, dutA. Expression of dutA is specific to the pstA zone, the region where Dd-STATa is activated. In suppressed strains the expression patterns of several putative Dd-STATa target genes become similar to the wild-type strain. In addition, the amount of the tyrosine-phosphorylated form of Dd-STATa is significantly increased in the suppressed strain. These results indicate that partial copies of dutA may act upstream of Dd-STATa to regulate tyrosine phosphorylation by an unknown mechanism. PMID:17435008

The association of visuospatial working memory with dysthymic disorder in pre-pubertal children.

PubMed

Franklin, T; Lee, A; Hall, N; Hetrick, S; Ong, J; Haslam, N; Karsz, F; Vance, A

2010-02-01

Visuospatial working memory (VSWM) deficits have not been investigated specifically in children with dysthymic disorder (DD), although they are associated with impairments in attention that commonly occur in DD. This study investigates VSWM impairment in children with DD. A cross-sectional study of VSWM in 6- to 12-year-old children with medication-naive DD (n=26) compared to an age-, gender- and 'performance IQ' (PIQ)-matched healthy control group (n=28) was completed. The DD group demonstrated impairment in VSWM, including impairment in the spatial span and strategy components of VSWM. Furthermore, the VSWM impairment remained after controlling for spatial span. Inattentive symptoms were significantly associated with the VSWM impairment. This study of children with DD found deficits in performance on VSWM tasks, suggesting that fronto-striatal-parietal neural networks that underlie processes of attention and the executive component of VSWM are dysfunctional in children with DD. These findings further our understanding of DD and suggest more specific interventions that might improve functioning.

Red light-regulated growth. I. Changes in the abundance of indoleacetic acid and a 22-kilodalton auxin-binding protein in the maize mesocotyl

NASA Technical Reports Server (NTRS)

Jones, A. M.; Cochran, D. S.; Lamerson, P. M.; Evans, M. L.; Cohen, J. D.

1991-01-01

We examined the changes in the levels of indoleacetic acid (IAA), IAA esters, and a 22-kilodalton subunit auxin-binding protein (ABP1) in apical mesocotyl tissue of maize (Zea mays L.) during continuous red light (R) irradiation. These changes were compared with the kinetics of R-induced growth inhibition in the same tissue. Upon the onset of continuous irradiation, growth decreased in a continuous manner following a brief lag period. The decrease in growth continued for 5 hours, then remained constant at 25% of the dark rate. The abundance of ABP1 and the level of free IAA both decreased in the mesocotyl. Only the kinetics of the decrease in IAA within the apical mesocotyl correlated with the initial change in growth, although growth continued to decrease even after IAA content reached its final level, 50% of the dark control. This decrease in IAA within the mesocotyl probably occurs primarily by a change in its transport within the shoot since auxin applied as a pulse move basipetally in R-irradiated tissue at the same rate but with half the area as dark control tissue. In situ localization of auxin in etiolated maize shoots revealed that R-irradiated shoots contained less auxin in the epidermis than the dark controls. Irradiated mesocotyl grew 50% less than the dark controls even when incubated in an optimal level of auxin. However, irradiated and dark tissue contained essentially the same amount of radioactivity after incubation in [14C]IAA indicating that the light treatment does not affect the uptake into the tissue through the cut end, although it is possible that a small subset of cells within the mesocotyl is affected. These observations support the hypothesis that R causes a decrease in the level of auxin in epidermal cells of the mesocotyl, consequently constraining the growth of the entire mesocotyl.

Seizure phenotypes, periodicity, and sleep-wake pattern of seizures in Kcna-1 null mice.

PubMed

Wright, Samantha; Wallace, Eli; Hwang, Youngdeok; Maganti, Rama

2016-02-01

This study was undertaken to describe seizure phenotypes, natural progression, sleep-wake patterns, as well as periodicity of seizures in Kcna-1 null mutant mice. These mice were implanted with epidural electroencephalography (EEG) and electromyography (EMG) electrodes, and simultaneous video-EEG recordings were obtained while animals were individually housed under either diurnal (LD) condition or constant darkness (DD) over ten days of recording. The video-EEG data were analyzed to identify electrographic and behavioral phenotypes and natural progression and to examine the periodicity of seizures. Sleep-wake patterns were analyzed to understand the distribution and onset of seizures across the sleep-wake cycle. Four electrographically and behaviorally distinct seizure types were observed. Regardless of lighting condition that animals were housed in, Kcna-1 null mice initially expressed only a few of the most severe seizure types that progressively increased in frequency and decreased in seizure severity. In addition, a circadian periodicity was noted, with seizures peaking in the first 12h of the Zeitgeber time (ZT) cycle, regardless of lighting conditions. Interestingly, seizure onset differed between lighting conditions where more seizures arose out of sleep in LD conditions, whereas under DD conditions, the majority occurred out of the wakeful state. We suggest that this model be used to understand the circadian pattern of seizures as well as the pathophysiological implications of sleep and circadian disturbances in limbic epilepsies. Copyright © 2015 Elsevier Inc. All rights reserved.

Detailing Dark Spokes

NASA Image and Video Library

2010-03-09

NASA Cassini spacecraft images dark spokes on Saturn B ring. Spokes are radial markings on Saturn rings that continue to interest scientists, and they can be seen here stretching left to right across the image.

Structure and anticancer activity of native and modified polysaccharides from brown alga Dictyota dichotoma.

PubMed

Usoltseva, Roza V; Shevchenko, Natalia M; Malyarenko, Olesya S; Ishina, Irina A; Ivannikova, Svetlana I; Ermakova, Svetlana P

2018-01-15

The laminaran DdL and fucoidan DdF were obtained from the brown alga Dictyota dichotoma. DdF was a sulfated (28.9%) and acetylated heteropolysaccharide containing fucose, galactose, mannose and glucose (57.9, 20.4, 12.4 and 9.2mol%, respectively). DdL was a 1,3;1,6-β-d-glucan with the main chain built from 1,3-linked glucose residues and single glucose residue in branches at C6 (one branch on three glucose residues of the main chain). Sulfated (43.7%) laminaran DdLs was obtained from DdL by sulfation. It was determined that sulfates occur at C2, C4 and C6 of glucose residues. The anticancer effect of DdF, DdL, and DdLs (200μg/mL) was studied in vitro on colon cancer cells HCT-116, HT-29, and DLD-1. The effect of polysaccharides (40μg/mL) on colony formation of DLD-1 cancer cells after irradiation (4Gy) was investigated first. All polysaccharides showed a synergistic effect with X-ray irradiation against cancer cells, decreasing the amount and size of cancer cells colonies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human sperm DNA integrity: correlation with sperm cytoplasmic droplets.

PubMed

Fischer, Marc Anthony; Willis, Jennifer; Zini, Armand

2003-01-01

To examine the retention of sperm cytoplasmic droplets (CD) and DNA denaturation (DD) in semen from fertile and infertile men. Semen samples were obtained from consecutive nonazoospermic men presenting for infertility evaluation (n = 101) and fertile men presenting for vasectomy (n = 13). The standard semen parameters (sperm concentration, motility, and morphology), sperm DD, and sperm CD were monitored. Sperm DD was evaluated by flow cytometry analysis of acridine orange-treated spermatozoa and expressed as the percentage of spermatozoa demonstrating denatured DNA. The mean (+/-SE) percentages of spermatozoa with CD and DD were significantly higher in infertile than in fertile men (sperm CD 15.7% +/- 0.8% versus 4.8% +/- 0.7% and sperm DD 22.0% +/- 1.5% versus 10.8% +/- 1.8%, respectively). Sperm CD and DD were positively correlated (r = 0.59). Also, sperm CD and DD values correlated inversely with the standard semen parameters. Our data demonstrate that the retention of sperm CD correlates positively with sperm DD and that significantly higher sperm DD and CD are found in infertile than in fertile men. These data suggest that the enhanced susceptibility of sperm DNA to denaturation is associated with the abnormal disposal of residual sperm cytoplasm in the testis and/or epididymis.

32 CFR 728.112 - Responsibilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... unless patient administration departments take the initial step to complete: (1) DD 7, Report of Treatment Furnished Pay Patients, Hospitalization Furnished (part A). Prepare a separate substantiating DD 7... any pay patient is admitted, submit DD 7's to the collection agent. (2) DD 7A, Report of Treatment...

Compact D-D Neutron Source-Driven Subcritical Multiplier and Beam-Shaping Assembly for Boron Neutron Capture Therapy

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

Francesco Ganda; Jasmina Vujic; Ehud Greenspan

2010-12-01

This work assesses the feasibility of using a small, safe, and inexpensive keff 0.98 subcritical fission assembly [subcritical neutron multiplier (SCM)] to amplify the treatment neutron beam intensity attainable from a compact deuterium-deuterium (D-D) fusion neutron source delivering [approximately]1012 n/s. The objective is to reduce the treatment time for deep-seated brain tumors to [approximately]1 h. The paper describes the optimal SCM design and two optimal beam-shaping assemblies (BSAs) - one designed to maximize the dose rate and the other designed to maximize the total dose that can be delivered to a deep-seated tumor. The neutron beam intensity amplification achieved withmore » the optimized SCM and BSA results in an increase in the treatment dose rate by a factor of 18: from 0.56 Gy/h without the SCM to 10.1 Gy/h. The entire SCM is encased in an aluminum structure. The total amount of 20% enriched uranium required for the SCM is 8.5 kg, and the cost (not including fabrication) is estimated to be less than $60,000. The SCM power level is estimated at 400 W when driven by a 1012 n/s D-D neutron source. This translates into consumption of only [approximately]0.6% of the initially loaded 235U atoms during 50 years of continuous operation and implies that the SCM could operate continuously for the entire lifetime of the facility without refueling. Cooling the SCM does not pose a challenge; it may be accomplished by natural circulation as the maximum heat flux is only 0.034 W/cm2.« less

The "where" and "what" in developmental dyscalculia.

PubMed

Henik, Avishai; Rubinsten, Orly; Ashkenazi, Sarit

2011-08-01

Developmental dyscalculia (DD) is a congenital deficit that affects the ability to acquire arithmetical skills. Individuals with DD have problems learning standard number facts and procedures. Estimates of the prevalence rate of DD are similar to those of developmental dyslexia. Recent reports and discussions suggest that those with DD suffer from specific deficits (e.g., subitizing, comparative judgment). Accordingly, DD has been described as a domain-specific disorder that involves particular brain areas (e.g., intra-parietal sulcus). However, we and others have found that DD is characterized by additional deficiencies and may be affected by domain-general (e.g., attention) factors. Hence "pure DD" might be rather rare and not as pure as one would think. We suggest that the heterogeneity of symptoms that commonly characterize learning disabilities needs to be taken into account in future research and treatment.

The safe enterocin DD14 is a leaderless two-peptide bacteriocin with anti-Clostridium perfringens activity.

PubMed

Caly, Delphine L; Chevalier, Mickaël; Flahaut, Christophe; Cudennec, Benoit; Al Atya, Ahmed Khassaf; Chataigné, Gabrielle; D'Inca, Romain; Auclair, Eric; Drider, Djamel

2017-03-01

Enterococcus faecalis 14, a strain previously isolated from meconium, displayed activity against four Clostridium perfringens isolates when co-cultured on agar plates. The anti-Clostridium activity was ascribed to the production of enterocin DD14, which was subsequently purified. The minimum inhibitory concentration (MIC) of enterocin DD14 against one collection strain and one clinical C. perfringens strain was determined at 50 µg/mL. Furthermore, using the intestinal epithelial cell line IPEC-1, it was shown that E. faecalis 14 was not cytotoxic after 24 h of contact, and no cytotoxicity was observed when IPEC-1 cells were incubated with pure enterocin DD14 for 4 h. Enterocin DD14 was characterised using mass spectrometry and was shown to consist of two small proteins of 5200.74 Da and 5206.41 Da, respectively. The two peptides (DD14A and DD14B) have highly similar amino acid sequences and no signal peptide, which classifies enterocin DD14 as a class IIb leaderless two-peptide bacteriocin. The genes encoding DD14A and DD14B were sequenced and were shown to be 100% identical to other previously described enterocins MR10A and MR10B, in contrast to the producing strains, which are different. Consequently, the present in vitro study supports the potential of this E. faecalis 14 strain and/or its purified enterocin DD14 as putative anti-C. perfringens compounds in chickens. Copyright © 2017. Published by Elsevier B.V.

78 FR 54633 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-05

... Child Development Program (CDP); DD 2652, DD 2606; OMB Control Number 0704- TBD. Needs and Uses: The... Respondent: 1. Average Burden per Response: 10 minutes. Frequency: On occasion. The information from the DD... projection of future program requirements. The information in DD 2652 is used to apply child care fee...

DD-bar production and their interactions

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

Liu Yanrui; Oka, Makoto; Takizawa, Makoto

2011-05-23

We have explored the bound state problem and the scattering problem of the DD-bar pair in a meson exchange model. When considering their production in the e{sup +}e{sup -} process, we included the DD-bar rescattering effect. Although it is difficult to answer whether the S-wave DD-bar bound state exists or not from the binding energies and the phase shifts, one may get an upper limit of the binding energy from the production of the BB-bar, the bottom analog of DD-bar.

Development of a force sensor using atom interferometry to constrain theories on dark matter and dark energy

NASA Astrophysics Data System (ADS)

Schlupf, Chandler; Niederriter, Robert; Bohr, Eliot; Khamis, Sami; Park, Youna; Szwed, Erik; Hamilton, Paul

2017-04-01

Atom interferometry has been used in many precision measurements such as Newton's gravitational constant, the fine structure constant, and tests of the equivalence principle. We will perform atom interferometry in an optical lattice to measure the force felt by an atom due to a test mass in search of new forces suggested by dark matter and dark energy theories. We will be developing a new apparatus using laser-cooled ytterbium to continuously measure this force by observing their Bloch oscillations. Interfering atoms in an optical lattice allows continuous measurements in a small volume over a long period of time, enabling our device to be sensitive to time-varying forces while minimizing vibrational noise. We present the details of this experiment and the progress on it thus far.

48 CFR 253.215-70 - DD Form 1547, Record of Weighted Guidelines Application.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false DD Form 1547, Record of... Forms 253.215-70 DD Form 1547, Record of Weighted Guidelines Application. Follow the procedures at PGI 253.215-70 for completing DD Form 1547. [71 FR 69495, Dec. 1, 2006] ...

48 CFR 247.372 - DD Form 1654, Evaluation of Transportation Cost Factors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false DD Form 1654, Evaluation... Transportation in Supply Contracts 247.372 DD Form 1654, Evaluation of Transportation Cost Factors. Contracting personnel may use the DD Form 1654 to furnish information to the transportation office for development of...

32 CFR Appendix C to Part 45 - DD Form 215

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false DD Form 215 C Appendix C to Part 45 National... CERTIFICATE OF RELEASE OR DISCHARGE FROM ACTIVE DUTY (DD FORM 214/5 SERIES) Pt. 45, App. C Appendix C to Part 45—DD Form 215 EC21OC91.050 ...

Utilization of Deceased Donor Kidneys to Initiate Living Donor Chains.

PubMed

Melcher, M L; Roberts, J P; Leichtman, A B; Roth, A E; Rees, M A

2016-05-01

We propose that some deceased donor (DD) kidneys be allocated to initiate nonsimultaneous extended altruistic donor chains of living donor (LD) kidney transplants to address, in part, the huge disparity between patients on the DD kidney waitlist and available donors. The use of DD kidneys for this purpose would benefit waitlisted candidates in that most patients enrolled in kidney paired donation (KPD) systems are also waitlisted for a DD kidney transplant, and receiving a kidney through the mechanism of KPD will decrease pressure on the DD pool. In addition, a LD kidney usually provides survival potential equal or superior to that of DD kidneys. If KPD chains that are initiated by a DD can end in a donation of an LD kidney to a candidate on the DD waitlist, the quality of the kidney allocated to a waitlisted patient is likely to be improved. We hypothesize that a pilot program would show a positive impact on patients of all ethnicities and blood types. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

The enemy in the mirror: self-perception-induced stress results in dissociation of psychological and physiological responses in patients with dissociative disorder

PubMed Central

Sattel, Heribert; Schmidt, Ulrike; Sack, Martin

2018-01-01

ABSTRACT Background: Patients suffering from dissociative disorders (DD) are characterized by an avoidance of aversive stimuli. Clinical experience has shown that DD patients typically avoid the confrontation with their own faces in a mirror (CFM). Objective: To investigate potential CFM-associated self-reported and psychophysiological stress reactions of DD patients, which most likely inform on the still unknown pathophysiology of dysfunctional self-perception in DD. Method: Eighteen DD patients and 18 healthy controls (HCs) underwent CFM. They were assessed for CFM-induced subjective self-reported stress, acute dissociative symptoms and sympathetic and parasympathetic drive using impedance cardiography. Results: DD patients experienced more subjective stress and acute dissociation than HCs upon CFM. Their psychological stress response did not activate the sympathetic and parasympathetic nervous system. Conclusions: In DD patients, CFM constitutes serious self-reported stress and is associated with a blunted autonomic reactivity. Therapeutic approaches promoting self-perception and self-compassion, in particular by using CFM, might serve as goal-oriented diagnostic and therapeutic tools in DD.

The enemy in the mirror: self-perception-induced stress results in dissociation of psychological and physiological responses in patients with dissociative disorder.

PubMed

Schäflein, Eva; Sattel, Heribert; Schmidt, Ulrike; Sack, Martin

2018-01-01

Background : Patients suffering from dissociative disorders (DD) are characterized by an avoidance of aversive stimuli. Clinical experience has shown that DD patients typically avoid the confrontation with their own faces in a mirror (CFM). Objective : To investigate potential CFM-associated self-reported and psychophysiological stress reactions of DD patients, which most likely inform on the still unknown pathophysiology of dysfunctional self-perception in DD. Method : Eighteen DD patients and 18 healthy controls (HCs) underwent CFM. They were assessed for CFM-induced subjective self-reported stress, acute dissociative symptoms and sympathetic and parasympathetic drive using impedance cardiography. Results : DD patients experienced more subjective stress and acute dissociation than HCs upon CFM. Their psychological stress response did not activate the sympathetic and parasympathetic nervous system. Conclusions : In DD patients, CFM constitutes serious self-reported stress and is associated with a blunted autonomic reactivity. Therapeutic approaches promoting self-perception and self-compassion, in particular by using CFM, might serve as goal-oriented diagnostic and therapeutic tools in DD.

Growth and tuberization of potato (Solanum tuberosum L.) under continuous light

NASA Technical Reports Server (NTRS)

Wheeler, R. M.; Tibbitts, T. W.

1986-01-01

The growth and tuberization of potatoes (Solanum tuberosum L.) maintained for 6 weeks under four different regimes of continuous irradiance were compared to plants given 12 hours light and 12 hours dark. Treatments included: (a) continuous photosynthetic photon flux of 200 micromoles per square meter per second cool-white fluorescent (CWF); (b) continuous 400 micromoles per square meter per second CWF; (c) 12 hours 400 micromoles per square meter per second CWF plus 12 hours dim CWF at 5 micromoles per square meter per second; (d) 12 hours [400] micromoles per square meter per second CWF plus 12 hours dim incandescent (INC) at 5 micromoles per square meter per second and a control treatment of 12 hours light at 400 micromoles per square meter per second CWF and 12 hours dark. The study included five cultivars ranging from early- to late-season types: 'Norland,' 'Superior,''Norchip,' 'Russet Burbank,' and 'Kennebec,' Tuber development progressed well under continuous irradiation at 400 micromoles per square meter per second and under 12 hours irradiance and 12 hours dark, while tuber development was suppressed in all other light treatments. Continuous irradiation at 200 or 400 micromoles per square meter per second resulted in severe stunting and leaf malformation on 'Superior' and 'Kennebec' plants, but little or no injury and vigorous shoot growth in the other cultivars. No injury or stunting were apparent under 12-dim light or 12-dark treatments. Plants given 12 hours dim INC showed significantly greater stem elongation but less total biomass than plants in other treatments. The continuous light encouraged shoot growth over tuber growth but this trend was overridden by providing a high irradiance level. The variation among cultivars for tolerance to continuous lighting indicates that potato may be a useful species for photoinhibition studies.

Growth and Tuberization of Potato (Solanum tuberosum L.) under Continuous Light 1

PubMed Central

Wheeler, Raymond M.; Tibbitts, Theodore W.

1986-01-01

The growth and tuberization of potatoes (Solanum tuberosum L.) maintained for 6 weeks under four different regimes of continuous irradiance were compared to plants given 12 hours light and 12 hours dark. Treatments included: (a) continuous photosynthetic photon flux of 200 micromoles per square meter per second cool-white fluorescent (CWF); (b) continuous 400 micromoles per square meter per second CWF; (c) 12 hours 400 micromoles per square meter per second CWF plus 12 hours dim CWF at 5 micromoles per square meter per second; (d) 12 hours micromoles per square meter per second CWF plus 12 hours dim incandescent (INC) at 5 micromoles per square meter per second and a control treatment of 12 hours light at 400 micromoles per square meter per second CWF and 12 hours dark. The study included five cultivars ranging from early- to late-season types: `Norland,' `Superior,' `Norchip,' `Russet Burbank,' and `Kennebec.' Tuber development progressed well under continuous irradiation at 400 micromoles per square meter per second and under 12 hours irradiance and 12 hours dark, while tuber development was suppressed in all other light treatments. Continuous irradiation at 200 or 400 micromoles per square meter per second resulted in severe stunting and leaf malformation on `Superior' and `Kennebec' plants, but little or no injury and vigorous shoot growth in the other cultivars. No injury or stunting were apparent under 12-dim light or 12-dark treatments. Plants given 12 hours dim INC showed significantly greater stem elongation but less total biomass than plants in other treatments. The continuous light encouraged shoot growth over tuber growth but this trend was overridden by providing a high irradiance level. The variation among cultivars for tolerance to continuous lighting indicates that potato may be a useful species for photoinhibition studies. PMID:11539039

Lack of immunotoxicity of saquinavir (Ro 31-8959) used alone or in double or triple combination with AZT and ddC.

PubMed

Viora, M; Di Genova, G; Quaranta, M G; Boirivant, M; Camponeschi, B

1998-09-01

Saquinavir (Ro 31-8959; SQV) has been demonstrated to be a potent inhibitor of human immunodeficiency virus (HIV) proteinases and acts synergistically with dideoxynucleoside analogues. The aim of this study was to investigate the in vitro immunomodulatory effects of SQV on normal human peripheral blood mononuclear cells (PBMC) and on lamina propria mononuclear cells (LPMC). We used the drug either alone or in double and triple combination with AZT and ddC to assess whether SQV enhances the immunomodulatory effects induced by AZT and ddC that we previously observed. We demonstrated that SQV did not induce any modulation of the proliferative response either in PBMC or in LPMC. Similarly, NK cell-mediated cytotoxic activity and cytokine production were not modified by SQV. More importantly, SQV/AZT, SQV/ddC, and SQV/AZT/ddC combinations did not strengthen neither the inhibition of PBMC and LPMC proliferative response or the modulation of cytokine production induced by AZT, ddC, and AZT/ddC. On the other hand, the increased IL-2 production induced by AZT and ddC was not observed adding SQV to the dideoxynucleoside analogues. In conclusion, we demonstrated that SQV used in combination with AZT and ddC did not add any further immunotoxicity.

Physicochemical properties and biocompatibility of N-trimethyl chitosan: effect of quaternization and dimethylation.

PubMed

Jintapattanakit, Anchalee; Mao, Shirui; Kissel, Thomas; Junyaprasert, Varaporn Buraphacheep

2008-10-01

The aim of this research was to investigate the effect of degrees of quaternization (DQ) and dimethylation (DD) on physicochemical properties and cytotoxicity of N-trimethyl chitosan (TMC). TMC was synthesized by reductive methylation of chitosan in the presence of a strong base at elevated temperature and polymer characteristics were investigated. The number of methylation process and duration of reaction were demonstrated to affect the DQ and DD. An increased number of reaction steps increased DQ and decreased DD, while an extended duration of reaction increased both DQ and DD. The molecular weight of TMC was in the range of 60-550kDa. From the Mark-Houwink equation, it was found that TMC in 2% acetic acid/0.2M sodium acetate behaved as a spherical structure, approximating a random coil. The highest solubility was found with TMC of an intermediate DQ (40%) regardless of DD and molecular weight. The effect of DD on the physicochemical properties and cytotoxicity was obviously observed when proportion of DD to DQ was higher than 1. TMC with relatively high DD showed reduction in both solubility and mucoadhesion and hence decreased cytotoxicity. However, the influence of DD was insignificant when DQ of TMC was higher than 40% at which physicochemical properties and cytotoxicity were mainly dependent upon DQ.

Characterization of stem cells in Dupuytren's disease.

PubMed

Hindocha, S; Iqbal, S A; Farhatullah, S; Paus, R; Bayat, A

2011-02-01

Dupuytren's disease (DD) is a common fibroproliferative disease of unknown origin. The source of abnormal cells leading to DD formation remains underexplored. In addition to fascia, palmar skin and fat-derived cells may be a potential source of cells causing DD. This study aimed to profile haematopoietic and mesenchymal stem cells in different DD tissue components compared with tissue removed at carpal tunnel surgery (control). Biopsies were taken from the diseased cord, nodule, perinodular fat and skin overlying the nodule of ten patients with DD and compared with control tissue from seven patients having surgery for carpal tunnel syndrome. Fluorescence-activated cell sorting (FACS), immunohistochemistry and quantitative real-time polymerase chain reaction (QRT-PCR) were used to identify expression of selected stem cell markers. FACS and QRT-PCR analysis identified the highest RNA expression and number of cells positive for adipocyte stem cell markers (CD13 and CD29) in the DD nodule in comparison with carpal tunnel control tissue (P = 0·053). CD34 RNA was overexpressed, and a higher percentage of these cells was present in DD skin compared with carpal tunnel skin (P = 0·001). Each structural component of DD (cord, nodule, perinodular fat and skin) had distinct stem cell populations. These findings support the hypothesis that DD may result from mesenchymal progenitor cell expansion.

Dupuytren's: a systems biology disease

PubMed Central

2011-01-01

Dupuytren's disease (DD) is an ill-defined fibroproliferative disorder of the palm of the hands leading to digital contracture. DD commonly occurs in individuals of northern European extraction. Cellular components and processes associated with DD pathogenesis include altered gene and protein expression of cytokines, growth factors, adhesion molecules, and extracellular matrix components. Histology has shown increased but varying levels of particular types of collagen, myofibroblasts and myoglobin proteins in DD tissue. Free radicals and localised ischaemia have been suggested to trigger the proliferation of DD tissue. Although the existing available biological information on DD may contain potentially valuable (though largely uninterpreted) information, the precise aetiology of DD remains unknown. Systems biology combines mechanistic modelling with quantitative experimentation in studies of networks and better understanding of the interaction of multiple components in disease processes. Adopting systems biology may be the ideal approach for future research in order to improve understanding of complex diseases of multifactorial origin. In this review, we propose that DD is a disease of several networks rather than of a single gene, and show that this accounts for the experimental observations obtained to date from a variety of sources. We outline how DD may be investigated more effectively by employing a systems biology approach that considers the disease network as a whole rather than focusing on any specific single molecule. PMID:21943049

A putative low-molecular-mass penicillin-binding protein (PBP) of Mycobacterium smegmatis exhibits prominent physiological characteristics of DD-carboxypeptidase and beta-lactamase.

PubMed

Bansal, Ankita; Kar, Debasish; Murugan, Rajagopal A; Mallick, Sathi; Dutta, Mouparna; Pandey, Satya Deo; Chowdhury, Chiranjit; Ghosh, Anindya S

2015-05-01

DD-carboxypeptidases (DD-CPases) are low-molecular-mass (LMM) penicillin-binding proteins (PBPs) that are mainly involved in peptidoglycan remodelling, but little is known about the dd-CPases of mycobacteria. In this study, a putative DD-CPase of Mycobacterium smegmatis, MSMEG_2433 is characterized. The gene for the membrane-bound form of MSMEG_2433 was cloned and expressed in Escherichia coli in its active form, as revealed by its ability to bind to the Bocillin-FL (fluorescent penicillin). Interestingly, in vivo expression of MSMEG_2433 could restore the cell shape oddities of the septuple PBP mutant of E. coli, which was a prominent physiological characteristic of DD-CPases. Moreover, expression of MSMEG_2433 in trans elevated beta-lactam resistance in PBP deletion mutants (ΔdacAdacC) of E. coli, strengthening its physiology as a dd-CPase. To confirm the biochemical reason behind such physiological behaviours, a soluble form of MSMEG_2433 (sMSMEG_2433) was created, expressed and purified. In agreement with the observed physiological phenomena, sMSMEG_2433 exhibited DD-CPase activity against artificial and peptidoglycan-mimetic DD-CPase substrates. To our surprise, enzymic analyses of MSMEG_2433 revealed efficient deacylation for beta-lactam substrates at physiological pH, which is a unique characteristic of beta-lactamases. In addition to the MSMEG_2433 active site that favours dd-CPase activity, in silico analyses also predicted the presence of an omega-loop-like region in MSMEG_2433, which is an important determinant of its beta-lactamase activity. Based on the in vitro, in vivo and in silico studies, we conclude that MSMEG_2433 is a dual enzyme, possessing both DD-CPase and beta-lactamase activities. © 2015 The Authors.

Why Some People Discount More than Others: Baseline Activation in the Dorsal PFC Mediates the Link between COMT Genotype and Impatient Choice

PubMed Central

Gianotti, Lorena R. R.; Figner, Bernd; Ebstein, Richard P.; Knoch, Daria

2012-01-01

Individuals differ widely in how steeply they discount future rewards. The sources of these stable individual differences in delay discounting (DD) are largely unknown. One candidate is the COMT Val158Met polymorphism, known to modulate prefrontal dopamine levels and affect DD. To identify possible neural mechanisms by which this polymorphism may contribute to stable individual DD differences, we measured 73 participants’ neural baseline activation using resting electroencephalogram (EEG). Such neural baseline activation measures are highly heritable and stable over time, thus an ideal endophenotype candidate to explain how genes may influence behavior via individual differences in neural function. After EEG-recording, participants made a series of incentive-compatible intertemporal choices to determine the steepness of their DD. We found that COMT significantly affected DD and that this effect was mediated by baseline activation level in the left dorsal prefrontal cortex (DPFC): (i) COMT had a significant effect on DD such that the number of Val alleles was positively correlated with steeper DD (higher numbers of Val alleles means greater COMT activity and thus lower dopamine levels). (ii) A whole-brain search identified a cluster in left DPFC where baseline activation was correlated with DD; lower activation was associated with steeper DD. (iii) COMT had a significant effect on the baseline activation level in this left DPFC cluster such that a higher number of Val alleles was associated with lower baseline activation. (iv) The effect of COMT on DD was explained by the mediating effect of neural baseline activation in the left DPFC cluster. Our study thus establishes baseline activation level in left DPFC as salient neural signature in the form of an endophenotype that mediates the link between COMT and DD. PMID:22586360

N-Terminal pro-brain natriuretic peptide levels in dichorionic diamniotic twins with selective intrauterine growth restriction.

PubMed

Fujioka, Kazumichi; Mizobuchi, Masami; Sakai, Hitomi; Iwatani, Sota; Wada, Keiko; Yoshimoto, Seiji; Nakao, Hideto

2014-03-04

Monochorionic diamniotic (MD) twins with selective intrauterine growth restriction (sIUGR) have known associations with cardiac complications. However, the cardiac load of dichorionic diamniotic (DD) twins with sIUGR (DD-sIUGR) remains unclear. N-terminal pro-brain natriuretic peptide (NT-pro BNP) is a convenient marker of cardiac dysfunction in neonates, and is elevated in MD twins with sIUGR (MD-sIUGR). However, there are no reports assessing serum NT-pro BNP levels in DD-sIUGR. Here, we aimed to clarify serum NT-pro BNP levels at birth in DD-sIUGR, and to compare them with those of MD-sIUGR. Forty-one DD twin pairs admitted to our center between October 2007 and January 2013 were enrolled in this study and separated into two groups: nine twins with sIUGR (DD-sIUGR group) and 32 twins without sIUGR (DD without sIUGR group). Sixteen MD twins with sIUGR (MD-sIUGR group) served as positive controls. Serum NT-pro BNP levels at birth in DD-sIUGR [median 2,115 pg/ml (range, 443-6,590 pg/ml)] were significantly higher than in DD without sIUGR [1,080 pg/ml (range, 313-3,470 pg/ml); p=0.001], and significantly lower than in MD twins with sIUGR [4,520 pg/ml (range, 529-62,400 pg/ml); p=0.04]. Serum NT-pro BNP levels between larger and smaller DD co-twins were significantly correlated (r = 0.582; p<0.0001). In conclusion, serum NT-pro BNP levels at birth in DD twins with sIUGR were higher than those without, and lower than in MD twins with sIUGR.

Is season of birth related to developmental dyslexia?

PubMed

Donfrancesco, Renato; Iozzino, Roberto; Caruso, Barbara; Ferrante, Laura; Mugnaini, Daniele; Talamo, Alessandra; Miano, Silvia; Dimitri, Andrea; Masi, Gabriele

2010-12-01

Different moderators/mediators of risk are involved in developmental dyslexia (DD), but data are inconsistent. We explored the prevalence of season of birth and its association with gender and age of school entry in an Italian sample of dyslexic children compared to an Italian normal control group. The clinical sample included 498 children (345 boys, mean age 10.3 ± 2.1 years) with DD, the control sample 1,276 children (658 boys, mean age 10.8 ± 2.2 years) from four elementary schools from the same urban area, and with the same socio-economic status level. A prevalence of birth in autumn was found among children with DD compared to controls (34% versus 24%, p < 0.0001). Children with DD were more frequently males (p < 0.0001) and had a lower mean age of school entry (p < 0.0001). Regarding the distribution of ages, 11.4% of children with DD, but none of the subjects in the control group, started school before 5.7 years. Therefore, greater risk of DD was related to age of school entry (OR = 2.72), gender (OR = 2.16), and season of birth (OR = 1.21). Significant interactions between boys with DD born in autumn, and correct school of entry (OR = 2.56) were joint predictors of higher risk of DD. The association between birth in autumn and DD may be explained by the earlier age of school entry, which may be a critical element in the youngest children with DD or at risk to DD. Whether Italian school policy is oriented to anticipate the school entry, a closer detection of early learning disorders and associated risk factors (familial load, specific language disorders, and attention deficit hyperactivity disorder) should be warranted.

Characteristics of internalizing and externalizing disorders in medication-naive, clinically referred children with attention deficit hyperactivity disorder, combined type and dysthymic disorder.

PubMed

Sanders, Michelle; Arduca, Yolanda; Karamitsios, Mary; Boots, Marilyn; Vance, Alasdair

2005-05-01

Internalizing and externalizing disorders are frequently comorbid with attention deficit hyperactivity disorder, combined type (ADHD-CT) and dysthymic disorder (DD) in referred primary school-age children, yet there has been relatively little systematic research of the nature of these comorbid disorders. We describe the characteristics of parent- and child-reported internalizing and externalizing disorders in primary school-age children with ADHD-CT and DD. A cross-sectional study of 45 clinically referred medication naive children with ADHD-CT and DD, examining parent and child reports of internalizing and externalizing disorders, defined categorically and dimensionally. Generalized anxiety disorder and separation anxiety disorder were increased in the DD groups, whether ADHD-CT was present or not. Major depressive disorder was increased in the ADHD-CT and DD group compared to the ADHD-CT alone and the DD alone groups. Conduct disorder was increased in the ADHD-CT alone group compared to the DD with and without ADHD-CT groups. Verbal and fullscale IQ were increased in the DD groups, whether ADHD-CT was present or not, compared to the ADHD-CT alone group. There is emerging evidence that DD and anxiety may represent a different phenotypic expression of a common underlying aetiological process, while the co-occurrence of ADHD-CT and anxiety disorders remains unclear. Only the ADHD-CT and DD group is significantly associated with major depressive disorder, which suggests an additive effect. In contrast, conduct disorder and decreased verbal and fullscale IQ are only associated with the ADHD-CT group, which may suggest a protective effect of DD when comorbid with ADHD-CT. From a research perspective, it is important to confirm these found associations in larger samples derived from epidemiological populations.

Enzymatic characterization of a novel bovine liver dihydrodiol dehydrogenase--reaction mechanism and bile acid dehydrogenase activity.

PubMed

Nanjo, H; Adachi, H; Morihana, S; Mizoguchi, T; Nishihara, T; Terada, T

1995-05-11

Bovine liver cytosolic dihydrodiol dehydrogenase (DD3) has been characterized by its unique dihydrodiol dehydrogenase activity for trans-benzenedihydrodiol (trans-1,2-dihydrobenzene-1,2-diol) with the highest affinity and the greatest velocity among three multiple forms of dihydrodiol dehydrogenases (DD1-DD3). It is the first time that DD3 has shown a significant dehydrogenase activity for (S)-(+)-1-indanol with low Km value (0.33 +/- 0.022 mM) and high K(cat) value (25 +/- 0.79 min-1). The investigation of the product inhibition of (S)-(+)-1-indanol with NADP+ versus 1-indanone and NADPH clearly showed that the enzymatic reaction of DD3 may follow a typical ordered Bi Bi mechanism similar to many aldo/keto reductases. Additionally, DD3 was shown to catalyze the dehydrogenation of bile acids (lithocholic acid, taurolithocholic acid and taurochenodeoxycholic acid) having no 12-hydroxy groups with low Km values (17 +/- 0.65, 33 +/- 1.9 and 890 +/- 73 microM, respectively). In contrast, DD1, 3 alpha-hydroxysteroid dehydrogenase, shows a broad substrate specificity for many bile acids with higher affinity than those of DD3. Competitive inhibition of DD3 with androsterone against dehydrogenase activity for (S)-(+)-1-indanol, trans-benzenedihydrodiol or lithocholic acid suggests that these three substrates bind to the same substrate binding site of DD3, different from the case of human liver bile acid binder/dihydrodiol dehydrogenase (Takikawa, H., Stolz, A., Sugiyama, Y., Yoshida, H., Yamamoto, M. and Kaplowitz, N. (1990) J. Biol. Chem. 265, 2132-2136). Considering the reaction mechanism, DD3 may also play an important role in bile acids metabolism as well as the detoxication of aromatic hydrocarbons.

12 CFR Appendix C to Part 230 - Effect on State Laws

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Effect on State Laws C Appendix C to Part 230 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM TRUTH IN SAVINGS (REGULATION DD) Pt. 230, App. C Appendix C to Part 230—Effect on State Laws (a...

12 CFR Appendix C to Part 230 - Effect on State Laws

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 4 2013-01-01 2013-01-01 false Effect on State Laws C Appendix C to Part 230... (CONTINUED) TRUTH IN SAVINGS (REGULATION DD) Pt. 230, App. C Appendix C to Part 230—Effect on State Laws (a) Inconsistent Requirements State law requirements that are inconsistent with the requirements of the act and...

A temporal stable isotopic (d18O, dD, d-excess) comparison in glacier meltwater streams, Taylor Valley, Antarctica

USDA-ARS?s Scientific Manuscript database

In this paper, we describe the importance of hyporheic dynamics within Andersen Creek and Von Guerard Stream, Taylor Valley, Antarctica, from the 2010-11 melt season using natural tracers. Water collection started at flow onset and continued, with weekly hyporheic zone sampling. The water d18O and d...

A Zero-One Dichotomy Theorem for r-Semi-Stable Laws on Infinite Dimensional Linear Spaces.

DTIC Science & Technology

1978-10-01

SEMISTABLE LAWS - LIKE STABLE ONES - ARE CONTINUOUS: i.e. THEY ASSIGN’ ZERO MASS TO SIIMGLETONS.. DD 172 1 1473 sov’ow as, IMail , 62 i 1 SOee..S $.M 0 102 LfP.Of 4 6601 1ECIuatY CLASSI’PICA1 130N 00 1 100 0449 (W%4 Dma rwer

Linkage analyses in Darier disease (DD) and Halley-Halley disease (HHD): Fine mapping of the DD locus on chromosome 12q and rejection of the hypothesis that HHD is allelic to DD

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

Richard, G.; Wright, A.R.; Compton, J.G.

1994-09-01

DD and HHD are rare autosomal dominant genodermatoses. These disorders of cornification share some clinical and histologic features and for many years were thought to be variants of the same disease. DD presents as hyperkeratotic papules and plaques, usually in a seborrheic distribution; rarely, blisters can occur. Mucous membranes and nails may also be involved. Skin involvement in HHD includes erythematous and scaly plaques, and vesicular or crusted lesions, often in intertriginous areas. Both diseases have age-dependent penetrance and are characterized histologically by a focal loss of cell adhesion in the suprabasal epidermis leading to lacunaes (acantholysis) and premature keratinizationmore » (dyskeratosis). We analyzed linkage of DD in ten families with markers in 12q23-q24.1, the region to which it has been mapped. Detailed genotype analysis of recombinant chromosomes in our families, along with previously reported data, refine the location of the DD gene to about a 4 cM interval flanked by the loci D12S129 and D12S105. We have excluded two genes in 12q22-q24, PLA2A and PAH, as candidate loci for DD. Three other gene loci (PPP1C, PMCH and PMCA1) mapping in 12q21-q24, remain potential candidates. The region containing the DD gene is an obvious candidate location to test for HHD. We investigated four multigeneration families with HHD for linkage to the DD gene locus using several tightly linked microsatellite markers. Obligate recombination with each marker tested was observed, and the HHD locus was excluded from about 37 cM around the DD locus, proving that DD and HHD are not allelic disorders.« less

Insulin-like growth factor-1 prevents dorsal root ganglion neuronal tyrosine kinase receptor expression alterations induced by dideoxycytidine in vitro.

PubMed

Liu, Huaxiang; Lu, Jing; He, Yong; Yuan, Bin; Li, Yizhao; Li, Xingfu

2014-03-01

Dideoxycytidine (zalcitabine, ddC) produces neurotoxic effects. It is particularly important to understand the toxic effects of ddC on different subpopulations of dorsal root ganglion (DRG) neurons which express distinct tyrosine kinase receptor (Trk) and to find therapeutic factors for prevention and therapy for ddC-induced peripheral sensory neuropathy. Insulin-like growth factor-1 (IGF-1) has been shown to have neurotrophic effects on DRG sensory neurons. However, little is known about the effects of ddC on distinct Trk (TrkA, TrkB, and TrkC) expression in DRG neurons and the neuroprotective effects of IGF-1 on ddC-induced neurotoxicity. Here, we have tested the extent to which the expression of TrkA, TrkB, and TrkC receptors in primary cultured DRG neurons is affected by ddC in the presence or absence of IGF-1. In this experiment, we found that exposure of 5, 25, and 50 μmol/L ddC caused a dose-dependent decrease of the mRNA, protein, and the proportion of TrkA-, TrkB-, and TrkC-expressing neurons. IGF-1 (20 nmol/L) could partially reverse the decrease of TrkA and TrkB, but not TrkC, expression with ddC exposure. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (10 μmol/L) blocked the effects of IGF-1. These results suggested that the subpopulations of DRG neurons which express distinct TrkA, TrkB, and TrkC receptors were affected by ddC exposure. IGF-1 might relieve the ddC-induced toxicity of TrkA- and TrkB-, but not TrkC-expressing DRG neurons. These data offer new clues for a better understanding of the association of ddC with distinct Trk receptor expression and provide new evidence of the potential therapeutic role of IGF-1 on ddC-induced neurotoxicity.

An experimental infection model to induce digital dermatitis infection in cattle.

PubMed

Gomez, A; Cook, N B; Bernardoni, N D; Rieman, J; Dusick, A F; Hartshorn, R; Socha, M T; Read, D H; Döpfer, D

2012-04-01

Bovine digital dermatitis (DD), also known as papillomatous digital dermatitis (foot warts), has been recognized as a major cause of lameness in cattle, with important economic and welfare consequences. The evaluation of therapeutic and preventive interventions aiming to control DD infections in dairy cattle is often challenged by the complex multifactorial etiology of the disease. An experimental infection model to induce acute DD lesions in a controlled environment is proposed. The goal was to provide a standard way of reproducing DD infections independent of external factors that could confound the natural course of the disease, such as management practices or infection pressure, resulting in transmission of DD between animals. A group of 4 yearling Holstein heifers free of any clinical evidence of hoof disease was recruited from a commercial dairy farm and housed in an experimental facility in 1 pen with slatted flooring. The hind feet were wrapped to mimic conditions of prolonged moisture (maceration) and reduced access to air (closure) and inoculated at the heel and dewclaw areas with a homogenate of a naturally occurring DD lesion skin biopsy or a culture broth of Treponema spp. After a period of 12 to 25 d, 4 of 6 and 1 of 4 dewclaw areas inoculated with biopsied DD lesion or a Treponema spp. culture, respectively, had gross lesions compatible with DD. Histopathology confirmed the gross diagnosis in the sites inoculated with tissue homogenate. In the site inoculated with Treponema spp. culture broth, histopathology revealed an incipient DD lesion. Treponema spp. were detected by PCR in both naturally occurring DD homogenate and Treponema spp. culture broth inoculation sites. An experimental infection model to induce acute DD in cattle was developed, which may be used to evaluate interventions to control DD and study the pathogenesis of this infectious hoof disease in a controlled manner. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

First Identification of Resident and Circulating Fibrocytes in Dupuytren’s Disease Shown to Be Inhibited by Serum Amyloid P and Xiapex

PubMed Central

Iqbal, Syed Amir; Hayton, Michael John; Watson, James Stewart; Szczypa, Piotr; Bayat, Ardeshir

2014-01-01

Dupuytren’s disease (DD) is a common progressive fibroproliferative disorder causing permanent digital contracture. Proliferative myofibroblasts are thought to be the cells responsible for DD initiation and recurrence, although their source remains unknown. DD tissue has also been shown to harbor mesenchymal and hematopoietic stem cells. Fibrocytes are circulating cells that show characteristics of fibroblasts and they express surface markers for both hematopoietic and mesenchymal stromal cells. Fibrocytes differentiate from peripheral CD14+ mononuclear cells, which can be inhibited by serum amyloid P (SAP). In this study we have demonstrated the presence of fibrocytes in DD blood and tissue, moreover we have evaluated the effects of SAP and Xiapex (Collagenase Clostridium histolyticum) on fibrocytes derived from DD. H&E staining showed typical Spindle shaped morphology of fibrocytes. FACS analysis based on a unique combination of 3 markers, revealed the increased presence of fibrocytes in blood and tissue of DD patients. Additionally, immunohistology of DD nodule and cord tissue showed the presence of collagen 1+/CD34+ cells. No difference in plasma SAP levels was observed between DD and control. Higher concentrations of SAP significantly inhibited fibrocytes differentiated from DD derived monocytes compared to control. DD fascia derived fibrocytes showed resistance to growth inhibition by SAP, particularly nodule derived fibrocytes showed robust growth even at higher SAP concentrations compared to control. DD derived fibrocytes were positive for typical fibrocyte dual markers, i.e. Collagen 1/LSP-1 and collagen 1/CD34. Xiapex was more effective in inhibiting the growth of nodule derived cells compared to commercially available collagenase A. Our results show for the first time the increased presence of fibrocytes in DD patient’s blood and disease tissue compared to control tissue. Additionally, we evaluate the response of these fibrocytes to SAP and Xiapex therapy. PMID:24933153

Sphingomonas wittichii Strain RW1 Genome-Wide Gene Expression Shifts in Response to Dioxins and Clay

PubMed Central

Tsoi, Tamara V.; Iwai, Shoko; Liu, Cun; Fish, Jordan A.; Gu, Cheng; Johnson, Timothy A.; Zylstra, Gerben; Teppen, Brian J.; Li, Hui; Hashsham, Syed A.; Boyd, Stephen A.; Cole, James R.; Tiedje, James M.

2016-01-01

Sphingomonas wittichii strain RW1 (RW1) is one of the few strains that can grow on dibenzo-p-dioxin (DD). We conducted a transcriptomic study of RW1 using RNA-Seq to outline transcriptional responses to DD, dibenzofuran (DF), and the smectite clay mineral saponite with succinate as carbon source. The ability to grow on DD is rare compared to growth on the chemically similar DF even though the same initial dioxygenase may be involved in oxidation of both substrates. Therefore, we hypothesized the reason for this lies beyond catabolic pathways and may concern genes involved in processes for cell-substrate interactions such as substrate recognition, transport, and detoxification. Compared to succinate (SUC) as control carbon source, DF caused over 240 protein-coding genes to be differentially expressed, whereas more than 300 were differentially expressed with DD. Stress response genes were up-regulated in response to both DD and DF. This effect was stronger with DD than DF, suggesting a higher toxicity of DD compared to DF. Both DD and DF caused changes in expression of genes involved in active cross-membrane transport such as TonB-dependent receptor proteins, but the patterns of change differed between the two substrates. Multiple transcription factor genes also displayed expression patterns distinct to DD and DF growth. DD and DF induced the catechol ortho- and the salicylate/gentisate pathways, respectively. Both DD and DF induced the shared down-stream aliphatic intermediate compound pathway. Clay caused category-wide down-regulation of genes for cell motility and chemotaxis, particularly those involved in the synthesis, assembly and functioning of flagella. This is an environmentally important finding because clay is a major component of soil microbes’ microenvironment influencing local chemistry and may serve as a geosorbent for toxic pollutants. Similar to clay, DD and DF also affected expression of genes involved in motility and chemotaxis. PMID:27309357

A continuously self regenerating high-flux neutron-generator facility

NASA Astrophysics Data System (ADS)

Rogers, A. M.; Becker, T. A.; Bernstein, L. A.; van Bibber, K.; Bleuel, D. L.; Chen, A. X.; Daub, B. H.; Goldblum, B. L.; Firestone, R. B.; Leung, K.-N.; Renne, P. R.; Waltz, C.

2013-10-01

A facility based on a next-generation, high-flux D-D neutron generator (HFNG) is being constructed at UC Berkeley. The current generator, designed around two RF-driven multicusp deuterium ion sources, is capable of producing a neutron output of >1011 n/s. A specially designed titanium-coated copper target located between the ion sources accelerates D+ ions up to 150 keV, generating 2.45 MeV neutrons through the d(d,3He)n fusion reaction. Deuterium in the target is self loaded and regenerating through ion implantation, enabling stable and continuous long-term operation. The proposed science program is focused on pioneering advances in the 40Ar/39Ar dating technique for geochronology, new nuclear data measurements, basic nuclear science research including statistical model studies of radiative-strength functions and level densities, and education. An overview of the facility and its unique capabilities as well as first measurements from the HFNG commissioning will be presented. Work supported by NSF Grant No. EAR-0960138, U.S. DOE LBL Contract No. DE-AC02-05CH11231, and U.S. DOE LLNL Contract No. DE-AC52-07NA27344.

Variations of L- and D-amino acid levels in the brain of wild-type and mutant mice lacking D-amino acid oxidase activity.

PubMed

Du, Siqi; Wang, Yadi; Weatherly, Choyce A; Holden, Kylie; Armstrong, Daniel W

2018-05-01

D-amino acids are now recognized to be widely present in organisms and play essential roles in biological processes. Some D-amino acids are metabolized by D-amino acid oxidase (DAO), while D-Asp and D-Glu are metabolized by D-aspartate oxidase (DDO). In this study, levels of 22 amino acids and the enantiomeric compositions of the 19 chiral proteogenic entities have been determined in the whole brain of wild-type ddY mice (ddY/DAO +/+ ), mutant mice lacking DAO activity (ddY/DAO -/- ), and the heterozygous mice (ddY/DAO +/- ) using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). No significant differences were observed for L-amino acid levels among the three strains except for L-Trp which was markedly elevated in the DAO +/- and DAO -/- mice. The question arises as to whether this is an unknown effect of DAO inactivity. The three highest levels of L-amino acids were L-Glu, L-Asp, and L-Gln in all the three strains. The lowest L-amino acid level was L-Cys in ddY/DAO +/- and ddY/DAO -/- mice, while L-Trp showed the lowest level in ddY/DAO +/+ mice. The highest concentration of D-amino acid was found to be D-Ser, which also had the highest % D value (~ 25%). D-Glu had the lowest % D value (~ 0.01%) in all the three strains. Significant differences of D-Leu, D-Ala, D-Ser, D-Arg, and D-Ile were observed in ddY/DAO +/- and ddY/DAO -/- mice compared to ddY/DAO +/+ mice. This work provides the most complete baseline analysis of L- and D-amino acids in the brains of ddY/DAO +/+ , ddY/DAO +/- , and ddY/DAO -/- mice yet reported. It also provides the most effective and efficient analytical approach for measuring these analytes in biological samples. This study provides fundamental information on the role of DAO in the brain and may be relevant for future development involving novel drugs for DAO regulation.

Injury prevention programs against distracted driving among students.

PubMed

Joseph, Bellal; Haider, Ansab; Hassan, Ahmed; Kulvatunyou, Narong; Bains, Sandeep; Tang, Andrew; Zangbar, Bardiya; OʼKeeffe, Terence; Vercruysse, Gary; Gries, Lynn; Rhee, Peter

2016-07-01

Motor vehicle crashes are the leading cause of death and nonfatal injury among young adults. The aims of this study were to assess the magnitude of distracted driving (DD) among students and to examine the effectiveness of awareness campaign against DD. We hypothesized that DD is prevalent among students and educational efforts such as DD awareness campaign can effectively reduce it. This study was conducted within the University of Arizona that has a student enrollment of 42,000 students. We conducted our prospective interventional study in four phases at the university campus. Phase 1 involved 1-week preintervention observation, Phase 2 involved 1-week intervention, Phase 3 involved 1-week postintervention observation, and Phase 4 involved 1-week 6-month postintervention observation. We used a combination of e-mails, pamphlets, interactive sessions, and banners as intervention tools in student union. Our primary outcome was the prevalence of DD before, after, and 6 months after intervention. A total of 47,764 observations (before, 14,844; after, 17,939; 6 months after, 14,981) were performed. During the study period, overall rate of DD rate among the students was 8.8 (5.4) per 100 drivers (texting, 4.8 [3.7] per 100 drivers; talking, 3.9 [2.0] per 100 drivers).The baseline rate of DD among students during the phase one was 9.0 (1.2) per 100 drivers (texting, 4.8 [1.7] per 100 drivers; talking, 4.1 [1.1] per 100 drivers). Following intervention, there was a 32% significant reduction in overall DD (9.0 [1.2] vs. 6.1 [1.7], p < 0.001) in the immediate postintervention phase; however, the rate of DD returned to baseline at 6 months after intervention and trended toward increase (9.0 [1.2] vs. 11.1 [8.4], p = 0.34). DD is prevalent among university students. Following a comprehensive preventive campaign against DD, there was a 32% reduction in the rate of DD in the immediate postintervention period. However, a single episode of intervention did not have a sustainable preventive effect on the DD, and the rate increased to the baseline at 6-month follow-up. Targeting DD with a successful injury prevention campaign with repeated boosters may decrease its prevalence among the students.

Genome-wide high-resolution screening in Dupuytren's disease reveals common regions of DNA copy number alterations.

PubMed

Shih, Barbara B; Tassabehji, May; Watson, James S; McGrouther, Angus D; Bayat, Ardeshir

2010-07-01

Dupuytren's disease (DD) is a familial disorder with a high genetic susceptibility in white people; however, its etiopathogenesis remains unknown. Previous comparative genomic hybridization studies using lower-resolution, 44-k oligonucleotide-based arrays revealed no copy number variation (CNV) changes in DD. In this study, we used a higher-resolution genome-wide screening (next-generation microarrays) comprising 963,331 human sequences (3 kb spacing between probes) for whole genome DNA variation analysis. The objective was to detect cryptic chromosomal imbalances in DD. Agilent SurePrint G3 microarrays, one million format (Agilent Technologies, Santa Clara, CA), were used to detect CNV regions (CNVRs) in DNA extracted from nodules of 4 white men with DD (age, 69 +/- 4 y). Reference samples were from the DNA of 10 men who served as control patients. Copy number variations that were common to greater than 3 assessed DD individuals (p < .05) were selected as candidate loci for DD etiology. In addition, quantitative polymerase chain reactions (qPCR) assays were designed for selected CNVRs on DNA from 13 DD patients and 11 control patients. Independent t-tests and Fisher's exact tests were carried out for statistical analysis. Three novel CNVs previously unreported in the phenotypically normal population were detected in 3 DD cases, located at 10q22, 16p12.1, and 17p12. Nine polymorphic CNVRs potentially associated with DD were determined using our strategic selection criteria, locating to chromosomes 1q31, 6p21, 7p14, 8p11, 12p13, 14q11, 17q21 and 20p13. More than 3 of the DD cases tested had a CNVR located to a small region on 6p21 and 4 CNVRs within 6p21-22 of the human leukocyte antigen (HLA) genes. Three novel copy number alterations were observed in 3 unrelated patients with sporadic (no known family history) DD. Nine polymorphic CNVRs were found to be common among the DD cases. These variants might contain genes involved in DD formation, indicating that important gene networks expressed within the palmar fascia might contribute to genetic susceptibility of DD. Copyright 2010. Published by Elsevier Inc.

Microbiota Analysis of an Environmental Slurry and Its Potential Role as a Reservoir of Bovine Digital Dermatitis Pathogens.

PubMed

Klitgaard, Kirstine; Strube, Mikael L; Isbrand, Anastasia; Jensen, Tim K; Nielsen, Martin W

2017-06-01

At present, very little information exists regarding what role the environmental slurry may play as an infection reservoir and/or route of transmission for bovine digital dermatitis (DD), a disease which is a global problem in dairy herds. To investigate whether DD-related bacteria belong to the indigenous microbiota of the dairy herd environment, we used deep amplicon sequencing of the 16S rRNA gene in 135 slurry samples collected from different sites in 22 dairy farms, with and without DD-infected cows. Both the general bacterial populations and digital dermatitis-associated Treponema were targeted in this study. The results revealed significant differences in the bacterial communities between the herds, with only 12 bacterial taxa shared across at least 80% of all the individual samples. These differences in the herd microbiota appeared to reflect mainly between-herd variation. Not surprisingly, the slurry was dominated by ubiquitous gastrointestinal bacteria, such as Ruminococcaceae and Lachnospiraceae Despite the low relative abundance of spirochetes, which ranged from 0 to 0.6%, we were able to detect small amounts of bacterial DNA from DD-associated treponemes in the slurry. However, the DD-associated Treponema spp. were detected only in samples from herds with reported DD problems. These data indicate that treponemes involved in the pathogenesis of DD are not part of the normal environmental microflora in dairy herds without clinical DD and, consequently, that slurry is not a primary reservoir of infection. IMPORTANCE Bovine digital dermatitis (DD), a dermal disease which causes lameness in dairy cattle, is a serious problem worldwide. To control this disease, the infection reservoirs and transmission routes of DD pathogens need to be clarified. The dairy herd slurry may be a pathogen reservoir of DD-associated bacteria. The rationale for the present study was, therefore, to examine whether DD-associated bacteria are always present in slurry or if they are found only in DD-afflicted herds. The results strongly indicated that DD Treponema spp. are not part of the indigenous slurry and, therefore, do not comprise an infection reservoir in healthy herds. This study applied next-generation sequencing technology to decipher the microbial compositions of environmental slurry of dairy herds with and without digital dermatitis. Copyright © 2017 American Society for Microbiology.

[Tuscan Chronic Care Model: a preliminary analysis].

PubMed

Barbato, Angelo; Meggiolaro, Angela; Rossi, Luigi; Fioravanti, C; Palermita, F; La Torre, Giuseppe

2015-01-01

the aim of this study is to present a preliminary analysis of efficacy and effectiveness of a model of chronically ill care (Chronic Care Model, CCM). the analysis took into account 106 territorial modules, 1016 General Practitioners and 1,228,595 patients. The diagnostic and therapeutic pathways activated (PDTA), involved four chronic conditions, selected according to the prevalence and incidence, in Tuscany Region: Diabetes Mellitus (DM), Heart Failure (SC), Chronic Obstructive Pulmonary Disease (COPD) and stroke. Six epidemiological indicators of process and output were selected, in order to measure the model of care performed, before and after its application: adherence to specific follow-up for each pathology (use of clinical and laboratory indicators), annual average of expenditure per/capita/euro for diagnostic tests, in laboratory and instrumental, average expenditure per/capita/year for specialist visits; hospitalization rate for diseases related to the main pathology, hospitalization rate for long-term complications and rate of access to the emergency department (ED). Data were collected through the database; the differences before and after the intervention and between exposed and unexposed, were analyzed by method "Before-After (Controlled and Uncontrolled) Studies". The impact of the intervention was calculated as DD (difference of the differences). DM management showed an increased adhesion to follow-up (DD: +8.1%), and the use of laboratory diagnostics (DD: +4,9 €/year/pc), less hospitalization for long-term complications and for endocrine related diseases (DD respectively: 5.8/1000 and DD: +1.2/1000), finally a smaller increase of access to PS (DD: -1.6/1000), despite a slight increase of specialistic visits (DD: +0,38 €/year/pc). The management of SC initially showed a rising adherence to follow-up (DD: +2.3%), a decrease of specialist visits (DD:E 1.03 €/year/pc), hospitalization and access to PS for exacerbations (DD: -4.4/1000 and DD: -6.1/100, respectively), compared with a slight increase of diagnostic tests (DD: +2.10 €/year/pc). Stroke showed the following outcomes: increased consumption of instrumental diagnostics and imaging (DD: +1.65 €/year/pc) and growing hospitalizations for related conditions (DD 6.1/1,000). The care of patients with COPD, finally, has produced an increase in overall expenditure on medicines (DD: +39.71/year/pc) associated with the decrease of hospitalization for related conditions (DD: -2.7/1,000). the Tuscany CCM has proven a promising model of integrated management and taking care for chronic patients, can have a positive impact on the quality of life and on the total health expenditure. Additional monitoring studies are desirable in perspective of expanding the model on all over the national territory.

Phase I study of 2'-3'-dideoxyinosine administered orally twice daily to patients with AIDS or AIDS-related complex and hematologic intolerance to zidovudine.

PubMed

Connolly, K J; Allan, J D; Fitch, H; Jackson-Pope, L; McLaren, C; Canetta, R; Groopman, J E

1991-11-01

To evaluate the safety and hematologic tolerance of 2'-3'-dideoxyinosine (didanosine, ddI) in subjects with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and prior hematologic intolerance to zidovudine. A Phase I trial with two dose groups at a single-center, university-affiliated hospital ambulatory care center. Of 30 subjects enrolled, 21 had AIDS and nine had AIDS-related complex. All had CD4 lymphocyte counts less than 0.2 x 10(9)/L at entry. Didanosine was administered orally twice daily at a total daily dose of 750 mg or 1,500 mg for 12 weeks. Subjects who completed the 12-week study continued to receive ddI at the lower dose. All subjects were monitored for toxicity. Virologic and immunologic response markers were also measured. For the group as a whole, there was no significant decrease in mean hemoglobin level or leukocyte or platelet counts. The dose-limiting toxicity was peripheral neuropathy. Other significant toxicities included pancreatitis and hypocalcemia. Uric acid elevations were common but were without clinical consequence. A sustained decrease in serum p24 antigen of at least 50% was noted in 42% of subjects who were p24 antigen-positive at entry. The mean CD4 lymphocyte count showed an initial increase that was not sustained over the 12-week study. All subjects remained anergic to skin testing. Didanosine is well tolerated hematologically in some patients with prior significant hematologic intolerance to zidovudine. The toxicity profile for ddI differs from that of zidovudine and includes peripheral neuropathy and pancreatitis. Changes in CD4 lymphocyte number and HIV p24 antigen levels in some patients suggest antiviral activity of ddI in this population.

Phenology, natural enemies, and efficacy of horticultural oil for control of Chionaspis heterophyllae (Homoptera: Diaspididae) on Christmas tree plantations.

PubMed

Fondren, Kirsten M; McCullough, Deborah G

2005-10-01

Pine needle scale, Chionaspis pinifoliae (Fitch), and Chionaspis heterophyllae Cooley are important pests of Scots pine, Pinus sylvestris L., and other conifers in much of North America. On Christmas tree plantations, these insects are typically controlled by spraying broad-spectrum insecticides when the vulnerable immature stages are present. However, effective control of bivoltine populations can be difficult to achieve due to asynchronous hatch and development of the second generation. Our objectives were to 1) determine the phenology of the second generation of C. heterophyllae in Michigan; 2) characterize the natural enemy complex; and 3) assess the effectiveness of horticultural oil for control of C. heterophyllae on P. sylvestris Christmas tree plantations. We monitored scale populations in three counties in lower Michigan for 3 yr. Scale phenology was consistently associated with cumulative degree-days base 10 degrees C (DD(10 degrees C)). Second-generation egg hatch began at approximately 1230-1300 DD(10 degrees C), and continued for approximately 3 wk. The peak of the second instar coincided with 1500-1600 DD(10 degrees C). Common predators included the coccinellids Chilocorus stigma (Say) and Microweisia misella (LeConte). On average, 70% of the C. heterophyllae population in unsprayed fields was killed by predators in 1999. Two endoparasitic wasps, Encarsia bella Gahan and Marietta mexicana Howard (Hymenoptera: Aphelinidae), also were recovered. In 2000 and 2001, we applied a highly refined horticultural spray oil with a backpack mist blower at 1500-1600 DD(10 degrees). Scale mortality on trees treated with oil ranged from 66 to 80% and was similar to control achieved using conventional insecticides in both years.

A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

PubMed

Stevens, R B; Wrenshall, L E; Miles, C D; Farney, A C; Jie, T; Sandoz, J P; Rigley, T H; Osama Gaber, A

2016-06-01

A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.). © Copyright 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of the American Society of Transplantation and the American Society of Transplant Surgeons.

Deuterium-rich Water in Meteorites

NASA Astrophysics Data System (ADS)

Deloule, E.; Robert, F.

1995-09-01

D/H ratios of 2 meteorites (Renazzo CR and Semarkona LL3), which are known to exhibit the largest departures from the terrestrial hydrogen isotopic ratios, have been determined with the CRPG Nancy ion-microprobe. Correlations between the D/H ratios and the chemical compositions (H2O, K, Si, C/H) of plausible hydrogen carriers were observed. From these correlations, it is possible to show that, contrary to previous interpretations, phyllosilicates are the carriers of the deuterium-rich hydrogen in Semarkona and Renazzo : 870 x10-6 D/H 670 x106 (+4600 dD 3300) and 320 x10-6 (dD 1050), respectively. Hydrogen is also present in the chondrules of these two deuterium-rich meteorites. Isotopic equilibrium between the deuterium depleted phases and the deuterium-rich phyllosilicates was never attained. This is illustrated at a micron scale by the D/H ratios obtained continuously during a 3 hours measurement on a same position (see figure below). It can be seen that water-rich mineral(s) having D/H up to 550 x10-6 (dD = +2500) are in contact with a mineral having D/H = 234 x10-6 (dD = +500). The thickness of the boundary where the diffusion of hydrogen took place is restricted to less than 0.2 mm. Such isotopic heterogeneity is quite spectacular if one remembers that the isotopic variations that we can see within these 0.2 mm are an order of magnitude larger than the total observed variations on Earth. The large differences in D/H ratios between matrix (up to 700 x 10-6, dD up to +3500) and chondrules (from 120 x10-6 (dD = -230) to 230 x10-6 (dD = +475)) show that hydrogen in chondrules cannot originate from the matrix by simple contamination or diffusion processes. The high D/H ratios measured in water bearing minerals could not have been produced thermally within a dense solar nebula. Chemical reactions (i.e. involving ions or radicals), taking place in interstellar space or in the outer regions of the nebula at 110-140K are presently the only conceivable mechanisms capable of yielding such isotopic enrichments. Hydrogen isotopic composition and water concentration versus depth in the matrix of Semarkona. The profile was obtained by sputtering the minerals with the primary beam of the ion-probe (0 stands for the surface mineral). Note the complete lack of isotopic homogenisation between the hydrogen bearing phases : the D/H ratio increases within 0.2 mm by more than 300x10-6; that is one order of magnitude larger than the total variations on Earth. Such a distribution demonstrates that no secondary processes altered the pristine isotopic ratios established at the time of mineral formation.

32 CFR Appendix B to Part 45 - DD Form 214ws

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false DD Form 214ws B Appendix B to Part 45 National... CERTIFICATE OF RELEASE OR DISCHARGE FROM ACTIVE DUTY (DD FORM 214/5 SERIES) Pt. 45, App. B Appendix B to Part 45—DD Form 214ws EC23OC91.007 ...

48 CFR 215.404-70 - DD Form 1547, Record of Weighted Guidelines Method Application.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false DD Form 1547, Record of... TYPES CONTRACTING BY NEGOTIATION Contract Pricing 215.404-70 DD Form 1547, Record of Weighted Guidelines Method Application. Follow the procedures at PGI 215.404-70 for use of DD Form 1547 whenever a structured...

48 CFR 253.213-70 - Completion of DD Form 1155, Order for Supplies or Services.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Completion of DD Form 1155... Forms 253.213-70 Completion of DD Form 1155, Order for Supplies or Services. Follow the procedures at PGI 253.213-70 for completion of DD Form 1155. [71 FR 3413, Jan. 23, 2006] ...

48 CFR 1846.673 - Distribution of DD Forms 250 and 250c.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Distribution of DD Forms 250 and 250c. 1846.673 Section 1846.673 Federal Acquisition Regulations System NATIONAL AERONAUTICS... Reports 1846.673 Distribution of DD Forms 250 and 250c. (a) DD Forms 250 and 250c shall be distributed in...

[Effect of developmental disorders on personality and personality disorders].

PubMed

Honda, Hideo

2013-01-01

Developmental disorders (DD) are now so common that it is even more necessary to investigate the relationship between DD and personality disorders (PD). Despite the lack of studies, DD and PD have much in common. For research on personality and its disorders, direct, real-time observation by researchers themselves on the "black box" of temperament and its interaction with the environment is needed. For research on DD, especially in those with mild DD symptoms, how developmental characteristics and their interaction with the environment affect the personality in adulthood should be investigated.

Clarus : a clear solution for road weather information.

DOT National Transportation Integrated Search

2011-01-01

Weather forecast for tonight: Dark. Continued dark overnight, with widely scattered light by morning. These words by comedian George Carlin, while not a real weather forecast, demonstrate how insuffi cient forecasting can be. While the accuracy...

A Regional, Multi-Stakeholder Collaboration for Dark-Sky Protection in Flagstaff, Arizona

NASA Astrophysics Data System (ADS)

Hall, Jeffrey C.

2018-01-01

Flagstaff, Arizona is home to almost $200M in astronomical assets, including Lowell Observatory's 4.3-meter Discovery Channel Telescope and the Navy Precision Optical Interferometer, a partnership of Lowell, the U. S. Naval Observatory, and the Naval Research Laboratory. The City of Flagstaff and surrounding Coconino County have comprehensive and effective dark-sky ordinances, but continued regional growth has the potential to degrade the area's dark skies to a level at which observatory missions could be compromised. As a result, a wide array of stakeholders (the observatories, the City, the County, local dark-sky advocates, the business and tourism communities, the national parks and monuments, the Navajo Nation, the U. S. Navy, and others) have engaged in three complementary efforts to ensure that Flagstaff and Coconino County protect the area's dark skies while meeting the needs of the various communities and providing for continued growth and development. In this poster, I will present the status of Flagstaff's conversion to LED outdoor lighting, the Mission Compatibility Study carried out by the Navy to evaluate the dark-sky effects of buildout in Flagstaff, and the Joint Land Use Study (JLUS) presently underway among all the aforementioned stakeholders. Taken in sum, the efforts represent a comprehensive and constructive approach to dark-sky preservation region-wide, and they show what can be achieved when a culture of dark-sky protection is present and deliberate efforts are undertaken to maintain it for decades to come.

Delusional disorders--are they simply paranoid schizophrenia?

PubMed

Marneros, Andreas; Pillmann, Frank; Wustmann, Tobias

2012-05-01

This article tries to give an answer to the question of whether International Classification of Diseases (ICD-10) persistent delusional disorder (PDD) or Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) delusional disorder (DD) is simply paranoid schizophrenia (PS). Because ICD-10 PDD and DSM-IV DD are identical, we use DD as a synonym. A prospective and longitudinal study compared all inpatients with DD treated at the Halle-Wittenberg university hospital during a 14-year period with a previously investigated selected cohort of patients with PS. Sociodemographic data, symptomatology, course, and outcome parameters were examined using standardized instruments. The duration of the follow-up period in patients with DD was 10.8 years and for the PS patients 12.9 years. Significant differences between DD and PS were found: DD patients are, in comparison to patients with PS, significantly older at onset. Less of their first-degree relatives have mental disorders. They less frequently come from a broken home situation. First-rank symptoms, relevant negative symptoms, and primary hallucinations did not occur in patients with DD. Patients with DD were less frequently hospitalized, and the duration of their hospitalization was shorter. Their outcome is much better regarding employment, early retirement due to the disorder, and psychopharmacological medication. They more often had stable heterosexual partnerships and were autarkic. They had lower scores in the Disability Assessment Scale and in Positive and Negative Syndrome Scale. The diagnosis of DD is very stable over time. The findings of this study support the assumption that DDs are a separate entity and only exceptionally can be a prodrome of schizophrenia.

Application of chromosome microarray analysis in patients with unexplained developmental delay/intellectual disability in South China.

PubMed

Wang, Rongyue; Lei, Tingying; Fu, Fang; Li, Ru; Jing, Xiangyi; Yang, Xin; Liu, Juan; Li, Dongzhi; Liao, Can

2018-03-26

Chromosome microarray analysis (CMA) is currently the first-tier diagnostic assay for the evaluation of developmental delay (DD) and intellectual disability (ID) with unknown etiology. Here, we present our clinical experience in implementing whole-genome high-resolution single nucleotide polymorphism (SNP) arrays to investigate 489 patients with unexplained DD/ID in whom standard karyotyping analyses showed normal karyotypes. This study aimed to assess the usefulness of CMA for clinical diagnostic testing in the Chinese population. A total of 489 children were classified into three groups: isolated DD/ID (n = 358), DD/ID with epilepsy (n = 49), and DD/ID with other structural anomalies (n = 82). We identified 126 cases (25.8%, 126/489) of pathogenic copy number variants (CNVs) by CMA, including 89 (24.9%, 89/358) with isolated DD/ID, 13 (26.5%, 13/49) with DD/ID with epilepsy, and 24 (29.3%, 24/82) with DD/ID with other structural anomalies. Among the 126 cases of pathogenic CNVs, 79 cases were identified as microdeletion/microduplication syndromes, among which 76 cases were classified as common syndromes, and 3 cases were classified as rare syndromes, including 15q24 microdeletion syndrome, Xq28 microduplication syndrome and Lowe syndrome. Additionally, there were forty-seven cases of non-syndromic pathogenic CNVs. The ABAT, FTSJ1, DYNC1H1, and SETBP1 genes were identified as DD/ID candidate genes. Our findings suggest the necessity of CMA as a routine diagnostic test for unexplained DD/ID in South China. Copyright © 2018. Published by Elsevier B.V.

The occurrence and suspected mode of inheritance of congenital subaortic stenosis and tricuspid valve dysplasia in Dogue de Bordeaux dogs.

PubMed

Ohad, D G; Avrahami, A; Waner, T; David, L

2013-08-01

The Dogue de Bordeaux (DdB) breed has gone through several genetic 'bottle necks' and has a relatively small effective population size. Importing new stock into Israel has been limited, further narrowing the already restricted local gene-pool and increasing the chances of inherited defects. In 56 DdB dogs examined between 2003 and 2010, the authors sought to study the proportion congenital subaortic stenosis (SAS) and tricuspid valve dysplasia (TVD). The aim was also to identify a probable mode of inheritance (MOI) using segregation and pedigree analyses of genealogical data available from 13/21 DdB dogs diagnosed with these conditions between 2004 and 2007. Among all breeds in the country, TVD was highest in the DdB breed, which also displayed the second highest proportion of SAS. Echocardiographic measurements and selected physical examination findings from 26 normal DdB dogs, 18 DdB dogs with SAS, and 12 DdB dogs with TVD are reported. Based on pedigree and segregation analyses, the most probable MOI appeared to be autosomal recessive. Pedigree analyses helped to identify three ancestors that might have introduced these two congenital heart defects into the local DdB population. Excluding those three dogs and their progeny from future mating could therefore reduce the prevalence of these diseases in the DdB population in Israel. The unusual local breeding circumstances may offer a unique opportunity to identify associated SAS and TVD genes in the DdB, as well as in other dog breeds. Copyright © 2013 Elsevier Ltd. All rights reserved.

32 CFR 881.5 - If an application is approved.

Code of Federal Regulations, 2010 CFR

2010-07-01

... be honorable, HQ AFPC/DPPRSO issues the applicant a DD Form 256AF, Honorable Discharge, and a DD Form... (formerly AFR 35-6). (b) Enter a military grade on the DD Form 214 only if the Administrator of Veterans' Affairs requests it. (c) Enter a pay grade on the DD Form 214 only for individuals who were killed or...

48 CFR 253.208-2 - DD Form 448-2, Acceptance of MIPR.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false DD Form 448-2, Acceptance... REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CLAUSES AND FORMS FORMS Prescription of Forms 253.208-2 DD Form 448-2, Acceptance of MIPR. Follow the procedures at PGI 253.208-2 for use of DD Form 448-2. [71 FR 39005...

Identification of amino acid residues responsible for differences in substrate specificity and inhibitor sensitivity between two human liver dihydrodiol dehydrogenase isoenzymes by site-directed mutagenesis.

PubMed Central

Matsuura, K; Deyashiki, Y; Sato, K; Ishida, N; Miwa, G; Hara, A

1997-01-01

Human liver dihydrodiol dehydrogenase isoenzymes (DD1 and DD2), in which only seven amino acid residues are substituted, differ remarkably in specificity for steroidal substrates and inhibitor sensitivity: DD1 shows 20alpha-hydroxysteroid dehydrogenase activity and sensitivity to 1,10-phenanthroline, whereas DD2 oxidizes 3alpha-hydroxysteroids and is highly inhibited by bile acids. In the present study we performed site-directed mutagenesis of the seven residues (Thr-38, Arg-47, Leu-54, Cys-87, Val-151, Arg-170 and Gln-172) of DD1 to the corresponding residues (Val, His, Val, Ser, Met, His and Leu respectively) of DD2. Of the seven mutations, only the replacement of Leu-54 with Val produced an enzyme that had almost the same properties as DD2. No significant changes were observed in the other mutant enzymes. An additional site-directed mutagenesis of Tyr-55 of DD1 to Phe yielded an inactive protein, suggesting the catalytically important role of this residue. Thus a residue at a position before the catalytic Tyr residue might play a key role in determining the orientation of the substrates and inhibitors. PMID:9173902

Dissociative disorders among adults in the community, impaired functioning, and axis I and II comorbidity.

PubMed

Johnson, Jeffrey G; Cohen, Patricia; Kasen, Stephanie; Brook, Judith S

2006-03-01

To investigate the association of dissociative disorder (DD) with impaired functioning and co-occurring Axis I and personality disorders among adults in the community. Psychiatric interviews were administered to a sample of 658 adult participants in the Children in the Community Study, a community-based longitudinal study. Depersonalization disorder (prevalence: 0.8%), dissociative amnesia (prevalence: 1.8%), dissociative identity disorder (prevalence: 1.5%), and dissociative disorder not otherwise specified (prevalence: 4.4%), evident within the past year, were each associated with impaired functioning, as assessed by the clinician-administered Global Assessment of Functioning Scale. These associations remained significant after controlling for age, sex, and co-occurring disorders. Individuals with anxiety, mood, and personality disorders were significantly more likely than individuals without these disorders were to have DD, after the covariates were controlled. Individuals with Cluster A (DD prevalence: 58%), B (DD prevalence: 68%), and C (DD prevalence: 37%) personality disorders were substantially more likely than those without personality disorders were to have DD. DD is associated with clinically significant impairment among adults in the community. DD may be particularly prevalent among individuals with personality disorders.

Dysthymic disorder contributes to oppositional defiant behaviour in children with Attention Deficit Hyperactivity Disorder, combined type (ADHD-CT).

PubMed

Vance, Alasdair; Sanders, Michelle; Arduca, Yolanda

2005-06-01

The specific relationships between oppositional defiant disorder (ODD), ADHD-CT, dysthymic disorder (DD) and anxiety disorders symptoms have not been studied in children with ADHD-CT. The relationship to DD is important because DD is common, has an earlier age of onset, is associated with significant morbidity and with increased rates of treatment non-responsiveness when comorbid with major depressive disorder and/or ADHD-CT. 200 clinically referred children with ADHD-CT, without comorbid major depressive disorder, were identified. "ODD", "ADHD-CT", "DD" and "anxiety disorders" symptoms were defined by composite measures of (1) semi-structured clinical interview and (2) parent and/or child standardized questionnaires. Standard multiple regression was used to examine how well "ADHD-CT", "DD" and "anxiety disorders" symptoms predict "ODD" symptoms. Only "ADHD-CT" (15% of the variance) and "DD" (8% of the variance) symptoms made independent significant contributions to the prediction of "ODD" symptoms. The study's sample size did not allow "ODD" and "conduct disorder" symptoms to be analysed separately. The association of DD with ODD may reflect a unique contribution of DD to ODD in children, whether ADHD-CT is present or not, or only when ADHD-CT is present.

Targeted expression of BikDD combined with metronomic doxorubicin induces synergistic antitumor effect through Bax activation in hepatocellular carcinoma

PubMed Central

Dai, Huei-Yue; Chen, Hui-Yu; Lai, Wei-Chen; Hung, Mien-Chie; Li, Long-Yuan

2015-01-01

Conventional chemotherapy is commonly used to treat advanced non-resectable hepatocellular carcinoma (HCC) but this treatment modality has not demonstrated convincing survival benefit in HCC patients. Our previous studies indicated that targeted expression of therapeutic BikDD driven by a liver cancer-specific α-fetoprotein promoter/enhancer (eAFP) in the VISA backbone (eAFP-VISA-BikDD) significantly and specifically kills HCC cells in multiple orthotopic animal models. To enhance its therapeutic efficacy, we combined eAFP-VISA-BikDD with chemotherapeutic agents and found that eAFP-VISA-BikDD plus doxorubicin (Dox) or 5-fluorouracil (5-FU) demonstrated synergistic cytotoxicity in HCC cells. Specifically, the combination of eAFP-VISA-BikDD plus Dox markedly induced apoptosis via increased Bax mitochondrial translocation and cytoplasmic cytochrome c release. Compared with either agent alone, a low dose of Dox combined with eAFP-VISA-BikDD induced better antitumor effect and prolonged longer survival of mice in two orthotopic liver cancer xenograft models. Our findings provide strong preclinical support for evaluating the combined therapy of eAFP-VISA-BikDD and Dox in a clinical setting as a treatment option for HCC. PMID:26247632

Dark soliton dynamics and interactions in continuous-wave-induced lattices.

PubMed

Tsopelas, Ilias; Kominis, Yannis; Hizanidis, Kyriakos

2007-10-01

The dynamics of dark spatial soliton beams and their interaction under the presence of a continuous wave (CW), which dynamically induces a photonic lattice, are investigated. It is shown that appropriate selection of the characteristic parameters of the CW result in controllable steering of a single soliton as well as controllable interaction between two solitons. Depending on the CW parameters, the soliton angle of propagation can be changed drastically, while two-soliton interaction can be either enhanced or reduced, suggesting a reconfigurable soliton control mechanism. Our analytical approach, based on the variational perturbation method, provides a dynamical system for the dark soliton evolution parameters. Analytical results are shown in good agreement with direct numerical simulations.

Evidence for X(3872) from DD* scattering on the lattice.

PubMed

Prelovsek, Sasa; Leskovec, Luka

2013-11-08

A candidate for the charmonium(like) state X(3872) is found 11±7 MeV below the DD* threshold using dynamical N(f)=2 lattice simulation with J(PC)=1(++) and I=0. This is the first lattice simulation that establishes a candidate for X(3872) in addition to the nearby scattering states DD* and J/ψω, which inevitably have to be present in dynamical QCD. We extract large and negative DD* scattering length a(0)(DD*)=-1.7±0.4 fm and the effective range r(0)(DD*)=0.5±0.1 fm, but their reliable determination will have to wait for a simulation on a larger volume. In I=1 channel, only the DD* and J/ψρ scattering states are found and no candidate for X(3872). This is in agreement with the interpretation that X(3872) is dominantly I=0, while its small I=1 component arises solely from the isospin breaking and is therefore absent in our simulation with m(u)=m(d).

Antimicrobial and anti-biofilm activities of Lactobacillus kefiranofaciens DD2 against oral pathogens

PubMed Central

2018-01-01

ABSTRACT Background: Streptococcus mutans and Streptococcus sobrinus are major causative bacterial pathogens of dental caries. Objective: We investigated the applicability of three Lactobacillus strains (L. kefiranofaciens DD2, DD5, and DD6) isolated from kefir and three commercial Lactobacillus strains (L. plantarum ATCC 10,012, L. johnsonii JCM 1022, and L. rhamnosus ATCC 7469) as potential oral probiotics with respect to their survivability in an experimental oral environment, antimicrobial activity, and anti-biofilm formation activity against S. mutans and S. sobrinus. Results: Strains DD2, ATCC 10012, ATCC 7469, and JCM 1022 had the best oral survivability, including aerotolerance and enzymatic resistance, and inhibited the growth and biofilm formation of S. mutans and S. sobrinus. In particular, DD2 suppressed all three classes of biofilm formation-associated genes: those associated with carbohydrate metabolism and those encoding regulatory biofilm and adhesion proteins. Conclusions: These results indicate that the novel kefir isolate L. kefiranofaciens DD2 effectively and directly inhibits S. mutans and S. sobrinus. PMID:29868163

Antimicrobial and anti-biofilm activities of Lactobacillus kefiranofaciens DD2 against oral pathogens.

PubMed

Jeong, Dana; Kim, Dong-Hyeon; Song, Kwang-Young; Seo, Kun-Ho

2018-01-01

Background : Streptococcus mutans and Streptococcus sobrinus are major causative bacterial pathogens of dental caries. Objective : We investigated the applicability of three Lactobacillus strains ( L. kefiranofaciens DD2, DD5, and DD6) isolated from kefir and three commercial Lactobacillus strains ( L. plantarum ATCC 10,012, L. johnsonii JCM 1022, and L. rhamnosus ATCC 7469) as potential oral probiotics with respect to their survivability in an experimental oral environment, antimicrobial activity, and anti-biofilm formation activity against S. mutans and S. sobrinus . Results : Strains DD2, ATCC 10012, ATCC 7469, and JCM 1022 had the best oral survivability, including aerotolerance and enzymatic resistance, and inhibited the growth and biofilm formation of S. mutans and S. sobrinus . In particular, DD2 suppressed all three classes of biofilm formation-associated genes: those associated with carbohydrate metabolism and those encoding regulatory biofilm and adhesion proteins. Conclusions : These results indicate that the novel kefir isolate L. kefiranofaciens DD2 effectively and directly inhibits S. mutans and S. sobrinus .

Hypothesis: The Intratumoral Immune Response against a Cancer Progenitor Cell Impacts the Development of Well-Differentiated versus Dedifferentiated Disease in Liposarcoma

PubMed Central

Tseng, William W.; Chopra, Shefali; Engleman, Edgar G.; Pollock, Raphael E.

2016-01-01

Well-differentiated/dedifferentiated (WD/DD) liposarcoma is a rare malignancy of adipocyte origin (“fat cancer”). Tumors may be entirely WD, WD with a DD component, or rarely DD without a clear WD component. WD tumors are low grade and generally indolent, while tumors with a DD component are high grade and behave much more aggressively, with a modest potential for distant metastasis. The presence of cancer progenitor cells in WD/DD liposarcoma is suggested by clinical evidence and reported research findings. In addition, there are emerging data to support the existence of a naturally occurring, antigen-driven, and adaptive immune response within the tumor microenvironment. We hypothesize that the intratumoral immune response is directed against a cancer progenitor cell and that the outcome of this response impacts the development of WD versus DD disease. Further study will likely provide interesting insights into the disease biology of WD/DD liposarcoma that may be readily translated to other more common cancers. PMID:27376027

Relationship between fresh-packaged spinach leaves exposed to continuous light or dark and bioactive contents: effects of cultivar, leaf size, and storage duration.

PubMed

Lester, Gene E; Makus, Donald J; Hodges, D Mark

2010-03-10

Current retail marketing conditions allow produce to receive artificial light 24 h per day during its displayed shelf life. Essential human-health vitamins [ascorbic acid (vit C), folate (vit B(9)), phylloquinone (vit K(1)), alpha-tocopherol (vit E), and the carotenoids lutein, violaxanthin, zeaxanthin, and beta-carotene (provit A)] also are essential for photosynthesis and are biosynthesized in plants by light conditions even under chilling temperatures. Spinach leaves, notably abundant in the aforementioned human-health compounds, were harvested from flat-leaf 'Lazio' and crinkle-leafed 'Samish' cultivars at peak whole-plant maturity as baby (top- and midcanopy) and larger (lower-canopy) leaves. Leaves were placed as a single layer in commercial, clear-polymer retail boxes and stored at 4 degrees C for up to 9 days under continuous light (26.9 micromol.m(2 ).s) or dark. Top-canopy, baby-leaf spinach generally had higher concentrations of all bioactive compounds, on a dry weight basis, with the exception of carotenoids, than bottom-canopy leaves. All leaves stored under continuous light generally had higher levels of all bioactive compounds, except beta-carotene and violaxanthin, and were more prone to wilting, especially the flat-leafed cultivar. All leaves stored under continuous darkness had declining or unchanged levels of the aforementioned bioactive compounds. Findings from this study revealed that spinach leaves exposed to simulated retail continuous light at 4 degrees C, in clear plastic containers, were overall more nutritionally dense (enriched) than leaves exposed to continuous darkness.

Analytic study of the effect of dark energy-dark matter interaction on the growth of structures

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

Marcondes, Rafael J.F.; Landim, Ricardo C.G.; Costa, André A.

2016-12-01

Large-scale structure has been shown as a promising cosmic probe for distinguishing and constraining dark energy models. Using the growth index parametrization, we obtain an analytic formula for the growth rate of structures in a coupled dark energy model in which the exchange of energy-momentum is proportional to the dark energy density. We find that the evolution of f σ{sub 8} can be determined analytically once we know the coupling, the dark energy equation of state, the present value of the dark energy density parameter and the current mean amplitude of dark matter fluctuations. After correcting the growth function formore » the correspondence with the velocity field through the continuity equation in the interacting model, we use our analytic result to compare the model's predictions with large-scale structure observations.« less

Ratcheting Up The Search for Dark Matter

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

McDermott, Samuel Dylan

2014-01-01

The last several years have included remarkable advances in two of the primary areas of fundamental particle physics: the search for dark matter and the discovery of the Higgs boson. This dissertation will highlight some contributions made on the forefront of these exciting fields. Although the circumstantial evidence supporting the dark matter hypothesis is now almost undeniably significant, indisputable direct proof is still lacking. As the direct searches for dark matter continue, we can maximize our prospects of discovery by using theoretical techniques complementary to the observational searches to rule out additional, otherwise accessible parameter space. In this dissertation, Imore » report bounds on a wide range of dark matter theories. The models considered here cover the spectrum from the canonical case of self-conjugate dark matter with weak-scale interactions, to electrically charged dark matter, to non-annihilating, non-fermionic dark matter. These bounds are obtained from considerations of astrophysical and cosmological data, including, respectively: diffuse gamma ray photon observations; structure formation considerations, along with an explication of the novel local dark matter structure due to galactic astrophysics; and the existence of old pulsars in dark-matter-rich environments. I also consider the prospects for a model of neutrino dark matter which has been motivated by a wide set of seemingly contradictory experimental results. In addition, I include a study that provides the tools to begin solving the speculative ``inverse'' problem of extracting dark matter properties solely from hypothetical nuclear energy spectra, which we may face if dark matter is discovered with multiple direct detection experiments. In contrast to the null searches for dark matter, we have the example of the recent discovery of the Higgs boson. The Higgs boson is the first fundamental scalar particle ever observed, and precision measurements of the production and decay of the Higgs boson represent a unique entry p! oint to searches for new kinds of physics. Continuing to refine our understanding of the Higgs boson will also allow us to learn about a vast array of possible new physics. This dissertation includes work parameterizing some of the scenarios that are most likely to be discovered with future Higgs data.« less

Late onset dysthymic disorder and major depression differ from early onset dysthymic disorder and major depression in elderly outpatients.

PubMed

Devanand, D P; Adorno, Elizabeth; Cheng, Jocelyn; Burt, Tal; Pelton, G H Gregory H; Roose, S P Steven P; Sackeim, H A Harold A

2004-03-01

Age of onset may affect clinical features and prognosis in elderly patients with major depression (MDD), but there is a lack of such data in elderly patients with dysthymic disorder (DD) and systematic comparisons of late onset MDD and DD have not been conducted. In a Late Life Depression Clinic, patients > or = 60 years old who met DSM-III-R or DSM-IV criteria for MDD or DD were studied. The 24-item Hamilton Rating Scale for Depression (HRSD) and SCID-P were completed, family history was obtained, and medical illnesses were assessed. In the total sample (n=370; 211 MDD and 159 DD), compared to early onset patients, late onset (onset > or =60 years) patients had a higher rate of cardiovascular disease (chi(2)=4.12, df=1, P<0.05), lower rate of anxiety disorder (chi(2)=4.19, df=1, P<0.05), and a lower rate of family history of affective disorder (chi(2)=9.37, df=1, P<0.002). Late onset DD patients were more likely to have cardiovascular disease than early onset DD patients (chi(2)=5.63, df=1, P<0.02), but the rate of cardiovascular disease did not differ between late and early onset MDD patients (chi(2)=0.35, df=1, P<0.6). Late onset MDD patients were less likely to have a family history of affective disorder than early onset MDD patients (chi(2)=10.71, df=1, P<0.001). Prevalence of anxiety disorders did not differ between the early and late onset MDD patients (chi(2)=0.07, df=1, P<0.79), but was more common in the early onset DD compared to the late onset DD patients (17.98% versus 4.29%, chi(2)=6.98, df=1, P<0.01). Late onset DD did not differ from late onset MDD in the rates of cardiovascular disease, anxiety disorders, and family history of affective disorder. Excluding patients with double depression (n=32) did not alter the cardiovascular or family history findings, but the difference in anxiety disorders between early and late onset DD patients was no longer significant. Academic clinic sample results may not generalize to community populations. In the elderly, late-onset DD is typically different from early onset DD. Cerebrovascular disease appears to play a role in the etiology of late onset DD. The similarities between late onset DD and late onset MDD suggest a single condition along a continuum.

The effect of digital dermatitis on hoof conformation.

PubMed

Gomez, A; Cook, N B; Rieman, J; Dunbar, K A; Cooley, K E; Socha, M T; Döpfer, D

2015-02-01

Digital dermatitis (DD) is the most prevalent cause of lameness of infectious origin in cattle. However, little is known about the effects of DD on hoof conformation (HC) during the clinical disease. The objectives of the present study were to (1) evaluate the changes in HC observed in feet affected with clinical DD lesions and (2) investigate the temporal relationship between DD and heel horn erosion (HHE). A longitudinal study was carried out including a cohort of 644 Holstein heifers. Digital dermatitis, HC, and presence of HHE in the rear feet of each heifer were assessed during a period of 6 mo. A total of 1,979 feet evaluations were included in the data set, of which 157 corresponded to feet presenting DD lesions >20mm [mean (SD) size of 27.2 (8.2) mm]. Age, days of pregnancy, hip height, and girth circumference were also recorded at cow level. Significant HC changes were observed in DD-affected feet. Results standardized to a period of 90d of follow-up showed an increase in heel height [mean (95% CI) 3.4 (2.5, 4.4) and 2.8 (2.0, 3.7) mm] and claw angle [0.8 (0.2, 1.4) and 1.4 (0.7, 2.0) degrees] of the medial and lateral claws, respectively. In addition, an increase in depth of the interdigital cleft [3.2 (2.7, 3.7) mm] and on debris accumulation [14% (7, 21) of feet] was also observed. Feet affected with clinical DD lesions also experienced a 46% point increase in the presence of severe HHE. In the short term, HC changes returned to normal levels when clinical cure of DD was achieved after topical treatment. In conclusion, significant HC changes occur in heifers affected by clinical DD before lameness symptoms are detected. The transformation of the heel area in feet affected by DD likely promotes the creation of a local environment that favors the persistence of the disease and the occurrence of severe HHE. To avoid further hoof damage, active surveillance and early intervention to reduce HC changes are recommended to improve DD control programs. Successful restoration of HC can be achieved upon clinical cure of DD. The long-term effects in lifetime performance of the HC changes due to DD remain to be further investigated. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Neglect-like characteristics of developmental disregard in children with cerebral palsy revealed by event related potentials.

PubMed

Zielinski, Ingar M; Steenbergen, Bert; Baas, C Marjolein; Aarts, Pauline Bm; Jongsma, Marijtje L A

2014-11-30

Children with unilateral Cerebral Palsy (CP) often show diminished awareness of the remaining capacity of their affected upper limb. This phenomenon is known as Developmental Disregard (DD). DD has been explained by operant conditioning. Alternatively, DD can be described as a developmental delay resulting from a lack of use of the affected hand during crucial developmental periods. We hypothesize that this delay is associated with a general delay in executive functions (EF) related to motor behavior, also known as motor EFs. Twenty-four children with unilateral CP participated in this cross-sectional study, twelve of them diagnosed with DD. To test motor EFs, a modified go/nogo task was presented in which cues followed by go- or nogo-stimuli appeared at either the left or right side of a screen. Children had to press a button with the hand corresponding to the side of stimulus presentation. Apart from response accuracy, Event-Related Potentials (ERPs) extracted from the ongoing EEG were used to register covert cognitive processes. ERP N1, P2, N2, and P3 components elicited by cue-, go-, and nogo-stimuli were further analyzed to differentiate between different covert cognitive processes. Children with DD made more errors. With respect to the ERPs, the P3 component to go-stimuli was enhanced in children with DD. This enhancement was related to age, such that younger children with DD showed stronger enhancements. In addition, in DD the N1 component to cue- and go-stimuli was decreased. The behavioral results show that children with DD experience difficulties when performing the task. The finding of an enhanced P3 component to go-stimuli suggests that these difficulties are due to increased mental effort preceding movement. As age in DD mediated this enhancement, it seems that this increased mental effort is related to a developmental delay. The additional finding of a decreased N1 component in DD furthermore suggests a general diminished visuo-spatial attention. This effect reveals that DD might be a neuropsychological phenomenon similar to post-stroke neglect syndrome that does not resolve during development. These findings suggest that therapies aimed at reducing neglect could be a promising addition to existing therapies for DD.

Structural and Functional Characterization of the Recombinant Death Domain from Death-Associated Protein Kinase

PubMed Central

Dioletis, Evangelos; Dingley, Andrew J.; Driscoll, Paul C.

2013-01-01

Death-associated protein kinase (DAPk) is a calcium/calmodulin-regulated Ser/Thr-protein kinase that functions at an important point of integration for cell death signaling pathways. DAPk has a structurally unique multi-domain architecture, including a C-terminally positioned death domain (DD) that is a positive regulator of DAPk activity. In this study, recombinant DAPk-DD was observed to aggregate readily and could not be prepared in sufficient yield for structural analysis. However, DAPk-DD could be obtained as a soluble protein in the form of a translational fusion protein with the B1 domain of streptococcal protein G. In contrast to other DDs that adopt the canonical six amphipathic α-helices arranged in a compact fold, the DAPk-DD was found to possess surprisingly low regular secondary structure content and an absence of a stable globular fold, as determined by circular dichroism (CD), NMR spectroscopy and a temperature-dependent fluorescence assay. Furthermore, we measured the in vitro interaction between extracellular-regulated kinase-2 (ERK2) and various recombinant DAPk-DD constructs. Despite the low level of structural order, the recombinant DAPk-DD retained the ability to interact with ERK2 in a 1∶1 ratio with a K d in the low micromolar range. Only the full-length DAPk-DD could bind ERK2, indicating that the apparent ‘D-motif’ located in the putative sixth helix of DAPk-DD is not sufficient for ERK2 recognition. CD analysis revealed that binding of DAPk-DD to ERK2 is not accompanied by a significant change in secondary structure. Taken together our data argue that the DAPk-DD, when expressed in isolation, does not adopt a classical DD fold, yet in this state retains the capacity to interact with at least one of its binding partners. The lack of a stable globular structure for the DAPk-DD may reflect either that its folding would be supported by interactions absent in our experimental set-up, or a limitation in the structural bioinformatics assignment of the three-dimensional structure. PMID:23922916

Structural and functional characterization of the recombinant death domain from death-associated protein kinase.

PubMed

Dioletis, Evangelos; Dingley, Andrew J; Driscoll, Paul C

2013-01-01

Death-associated protein kinase (DAPk) is a calcium/calmodulin-regulated Ser/Thr-protein kinase that functions at an important point of integration for cell death signaling pathways. DAPk has a structurally unique multi-domain architecture, including a C-terminally positioned death domain (DD) that is a positive regulator of DAPk activity. In this study, recombinant DAPk-DD was observed to aggregate readily and could not be prepared in sufficient yield for structural analysis. However, DAPk-DD could be obtained as a soluble protein in the form of a translational fusion protein with the B1 domain of streptococcal protein G. In contrast to other DDs that adopt the canonical six amphipathic α-helices arranged in a compact fold, the DAPk-DD was found to possess surprisingly low regular secondary structure content and an absence of a stable globular fold, as determined by circular dichroism (CD), NMR spectroscopy and a temperature-dependent fluorescence assay. Furthermore, we measured the in vitro interaction between extracellular-regulated kinase-2 (ERK2) and various recombinant DAPk-DD constructs. Despite the low level of structural order, the recombinant DAPk-DD retained the ability to interact with ERK2 in a 1∶1 ratio with a K d in the low micromolar range. Only the full-length DAPk-DD could bind ERK2, indicating that the apparent 'D-motif' located in the putative sixth helix of DAPk-DD is not sufficient for ERK2 recognition. CD analysis revealed that binding of DAPk-DD to ERK2 is not accompanied by a significant change in secondary structure. Taken together our data argue that the DAPk-DD, when expressed in isolation, does not adopt a classical DD fold, yet in this state retains the capacity to interact with at least one of its binding partners. The lack of a stable globular structure for the DAPk-DD may reflect either that its folding would be supported by interactions absent in our experimental set-up, or a limitation in the structural bioinformatics assignment of the three-dimensional structure.

Unitary Suprathreshold Color-Difference Metrics of Legibility for CRT Raster Imagery.

DTIC Science & Technology

1986-09-01

observers possessing norma vision could accurately read random numeral strings of one color displayed DD J 4-73 EDITION OF C 6S IS OBSOLETE - SEURT CLSIICTO...34 Table 2, continued. SAE (L*,u*,v*) : .909 .940 Intercept 1. 8581 1. 8022 " N -0. 3980 -0.3655 m .AE 0. 1217 0. 1206-" =, E -0. 0019 -0. 0017 * all t > 3

A pilot study of denileukin diftitox (DD) in combination with high-dose interleukin-2 (IL-2) for patients with metastatic renal cell carcinoma (RCC).

PubMed

Atchison, Elizabeth; Eklund, John; Martone, Brenda; Wang, Lili; Gidron, Adi; Macvicar, Gary; Rademaker, Alfred; Goolsby, Charles; Marszalek, Laura; Kozlowski, James; Smith, Norm; Kuzel, Timothy M

2010-09-01

High-dose (HD) IL-2 is approved to treat renal cell carcinoma (RCC) with modest response rates and significant toxicity. Enhancement of cytotoxic T-cell activity by IL-2 is 1 mechanism of action. IL-2 also stimulates regulatory T lymphocytes (Tregs), which are associated with poor prognosis. Favorable outcomes are associated with greater rebound absolute lymphocyte count (Fumagalli 2003). DD depletes IL-2 receptor (CD25 component) expressing cells. We hypothesized that sequential therapy could complement each other; DD would deplete Tregs so IL-2 could more effectively stimulate proliferation and activity of cytotoxic T lymphocytes. Patients (n=18) received standard HD IL-2 and 1 dose of DD daily for 3 days; periodic flow cytometry and complete blood counts were performed. Group A included 3 patients to assess safety only with DD 6 μg/kg between the IL-2 courses. Group B included 9 patients at 9 μg/kg DD before the IL-2 courses. Group C included 6 patients at 9 μg/kg DD between the IL-2 courses. Efficacy using the RECIST criteria was assessed after the treatment. Fifteen patients from a study of IL-2 without DD served as controls for toxicity comparison and 13 of these for flow cytometry comparisons. No unusual toxicity was noted. For group B/C patients receiving DD, the median decline in Tregs was 56.3% from pre-DD to post-DD (P=0.013). Peak absolute lymphocyte count change from baseline was +9980/μL for group B, +4470/μL for group C, and +4720/μL for the controls (P=0.005 B vs. C). The overall response rate was 5 of 15 (33%); 3 of 9 (33%) and 2 of 6 (33%) for groups B and C, respectively, including 2 patients with sarcomatoid RCC and 1 with earlier sunitinib therapy.

Right heart function in impaired left ventricular diastolic function: 2D speckle tracking echocardiography-based and Doppler tissue imaging-based analysis of right atrial and ventricular function.

PubMed

Brand, Anna; Bathe, Marny; Oertelt-Prigione, Sabine; Seeland, Ute; Rücke, Mirjam; Regitz-Zagrosek, Vera; Stangl, Karl; Knebel, Fabian; Stangl, Verena; Dreger, Henryk

2018-01-01

The aim of our study was to describe right atrial (RA) and right ventricular (RV) function, assessed by Doppler tissue imaging and 2D speckle tracking echocardiography (2DSTE), in women with signs of early impaired left ventricular diastolic function (DD). In a cross-sectional trial, standard parameters of diastolic and right heart function were investigated in 438 women of the Berlin Female Risk Evaluation (BEFRI) study. In a subset of women, average peak systolic RA strain (RAS), as well as the average peak systolic RV strain of the free wall (RVS free wall) and of all RV segments (average RV strain; RVS Avg), was analyzed using 2DSTE. Compared to women with normal diastolic function (DD0), RAS, RVS free wall and RVS Avg were significantly reduced in DD (43.1% ± 11.9%, -26.7% ± 5.6%, and -23.3% ± 3.5% in DD0; vs 35.1% ± 10.4%, -23.9% ± 5.5%, and -20.6% ± 3.8% in DD; P < .01). Peak RV myocardial velocity (RV-IVV) and acceleration during isovolumetric contraction (RV-IVA) were markedly higher in DD (15.0 ± 3.9 cm/s and 3.1 ± 1.0 m/s² in DD vs 11.9 ± 3.2 cm/s and 2.8 ± 0.8 m/s² in DD0; P < .05). RAS and RV-IVV were significantly associated with DD after adjustment to age, BMI, and left atrial strain in multivariate regression analysis. Systolic right heart function is significantly altered in DD. DTI as well as 2DSTE constitute sensitive echocardiographic tools that enable the diagnosis of impaired right heart mechanics in early-staged DD. © 2017 Wiley Periodicals, Inc.

The ACE/DD genotype is associated with the extent of exercise-induced left ventricular growth in endurance athletes.

PubMed

Hernández, Domingo; de la Rosa, Alejandro; Barragán, Antonio; Barrios, Ysamar; Salido, Eduardo; Torres, Armando; Martín, Basilio; Laynez, Ignacio; Duque, Amelia; De Vera, Antonia; Lorenzo, Victor; González, Antonio

2003-08-06

We studied the impact of the angiotensin-converting enzyme (ACE)/DD genotype on morphologic and functional cardiac changes in adult endurance athletes. Trained athletes usually develop adaptive left ventricular hypertrophy (LVH), and ACE gene polymorphisms may regulate myocardial growth. However, little is known about the impact of the ACE/DD genotype and D allele dose on the cardiac changes in adult endurance athletes. METHODS; Echocardiographic studies (including tissue Doppler) were performed in 61 male endurance athletes ranging in age from 25 to 40 years, with a similar period of training (15.6 +/- 4 h/week for 12.6 +/- 5.7 years). The ACE genotype (insertion [I] or deletion [D] alleles) was ascertained by polymerase chain reaction (DD = 27, ID = 31, and II = 3). Athletes with the DD genotype were compared with their ID counterparts. The DD genotype was associated with a higher left ventricular mass index (LVMI) than the ID genotype (162.6 +/- 36.5 g/m(2) vs. 141.6 +/- 34 g/m(2), p = 0.031), regardless of other confounder variables. As a result, 70.4% of DD athletes and only 42% of ID athletes met the criteria for LVH (p = 0.037). Although systolic and early diastolic myocardial velocities were similar in DD and ID subjects, a more prolonged E-wave deceleration time (DT) was observed in DD as compared with ID athletes, after adjusting for other biologic variables (210 +/- 48 ms vs. 174 +/- 36 ms, respectively; p = 0.008). Finally, a positive association between DT and myocardial systolic peak velocity (medial and lateral peak S(m)) was only observed in DD athletes (p = 0.013, r = 0.481). The ACE/DD genotype is associated with the extent of exercise-induced LVH in endurance athletes, regardless of other known biologic factors.

The contribution of discrete-trial naming and visual recognition to rapid automatized naming deficits of dyslexic children with and without a history of language delay

PubMed Central

Gasperini, Filippo; Brizzolara, Daniela; Cristofani, Paola; Casalini, Claudia; Chilosi, Anna Maria

2014-01-01

Children with Developmental Dyslexia (DD) are impaired in Rapid Automatized Naming (RAN) tasks, where subjects are asked to name arrays of high frequency items as quickly as possible. However the reasons why RAN speed discriminates DD from typical readers are not yet fully understood. Our study was aimed to identify some of the cognitive mechanisms underlying RAN-reading relationship by comparing one group of 32 children with DD with an age-matched control group of typical readers on a naming and a visual recognition task both using a discrete-trial methodology, in addition to a serial RAN task, all using the same stimuli (digits and colors). Results showed a significant slowness of DD children in both serial and discrete-trial naming (DN) tasks regardless of type of stimulus, but no difference between the two groups on the discrete-trial recognition task. Significant differences between DD and control participants in the RAN task disappeared when performance in the DN task was partialled out by covariance analysis for colors, but not for digits. The same pattern held in a subgroup of DD subjects with a history of early language delay (LD). By contrast, in a subsample of DD children without LD the RAN deficit was specific for digits and disappeared after slowness in DN was partialled out. Slowness in DN was more evident for LD than for noLD DD children. Overall, our results confirm previous evidence indicating a name-retrieval deficit as a cognitive impairment underlying RAN slowness in DD children. This deficit seems to be more marked in DD children with previous LD. Moreover, additional cognitive deficits specifically associated with serial RAN tasks have to be taken into account when explaining deficient RAN speed of these latter children. We suggest that partially different cognitive dysfunctions underpin superficially similar RAN impairments in different subgroups of DD subjects. PMID:25237301

42 CFR 418.1 - Statutory basis.

Code of Federal Regulations, 2010 CFR

2010-10-01

... section 1861(dd) of the Social Security Act (the Act). Section 1861(dd) of the Act specifies services... Medicare program. Section 1861(dd) also specifies limitations on coverage of, and payment for, inpatient...

75 FR 60434 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

... Certificate of Insurance, DD Form 2400; Civil Aircraft Landing Permit, DD Form 2401; Civil Aircraft Hold Harmless Agreement, DD Form 2402; OMB Control Number 0701-0050. Needs and Uses: The collection of...

Dark energy and modified gravity in the Effective Field Theory of Large-Scale Structure

NASA Astrophysics Data System (ADS)

Cusin, Giulia; Lewandowski, Matthew; Vernizzi, Filippo

2018-04-01

We develop an approach to compute observables beyond the linear regime of dark matter perturbations for general dark energy and modified gravity models. We do so by combining the Effective Field Theory of Dark Energy and Effective Field Theory of Large-Scale Structure approaches. In particular, we parametrize the linear and nonlinear effects of dark energy on dark matter clustering in terms of the Lagrangian terms introduced in a companion paper [1], focusing on Horndeski theories and assuming the quasi-static approximation. The Euler equation for dark matter is sourced, via the Newtonian potential, by new nonlinear vertices due to modified gravity and, as in the pure dark matter case, by the effects of short-scale physics in the form of the divergence of an effective stress tensor. The effective fluid introduces a counterterm in the solution to the matter continuity and Euler equations, which allows a controlled expansion of clustering statistics on mildly nonlinear scales. We use this setup to compute the one-loop dark-matter power spectrum.

Lobar lung transplantation from deceased donors: A systematic review

PubMed Central

Eberlein, Michael; Reed, Robert M; Chahla, Mayy; Bolukbas, Servet; Blevins, Amy; Van Raemdonck, Dirk; Stanzi, Alessia; Inci, Ilhan; Marasco, Silvana; Shigemura, Norihisa; Aigner, Clemens; Deuse, Tobias

2017-01-01

AIM To systematically review reports on deceased-donor-lobar lung transplantation (ddLLTx) and uniformly describe size matching using the donor-to-recipient predicted-total lung-capacity (pTLC) ratio. METHODS We set out to systematically review reports on ddLLTx and uniformly describe size matching using the donor-to-recipient pTLC ratio and to summarize reported one-year survival data of ddLLTx and conventional-LTx. We searched in PubMed, CINAHL via EBSCO, Cochrane Database of Systematic Reviews via Wiley (CDSR), Database of Abstracts of Reviews of Effects via Wiley (DARE), Cochrane Central Register of Controlled Trials via Wiley (CENTRAL), Scopus (which includes EMBASE abstracts), and Web of Science for original reports on ddLLTx. RESULTS Nine observational cohort studies reporting on 301 ddLLTx met our inclusion criteria for systematic review of size matching, and eight for describing one-year-survival. The ddLLTx-group was often characterized by high acuity; however there was heterogeneity in transplant indications and pre-operative characteristics between studies. Data to calculate the pTLC ratio was available for 242 ddLLTx (80%). The mean pTLCratio before lobar resection was 1.25 ± 0.3 and the transplanted pTLCratio after lobar resection was 0.76 ± 0.2. One-year survival in the ddLLTx-group ranged from 50%-100%, compared to 72%-88% in the conventional-LTx group. In the largest study ddLLTx (n = 138) was associated with a lower one-year-survival compared to conventional-LTx (n = 539) (65.1% vs 84.1%, P < 0.001). CONCLUSION Further investigations of optimal donor-to-recipient size matching parameters for ddLLTx could improve outcomes of this important surgical option. PMID:28280698

Lobar lung transplantation from deceased donors: A systematic review.

PubMed

Eberlein, Michael; Reed, Robert M; Chahla, Mayy; Bolukbas, Servet; Blevins, Amy; Van Raemdonck, Dirk; Stanzi, Alessia; Inci, Ilhan; Marasco, Silvana; Shigemura, Norihisa; Aigner, Clemens; Deuse, Tobias

2017-02-24

To systematically review reports on deceased-donor-lobar lung transplantation (ddLLTx) and uniformly describe size matching using the donor-to-recipient predicted-total lung-capacity (pTLC) ratio. We set out to systematically review reports on ddLLTx and uniformly describe size matching using the donor-to-recipient pTLC ratio and to summarize reported one-year survival data of ddLLTx and conventional-LTx. We searched in PubMed, CINAHL via EBSCO, Cochrane Database of Systematic Reviews via Wiley (CDSR), Database of Abstracts of Reviews of Effects via Wiley (DARE), Cochrane Central Register of Controlled Trials via Wiley (CENTRAL), Scopus (which includes EMBASE abstracts), and Web of Science for original reports on ddLLTx. Nine observational cohort studies reporting on 301 ddLLTx met our inclusion criteria for systematic review of size matching, and eight for describing one-year-survival. The ddLLTx-group was often characterized by high acuity; however there was heterogeneity in transplant indications and pre-operative characteristics between studies. Data to calculate the pTLC ratio was available for 242 ddLLTx (80%). The mean pTLCratio before lobar resection was 1.25 ± 0.3 and the transplanted pTLCratio after lobar resection was 0.76 ± 0.2. One-year survival in the ddLLTx-group ranged from 50%-100%, compared to 72%-88% in the conventional-LTx group. In the largest study ddLLTx ( n = 138) was associated with a lower one-year-survival compared to conventional-LTx ( n = 539) (65.1% vs 84.1%, P < 0.001). Further investigations of optimal donor-to-recipient size matching parameters for ddLLTx could improve outcomes of this important surgical option.

The distribution of the anti-HIV drug, 2'3'-dideoxycytidine (ddC), across the blood-brain and blood-cerebrospinal fluid barriers and the influence of organic anion transport inhibitors.

PubMed

Gibbs, J E; Thomas, S A

2002-02-01

The brain and CSF distribution of the HIV reverse transcriptase inhibitor, 2'3'-dideoxycytidine (ddC), was investigated by the in situ brain perfusion and isolated incubated choroid plexus methods in the guinea pig. Multiple-time brain perfusions indicated that the distribution of [3H]ddC to the brain and CSF was low and the unidirectional rate constant (K(in)) for the brain uptake of this nucleoside analogue (0.52 +/- 0.10 microL/min/g) was not significantly different to that for the vascular marker, [14C]mannitol (0.44 +/- 0.09 microL/min/g). The influence of unlabelled ddC, six organic anion transport inhibitors and 3'-azido 3'-deoxythymidine (AZT) on the CNS uptake of [3H]ddC was examined in situ and in vitro. ddC, probenecid and 2,4-dichlorophenoxyacetic acid altered the distribution of [3H]ddC into the brain and choroid plexuses, indicating that the limited distribution of [3H]ddC was a result of an organic anion efflux transporter, in addition to the low lipophilicity of this drug (octanol-saline partition coefficient, 0.047 +/- 0.001). The CNS distribution was also sensitive to p-aminohippurate and deltorphin II, but not digoxin, suggesting the involvement of organic anion transporters (OAT1/OAT3-like) and organic anion transporting polypeptides (OATP1/OATPA-like). AZT did not effect the accumulation of [3H]ddC, indicating that when these nucleoside analogues are used in anti-HIV combination therapy, the CNS distribution of ddC is unchanged.

[Clinical Values of Combined Detection of CRP and D-D for AL Patients Complicated with DIC].

PubMed

Ji, Xue-Hong

2015-12-01

To explore the clinical values of the combined detection of C-reactive protein (CRP) and D-dimer (D-D) for acute leukemia (AL) patients complicated with disseminated intravascular coagulation (DIC). Among 52 cases of AL, 20 cases of AL complicated with DIC were selected as AL+DIC group, 32 cases of AL were selected as AL group, 30 healthy volunteers were used as control group; the detected values of CRP and D-D in 3 groups were compared. The CRP and D-D levels in AL+DIC group were significantly higher than those in AL and control groups (P < 0.05); the CRP and D-D levels in AL group were significatly higher than those in control group (P < 0.05). The D-D level and complicated DIC rate in patients with CRP < 10 mg/L were significantly lower than those in patients with CRP 10-100 and >100 mg/L (P <0.05), while the D-D level and complicated DIC rate in patients with 10-100 mg/L were significantly lower than those in patients with CRP > 100 mg/L (P <0.05). After treatment of patients, the CRP and D-D levels in AL and AL+DIC groups were obviously reduced as compared with levels of these 2 groups before treatment (P <0.05); the CRP and D-D levels in AL+DIC after treatment were significantly higher than those in AL group (P <0.05). The combined detection of CRP and D-D possesses a higher reference value for diagnosis and differentiation of AL and AL complicated with DIC, thus also has an important role in evaluation of therapeutic efficacy of AL.

Relationship of angiotensin I-converting enzyme (ACE) and bradykinin B2 receptor (BDKRB2) polymorphism with diabetic nephropathy.

PubMed

Zou, Honghong; Wu, Guoqing; Lv, Jinlei; Xu, Gaosi

2017-06-01

To determine whether ACE 2 I/D and BDKRB2 3 +9/-9 polymorphism causatively affect diabetic nephropathy progression RESULTS: STZ-induced metabolic disorder, as well as inflammatory responses, was significantly aggravated in ACE II-B2R 4 +9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp diabetic mice but not ACE II-B2R-9bp, indicating the genetic susceptibility of ACE DD or B2R+9bp to diabetic nephropathy. Furthermore, ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp rather than ACE II-B2R-9bp, worsened renal performance and enhanced pathological alterations induced by STZ. Markedly elevated monocyte chemoattractant protein-1(MCP-1), podocin, osteopontin (OPN), transforming growth factor-β1 (TGF-β1), and reduced nephrin, podocin were also detected both in diabetic mice and podocytes under hyperglycemic conditions in response to ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp, versus ACE II-B2R-9bp. In addition, high glucose-induced mitochondrial oxidative stress and cell apoptosis were observably increased in response to ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp but not ACE II-B2R-9bp. We provide first evidence indicating the causation between ACE DD or B2R+9bp genotype and the increased risk for diabetic nephropathy, broadening our horizon about the role of genetic modulators in this disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Poor clinical outcomes among pneumonia patients with depressive disorder.

PubMed

Kao, Li-Ting; Liu, Shih-Ping; Lin, Herng-Ching; Lee, Hsin-Chien; Tsai, Ming-Chieh; Chung, Shiu-Dong

2014-01-01

Some studies suggested that psychological stress may be associated with the severity and duration of infectious diseases. In this population-based study, we investigated associations between depressive disorder (DD) and pneumonia outcomes in Taiwan with a large-scale database from the National Health Insurance. Our study defined 112,198 patients who were hospitalized with a principal diagnosis of pneumonia. We defined their admission date for treatment of pneumonia as the index date. Subsequently, we selected 2,394 patients with DD within 3 years prior to their index date and 11,970 matched patients without DD. We carried out separate conditional logistic regressions to explore the association of clinical pneumonia treatment outcome (ICU admission, use of mechanical ventilation, acute respiratory failure and in-hospital death) with previously diagnosed DD. Patients with DD had a significantly higher probability of an intensive care unit admission (18.1% vs. 12.9%; p<0.001), need for mechanical ventilation (21.9% vs. 18.1%; p<0.001) and in-hospital death (10.4% vs. 9.0%; p = 0.025) than patients without DD. The study showed that pneumonia patients with DD were respectively 1.41- (95% CI: 1.25∼1.59, p<0.001), 1.28- (95% CI: 1.14∼1.43, p<0.001), and 1.17- times (95% CI: 1.01∼1.36, p = 0.039) greater odds of being admitted to the ICU, need for mechanical ventilation, and in-hospital death than patients without DD after adjusting for monthly income, urbanization level, geographic region and Charlson Comorbidity Index score. In conclusion, we found that pneumonia patients with DD were associated with poor treatment outcomes compared to patients without DD.

Innate immunity phenotypic features point toward simultaneous raise of activation and modulation events following 17DD live attenuated yellow fever first-time vaccination.

PubMed

Martins, Marina Angela; Silva, Maria Luiza; Elói-Santos, Silvana Maria; Ribeiro, José Geraldo Leite; Peruhype-Magalhães, Vanessa; Marciano, Ana Paula Vieira; Homma, Akira; Kroon, Erna Geessien; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis

2008-02-26

Detailed multiparametric phenotypic investigation aiming to characterize the kinetics of the innate immune response in the peripheral blood following 17DD yellow fever (17DD-YF) first-time vaccination was performed. Results showed increased frequency of monocytes and NK cell subpopulations besides unexpected up-regulation of granulocytes activation status (CD28+/CD23+ and CD28+/HLA-DR+, respectively). Up-regulation of Fcgamma-R and IL-10-R expression emerge as putative events underlying the mixed pattern of phenotypic features triggered by the 17DD yellow fever (17DD-YF) vaccination. Mixed pattern of chemokine receptors expression further support our hypothesis that a parallel establishment of activation/modulation microenvironment plays a pivotal role in the protective immunity triggered by the 17DD-YF vaccine.

Study of the branching ratio of {psi}(3770){yields}DD in e{sup +}e{sup -{yields}}DD scattering

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

Li Haibo; Qin Xiaoshuai; Yang Maozhi

2010-01-01

Based on the data of BES and Belle, the production of DD in the e{sup +}e{sup -{yields}}DD scattering process is studied in this paper. We analyze the continuum and resonant contributions in the energy region from 3.7 to 4.4 GeV. In the {chi}{sup 2} fit to data, we obtain the resonance parameters of {psi}(3770), the branching ratio of {psi}(3770){yields}DD decay by confronting the data to the theoretical formula where both the contributions of the resonances, continuum and interference effects are included. We obtain the branching ratio of {psi}(3770){yields}DD decay is 97.2%{+-}8.9%, as well as the branching ratio of {psi}(4040), {psi}(4160){yields}DDmore » decays.« less

Childhood maltreatment and intimate partner violence in dissociative disorder patients.

PubMed

Webermann, Aliya R; Brand, Bethany L; Chasson, Gregory S

2014-01-01

Childhood maltreatment (CM) is a risk factor for subsequent intimate partner violence (IPV) in adulthood, with high rates of retrospectively reported CM among IPV victims and perpetrators. A theorized mechanism of the link between CM and IPV is dissociation. Dissociation may allow perpetrators of violence to remain emotionally distant from their behavior and minimize empathy toward those they victimize, enabling them to commit acts of violence similar to their own experiences. Indeed, elevated rates of dissociation and dissociative disorders (DD) have been found among IPV survivors and perpetrators. In addition, in pilot studies, DD clinicians have reported high levels of violent behavior among DD patients. The present study investigates IPV among DD patients with Dissociative Identity Disorder and Dissociative Disorder Not Otherwise Specified, a group with CM rates of 80-95% and severe dissociative symptoms. DD clinicians reported on rates of CM and IPV among 275 DD patients in outpatient treatment. DD patients also completed a self-report measure of dissociation. Analyses assessed the associations between CM typologies and IPV, as well as trait dissociation and IPV. Physical and emotional child abuse were associated with physical IPV, and childhood witnessing of domestic violence (DV) and childhood neglect were associated with emotional IPV. The present study is the first to provide empirical support for a possible CM to adult IPV developmental trajectory among DD patients. Future research is needed to better understand the link between CM and IPV among those with trauma and DD.

Gastric cancer-derived MSC-secreted PDGF-DD promotes gastric cancer progression.

PubMed

Huang, Feng; Wang, Mei; Yang, Tingting; Cai, Jie; Zhang, Qiang; Sun, Zixuan; Wu, Xiaodan; Zhang, Xu; Zhu, Wei; Qian, Hui; Xu, Wenrong

2014-11-01

This study was designed to investigate the role of PDGF-DD secreted by gastric cancer-derived mesenchymal stem cells (GC-MSCs) in human gastric cancer progression. Gastric cancer cells were indirectly co-cultured with GC-MSCs in a transwell system. The growth and migration of gastric cancer cells were evaluated by cell colony formation assay and transwell migration assay, respectively. The production of PDGF-DD in GC-MSCs was determined by using Luminex and ELISA. Neutralization of PDGFR-β by su16f and siRNA interference of PDGF-DD in GC-MSCs was used to demonstrate the role of PDGF-DD produced by GC-MSCs in gastric cancer progression. GC-MSC conditioned medium promoted gastric cancer cell proliferation and migration in vitro and in vivo. Co-culture with GC-MSCs increased the phosphorylation of PDGFR-β in SGC-7901 cells. Neutralization of PDGFR-β by su16f blocked the promoting role of GC-MSC conditioned medium in gastric cancer cell proliferation and migration. Recombinant PDGF-DD duplicated the effects of GC-MSC conditioned medium on gastric cancer cells. Knockdown of PDGF-DD in GC-MSCs abolished its effects on gastric cancer cells in vitro and in vivo. PDGF-DD secreted by GC-MSCs is capable of promoting gastric cancer cell progression in vitro and in vivo. Targeting the PDGF-DD/PDGFR-β interaction between MSCs and gastric cancer cells may represent a novel strategy for gastric cancer therapy.

Plasminogen fragments K 1-3 and K 5 bind to different sites in fibrin fragment DD.

PubMed

Grinenko, T V; Kapustianenko, L G; Yatsenko, T A; Yusova, O I; Rybachuk, V N

2016-01-01

Specific plasminogen-binding sites of fibrin molecule are located in Аα148-160 regions of C-terminal domains. Plasminogen interaction with these sites initiates the activation process of proenzyme and subsequent fibrin lysis. In this study we investigated the binding of plasminogen fragments K 1-3 and K 5 with fibrin fragment DD and their effect on Glu-plasminogen interaction with DD. It was shown that the level of Glu-plasminogen binding to fibrin fragment DD is decreased by 50-60% in the presence of K 1-3 and K 5. Fragments K 1-3 and K 5 have high affinity to fibrin fragment DD (Kd is 0.02 for K 1-3 and 0.054 μМ for K 5). K 5 interaction is independent and K 1-3 is partly dependent on C-terminal lysine residues. K 1-3 interacts with complex of fragment DD-immobilized K 5 as well as K 5 with complex of fragment DD-immobilized K 1-3. The plasminogen fragments do not displace each other from binding sites located in fibrin fragment DD, but can compete for the interaction. The results indicate that fibrin fragment DD contains different binding sites for plasminogen kringle fragments K 1-3 and K 5, which can be located close to each other. The role of amino acid residues of fibrin molecule Аα148-160 region in interaction with fragments K 1-3 and K 5 is discussed.

Heterogeneity of Developmental Dyscalculia: Cases with Different Deficit Profiles

PubMed Central

Träff, Ulf; Olsson, Linda; Östergren, Rickard; Skagerlund, Kenny

2017-01-01

Developmental Dyscalculia (DD) has long been thought to be a monolithic learning disorder that can be attributed to a specific neurocognitive dysfunction. However, recent research has increasingly recognized the heterogeneity of DD, where DD can be differentiated into subtypes in which the underlying cognitive deficits and neural dysfunctions may differ. The aim was to further understand the heterogeneity of developmental dyscalculia (DD) from a cognitive psychological perspective. Utilizing four children (8–9 year-old) we administered a comprehensive cognitive test battery that shed light on the cognitive-behavioral profile of each child. The children were compared against norm groups of aged-matched peers. Performance was then contrasted against predominant hypotheses of DD, which would also give insight into candidate neurocognitive correlates. Despite showing similar mathematical deficits, these children showed remarkable interindividual variability regarding cognitive profile and deficits. Two cases were consistent with the approximate number system deficit account and also the general magnitude-processing deficit account. These cases showed indications of having domain-general deficits as well. One case had an access deficit in combination with a general cognitive deficit. One case suffered from general cognitive deficits only. The results showed that DD cannot be attributed to a single explanatory factor. These findings support a multiple deficits account of DD and suggest that some cases have multiple deficits, whereas other cases have a single deficit. We discuss a previously proposed distinction between primary DD and secondary DD, and suggest hypotheses of dysfunctional neurocognitive correlates responsible for the displayed deficits. PMID:28101068

Heterogeneity of Developmental Dyscalculia: Cases with Different Deficit Profiles.

PubMed

Träff, Ulf; Olsson, Linda; Östergren, Rickard; Skagerlund, Kenny

2016-01-01

Developmental Dyscalculia (DD) has long been thought to be a monolithic learning disorder that can be attributed to a specific neurocognitive dysfunction. However, recent research has increasingly recognized the heterogeneity of DD, where DD can be differentiated into subtypes in which the underlying cognitive deficits and neural dysfunctions may differ. The aim was to further understand the heterogeneity of developmental dyscalculia (DD) from a cognitive psychological perspective. Utilizing four children (8-9 year-old) we administered a comprehensive cognitive test battery that shed light on the cognitive-behavioral profile of each child. The children were compared against norm groups of aged-matched peers. Performance was then contrasted against predominant hypotheses of DD, which would also give insight into candidate neurocognitive correlates. Despite showing similar mathematical deficits, these children showed remarkable interindividual variability regarding cognitive profile and deficits. Two cases were consistent with the approximate number system deficit account and also the general magnitude-processing deficit account. These cases showed indications of having domain-general deficits as well. One case had an access deficit in combination with a general cognitive deficit. One case suffered from general cognitive deficits only. The results showed that DD cannot be attributed to a single explanatory factor. These findings support a multiple deficits account of DD and suggest that some cases have multiple deficits, whereas other cases have a single deficit. We discuss a previously proposed distinction between primary DD and secondary DD, and suggest hypotheses of dysfunctional neurocognitive correlates responsible for the displayed deficits.

Does attentional training improve numerical processing in developmental dyscalculia?

PubMed

Ashkenazi, Sarit; Henik, Avishai

2012-01-01

Recently, a deficit in attention was found in those with pure developmental dyscalculia (DD). Accordingly, the present study aimed to examine the influence of attentional training on attention abilities, basic numerical abilities, and arithmetic in participants who were diagnosed as having DD. Nine university students diagnosed as having DD (IQ and reading abilities in the normal range and no indication of attention-deficit hyperactivity disorder) and nine matched controls participated in attentional training (i.e., video game training). First, training modulated the orienting system; after training, the size of the validity effect (i.e., effect of valid vs. invalid) decreased. This effect was comparable in the two groups. Training modulated abnormalities in the attention systems of those with DD, that is, it reduced their enlarged congruity effect (i.e., faster responding when flanking arrows pointed to the same location as a center arrow). Second, in relation to the enumeration task, training reduced the reaction time of the DD group in the subitizing range but did not change their smaller-than-normal subitizing range. Finally, training improved performance in addition problems in both the DD and control groups. These results imply that attentional training does improve most of the attentional deficits of those with DD. In contrast, training did not improve the abnormalities of the DD group in arithmetic or basic numerical processing. Thus, in contrast to the domain-general hypothesis, the deficits in attention among those with DD and the deficits in numerical processing appear to originate from different sources.

The ddY mouse: a model of postprandial hypertriglyceridemia in response to dietary fat

PubMed Central

Yamazaki, Tomomi; Kishimoto, Kyoko; Ezaki, Osamu

2012-01-01

Postprandial hyperlipidemia (lipemia) is a risk factor for atherosclerosis. However, mouse models of postprandial hyperlipidemia have not been reported. Here, we report that ddY mice display marked postprandial hypertriglyceridemia in response to dietary fat. In ddY mice, the fasting serum total triacylglyceride (TG) concentration was 134 mg/dl, which increased to 571 mg/dl after an intragastric safflower oil load (0.4 ml/mouse). In C57BL/6J mice, these concentrations were 57 and 106 mg/dl, respectively. By lipoprotein analysis, ddY mice showed increases in chylomicron- and VLDL-sized TG fractions (remnants and VLDL) after fat load. In C57BL/6J mice, post-heparin plasma LPL activity after fat load was increased 4.8-fold relative to fasting. However, in ddY mice, the increase of LPL activity after fat load was very small (1.2-fold) and not significant. High fat feeding for 10 weeks led to obesity in ddY mice. A difference in LPL amino acid composition between C57BL/6J and ddY mice was detected but was deemed unlikely to cause hypertriglyceridemia because hypertriglyceridemia was not evident in other strains harboring the ddY-type LPL sequence. These findings indicate that postprandial hypertriglyceridemia in ddY mice is induced by decreased LPL activity after fat load and is associated with obesity induced by a high-fat diet. PMID:22735545

Childhood maltreatment and intimate partner violence in dissociative disorder patients

PubMed Central

Webermann, Aliya R.; Brand, Bethany L.; Chasson, Gregory S.

2014-01-01

Background Childhood maltreatment (CM) is a risk factor for subsequent intimate partner violence (IPV) in adulthood, with high rates of retrospectively reported CM among IPV victims and perpetrators. A theorized mechanism of the link between CM and IPV is dissociation. Dissociation may allow perpetrators of violence to remain emotionally distant from their behavior and minimize empathy toward those they victimize, enabling them to commit acts of violence similar to their own experiences. Indeed, elevated rates of dissociation and dissociative disorders (DD) have been found among IPV survivors and perpetrators. In addition, in pilot studies, DD clinicians have reported high levels of violent behavior among DD patients. Objective The present study investigates IPV among DD patients with Dissociative Identity Disorder and Dissociative Disorder Not Otherwise Specified, a group with CM rates of 80–95% and severe dissociative symptoms. Methods DD clinicians reported on rates of CM and IPV among 275 DD patients in outpatient treatment. DD patients also completed a self-report measure of dissociation. Analyses assessed the associations between CM typologies and IPV, as well as trait dissociation and IPV. Results Physical and emotional child abuse were associated with physical IPV, and childhood witnessing of domestic violence (DV) and childhood neglect were associated with emotional IPV. Conclusions The present study is the first to provide empirical support for a possible CM to adult IPV developmental trajectory among DD patients. Future research is needed to better understand the link between CM and IPV among those with trauma and DD. PMID:25279109

Proteomic identification of rhythmic proteins in rice seedlings.

PubMed

Hwang, Heeyoun; Cho, Man-Ho; Hahn, Bum-Soo; Lim, Hyemin; Kwon, Yong-Kook; Hahn, Tae-Ryong; Bhoo, Seong Hee

2011-04-01

Many aspects of plant metabolism that are involved in plant growth and development are influenced by light-regulated diurnal rhythms as well as endogenous clock-regulated circadian rhythms. To identify the rhythmic proteins in rice, periodically grown (12h light/12h dark cycle) seedlings were harvested for three days at six-hour intervals. Continuous dark-adapted plants were also harvested for two days. Among approximately 3000 reproducible protein spots on each gel, proteomic analysis ascertained 354 spots (~12%) as light-regulated rhythmic proteins, in which 53 spots showed prolonged rhythm under continuous dark conditions. Of these 354 ascertained rhythmic protein spots, 74 diurnal spots and 10 prolonged rhythmic spots under continuous dark were identified by MALDI-TOF MS analysis. The rhythmic proteins were functionally classified into photosynthesis, central metabolism, protein synthesis, nitrogen metabolism, stress resistance, signal transduction and unknown. Comparative analysis of our proteomic data with the public microarray database (the Plant DIURNAL Project) and RT-PCR analysis of rhythmic proteins showed differences in rhythmic expression phases between mRNA and protein, suggesting that the clock-regulated proteins in rice are modulated by not only transcriptional but also post-transcriptional, translational, and/or post-translational processes. 2011 Elsevier B.V. All rights reserved.

Dark and background response stability for the Landsat 8 Thermal Infrared Sensor

USGS Publications Warehouse

Vanderwerff, Kelly; Montanaro, Matthew

2012-01-01

The Thermal Infrared Sensor (TIRS) is a pushbroom sensor that will be a part of the Landsat Data Continuity Mission (LDCM), which is a joint mission between NASA and the USGS. The TIRS instrument will continue to collect the thermal infrared data that are currently being collected by the Thematic Mapper and the Enhanced Thematic Mapper Plus on Landsats 5 and 7, respectively. One of the key requirements of the new sensor is that the dark and background response be stable to ensure proper data continuity from the legacy Landsat instruments. Pre launch testing of the instrument has recently been completed at the NASA Goddard Space Flight Center (GSFC), which included calibration collects that mimic those that will be performed on orbit. These collects include images of a cold plate meant to simulate the deep space calibration source as viewed by the instrument in flight. The data from these collects give insight into the stability of the instrument’s dark and background response, as well as factors that may cause these responses to vary. This paper quantifies the measured background and dark response of TIRS as well as its stability.

UNDERSTANDING THE SOURCES OF DIABETES DISTRESS IN ADULTS WITH TYPE 1 DIABETES

PubMed Central

Fisher, Lawrence; Polonsky, William H.; Hessler, Danielle M.; Masharani, Umesh; Blumer, Ian; Peters, Anne L.; Strycker, Lisa A.; Bowyer, Vicky

2015-01-01

Aims To identify the unique sources of diabetes distress (DD) for adults with type 1 diabetes (T1D). Methods Sources of DD were developed from qualitative interviews with 25 T1D adults and 10 diabetes health care providers. Survey items were then developed and analyzed using both exploratory (EFA) and confirmatory CFA) analyses on two patient samples. Construct validity was assessed by correlations with depressive symptoms (PHQ8), complications, HbA1C, BMI, and hypoglycemia worry scale (HWS). Scale cut-points were created using multiple regression. Results An EFA with 305 U.S. participants yielded 7 coherent, reliable sources of distress that were replicated by a CFA with 109 Canadian participants: Powerlessness, Negative Social Perceptions, Physician Distress, Friend/Family Distress, Hypoglycemia Distress, Management Distress, Eating Distress. Prevalence of DD was high with 41.6% reporting at least moderate DD. Higher DD was reported for women, those with complications, poor glycemic control, younger age, without a partner, and non-White patients. Conclusions We identified a profile of seven major sources of DD among T1D using a newly developed assessment instrument. The prevalence of DD is high and is related to glycemic control and several patient demographic and disease-related patient characteristics, arguing for a need to address DD in clinical care. PMID:25765489

Weak task-related modulation and stimulus representations during arithmetic problem solving in children with developmental dyscalculia

PubMed Central

Ashkenazi, Sarit; Rosenberg-Lee, Miriam; Tenison, Caitlin; Menon, Vinod

2015-01-01

Developmental dyscalculia (DD) is a disability that impacts math learning and skill acquisition in school-age children. Here we investigate arithmetic problem solving deficits in young children with DD using univariate and multivariate analysis of fMRI data. During fMRI scanning, 17 children with DD (ages 7–9, grades 2 and 3) and 17 IQ- and reading ability-matched typically developing (TD) children performed complex and simple addition problems which differed only in arithmetic complexity. While the TD group showed strong modulation of brain responses with increasing arithmetic complexity, children with DD failed to show such modulation. Children with DD showed significantly reduced activation compared to TD children in the intraparietal sulcus, superior parietal lobule, supramarginal gyrus and bilateral dorsolateral prefrontal cortex in relation to arithmetic complexity. Critically, multivariate representational similarity revealed that brain response patterns to complex and simple problems were less differentiated in the DD group in bilateral anterior IPS, independent of overall differences in signal level. Taken together, these results show that children with DD not only under-activate key brain regions implicated in mathematical cognition, but they also fail to generate distinct neural responses and representations for different arithmetic problems. Our findings provide novel insights into the neural basis of DD. PMID:22682904

The immune complex CTA1-DD/IgG adjuvant specifically targets connective tissue mast cells through FcγRIIIA and augments anti-HPV immunity after nasal immunization.

PubMed

Fang, Y; Zhang, T; Lidell, L; Xu, X; Lycke, N; Xiang, Z

2013-11-01

We have previously reported that CTA1-DD/IgG immune complexes augment antibody responses in a mast cell-dependent manner following intranasal (IN) immunizations. However, from a safety perspective, mast cell activation could preclude clinical use. Therefore, we have extended these studies and demonstrate that CTA1-DD/IgG immune complexes administered IN did not trigger an anaphylactic reaction. Importantly, CTA1-DD/IgE immune complexes did not activate mast cells. Interestingly, only connective tissue, but not mucosal, mast cells could be activated by CTA1-DD/IgG immune complexes. This effect was mediated by FcγRIIIA, only expressed on connective tissue mast cells, and found in the nasal submucosa. FcγRIIIA-deficient mice had compromised responses to immunization adjuvanted by CTA1-DD/IgG. Proof-of-concept studies revealed that IN immunized mice with human papillomavirus (HPV) type 16 L1 virus-like particles (VLP) and CTA1-DD/IgG immune complexes demonstrated strong and sustained specific antibody titers in serum and vaginal secretions. From a mast cell perspective, CTA1-DD/IgG immune complexes appear to be safe and effective mucosal adjuvants.

Weak task-related modulation and stimulus representations during arithmetic problem solving in children with developmental dyscalculia.

PubMed

Ashkenazi, Sarit; Rosenberg-Lee, Miriam; Tenison, Caitlin; Menon, Vinod

2012-02-15

Developmental dyscalculia (DD) is a disability that impacts math learning and skill acquisition in school-age children. Here we investigate arithmetic problem solving deficits in young children with DD using univariate and multivariate analysis of fMRI data. During fMRI scanning, 17 children with DD (ages 7-9, grades 2 and 3) and 17 IQ- and reading ability-matched typically developing (TD) children performed complex and simple addition problems which differed only in arithmetic complexity. While the TD group showed strong modulation of brain responses with increasing arithmetic complexity, children with DD failed to show such modulation. Children with DD showed significantly reduced activation compared to TD children in the intraparietal sulcus, superior parietal lobule, supramarginal gyrus and bilateral dorsolateral prefrontal cortex in relation to arithmetic complexity. Critically, multivariate representational similarity revealed that brain response patterns to complex and simple problems were less differentiated in the DD group in bilateral anterior IPS, independent of overall differences in signal level. Taken together, these results show that children with DD not only under-activate key brain regions implicated in mathematical cognition, but they also fail to generate distinct neural responses and representations for different arithmetic problems. Our findings provide novel insights into the neural basis of DD. Copyright © 2011 Elsevier Ltd. All rights reserved.

Greater impulsivity is associated with decreased brain activation in obese women during a delay discounting task.

PubMed

Stoeckel, Luke E; Murdaugh, Donna L; Cox, James E; Cook, Edwin W; Weller, Rosalyn E

2013-06-01

Impulsivity and poor inhibitory control are associated with higher rates of delay discounting (DD), or a greater preference for smaller, more immediate rewards at the expense of larger, but delayed rewards. Of the many functional magnetic resonance imaging (fMRI) studies of DD, few have investigated the correlation between individual differences in DD rate and brain activation related to DD trial difficulty, with difficult DD trials expected to activate putative executive function brain areas involved in impulse control. In the current study, we correlated patterns of brain activation as measured by fMRI during difficult vs. easy trials of a DD task with DD rate (k) in obese women. Difficulty was defined by how much a reward choice deviated from an individual's 'indifference point', or the point where the subjective preference for an immediate and a delayed reward was approximately equivalent. We found that greater delay discounting was correlated with less modulation of activation in putative executive function brain areas, such as the middle and superior frontal gyri and inferior parietal lobule, in response to difficult compared to easy DD trials. These results support the suggestion that increased impulsivity is associated with deficient functioning of executive function areas of the brain.

Multilocus Sequence Typing of Pathogenic Treponemes Isolated from Cloven-Hoofed Animals and Comparison to Treponemes Isolated from Humans

PubMed Central

Carter, Stuart D.; Birtles, Richard J.; Brown, Jennifer M.; Hart, C. Anthony; Evans, Nicholas J.

2016-01-01

ABSTRACT Treponema species are implicated in many diseases of humans and animals. Digital dermatitis (DD) treponemes are reported to cause severe lesions in cattle, sheep, pigs, goats, and wild elk, causing substantial global animal welfare issues and economic losses. The fastidiousness of these spirochetes has previously precluded studies investigating within-phylogroup genetic diversity. An archive of treponemes that we isolated enabled multilocus sequence typing to quantify the diversity and population structure of DD treponemes. Isolates (n = 121) were obtained from different animal hosts in nine countries on three continents. The analyses herein of currently isolated DD treponemes at seven housekeeping gene loci confirm the classification of the three previously designated phylogroups: the Treponema medium, Treponema phagedenis, and Treponema pedis phylogroups. Sequence analysis of seven DD treponeme housekeeping genes revealed a generally low level of diversity among the strains within each phylogroup, removing the need for the previously used “-like” suffix. Surprisingly, all isolates within each phylogroup clustered together, regardless of host or geographic origin, suggesting that the same sequence types (STs) can infect different animals. Some STs were derived from multiple animals from the same farm, highlighting probable within-farm transmissions. Several STs infected multiple hosts from similar geographic regions, identifying probable frequent between-host transmissions. Interestingly, T. pedis appears to be evolving more quickly than the T. medium or T. phagedenis DD treponeme phylogroup, by forming two unique ST complexes. The lack of phylogenetic discrimination between treponemes isolated from different hosts or geographic regions substantially contrasts with the data for other clinically relevant spirochetes. IMPORTANCE The recent expansion of the host range of digital dermatitis (DD) treponemes from cattle to sheep, goats, pigs, and wild elk, coupled with the high level of 16S rRNA gene sequence similarity across hosts and with human treponemes, suggests that the same bacterial species can cause disease in multiple different hosts. This multilocus sequence typing (MLST) study further demonstrates that these bacteria isolated from different hosts are indeed very similar, raising the potential for cross-species transmission. The study also shows that infection spread occurs frequently, both locally and globally, suggesting transmission by routes other than animal-animal transmission alone. These results indicate that on-farm biosecurity is important for controlling disease spread in domesticated species. Continued surveillance and vigilance are important for ascertaining the evolution and tracking any further host range expansion of these important pathogens. PMID:27208135

The role of coping strategies in predicting change in parenting efficacy and depressive symptoms among mothers of adolescents with developmental disabilities.

PubMed

Woodman, A C; Hauser-Cram, P

2013-06-01

Parents of children with developmental disabilities (DD) face greater caregiving demands than parents of children without DD. There is considerable variability in parents' adjustment to raising a child with DD, however. In line with a strengths-based approach, this study explores coping strategies as potential mechanisms of resilience among mothers of adolescents with DD. This study examines the frequency with which mothers use various coping strategies and the extent to which those strategies moderate the relationship between adolescent behaviour problems and aspects of maternal well-being. Both positive and negative dimensions of well-being are explored, with maternal depressive symptoms and perceived parenting efficacy examined as outcomes cross-sectionally and longitudinally. The present study focuses on 92 mothers and their adolescents with DD. The adolescents had a wide range of diagnoses, all with continuing special needs. Data were collected from mothers through interviews and self-administered questionnaires when their adolescents were aged 15 and aged 18. A structured assessment of the adolescent was completed during home visits at age 15. Mothers reported frequently using strategies of denial and planning but rarely using strategies of mental and behavioural disengagement to cope with recent stressful situations. Adolescent behaviour problems were found to contribute to greater symptoms of depression and lower feelings of parenting efficacy as well as increases in depressive symptoms over time. Mothers of sons, but not daughters, reported increases in parenting efficacy across their child's adolescent period. Above and beyond adolescent factors, several coping strategies emerged as significant predictors of mothers' symptoms of depression and perceived parenting efficacy. Moreover, use of Active Coping/Planning, Positive Reinterpretation/Growth, and Behavioural/Mental Disengagement as coping strategies moderated the impact of adolescent behaviour problems on maternal depressive symptoms. This study extends previous findings by focusing on both positive and negative dimensions of parent well-being during their child's adolescent period. Adolescence can be a stressful time for parents, with typical developmental tasks entailing additional strains for parents of adolescents with DD. The present findings point to several coping strategies that may reduce the impact of challenging behaviours during this period on mothers' symptoms of depression and feelings of parenting efficacy. Certain coping strategies were found to exert a greater impact on maternal well-being for parents of adolescents with higher levels of behaviour problems, suggesting that interventions may benefit from an increased focus on this group of mothers with heightened caregiving demands. © 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID.

Multilocus Sequence Typing of Pathogenic Treponemes Isolated from Cloven-Hoofed Animals and Comparison to Treponemes Isolated from Humans.

PubMed

Clegg, Simon R; Carter, Stuart D; Birtles, Richard J; Brown, Jennifer M; Hart, C Anthony; Evans, Nicholas J

2016-08-01

Treponema species are implicated in many diseases of humans and animals. Digital dermatitis (DD) treponemes are reported to cause severe lesions in cattle, sheep, pigs, goats, and wild elk, causing substantial global animal welfare issues and economic losses. The fastidiousness of these spirochetes has previously precluded studies investigating within-phylogroup genetic diversity. An archive of treponemes that we isolated enabled multilocus sequence typing to quantify the diversity and population structure of DD treponemes. Isolates (n = 121) were obtained from different animal hosts in nine countries on three continents. The analyses herein of currently isolated DD treponemes at seven housekeeping gene loci confirm the classification of the three previously designated phylogroups: the Treponema medium, Treponema phagedenis, and Treponema pedis phylogroups. Sequence analysis of seven DD treponeme housekeeping genes revealed a generally low level of diversity among the strains within each phylogroup, removing the need for the previously used "-like" suffix. Surprisingly, all isolates within each phylogroup clustered together, regardless of host or geographic origin, suggesting that the same sequence types (STs) can infect different animals. Some STs were derived from multiple animals from the same farm, highlighting probable within-farm transmissions. Several STs infected multiple hosts from similar geographic regions, identifying probable frequent between-host transmissions. Interestingly, T. pedis appears to be evolving more quickly than the T. medium or T. phagedenis DD treponeme phylogroup, by forming two unique ST complexes. The lack of phylogenetic discrimination between treponemes isolated from different hosts or geographic regions substantially contrasts with the data for other clinically relevant spirochetes. The recent expansion of the host range of digital dermatitis (DD) treponemes from cattle to sheep, goats, pigs, and wild elk, coupled with the high level of 16S rRNA gene sequence similarity across hosts and with human treponemes, suggests that the same bacterial species can cause disease in multiple different hosts. This multilocus sequence typing (MLST) study further demonstrates that these bacteria isolated from different hosts are indeed very similar, raising the potential for cross-species transmission. The study also shows that infection spread occurs frequently, both locally and globally, suggesting transmission by routes other than animal-animal transmission alone. These results indicate that on-farm biosecurity is important for controlling disease spread in domesticated species. Continued surveillance and vigilance are important for ascertaining the evolution and tracking any further host range expansion of these important pathogens. Copyright © 2016 Clegg et al.

Temporal abnormalities in children with developmental dyscalculia.

PubMed

Vicario, Carmelo Mario; Rappo, Gaetano; Pepi, Annamaria; Pavan, Andrea; Martino, Davide

2012-01-01

Recent imaging studies have associated Developmental dyscalculia (DD) to structural and functional alterations corresponding Parietal and the Prefrontal cortex (PFC). Since these areas were shown also to be involved in timing abilities, we hypothesized that time processing is abnormal in DD. We compared time processing abilities between 10 children with pure DD (8 years old) and 11 age-matched healthy children. Results show that the DD group underestimated duration of a sub-second scale when asked to perform a time comparison task. The timing abnormality observed in our DD participants is consistent with evidence of a shared fronto-parietal neural network for representing time and quantity.

Probiotics and Diverticular Disease: Evidence-based?

PubMed

Lahner, Edith; Annibale, Bruno

Diverticular disease (DD) is a common gastrointestinal condition. Clinical spectrum ranges from asymptomatic diverticulosis to symptomatic uncomplicated or complicated DD. Symptoms related to uncomplicated DD are not specific and may be indistinguishable from those of irritable bowel syndrome. Low-grade inflammation, altered intestinal microbiota, visceral hypersensitivity, and abnormal colonic motility have been identified as factors potentially contributing to symptoms. Probiotics may modify the gut microbial balance leading to health benefits. Probiotics, due to their anti-inflammatory effects and ability to maintain an adequate bacterial colonization in the colon, are promising treatment options for DD. This review focuses on the available evidence on the efficacy of prebiotics in uncomplicated DD.

Extensive circadian and light regulation of the transcriptome in the malaria mosquito Anopheles gambiae

PubMed Central

2013-01-01

Background Mosquitoes exhibit 24 hr rhythms in flight activity, feeding, reproduction and development. To better understand the molecular basis for these rhythms in the nocturnal malaria vector Anopheles gambiae, we have utilized microarray analysis on time-of-day specific collections of mosquitoes over 48 hr to explore the coregulation of gene expression rhythms by the circadian clock and light, and compare these with the 24 hr rhythmic gene expression in the diurnal Aedes aegypti dengue vector mosquito. Results In time courses from An. gambiae head and body collected under light:dark cycle (LD) and constant dark (DD) conditions, we applied three algorithms that detect sinusoidal patterns and an algorithm that detects spikes in expression. This revealed across four experimental conditions 393 probes newly scored as rhythmic. These genes correspond to functions such as metabolic detoxification, immunity and nutrient sensing. This includes glutathione S-transferase GSTE5, whose expression pattern and chromosomal location are shared with other genes, suggesting shared chromosomal regulation; and pulsatile expression of the gene encoding CYP6M2, a cytochrome P450 that metabolizes pyrethroid insecticides. We explored the interaction of light and the circadian clock and highlight the regulation of odorant binding proteins (OBPs), important components of the olfactory system. We reveal that OBPs have unique expression patterns as mosquitoes make the transition from LD to DD conditions. We compared rhythmic expression between An. gambiae and Ae. aegypti heads collected under LD conditions using a single cosine fitting algorithm, and report distinct similarities and differences in the temporal regulation of genes involved in tRNA priming, the vesicular-type ATPase, olfaction and vision between the two species. Conclusions These data build on our previous analyses of time-of-day specific regulation of the An. gambiae transcriptome to reveal additional rhythmic genes, an improved understanding of the co-regulation of rhythms in gene expression by the circadian clock and by light, and an understanding of the time-of-day specific regulation of some of these rhythmic processes in comparison with a different species of mosquito. Improved understanding of biological timing at the molecular level that underlies key physiological aspects of mosquito vectors may prove to be important to successful implementation of established and novel insect control methods. PMID:23552056

Inventory of African desert dust events in the north-central Iberian Peninsula in 2003-2014 based on sun-photometer-AERONET and particulate-mass-EMEP data

NASA Astrophysics Data System (ADS)

Cachorro, Victoria E.; Burgos, Maria A.; Mateos, David; Toledano, Carlos; Bennouna, Yasmine; Torres, Benjamín; de Frutos, Ángel M.; Herguedas, Álvaro

2016-07-01

A reliable identification of desert dust (DD) episodes over north-central Spain is carried out based on the AErosol RObotic NETwork (AERONET) columnar aerosol sun photometer (aerosol optical depth, AOD, and Ångström exponent, α) and European Monitoring and Evaluation Programme (EMEP) surface particulate-mass concentration (PMx, x = 10, 2.5, and 2.5-10 µm) as the main core data. The impact of DD on background aerosol conditions is detectable by means of aerosol load thresholds and complementary information provided by HYSPLIT (Hybrid Single Particle Lagrangian Integrated Trajectory Model) air mass back trajectories, MODIS (Moderate Resolution Imaging Spectroradiometer) images, forecast aerosol models, and synoptic maps, which have been carefully reviewed by a human observer for each day included in the DD inventory. This identification method allows the detection of low and moderate DD intrusions and also of mixtures of mineral dust with other aerosol types by means of the analysis of α. During the period studied (2003-2014), a total of 152 DD episodes composed of 418 days are identified. Overall, this means ˜ 13 episodes and ˜ 35 days per year with DD intrusion, representing 9.5 % days year-1. During the identified DD intrusions, 19 daily exceedances over 50 µg m-3 are reported at the surface. The occurrence of DD event days during the year peaks in March and June, with a marked minimum in April and lowest occurrence in winter. A large interannual variability is observed showing a statistically significant temporal decreasing trend of ˜ 3 days year-1. The DD impact on the aerosol climatology is addressed by evaluating the DD contribution in magnitude and percent (in brackets) for AOD, PM10, PM2.5, and PM2.5 - 10, obtaining mean values of 0.015 (11.5 %), 1.3 µg m-3 (11.8 %), 0.55 µg m-3 (8.5 %) and 0.79 µg m-3 (16.1 %), respectively. Annual cycles of the DD contribution for AOD and PM10 present two maxima - one in summer (0.03 and 2.4 µg m-3 for AOD in June and PM10 in August) and another in March (0.02 for AOD and 2.2 µg m-3 for PM10) - both displaying a similar evolution with exceptions in July and September. The seasonal cycle of the DD contribution to AOD does not follow the pattern of the total AOD (close to a bell shape), whereas both PM10 cycles (total and DD contribution) are more similar to each other in shape, with an exception in September. The interannual evolution of the DD contribution to AOD and PM10 has evidenced a progressive decrease. This decline in the levels of mineral dust aerosols can explain up to 30 % of the total aerosol load decrease observed in the study area during the period 2003-2014. The relationship between columnar and surface DD contribution shows a correlation coefficient of 0.81 for the interannual averages. Finally, synoptic conditions during DD events are also analysed, observing that the north African thermal low causes most of the events ( ˜ 53 %). The results presented in this study highlight the relevance of the area studied since it can be considered representative of the clean background in the western Mediterranean Basin where DD events have a high impact on aerosol load levels.

Regulation of Sleep by Insulin-like Peptide System in Drosophila melanogaster.

PubMed

Cong, Xiaona; Wang, Haili; Liu, Zhenxing; He, Chunxia; An, Chunju; Zhao, Zhangwu

2015-07-01

Most organisms have behavioral and physiological circadian rhythms, which are controlled by an endogenous clock. Although genetic analysis has revealed the intracellular mechanism of the circadian clock, the manner in which this clock communicates its temporal information to produce systemic regulation is still largely unknown. Sleep behavior was measured using the Drosophila Activity Monitoring System (DAMS) monitor under a 12 h light:12 h dark cycle and constant darkness (DD), and 5 min without recorded activity were defined as a bout of sleep. Here we show that Drosophila insulin-like peptides (DILPs) and their receptor (DInR) regulate sleep behavior. All mutants of the seven dilps and the mutant of their receptor exhibit decreases of total sleep except dilp4 mutants, whereas upregulation of DILP and DInR in the nervous system led to increased sleep. Histological analysis identified four previously unidentified neurons expressing DILP: D1, P1, L1, and L2, of which L1 and L2 belong to the LNd and LNv clock neurons that separately regulate different times of sleep. In addition, dilp2 levels significantly decrease when flies were fasted, which is consistent with a previous report that starvation inhibits sleep, further indicating that the dilp system is involved in sleep regulation. Taken together, the results indicate that the Drosophila insulin-like peptide system is a crucial regulator of sleep. © 2015 Associated Professional Sleep Societies, LLC.

PDF cycling in the dorsal protocerebrum of the Drosophila brain is not necessary for circadian clock function.

PubMed

Kula, Elzbieta; Levitan, Edwin S; Pyza, Elzbieta; Rosbash, Michael

2006-04-01

In Drosophila, the neuropeptide pigment-dispersing factor (PDF) is a likely circadian molecule, secreted by central pacemaker neurons (LNvs). PDF is expressed in both small and large LNvs (sLNvs and lLNvs), and there are striking circadian oscillations of PDF staining intensity in the small cell termini, which require a functional molecular clock. This cycling may be relevant to the proposed role of PDF as a synchronizer of the clock system or as an output signal connecting pacemaker cells to locomotor activity centers. In this study, the authors use a generic neuropeptide fusion protein (atrial natriuretic factor-green fluorescent protein [ANF-GFP]) and show that it can be expressed in the same neurons as PDF itself. Yet, ANF-GFP as well as PDF itself does not manifest any cyclical accumulation in sLNv termini in adult transgenic flies. Surprisingly, the absence of detectable PDF cycling is not accompanied by any detectable behavioral pheno-type, since these transgenic flies have normal morning and evening anticipation in a light-dark cycle (LD) and are fully rhythmic in constant darkness (DD). The molecular clock is also not compromised. The results suggest that robust PDF cycling in sLNv termini plays no more than a minor role in the Drosophila circadian system and is apparently not even necessary for clock output function.

Purification, crystallization and preliminary x-ray crystallographic studies of RAIDD Death-Domain (DD).

PubMed

Jang, Tae-ho; Park, Hyun Ho

2009-06-03

Caspase-2 activation by formation of PIDDosome is critical for genotoxic stress induced apoptosis. PIDDosome is composed of three proteins, RAIDD, PIDD, and Caspase-2. RAIDD is an adaptor protein containing an N-terminal Caspase-Recruiting-Domain (CARD) and a C-terminal Death-Domain (DD). Its interactions with Caspase-2 and PIDD through CARD and DD respectively and formation of PIDDosome are important for the activation of Caspase-2. RAIDD DD cloned into pET26b vector was expressed in E. coli cells and purified by nickel affinity chromatography and gel filtration. Although it has been known that the most DDs are not soluble in physiological condition, RAIDD DD was soluble and interacts tightly with PIDD DD in physiological condition. The purified RAIDD DD alone has been crystallized. Crystals are trigonal and belong to space group P3(1)21 (or its enantiomorph P3(2)21) with unit-cell parameters a = 56.3, b = 56.3, c = 64.9 A and gamma = 120 degrees . The crystals were obtained at room temperature and diffracted to 2.0 A resolution.

Prostate cancer and polymorphism D85Y in gene for dihydrotestosterone degrading enzyme UGT2B15: Frequency of DD homozygotes increases with Gleason Score.

PubMed

Hajdinjak, Tine; Zagradisnik, Boris

2004-06-01

Although, a functional rationale for influence of polymorphism D85Y in gene UGT2B15 on prostate cancer (PCa) exists (different V(max) of enzyme), conflicting results have been reported. DNA from 178 controls and 206 PCa patients with known Gleason score were genotyped using a newly developed RFLP assay, which allowed the detection of both alleles in an individual after single PCR amplification. 16% DD, 52% DY; PCa patients: 23% DD, 49% DY. Subgroups of PCa: well differentiated: 11% DD, 37% DY; moderately differentiated: 22% DD, 50% DY; poorly differentiated: 34% DD, 50% DY. Correlation was confirmed between Gleason score and number of D alleles (P = 0.018) and persisted after age adjustment. When comparing controls to patients with a Gleason score of 7 or more, difference for the frequency of homozygosity DD was significant between the groups (P = 0.032, OR = 2.04). Polymorphism D85Y in gene UGT2B15 correlates with differentiation of PCa. Copyright 2004 Wiley-Liss, Inc.

Understanding the Areas and Correlates of Diabetes-Related Distress in Parents of Teens With Type 1 Diabetes.

PubMed

Hessler, Danielle; Fisher, Lawrence; Polonsky, William; Johnson, Nicole

2016-08-01

To identify the unique areas of diabetes-related distress (DD) for parents of teens with type 1 diabetes and parent and teen characteristics associated with DD. Areas of DD were developed from structured interviews and translated into 46 survey items. Items were analyzed with exploratory factor analysis (EFA). An EFA with 332 parents (88% mothers) reduced items to four Parent Diabetes Distress Scale (PDDS) factors (20 items, α = .94): Personal, Teen Management, Parent/Teen Relationship, and Healthcare Team Distress. Parent DD was higher among fathers, younger or single parents, parents of teens with higher hemoglobin A1c or severe low blood glucose levels, authoritarian parenting, depressive symptoms, and low emotional support. 4 areas of parent DD were identified using a newly developed measure, the PDDS. DD was associated with family demographic, teen diabetes status, and parent contextual factors, and can help identify parents who may be more vulnerable to DD. © The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

High-resolution real-time optical studies of radiological air sample filtration processes in an environmental continuous air monitor

NASA Astrophysics Data System (ADS)

Rodgers, John C.; Wasiolek, Piotr T.; Schery, Stephen D.; Alcantara, Raul E.

1999-01-01

The need for a continuous air monitor capable of quick and accurate measurements of airborne radioactivity in close proximity to the work environment during waste management, site restoration, and D&D operations led to the Los Alamos National Laboratory development of an environmental continuous air monitor (ECAM). Monitoring the hostile work environment of waste recovery, for example, presents unique challenges for detector design for detectors previously used for the clean room conditions of the typical plutonium laboratory. The environmental and atmospheric conditions (dust, high wind, etc.) influence aerosol particle penetration into the ECAM sampling head as well as the build-up of deposits on the ECAM filter.

Contribution of parenting to complex syntax development in preschool children with developmental delays or typical development.

PubMed

Moody, C T; Baker, B L; Blacher, J

2018-05-10

Despite studies of how parent-child interactions relate to early child language development, few have examined the continued contribution of parenting to more complex language skills through the preschool years. The current study explored how positive and negative parenting behaviours relate to growth in complex syntax learning from child age 3 to age 4 years, for children with typical development or developmental delays (DDs). Participants were children with or without DD (N = 60) participating in a longitudinal study of development. Parent-child interactions were transcribed and coded for parenting domains and child language. Multiple regression analyses were used to identify the contribution of parenting to complex syntax growth in children with typical development or DD. Analyses supported a final model, F(9,50) = 11.90, P < .001, including a significant three-way interaction between positive parenting behaviours, negative parenting behaviours and child delay status. This model explained 68.16% of the variance in children's complex syntax at age 4. Simple two-way interactions indicated differing effects of parenting variables for children with or without DD. Results have implications for understanding of complex syntax acquisition in young children, as well as implications for interventions. © 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Comparison of dislocation density tensor fields derived from discrete dislocation dynamics and crystal plasticity simulations of torsion

DOE PAGES

Jones, Reese E.; Zimmerman, Jonathan A.; Po, Giacomo; ...

2016-02-01

Accurate simulation of the plastic deformation of ductile metals is important to the design of structures and components to performance and failure criteria. Many techniques exist that address the length scales relevant to deformation processes, including dislocation dynamics (DD), which models the interaction and evolution of discrete dislocation line segments, and crystal plasticity (CP), which incorporates the crystalline nature and restricted motion of dislocations into a higher scale continuous field framework. While these two methods are conceptually related, there have been only nominal efforts focused at the global material response that use DD-generated information to enhance the fidelity of CPmore » models. To ascertain to what degree the predictions of CP are consistent with those of DD, we compare their global and microstructural response in a number of deformation modes. After using nominally homogeneous compression and shear deformation dislocation dynamics simulations to calibrate crystal plasticity ow rule parameters, we compare not only the system-level stress-strain response of prismatic wires in torsion but also the resulting geometrically necessary dislocation density fields. To establish a connection between explicit description of dislocations and the continuum assumed with crystal plasticity simulations we ascertain the minimum length-scale at which meaningful dislocation density fields appear. Furthermore, our results show that, for the case of torsion, that the two material models can produce comparable spatial dislocation density distributions.« less

Gut Microbiota in Health, Diverticular Disease, Irritable Bowel Syndrome, and Inflammatory Bowel Diseases: Time for Microbial Marker of Gastrointestinal Disorders.

PubMed

Lopetuso, Loris Riccardo; Petito, Valentina; Graziani, Cristina; Schiavoni, Elisa; Paroni Sterbini, Francesco; Poscia, Andrea; Gaetani, Eleonora; Franceschi, Francesco; Cammarota, Giovanni; Sanguinetti, Maurizio; Masucci, Luca; Scaldaferri, Franco; Gasbarrini, Antonio

2018-01-01

Few data exist on differences in gut microbiota composition among principal gastrointestinal (GI) diseases. We evaluated the differences in gut microbiota composition among uncomplicated diverticular disease (DD), irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD) patients. DD, IBS, and IBD patients along with healthy controls (CT) were enrolled in our Italian GI outpatient clinic. Stool samples were collected. Microbiota composition was evaluated through a metagenomic gene-targeted approach. GI pathology represented a continuous spectrum of diseases where IBD displayed one extreme, while CT displayed the other. Among Phyla, Biplot PC2/PC3 and dendogram plot showed major differences in samples from IBS and IBD. DD resembled species CT composition, but not for Bacteroides fragilis. In IBS, Dialister spp. and then Faecalibacterium prausnitzii were the most representative species. Ulcerative colitis showed a reduced concentration of Clostridium difficile and an increase of Bacteroides fragilis. In Crohn's disease, Parabacteroides distasonis was the most represented, while Faecalibacterium prausnitzii and Bacteroides fragilis were significantly reduced. Each disorder has its definite overall microbial signature, which produces a clear differentiation from the others. On the other hand, shared alterations constitute the "core dysbiosis" of GI diseases. The assessment of these microbial markers represents a parameter that may complete the diagnostic assessment. © 2017 S. Karger AG, Basel.

32 CFR Appendix A to Part 45 - DD Form 214

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false DD Form 214 A Appendix A to Part 45 National... CERTIFICATE OF RELEASE OR DISCHARGE FROM ACTIVE DUTY (DD FORM 214/5 SERIES) Pt. 45, App. A Appendix A to Part 45—DD Form 214 EC23OC91.003 EC23OC91.004 EC23OC91.005 EC23OC91.006 [54 FR 9985, Mar. 9, 1989] ...

Defense Transportation Regulation Part 2, Cargo Movement.

DTIC Science & Technology

1998-08-01

Stop-Off Unloading Point (DD Form 1371) 202-18 202-7 Route Order Amendment (DD Form 2017 ) 202-19 204-1 Hazardous Materials Classification...DRO/IRO/SRO amendments will be submitted to the appropriate MTMC routing authority or theater CINC using DD Form 2017 , Route Order Amendment...Figure 202-5. 7. An example of a DD Form 2017 , Route Order Amendment, is provided in Figure 202.7. D. EXCEPTION Exceptions to assignment of routing

Developmental Dyscalculia in Adults: Beyond Numerical Magnitude Impairment.

PubMed

De Visscher, Alice; Noël, Marie-Pascale; Pesenti, Mauro; Dormal, Valérie

2017-09-01

Numerous studies have tried to identify the core deficit of developmental dyscalculia (DD), mainly by assessing a possible deficit of the mental representation of numerical magnitude. Research in healthy adults has shown that numerosity, duration, and space share a partly common system of magnitude processing and representation. However, in DD, numerosity processing has until now received much more attention than the processing of other non-numerical magnitudes. To assess whether or not the processing of non-numerical magnitudes is impaired in DD, the performance of 15 adults with DD and 15 control participants was compared in four categorization tasks using numerosities, lengths, durations, and faces (as non-magnitude-based control stimuli). Results showed that adults with DD were impaired in processing numerosity and duration, while their performance in length and face categorization did not differ from controls' performance. Our findings support the idea of a nonsymbolic magnitude deficit in DD, affecting numerosity and duration processing but not length processing.

Anti-MRSA Activities of Enterocins DD28 and DD93 and Evidences on Their Role in the Inhibition of Biofilm Formation.

PubMed

Al Atya, Ahmed K; Belguesmia, Yanath; Chataigne, Gabrielle; Ravallec, Rozenn; Vachée, Anne; Szunerits, Sabine; Boukherroub, Rabah; Drider, Djamel

2016-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) has become a worrisome superbug. This work aimed at studying the effects of two class IIb bacteriocins, enterocins DD28 and DD93 as anti-MRSA agents. Thus, these bacteriocins were purified, from the cultures supernatants of Enterococcus faecalis 28 and 93, using a simplified purification procedure consisting in a cation exchange chromatography and a reversed-phase high-performance liquid chromatography. The anti-Staphylococcal activity was shown in vitro by the assessment of the minimal inhibitory concentration (MIC), followed by a checkerboard and time-kill kinetics experiments. The data unveiled a clear synergistic effect of enterocins DD28 and DD93 in combination with erythromycin or kanamycin against the clinical MRSA-S1 strain. Besides, these combinations impeded as well the MRSA-S1 clinical strain to setup biofilms on stainless steel and glace devices.

Chronic complex dissociative disorders and borderline personality disorder: disorders of emotion dysregulation?

PubMed

Brand, Bethany L; Lanius, Ruth A

2014-01-01

Emotion dysregulation is a core feature of chronic complex dissociative disorders (DD), as it is for borderline personality disorder (BPD). Chronic complex DD include dissociative identity disorder (DID) and the most common form of dissociative disorder not otherwise specified (DDNOS, type 1), now known as Other Specified Dissociative Disorders (OSDD, type 1). BPD is a common comorbid disorder with DD, although preliminary research indicates the disorders have some distinguishing features as well as considerable overlap. This article focuses on the epidemiology, clinical presentation, psychological profile, treatment, and neurobiology of chronic complex DD with emphasis placed on the role of emotion dysregulation in each of these areas. Trauma experts conceptualize borderline symptoms as often being trauma based, as are chronic complex DD. We review the preliminary research that compares DD to BPD in the hopes that this will stimulate additional comparative research.

Anti-MRSA Activities of Enterocins DD28 and DD93 and Evidences on Their Role in the Inhibition of Biofilm Formation

PubMed Central

Al Atya, Ahmed K.; Belguesmia, Yanath; Chataigne, Gabrielle; Ravallec, Rozenn; Vachée, Anne; Szunerits, Sabine; Boukherroub, Rabah; Drider, Djamel

2016-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) has become a worrisome superbug. This work aimed at studying the effects of two class IIb bacteriocins, enterocins DD28 and DD93 as anti-MRSA agents. Thus, these bacteriocins were purified, from the cultures supernatants of Enterococcus faecalis 28 and 93, using a simplified purification procedure consisting in a cation exchange chromatography and a reversed-phase high-performance liquid chromatography. The anti-Staphylococcal activity was shown in vitro by the assessment of the minimal inhibitory concentration (MIC), followed by a checkerboard and time-kill kinetics experiments. The data unveiled a clear synergistic effect of enterocins DD28 and DD93 in combination with erythromycin or kanamycin against the clinical MRSA-S1 strain. Besides, these combinations impeded as well the MRSA-S1 clinical strain to setup biofilms on stainless steel and glace devices. PMID:27303396

Appearance of medium-large drusen and reticular pseudodrusen on adaptive optics in age-related macular degeneration.

PubMed

Querques, Giuseppe; Kamami-Levy, Cynthia; Blanco-Garavito, Rocio; Georges, Anouk; Pedinielli, Alexandre; Capuano, Vittorio; Poulon, Fanny; Souied, Eric H

2014-11-01

To investigate the appearance of medium-large drusen and reticular pseudodrusen on adaptive optics (AO). In 14 consecutive patients, AO infrared (IR) images were overlaid with confocal scanning-laser-ophthalmoscope IR reflectance images and IR-referenced spectral-domain optical coherence tomography. In eight eyes of six patients, a total of 19 images of medium-large drusen were investigated by AO imaging. En face AO revealed medium-large drusen as highly hyper-reflective round/oval lesions, always centred and/or surrounded by a continuous/discontinuous hyporeflectivity. Cone photoreceptors were detected overlying drusen, appearing either as continuous 'bright' hyper-reflective dots over a 'dark' hyporeflective background, or as continuous 'dark' hyporeflective dots over a 'bright' hyper-reflective background. In eight eyes from eight patients, a total of 14 images of pseudodrusen were investigated by AO imaging. En face AO revealed reticular pseudodrusen as isoreflective lesions, always surrounded by a continuous/discontinuous hyporeflectivity. Cone photoreceptors were detected overlying pseudodrusen as 'bright' hyper-reflective dots over either a hyporeflective or isoreflective background. No 'dark' hyporeflective dots were detected in eyes with reticular pseudodrusen only. Cone photoreceptors were counted on the border of the drusen and pseudodrusen, respectively, and in a visibly healthy zone in its absolute vicinity. A similar decrease in cone appearance was observed for drusen and pseudodrusen (15.7% vs 16.2%). AO allows differences in reflectivity between medium-large drusen and reticular pseudodrusen to be appreciated. The cone mosaics may be detected as continuous 'bright' hyper-reflective dots overlying/on the border of drusen and pseudodrusen deposits, and possibly as continuous 'dark' hyporeflective dots overlying drusen only. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The DD Check App for prevention and control of digital dermatitis in dairy herds.

PubMed

Tremblay, Marlène; Bennett, Tom; Döpfer, Dörte

2016-09-15

Digital dermatitis (DD) is the most important infectious claw disease in the cattle industry causing outbreaks of lameness. The clinical course of disease can be classified using 5 clinical stages. M-stages represent not only different disease severities but also unique clinical characteristics and outcomes. Monitoring the proportions of cows per M-stage is needed to better understand and address DD and factors influencing risks of DD in a herd. Changes in the proportion of cows per M-stage over time or between groups may be attributed to differences in management, environment, or treatment and can have impact on the future claw health of the herd. Yet trends in claw health regarding DD are not intuitively noticed without statistical analysis of detailed records. Our specific aim was to develop a mobile application (app) for persons with less statistical training, experience or supporting programs that would standardize M-stage records, automate data analysis including trends of M-stages over time, the calculation of predictions and assignments of Cow Types (i.e., Cow Types I-III are assigned to cows without active lesions, single and repeated cases of active DD lesions, respectively). The predictions were the stationary distributions of transitions between DD states (i.e., M-stages or signs of chronicity) in a class-structured multi-state Markov chain population model commonly used to model endemic diseases. We hypothesized that the app can be used at different levels of record detail to discover significant trends in the prevalence of M-stages that help to make informed decisions to prevent and control DD on-farm. Four data sets were used to test the flexibility and value of the DD Check App. The app allows easy recording of M-stages in different environments and is flexible in terms of the users' goals and the level of detail used. Results show that this tool discovers trends in M-stage proportions, predicts potential outbreaks of DD, and makes comparisons among Cow Types, signs of chronicity, scorers or pens. The DD Check App also provides a list of cows that should be treated augmented by individual Cow Types to help guide treatment and determine prognoses. Producers can be proactive instead of reactive in controlling DD in a herd by using this app. The DD Check App serves as an example of how technology makes knowledge and advice of veterinary epidemiology widely available to monitor, control and prevent this complex disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Angiotensin-converting enzyme DD genotype in patients with primary pulmonary hypertension: increased frequency and association with preserved haemodynamics.

PubMed

Abraham, William T; Raynolds, Mary V; Badesch, David B; Wynne, Kristine M; Groves, Bertron M; Roden, Robert L; Robertson, Alastair D; Lowes, Brian D; Zisman, Lawrence S; Voelkel, Norbert F; Bristow, Michael R; Perryman, M Benjamin

2003-03-01

HYPOTHESIS/INTRODUCTION: A polymorphic marker within the angiotensin- converting enzyme (ACE) gene has been associated with circulating and tissue ACE activity and with a variety of forms of cardiovascular disease. Since angiotensin II (Ang II) causes pulmonary vasoconstriction and vascular and myocardial remodelling, we postulated a role for the renin-angiotensin system and the ACE DD genotype in the pathophysiology of primary pulmonary hypertension (PPH) and in the right ventricular response to pressure overload in these patients. The incidence of the ACE DD genotype was evaluated in 60 patients with severe PPH compared with two normal control populations, a group of healthy population-based controls (n=158) and subjects found suitable for cardiac organ donation (n=79). Genomic DNA extracted from peripheral leukocytes was amplified using the polymerase chain reaction to detect polymorphic markers. Haemodynamics were determined by right heart catheterisation in a subset of the PPH patients. The frequency of the ACE DD genotype was 45% in the patients with PPH, compared with 24% in the organ donors, and 28% in population-based healthy controls (p=0.01 for chi-square test). Of the 32 PPH patients with baseline haemodynamics, 12 exhibited the ACE DD genotype and 20 were non-DD. While the mean pulmonary artery pressure and the duration of symptoms attributable to pulmonary hypertension was not different between the DD and non-DD groups, cardiac output was significantly lower (3.29+0.27 vs. 5.07+0.37 L/minute, p=0.002) and the mean right atrial pressure tended to be higher (8.85+1.29 vs. 4.92+1.27 mmHg, p=0.08) in the non-DD group. The reduction in cardiac output seen in the non-DD group was not due to a difference in heart rate, but to a significant reduction in stroke volume, consistent with a decreased contractile state. In addition, non-DD patients exhibited a significantly worse functional capacity (NYHA Class 3.14+0.12 vs. 2.40+0.28, p=0.02). 1) The ACE DD genotype is significantly increased in patients with severe PPH compared with normal controls, suggesting that certain individuals may be genetically predisposed to developing pulmonary hypertension. 2) The ACE DD genotype is associated with preserved right ventricular function in PPH patients, supporting a compensatory myocardial or inotropic role for Ang II in the pressure overloaded right ventricle.

DPSSL pumped 20-TW Ti:sapphire laser system for DD fusion experiment

NASA Astrophysics Data System (ADS)

Sekine, T.; Hatano, Y.; Takeuchi, Y.; Kawashima, T.

2016-03-01

A diode-pumped solid-state laser (DPSSL) pumped 20-TW output Ti:sapphire laser system has been developed. A diode-pumped Nd:glass laser with output energy of 12.7 J in 527 nm was used as a pump source for a 20-TW Ti:sapphire amplifier. A CeLiB6O10 nonlinear optical crystal was used as a frequency doubler of the Nd:glass DPSSL[1]. Figure 1 shows typical output pulse energy of the 20-TW amplifier as a function of pumping energy and a near field pattern. A 1.65 J pulse energy was obtained by 4.5 J pump energy. The amplified seed pulse is compressed to typically 60 fs as shown in Fig. 1 by a vacuumed pulse compressor with 80% of transmissivity. Encircled energy ratio, into a circled with 8 μm diameter area, of far field pattern focused by off-axis parabolic mirror with F# of 3 is numerically evaluated to 40% at TW class output condition. Then focal intensity would reach to 1018W/cm2. This all- DPSSL system contributes for stable and continual investigation of laser induced plasma experiment. We have succeeded continual and high efficient generation of DD fusion neutron from CD nano-particles by cluster fusion scheme using the 20-TW laser. A yield of ∼105 neutrons per shot was stably observed during continuous 100 shots with repetition rate of 0.1Hz.

Effect of endogenous reference genes on digital PCR assessment of genetically engineered canola events.

PubMed

Demeke, Tigst; Eng, Monika

2018-05-01

Droplet digital PCR (ddPCR) has been used for absolute quantification of genetically engineered (GE) events. Absolute quantification of GE events by duplex ddPCR requires the use of appropriate primers and probes for target and reference gene sequences in order to accurately determine the amount of GE materials. Single copy reference genes are generally preferred for absolute quantification of GE events by ddPCR. Study has not been conducted on a comparison of reference genes for absolute quantification of GE canola events by ddPCR. The suitability of four endogenous reference sequences ( HMG-I/Y , FatA(A), CruA and Ccf) for absolute quantification of GE canola events by ddPCR was investigated. The effect of DNA extraction methods and DNA quality on the assessment of reference gene copy numbers was also investigated. ddPCR results were affected by the use of single vs. two copy reference genes. The single copy, FatA(A), reference gene was found to be stable and suitable for absolute quantification of GE canola events by ddPCR. For the copy numbers measured, the HMG-I/Y reference gene was less consistent than FatA(A) reference gene. The expected ddPCR values were underestimated when CruA and Ccf (two copy endogenous Cruciferin sequences) were used because of high number of copies. It is important to make an adjustment if two copy reference genes are used for ddPCR in order to obtain accurate results. On the other hand, real-time quantitative PCR results were not affected by the use of single vs. two copy reference genes.

Genome Sequence of Microbulbifer mangrovi DD-13T Reveals Its Versatility to Degrade Multiple Polysaccharides.

PubMed

Imran, Md; Pant, Poonam; Shanbhag, Yogini P; Sawant, Samir V; Ghadi, Sanjeev C

2017-02-01

Microbulbifer mangrovi strain DD-13 T is a novel-type species isolated from the mangroves of Goa, India. The draft genome sequence of strain DD-13 comprised 4,528,106 bp with G+C content of 57.15%. Out of 3479 open reading frames, functions for 3488 protein coding sequences were predicted on the basis of similarity with the cluster of orthologous groups. In addition to protein coding sequences, 34 tRNA genes and 3 rRNA genes were detected. Analysis of nucleotide sequence of predicted gene using a Carbohydrate-Active Enzymes (CAZymes) Analysis Toolkit indicates that strain DD-13 encodes a large set of CAZymes including 255 glycoside hydrolases, 76 carbohydrate esterases, 17 polysaccharide lyases, and 113 carbohydrate-binding modules (CBMs). Many genes from strain DD-13 were annotated as carbohydrases specific for degradation of agar, alginate, carrageenan, chitin, xylan, pullulan, cellulose, starch, β-glucan, pectin, etc. Some of polysaccharide-degrading genes were highly modular and were appended at least with one CBM indicating the versatility of strain DD-13 to degrade complex polysaccharides. The cell growth of strain DD-13 was validated using pure polysaccharides such as agarose or alginate as carbon source as well as by using red and brown seaweed powder as substrate. The homologous carbohydrase produced by strain DD-13 during growth degraded the polysaccharide, ensuring the production of metabolizable reducing sugars. Additionally, several other polysaccharides such as carrageenan, xylan, pullulan, pectin, starch, and carboxymethyl cellulose were also corroborated as growth substrate for strain DD-13 and were associated with concomitant production of homologous carbohydrase.

Stable-isotope GC-MS/MS determination of aminoethylcysteine ketimine decarboxylated dimer in biological samples

PubMed Central

Tsikas, Dimitrios; Evans, Christopher E.; Denton, Travis T.; Mitschke, Anja; Gutzki, Frank-Mathias; Pinto, John T.; Khomenko, Tetyana; Szabo, Sandor; Cooper, Arthur J.L.

2012-01-01

Aminoethylcysteine ketimine decarboxylated dimer [AECK-DD; systematic name: 1,2–3,4–5,6–7,8-octahydro-1,8a-diaza-4,6-dithiafluoren-9(8aH)-one] is a previously described metabolite of cysteamine that has been reported to be present in mammalian brain, urine, plasma, cells in culture and vegetables, and to possess potent anti-oxidative properties. Here, we describe a stable-isotope GC-MS/MS method for specific and sensitive determination of AECK-DD in biological samples. 13C2-AECK-DD was synthesized and used as the internal standard. Derivatization was carried out by N-pentafluorobenzylation with pentafluorobenzyl bromide in acetonitrile. Quantification was performed by selected-reaction monitoring of the mass transitions m/z 328 to m/z 268 for AECK-DD and m/z 330 to m/z 270 for 13C2-AECK-DD in the electron-capture negative-ion chemical ionization mode. The procedure was systematically validated for human plasma and urine samples. AECK-DD was not detectable in human plasma above ~ 4 nM, but was present in urine samples of healthy humans at a maximal concentration of 46 nM. AECK-DD was detectable in rat brain at very low levels of about 8 pmol/g wet weight. Higher levels of AECK-DD were detected in mouse brain (~1 nmol/g wet weight). Among nine dietary vegetables evaluated, only shallots were found to contain trace amounts of AECK-DD (~ 6.8 pmol/g fresh tissue). PMID:22858756

Stable isotope gas chromatography-tandem mass spectrometry determination of aminoethylcysteine ketimine decarboxylated dimer in biological samples.

PubMed

Tsikas, Dimitrios; Evans, Christopher E; Denton, Travis T; Mitschke, Anja; Gutzki, Frank-Mathias; Pinto, John T; Khomenko, Tetyana; Szabo, Sandor; Cooper, Arthur J L

2012-11-01

Aminoethylcysteine ketimine decarboxylated dimer (AECK-DD; systematic name: 1,2-3,4-5,6-7,8-octahydro-1,8a-diaza-4,6-dithiafluoren-9(8aH)-one) is a previously described metabolite of cysteamine that has been reported to be present in mammalian brain, urine, plasma, and cells in culture and vegetables and to possess potent antioxidative properties. Here, we describe a stable isotope gas chromatography-tandem mass spectrometry (GC-MS/MS) method for specific and sensitive determination of AECK-DD in biological samples. (13)C(2)-labeled AECK-DD was synthesized and used as the internal standard. Derivatization was carried out by N-pentafluorobenzylation with pentafluorobenzyl bromide in acetonitrile. Quantification was performed by selected reaction monitoring of the mass transitions m/z 328 to 268 for AECK-DD and m/z 330 to 270 for [(13)C(2)]AECK-DD in the electron capture negative ion chemical ionization mode. The procedure was systematically validated for human plasma and urine samples. AECK-DD was not detectable in human plasma above approximately 4nM but was present in urine samples of healthy humans at a maximal concentration of 46nM. AECK-DD was detectable in rat brain at very low levels of approximately 8pmol/g wet weight. Higher levels of AECK-DD were detected in mouse brain (∼1nmol/g wet weight). Among nine dietary vegetables evaluated, only shallots were found to contain trace amounts of AECK-DD (∼6.8pmol/g fresh tissue). Copyright © 2012 Elsevier Inc. All rights reserved.

Plasma D-dimer concentrations during experimental EHV-1 infection of horses.

PubMed

Goehring, L S; Soboll Hussey, G; Gomez Diez, M; Benedict, K; Maxwell, L K; Morley, P S; Sloet van Oldruitenborgh-Oosterbaan, M M; Lunn, D P

2013-01-01

Central nervous system blood vessel thrombosis is a part of the pathogenesis of equid herpesvirus-associated myeloencephalopathy (EHM). D-dimers (DD) are stable breakdown products of cross-linked fibrin, and increased DD-plasma concentrations could reflect the degree of systemic coagulation during EHV-1 infection. We hypothesized that blood DD concentrations will be increased during periods of EHV-1 fever and viremia, reflecting an activated coagulation cascade with fibrinolysis. Twenty-eight equids were infected with EHV-1 in 3 experimental infection studies. Three (uninfected) horses were included in a separate study to evaluate methodology for DD concentration measurements. Clinical data and quantitative viremia were evaluated, and DD concentrations were measured in blood samples on the day before the infection and during days 1-12 postchallenge. Uninfected horses were sampled every 3 hours for 48 hours. Logistic and linear regression was used to investigate the potential association between the fever and viremia with the presence or absence of DD concentrations in peripheral blood. DD concentrations were increased for 1-8 days in the majority of infected animals. Both viremia (odds ratio [OR] 6.3; 95% confidence interval [CI] 3.4-11.8; P = .0013) and fever (OR 4.9; CI 2.3-10.1; P = .001) were strongly associated with the likelihood of detecting DD in peripheral blood. EHV-1 viremia is associated with increases in DD concentration in horses and ponies. This indicates that EHV-1 viremia can lead to an activation of coagulation and fibrinolysis. Copyright © 2013 by the American College of Veterinary Internal Medicine.

No neuronal loss, but alterations of the GDNF system in asymptomatic diverticulosis.

PubMed

Barrenschee, Martina; Wedel, Thilo; Lange, Christina; Hohmeier, Ines; Cossais, François; Ebsen, Michael; Vogel, Ilka; Böttner, Martina

2017-01-01

Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor known to promote the survival and maintenance of neurons not only in the developing but also in the adult enteric nervous system. As diverticular disease (DD) is associated with reduced myenteric neurons, alterations of the GDNF system were studied in asymptomatic diverticulosis (diverticulosis) and DD. Morphometric analysis for quantifying myenteric ganglia and neurons were assessed in colonic full-thickness sections of patients with diverticulosis and controls. Samples of tunica muscularis (TM) and laser-microdissected myenteric ganglia from patients with diverticulosis, DD and controls were analyzed for mRNA expression levels of GDNF, GFRA1, and RET by RT-qPCR. Myenteric protein expression of both receptors was quantified by fluorescence-immunohistochemistry of patients with diverticulosis, DD, and controls. Although no myenteric morphometric alterations were found in patients with diverticulosis, GDNF, GFRA1 and RET mRNA expression was down-regulated in the TM of patients with diverticulosis as well as DD. Furthermore GFRA1 and RET myenteric plexus mRNA expression of patients with diverticulosis and DD was down-regulated, whereas GDNF remained unaltered. Myenteric immunoreactivity of the receptors GFRα1 and RET was decreased in both asymptomatic diverticulosis and DD patients. Our data provide evidence for an impaired GDNF system at gene and protein level not only in DD but also during early stages of diverticula formation. Thus, the results strengthen the idea of a disturbed GDNF-responsiveness as contributive factor for a primary enteric neuropathy involved in the pathogenesis and disturbed intestinal motility observed in DD.

The neuropsychiatric phenotype in Darier disease.

PubMed

Gordon-Smith, K; Jones, L A; Burge, S M; Munro, C S; Tavadia, S; Craddock, N

2010-09-01

Darier disease (DD) is a rare autosomal dominantly inherited skin disorder in which co-occurrence of neuropsychiatric abnormalities has been frequently reported by dermatologists. It is caused by mutations in a single gene, ATP2A2, which is expressed in the skin and brain. To conduct the first systematic investigation of the neuropsychiatric phenotype in DD. One hundred unrelated individuals with DD were assessed using a battery of standardized neuropsychiatric measures. Data were also obtained on a number of clinical features of DD. Individuals with DD were found to have high lifetime rates of mood disorders (50%), specifically major depression (30%) and bipolar disorder (4%), and suicide attempts (13%) and suicidal thoughts (31%). These were more common in DD when compared with general population data. The prevalence of epilepsy (3%) in the sample was also higher than the prevalence in the general population. There was no consistent association of specific dermatological features of DD and presence of psychiatric features. These findings highlight the need for clinicians to assess and recognize neuropsychiatric symptoms in DD. The results do not suggest that neuropsychiatric symptoms are simply a psychological reaction to having a skin disease, but are consistent with the pleiotropy hypothesis that mutations in the ATP2A2 gene, in addition to causing DD, confer susceptibility to neuropsychiatric features. Further research is needed to investigate genotype-phenotype correlations between the types and/or locations of pathogenic mutations within ATP2A2 and the expressed neuropsychiatric phenotypes. © 2010 The Authors. Journal Compilation © 2010 British Association of Dermatologists.

Neural Systems Underlying Individual Differences in Intertemporal Decision-making.

PubMed

Elton, Amanda; Smith, Christopher T; Parrish, Michael H; Boettiger, Charlotte A

2017-03-01

Excessively choosing immediate over larger future rewards, or delay discounting (DD), associates with multiple clinical conditions. Individual differences in DD likely depend on variations in the activation of and functional interactions between networks, representing possible endophenotypes for associated disorders, including alcohol use disorders (AUDs). Numerous fMRI studies have probed the neural bases of DD, but investigations of large-scale networks remain scant. We addressed this gap by testing whether activation within large-scale networks during Now/Later decision-making predicts individual differences in DD. To do so, we scanned 95 social drinkers (18-40 years old; 50 women) using fMRI during hypothetical choices between small monetary amounts available "today" or larger amounts available later. We identified neural networks engaged during Now/Later choice using independent component analysis and tested the relationship between component activation and degree of DD. The activity of two components during Now/Later choice correlated with individual DD rates: A temporal lobe network positively correlated with DD, whereas a frontoparietal-striatal network negatively correlated with DD. Activation differences between these networks predicted individual differences in DD, and their negative correlation during Now/Later choice suggests functional competition. A generalized psychophysiological interactions analysis confirmed a decrease in their functional connectivity during decision-making. The functional connectivity of these two networks negatively correlates with alcohol-related harm, potentially implicating these networks in AUDs. These findings provide novel insight into the neural underpinnings of individual differences in impulsive decision-making with potential implications for addiction and related disorders in which impulsivity is a defining feature.

Usefulness of Electrocardiographic QT Interval to Predict Left Ventricular Diastolic Dysfunction

PubMed Central

Wilcox, Jane E.; Rosenberg, Jonathan; Vallakati, Ajay; Gheorghiade, Mihai; Shah, Sanjiv J.

2013-01-01

Whether a normal electrocardiogram excludes left ventricular (LV) diastolic dysfunction (DD) and whether electrocardiographic parameters are associated with DD is unknown. We therefore sought to investigate the relation between electrocardiographic parameters and DD. We first evaluated 75 consecutive patients referred for echocardiography for clinical suspicion of heart failure (phase 1). Electrocardiography and comprehensive echocardiography were performed on all patients and were analyzed separately in a blinded fashion. Receiver operating characteristic curves and multivariate regression analyses were used to determine which electrocardiographic parameters were most closely associated with DD. Next, we prospectively validated our results in 100 consecutive, unselected patients undergoing echocardiography (phase 2). In phase 1 of our study, the mean age was 59 ± 14 years, 41% were women, 31% had coronary disease, 53% had hypertension, and 25% had diabetes. The mean ejection fraction was 54 ± 15%, and 64% had DD. Of all the electrocardiographic parameters, the QTc interval was most closely associated with DD. QTc was inversely associated with E′ velocity (r = −0.54, p <0.0001), and the area under the receiver operating characteristic curve for QTc as a predictor of DD was 0.82. QTc prolongation was independently associated with reduced E′ velocity (p = 0.021 after adjustment for age, gender, medications, QRS duration, and ejection fraction). In phase 2 of our study QTc was the electrocardiographic parameter most associated with reduced E′ velocity (435 ± 31 vs 419 ± 24 ms; p = 0.004), confirming our phase 1 study findings. In conclusion, QTc prolongation was the electrocardiographic marker most predictive of DD and was independently associated with DD. PMID:21907948

Efficacy, safety and proper dose analysis of PEGylated granulocyte colony-stimulating factor as support for dose-dense adjuvant chemotherapy in node positive Chinese breast cancer patients.

PubMed

Zhang, Fan; LingHu, RuiXia; Zhan, XingYang; Li, Ruisheng; Feng, Fan; Gao, Xudong; Zhao, Lei; Yang, Junlan

2017-10-03

For high-risk breast cancer patients with positive axillary lymph nodes, dose-dense every-two-week epirubicin/cyclophosphamide-paclitaxel (ddEC-P) regimen is the optimal postoperative adjuvant therapy. However, this regimen is limited by the grade 3/4 neutropenia and febrile neutropenia (FN). There is an urgent need to explore the efficacy, safety and proper dosage of PEGylated granulocyte colony-stimulating factor (PEG-G-CSF) as support for ddEC-P in Chinese breast cancer patients with positive axillary lymph nodes. Prospectively, 40 women with stage IIIA to IIIC breast cancer received ddEC-P ± trastuzumab as adjuvant treatment. PEG-G-CSF was injected subcutaneously in a dose of 6 mg or 3 mg on the 2 th day of each treatment cycle. With administration of PEG-G-CSF, all of the 40 patients completed 8 cycles of ddEC-P ± trastuzumab regimen without dose reductions or treatment delays. Moreover, no FN cases were observed. Further analysis showed that the proper dosage of PEG-G-CSF was 6 mg for ddEC treatment, and 3 mg for ddP treatment. PEG-G-CSF exhibits advantages compared with G-CSF in convenient of administration and tolerance for high risk Chinese breast cancer patients. More importantly, the proper dose of PEG-G-CSF for high risk Chinese breast cancer patients during ddEC-P chemotherapy may be 6 mg for ddEC treatment and 3 mg for ddP treatment.

32 CFR 751.10 - Form of claim.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Claims Against the United States § 751.10 Form of claim. The claim should be submitted on DD Form 1842 (Claim for Personal Property) accompanied by DD Form 1844 (List of Property). If DD Forms 1842 and 1844 1...

Women's participation in household decision-making and higher dietary diversity: findings from nationally representative data from Ghana.

PubMed

Amugsi, Dickson A; Lartey, Anna; Kimani, Elizabeth; Mberu, Blessing U

2016-05-31

Low-quality monotonous diet is a major problem confronting resource-constrained settings across the world. Starchy staple foods dominate the diets in these settings. This places the population, especially women of reproductive age, at a risk of micronutrients deficiencies. This study seeks to examine the association between women's decision-making autonomy and women's achievement of higher dietary diversity (DD) and determine the socio-demographic factors that can independently predict women's attainment of higher DD. The study used data from the 2008 Ghana Demographic and Health Survey. The participants comprised of 2262 women aged 15-49 years and who have complete dietary data. The DD score was derived from a 24-h recall of intake of foods from nine groups. The score was dichotomized into lower DD (DD ≤4) and higher (DD ≥5). Logistic regression was used to assess the association between women decision-making autonomy (final say on how to spend money, making household purchases, own health care, opinions on wife-beating, and sexual intercourse with husband) and the achievement of higher DD. The logistic regression models were adjusted for covariates at the individual and household levels. The analysis showed that women participation in decision-making regarding household purchases was significantly associated with higher DD, after adjusting for individual and household level covariates. The odds of achieving higher DD were higher among women who had a say in deciding household purchases, compared to women who did not have a say (OR = 1.74, 95 % CI = 1.24, 2.42). Women who had more than primary education were 1.6 times more likely to achieve higher DD, compared to those with no education (95 % CI = 1.12, 2.20). Compared to women who lived in polygamous households, those who lived in monogamous households had higher odds of achieving higher DD (OR = 1.42, 95 % CI = 1.04, 1.93). Net other covariates, women who have a say in making household purchases are more likely to achieve higher DD compare to those who do not have a say. This may indicate autonomy to buy nutritious foods, suggesting that improving women decision-making autonomy could have a positive impact on women dietary intake.

Symbolic and non-symbolic number magnitude processing in children with developmental dyscalculia.

PubMed

Castro Cañizares, Danilka; Reigosa Crespo, Vivian; González Alemañy, Eduardo

2012-11-01

The aim of this study was to evaluate if children with Developmental Dyscalculia (DD) exhibit a general deficit in magnitude representations or a specific deficit in the connection of symbolic representations with the corresponding analogous magnitudes. DD was diagnosed using a timed arithmetic task. The experimental magnitude comparison tasks were presented in non-symbolic and symbolic formats. DD and typically developing (TD) children showed similar numerical distance and size congruity effects. However, DD children performed significantly slower in the symbolic task. These results are consistent with the access deficit hypothesis, according to which DD children's deficits are caused by difficulties accessing magnitude information from numerical symbols rather than in processing numerosities per se.

Tunable Optical Sources.

DTIC Science & Technology

1980-11-01

finite aperture size 5. A. E. Siegman , "Unstable optical resonators for laser of the YAG rod, applications," Proc. IEEE 53, 217-287 (1965); "Unstable...Pumped LiNbO3 Tunable Source Radial Birefringent Element Computer Controlled Laser Attenuator Slab Configuration Laser Source 20. ABSTRACT (Continue on...have invented and demonstrated a computer controlled laser attenu- ator. .... Cont inued DD Il 7 1473 EDITION OF I NOV 01 IS OBSOLETE UNCLASSIFIEDAN

Optimal Control of Stochastic Systems Driven by Fractional Brownian Motions

DTIC Science & Technology

2014-10-09

problems for stochastic partial differential equations driven by fractional Brownian motions are explicitly solved. For the control of a continuous time...linear systems with Brownian motion or a discrete time linear system with a white Gaussian noise and costs 1. REPORT DATE (DD-MM-YYYY) 4. TITLE AND...Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 stochastic optimal control, fractional Brownian motion , stochastic

Profile Similarity Metrics Increase Personality Scale Validity (Briefing Charts)

DTIC Science & Technology

2016-04-15

REPORT DATE (DD-MM-YYYY) April 2016 2. REPORT TYPE Final 3. DATES COVERED (From - To) April 2015 – August 2015 4. TITLE AND SUBTITLE... temperament scales are used in employment settings to predict performance because they are generally valid and reduce adverse impact. This research...personality and temperament scales against job continuance outcomes. Analyses documented that: PSMs consistently accounted for over 90% of the variance in

Asynchronous Discrete Control of Continuous Processes.

DTIC Science & Technology

1986-02-24

Input. When 40-lead dual-in-line ceramic packages (D suffix) and in the mode input is high IMOOE=1), the CDPIS54A is 40-lead dual-in-line plastic ...DYNAIC U ThIi. CA~ YRi5iC5 TACDPI8541 CDPI854C DYNAMC LECRICL CARA ERITIC atTA 40 o +UC. DD M W O 1110 VlH’& 7 VDD. VIL, 3 . LIIMTS ’.- CARACTERISTIC

Special Operations and the Soldier System: Critical Acquisition Issues

DTIC Science & Technology

1992-03-01

continues to exercise considerable interest in Ranger related material requirements through its responsibilities for all infantry combat development...UNCLASSIFIED 22a NAME OF RESPONSIBLE INDIVIDUAL 22b TELEPHONE (Include Area code) 22c OFFICE SYMBOL Dr Richard B. Doyle 408-646-3302 AS/Dy DD FORM 1473,84 MAR...34 study. Chapter V discusses the acquisition responsibilities of USSOCOM, detailing the evolving relationship with the Army requirement development

Phytochrome and Seed Germination. V. Changes of Phytochrome Content During the Germination of Cucumber Seeds 1

PubMed Central

Mancinelli, Alberto L.; Tolkowsky, Abby

1968-01-01

Cucumber seeds are light-sensitive, dark-germinating seeds. Inhibition of germination can be induced by prolonged exposure to continuous or intermittent FR. The dark germination process and the response to FR are phytochrome controlled. Phytochrome can be detected in these seeds by differential spectrophotometry in vivo. Spectrophotometrically measurable phytochrome increases during dark germination. The rate of increase is temperature dependent. Light treatments which are inhibitory for germination result in phytochrome contents lower than those of the seeds germinating in darkness. Treatments which restore germination also restore phytochrome formation. PMID:16656797

Impact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis

DTIC Science & Technology

2014-09-01

nucleoside reverse transcriptase inhibitor ddC as a small molecule inhibitor of HSATII reverse transcription. Initial data indicates there are anti...proliferative effects of ddC in cancer cell lines. We will evaluate ddC and anti-sense locked nucleic acids as methods for inhibiting this process and...of these hybrids, we tested the effect of the nucleoside analog RT inhibitor (NRTI) 2’,3’-dideoxycytidine ( ddC ) in COLO205 cells (Fig. 2e). Notably

MEDBASE: Strategic Planning and Implementation of an Army Medical Department Software Application

DTIC Science & Technology

2003-07-17

the application. These forms include Department of Defense (DD) Forms 2795, 2796, a more comprehensive version of DD Form 2766, the medical and dental ...include DD Forms 2795, 2796, a more comprehensive version of DD Form 2766, the medical and dental readiness portions of DA Form 7425, and an expanded...Readiness •Mobilization •Aggregation CDA • Dental Readiness TAPDB •Conglomerate Personnel Information MEBITT •Medical Boards •Perm Profiles VISION •Eye

Combined Wastewater Characterization and Hazardous Waste Survey, Davis-Monthan AFB, Arizona

DTIC Science & Technology

1990-04-01

drain to the sanitary sewer. The chemical additives contained in the cooling discharge are inhibitor (NSN 6850 0059 2537 and 6850 0059 2937) and Cooling...Vacuucleaner 480 DD 836 CES Heating Plant Phosphate 2400 DD 836 CES Refrigeration Inhibitor NQ DD 836 CES Refrigeration Cooling Tower Treat NQ DD 836 CES...BLDG PRODUCT QTY (GAL/YR) 836 CES Refrigeration 5309 Inhibitor NQ 836 CES Refrigeration 5309 Cooling Tower Treat NQ 836 CES Heating Plant 5309 Sodium

Clinical predictors and gender-wise variations in dyssynergic defecation disorders.

PubMed

Jain, Mayank; Baijal, Rajiv; Srinivas, Melpakkam; Venkataraman, Jayanthi

2018-06-12

There is insufficient data from India regarding clinical predictors of dyssynergic defecation. To identify demography, symptom, and colonoscopic parameters that can predict dyssynergic defecation (DD) among patients with chronic constipation (CC) and to compare the profile among male and female patients with DD. Data collected from three centers during June 2014 to May 2017 included age, gender, symptom duration, form and consistency of stools, digital examination, colonoscopy, and anorectal manometry (ARM). Patients were grouped based on ARM diagnosis: group I (normal study) and group II (DD). The two groups were compared for demography, symptom profile, and colonoscopy findings. Gender-wise subset analysis was done for those with the normal and abnormal ARM using chi-square and unpaired t tests. Of 236 patients with CC evaluated, 130 (55%) had normal ARM and 106 (45%) had DD. Male sex, straining during defecation, bleeding per rectum, and abnormal colonoscopic diagnosis were significantly more common in group II. While bleeding per rectum and absence of urge to defecate were more common in males (p < 0.02), straining, digital evacuation, and hard stools were commoner in females with DD. Straining during defecation, bleeding per rectum, and abnormal colonoscopy findings were more common in patients with DD. Symptoms of bleeding per rectum and absence of urge to defecate in men and straining during defecation in female patients were significantly associated with DD. Symptoms differ in males and females with DD.

Growth curves and morphology of three Treponema subtypes isolated from digital dermatitis in cattle.

PubMed

Döpfer, D; Anklam, K; Mikheil, D; Ladell, P

2012-09-01

Digital dermatitis (DD) is an infectious claw disease of cattle that causes painful lesions, principally along the coronary band of the claws. In the US alone, the estimated economic impact of DD is estimated to be $190 million. The etiology of DD remains unclear and there is no reliable laboratory test, so DD is most often diagnosed clinically. Spirochetal bacteria of the genera Treponema have been implicated in DD infections following their isolation using culture techniques, serological detection of bovine antibodies against treponemes, and amplification of treponemal 16s DNA sequences by PCR. During in vitro growth of spirochetes and treponemes isolated from DD, morphological changes have been observed indicating the presence of a spiral form and an encysted form. It is not known why encysted forms appear or what role they have in the progression of DD. The current study established growth curves for three subtypes of treponemes, Treponema denticola-like, Treponema phagedenis-like, and Treponema medium-like, while photographically monitoring changes in morphology. In addition to observing spiral and encysted forms, two intermediate forms were also observed. These appeared as either spiral forms with spherical bodies or as enveloped clusters of granules. The observation of encysted forms adds further support to the theory that treponemes causing recurrent infections deep in bovine skin have mechanisms to facilitate persistence and the chronic character of DD. Published by Elsevier Ltd.

Interrelationships between Marijuana Demand and Discounting of Delayed Rewards: Convergence in Behavioral Economic Methods

PubMed Central

Aston, Elizabeth R.; Metrik, Jane; Amlung, Michael; Kahler, Christopher W.; MacKillop, James

2016-01-01

Background Distinct behavioral economic domains, including high perceived drug value (demand) and delay discounting (DD), have been implicated in the initiation of drug use and the progression to dependence. However, it is unclear whether frequent marijuana users conform to a “reinforcer pathology” addiction model wherein marijuana demand and DD jointly increase risk for problematic marijuana use and cannabis dependence (CD). Methods Participants (n=88, 34% female, 14% cannabis dependent) completed a marijuana purchase task at baseline. A delay discounting task was completed following placebo marijuana cigarette (0% THC) administration during a separate experimental session. Results Marijuana demand and DD were quantified using area under the curve (AUC). In multiple regression models, demand uniquely predicted frequency of marijuana use while DD did not. In contrast, DD uniquely predicted CD symptom count while demand did not. There were no significant interactions between demand and DD in either model. Conclusions These findings suggest that frequent marijuana users exhibit key constituents of the reinforcer pathology model: high marijuana demand and steep discounting of delayed rewards. However, demand and DD appear to be independent rather than synergistic risk factors for elevated marijuana use and risk for progression to CD. Findings also provide support for using AUC as a singular marijuana demand metric, particularly when also examining other behavioral economic constructs that apply similar statistical approaches, such as DD, to support analytic methodological convergence. PMID:27810657

Community-Based Participatory Research to Adapt Health Measures for Use by People With Developmental Disabilities.

PubMed

Nicolaidis, Christina; Raymaker, Dora; Katz, Marsha; Oschwald, Mary; Goe, Rebecca; Leotti, Sandra; Grantham, Leah; Plourde, Eddie; Salomon, Janice; Hughes, Rosemary B; Powers, Laurie E

2015-01-01

People with developmental disabilities (DD) are often not included as participants in research owing to a variety of ethical and practical challenges. One major challenge is that traditional measurement instruments may not be accessible to people with DD. Participatory research approaches promise to increase the participation of marginalized communities in research, but few partnerships have successfully used such approaches to conduct quantitative studies people with DD. To use a community-based participatory research (CBPR) approach to create an accessible, computer-assisted survey about violence and health in people with DD, and to psychometrically test adapted health instruments. Our academic-community partnership, composed of academic researchers, people with DD, and supporters, collaboratively selected and modified data collection instruments, conducted cognitive interviews and pilot tests, and then administered the full survey to 350 people with DD. Although team members sometimes had opposing accommodation needs and adaptation recommendations, academic and community partners were able to work together successfully to adapt instruments to be accessible to participants with a wide range of DD. Results suggest the adapted health instruments had strong content validity and all but one had good to excellent internal consistency reliability (alpha, 0.81-0.94). The majority of participants (75%) responded that all or most of the questions were easy to understand. Researchers should consider using participatory approaches to adapting instruments so people with DD can be validly included in research.

Parental Attributions of Control for Child Behaviour and Their Relation to Discipline Practices in Parents of Children with and Without Developmental Delays.

PubMed

Jacobs, Myrthe; Marks Woolfson, Lisa; Hunter, Simon C

2017-01-01

Children with developmental delays (DD) are at risk for developing behavior problems. Research suggests that parents' causal attributions for child behavior are related to parenting. This study investigated this association in parents of children with DD compared to parents of typically developing (TD) children. It specifically focused on attributions of child control by separating these from attributions of responsibility, blame and intent, and from attributions of parent control and responsibility. Fifty-one parents of children with DD and 69 parents of TD children completed two questionnaires. The Written Analogue Questionnaire measured causal attributions. The Parenting Scale measured dysfunctional discipline practices. Parents of children with DD viewed the child's role in problematic behavior more positively while also viewing misbehavior as more fixed than parents of TD children. Parents of TD children who viewed their child as more in control over misbehavior used less dysfunctional discipline, but this association was not found for parents of children with DD. The results advance understanding of how parents perceive behavior problems in children with DD and the important role these perceptions play in parental behavior management strategies. More importantly, these perceptions relate to discipline practices differently for parents of children with DD compared to parents of TD children, highlighting that parent interventions should be adapted to the specific needs of parents of children with DD.

Site environmental report for Calendar Year 1994 on radiological and nonradiological parameters

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

NONE

1995-06-30

Battelle Memorial Institute`s nuclear research facilities are currently being maintained in a surveillance and maintenance (S&M) mode with continual decontamination and decommissioning (D&D) activities being conducted under Department of Energy (DOE) Contract W-7405-ENG-92. These activities are referred to under the Contract as the Battelle Columbus Laboratories Decommissioning Project (BCLDP). Operations referenced in this report are performed in support of S&M and D&D activities. Battelle`s King Avenue facility is not considered in this report to the extent that the West Jefferson facility is. The source term at the King Avenue site is a small fraction of the source term at themore » West Jefferson site. Off site levels of radionuclides that could be attributed to the west Jefferson and King Avenue nuclear operations wereindistinguishable from background levels at specific locations where air, water, and direct radiation measurements were performed. Environmental monitoring continued to demonstrate compliance by Battelle with federal, state and local regulations. Routine, nonradiological activities performed include monitoring liquid effluents and monitoring the ground water system for the West Jefferson North site. Samples of various environmental media including air, water, grass, fish, field and garden crops, sediment and soil were collected from the region surrounding the two sites and analyzed.« less

Site Environmental Report for Calendar Year 2008. DOE Operations at The Boeing Company Santa Susana Field Laboratory, Area IV

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

Liu, Ning; Rutherford, Phil; Amar, Ravnesh

2009-09-01

This Annual Site Environmental Report (ASER) for 2008 describes the environmental conditions related to work performed for the Department of Energy (DOE) at Area IV of Boeing’s Santa Susana Field Laboratory (SSFL). The Energy Technology Engineering Center (ETEC), a government-owned, company-operated test facility, was located in Area IV. The operations in Area IV included development, fabrication, and disassembly of nuclear reactors, reactor fuel, and other radioactive materials. Other activities in the area involved the operation of large-scale liquid metal facilities that were used for testing non-nuclear liquid metal fast breeder reactor components. All nuclear work was terminated in 1988; allmore » subsequent radiological work has been directed toward decontamination and decommissioning (D&D) of the former nuclear facilities and their associated sites. In May 2007, the D&D operations in Area IV were suspended by the DOE. The environmental monitoring programs were continued throughout the year. Results of the radiological monitoring program for the calendar year 2008 continue to indicate that there are no significant releases of radioactive material from Area IV of SSFL. All potential exposure pathways are sampled and/or monitored, including air, soil, surface water, groundwater, direct radiation, transfer of property (land, structures, waste), and recycling.« less

76 FR 72914 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Government...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-28

... Inventory Schedules; DD Form 1639, Scrap Warranty; DD Form 1640, Request for Plant Clearance; DD Form 1641... information collection on respondents, including the use of automated collection techniques or other forms of... Government property; [[Page 72915

Displacement of foveal area toward optic disc after macular hole surgery with internal limiting membrane peeling.

PubMed

Kawano, K; Ito, Y; Kondo, M; Ishikawa, K; Kachi, S; Ueno, S; Iguchi, Y; Terasaki, H

2013-07-01

To determine whether there is a displacement of the fovea toward the optic disc after successful macular hole (MH) surgery with internal limiting membrane (ILM) peeling. The medical records of 54 eyes of 53 patients that had undergone pars plana vitrectomy with ILM peeling and gas or air tamponade for an idiopathic MH were evaluated. Spectral-domain optical coherence tomography (OCT) had been performed before and >6 months after the surgery. The preoperative distances between the center of the MH and the optic disc (MH-OD), center of the MH and the bifurcation or crossing of retinal vessels (MH-RV) were measured in the OCT images. In addition, the postoperative distance between the center of the fovea and optic disc (F-OD) and the center of the fovea and the same bifurcation or crossing of retinal vessels (F-RV) were measured in the OCT images. The F-OD was 2.67±0.33 disc diameters (DD), which was significantly shorter than that of the MH-OD of 2.77±0.33 DD (P<0.001). The F-RV was also significantly shorter than the MH-RV on the inner nasal area (from 0.85±0.16DD to 0.79±0.15DD; P<0.001), the inner temporal area (from 0.82±0.15DD to 0.77±0.14DD; P<0.001), and outer nasal area (from 1.70±0.31DD to 1.65±0.32DD; P<0.001), but it was significantly longer than the MH-RV in the outer temporal area (from 1.65±0.29DD to 1.68±0.29DD; P<0.001). Our results showed that successful closure of a MH by vitrectomy with ILM peeling and gas tamponade leads to a displacement of the center of the macula toward the optic disc.

A new double digestion ligation mediated suppression PCR method for simultaneous bacteria DNA-typing and confirmation of species: an Acinetobacter sp. model.

PubMed

Stojowska, Karolina; Krawczyk, Beata

2014-01-01

We have designed a new ddLMS PCR (double digestion Ligation Mediated Suppression PCR) method based on restriction site polymorphism upstream from the specific target sequence for the simultaneous identification and differentiation of bacterial strains. The ddLMS PCR combines a simple PCR used for species or genus identification and the LM PCR strategy for strain differentiation. The bacterial identification is confirmed in the form of the PCR product(s), while the length of the PCR product makes it possible to differentiate between bacterial strains. If there is a single copy of the target sequence within genomic DNA, one specific PCR product is created (simplex ddLMS PCR), whereas for multiple copies of the gene the fingerprinting patterns can be obtained (multiplex ddLMS PCR). The described ddLMS PCR method is designed for rapid and specific strain differentiation in medical and microbiological studies. In comparison to other LM PCR it has substantial advantages: enables specific species' DNA-typing without the need for pure bacterial culture selection, is not sensitive to contamination with other cells or genomic DNA, and gives univocal "band-based" results, which are easy to interpret. The utility of ddLMS PCR was shown for Acinetobacter calcoaceticus-baumannii (Acb) complex, the genetically closely related and phenotypically similar species and also important nosocomial pathogens, for which currently, there are no recommended methods for screening, typing and identification. In this article two models are proposed: 3' recA-ddLMS PCR-MaeII/RsaI for Acb complex interspecific typing and 5' rrn-ddLMS PCR-HindIII/ApaI for Acinetobacter baumannii intraspecific typing. ddLMS PCR allows not only for DNA-typing but also for confirmation of species in one reaction. Also, practical guidelines for designing a diagnostic test based on ddLMS PCR for genotyping different species of bacteria are provided.

The Protective Effects of IGF-1 on Different Subpopulations of DRG Neurons with Neurotoxicity Induced by gp120 and Dideoxycytidine In Vitro.

PubMed

Lu, Lin; Dong, Haixia; Liu, Guixiang; Yuan, Bin; Li, Yizhao; Liu, Huaxiang

2014-11-01

Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC (50 μmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC (50 μmol/L) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (>25 μm), whereas ddC mainly affected small diameter DRG neurons (≤25 μm). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.

The Protective Effects of IGF-1 on Different Subpopulations of DRG Neurons with Neurotoxicity Induced by gp120 and Dideoxycytidine In Vitro

PubMed Central

Lu, Lin; Dong, Haixia; Liu, Guixiang; Yuan, Bin; Li, Yizhao; Liu, Huaxiang

2014-01-01

Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC (50 μmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC (50 μmol/L) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (>25 μm), whereas ddC mainly affected small diameter DRG neurons (≤25 μm). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies. PMID:25489421

Demographic determinants of risk, colon distribution and density scores of diverticular disease.

PubMed

Golder, Mark; Ster, Irina Chis; Babu, Pratusha; Sharma, Amita; Bayat, Muhammad; Farah, Abdulkadir

2011-02-28

To investigate associations between ethnicity, age and sex and the risk, colon distribution and density scores of diverticular disease (DD). Barium enemas were examined in 1000 patients: 410 male, 590 female; 760 whites, 62 Asians, 44 black africans (BAs), and 134 other blacks (OBs). Risks and diverticula density of left-sided DD (LSDD) and right-sided-component DD (RSCDD = right-sided DD + right and left DD + Pan-DD) were compared using logistic regression. Four hundred and forty-seven patients had DD (322 LSDD and 125 RSCDD). Adjusted risks: (1) LSDD: each year increase in age increased the odds by 6% (95% CI: 5-8, SE: 0.8%, P < 0.001); Asians: odds ratio (OR): 0.23 (95% CI: 0.10-0.53, SE: 0.1, P ≤ 0.001) and OBs: OR: 0.25 (95% CI: 0.14-0.43, SE: 0.07, P ≤ 0.001) appeared protected vs Whites; (2) RSCDD: each year increase in age increased the odds by 4% (95% CI: 2-6, SE: 1%, P < 0.001); females were 0.60 times (95% CI: 0.40-0.90, SE: 0.12, P = 0.01) less likely than males to have RSCDD; BAs were 3.51 times (95% CI: 1.70-7.24, SE: 1.30, P < 0.001) more likely than Whites to have RSCDD; and (3) DD density scores: each year increase in age increased the odds of high-density scores by 4% (95% CI: 1-6, SE: 1%, P < 0.001); RSCDD was 2.77 times (95% CI: 1.39-3.32, SE: 0.67, P < 0.001) more likely to be of high density than LSDD. No further significant differences were found in the adjusted models. Right colonic DD might be more common and has higher diverticula density in the west than previously reported. BAs appear predisposed to DD, whereas other ethnic differences appear conserved following migration.

Demographic determinants of risk, colon distribution and density scores of diverticular disease

PubMed Central

Golder, Mark; Ster, Irina Chis; Babu, Pratusha; Sharma, Amita; Bayat, Muhammad; Farah, Abdulkadir

2011-01-01

AIM: To investigate associations between ethnicity, age and sex and the risk, colon distribution and density scores of diverticular disease (DD). METHODS: Barium enemas were examined in 1000 patients: 410 male, 590 female; 760 whites, 62 Asians, 44 black africans (BAs), and 134 other blacks (OBs). Risks and diverticula density of left-sided DD (LSDD) and right-sided-component DD (RSCDD = right-sided DD + right and left DD + Pan-DD) were compared using logistic regression. RESULTS: Four hundred and forty-seven patients had DD (322 LSDD and 125 RSCDD). Adjusted risks: (1) LSDD: each year increase in age increased the odds by 6% (95% CI: 5-8, SE: 0.8%, P < 0.001); Asians: odds ratio (OR): 0.23 (95% CI: 0.10-0.53, SE: 0.1, P ≤ 0.001) and OBs: OR: 0.25 (95% CI: 0.14-0.43, SE: 0.07, P ≤ 0.001) appeared protected vs Whites; (2) RSCDD: each year increase in age increased the odds by 4% (95% CI: 2-6, SE: 1%, P < 0.001); females were 0.60 times (95% CI: 0.40-0.90, SE: 0.12, P = 0.01) less likely than males to have RSCDD; BAs were 3.51 times (95% CI: 1.70-7.24, SE: 1.30, P < 0.001) more likely than Whites to have RSCDD; and (3) DD density scores: each year increase in age increased the odds of high-density scores by 4% (95% CI: 1-6, SE: 1%, P < 0.001); RSCDD was 2.77 times (95% CI: 1.39-3.32, SE: 0.67, P < 0.001) more likely to be of high density than LSDD. No further significant differences were found in the adjusted models. CONCLUSION: Right colonic DD might be more common and has higher diverticula density in the west than previously reported. BAs appear predisposed to DD, whereas other ethnic differences appear conserved following migration. PMID:21448352

In Vitro Study of Novel Collagenase (XIAFLEX®) on Dupuytren's Disease Fibroblasts Displays Unique Drug Related Properties

PubMed Central

Singh, Subir; Kolluru, Venkatesh; Emeigh Hart, Susan G.; Bayat, Ardeshir

2012-01-01

Dupuytren's disease (DD) is a benign, fibroproliferative disease of the palmar fascia, with excessive extracellular matrix (ECM) deposition and over-production of cytokines and growth factors, resulting in digital fixed flexion contractures limiting hand function and patient quality of life. Surgical fasciectomy is the gold standard treatment but is invasive and has associated morbidity without limiting disease recurrence. Injectable Collagenase Clostridium histolyticum (CCH) - Xiaflex® - is a novel, nonsurgical option with clinically proven in vivo reduction of DD contractures but with limited in vitro data demonstrating its cellular and molecular effects. The aim of this study was to delineate the effects of CCH on primary fibroblasts isolated from DD and non-DD anatomical sites (using RTCA, LDH, WST-1, FACS, qRT-PCR, ELISA and In-Cell Quantitative Western Blotting) to compare the efficacy of varying concentrations of Xiaflex® against a reagent grade Collagenase, Collagenase A. Results demonstrated that DD nodule and cord fibroblasts had greater proliferation than those from fat and skin. Xiaflex® exposure resulted in dose- and time-dependent inhibition of cellular spreading, attachment and proliferation, with cellular recovery after enzyme removal. Unlike Collagenase A, Xiaflex® did not cause apoptosis. Collagen expression patterns were significantly (p<0.05) different in DD fibroblasts across anatomical sites - the highest levels of collagen I and III were detected in DD nodule, with DD cord and fat fibroblasts demonstrating a smaller increase in both collagen expression relative to DD skin. Xiaflex® significantly (p<0.05) down-regulated ECM components, cytokines and growth factors in a dose-dependent manner. An in vitro scratch wound assay model demonstrated that, at low concentrations, Xiaflex® enabled a faster fibroblast reparatory migration into the wound, whereas, at high concentrations, this process was significantly (p<0.05) inhibited. This is the first report elucidating potential mechanisms of action of Xiaflex® on Dupuytren fibroblasts, offering a greater insight and a better understanding of its effect in DD. PMID:22384021

Increased night duty loading of physicians caused elevated blood pressure and sympathetic tones in a dose-dependent manner.

PubMed

Lee, Hsiu-Hao; Lo, Shih-Hsiang; Chen, Bing-Yu; Lin, Yen-Hung; Chu, Dachen; Cheng, Tsun-Jen; Chen, Pau-Chung; Guo, Yue-Liang

2016-04-01

Night duty has been recognized as a significantly harmful stressor for physicians. However, the relationship between various levels of duty loading and stress response is unknown. This study examined whether duty load increases cardiovascular stress indicators in a dose-dependent manner. An unallocated prospective observational study was conducted among physicians performing various levels of duties in a secondary referral medical center between 2011 and 2012. Heart rate variability (HRV), blood pressure (BP), and other stress markers of 12 attending physicians were compared during different duty loads: non-duty day (NDD), duty day with one duty area and three wards (1DD), and duty day with two duty areas and six wards (2DD). During the regular sleep time (i.e., 11 p.m. to 5 a.m.), the relative sympathetic modulations measured using the HRV were 59.0 ± 9.3, 61.6 ± 10.4, and 64.4 ± 8.9 for NDD, 1DD, and 2DD, respectively (p = 0.0012); those for relative parasympathetic modulations were 37.4 ± 9.4, 34.8 ± 9.8, and 32.0 ± 8.8 for NDD, 1DD, and 2DD, respectively (p = 0.0015). The percentages of abnormal systolic BPs were 9.7 ± 13.2 %, 25.3 ± 21.8 %, and 31.5 ± 21.0 % for NDD, 1DD, and 2DD, respectively (p = 0.003), and the percentages of abnormal diastolic BP were 6.7 ± 11.0 %, 18.3 ± 11.1 %, and 27.1 ± 30.9 % for NDD, 1DD, and 2DD, respectively (p = 0.002). Total sleep time was negatively associated with sympathetic/parasympathetic balance and the percentage of abnormal diastolic BP. Admitting new patients was positively associated with the percentages of abnormal systolic BP. This observational analysis suggests that the dose-dependent stress responses of the cardiovascular system in physicians were caused by the duty load.

Differentiating lipedema and Dercum's disease.

PubMed

Beltran, K; Herbst, K L

2017-02-01

People with lipedema or Dercum's disease (DD) can have a similar distribution of excess painful nodular subcutaneous adipose tissue (SAT), making them difficult to differentiate. Case series of 94 patients with DD, 160 with lipedema and 18 with both diagnoses (Lip+DD) from a single clinic in an academic medical center to improve identification and differentiation of these disorders by comparison of clinical findings, prevalence of type 2 diabetes (DM2), hypermobility by the Beighton score and assessment of a marker of inflammation, Total complement activity (CH50). Differences between groups were by Student's t-test with α of 0.05. The Lipedema Group had significantly greater weight, body mass index (BMI), gynoid distributed nodular SAT and fibrotic and heavy tissue than the DD Group. Hypermobility was significantly higher in the Lipedema (58±0.5%) than DD Group (23±0.4%; P<0.0001). DM2 was significantly greater in the DD (16±0.2%; P=0.0007) than the Lipedema Group (6±0.2%). Average pain by an analog scale was significantly higher in the DD (6±2.5%) than the Lipedema Group (4±2.1%; P<0.0001). Fatigue and swelling were common in both groups. Easy bruising was more common in the Lipedema Group, whereas abdominal pain, shortness of breath, fibromyalgia, migraines and lipomas were more prevalent in the DD Group. The percentage of patients with elevated CH50 was significantly positive in both groups. The significantly lower prevalence of DM2 in people with lipedema compared with DD may be due to the greater amount of gynoid fat known to be protective against metabolic disorders. The high percentage of hypermobility in lipedema patients indicates that it may be a comorbid condition. The location of fat, high average daily pain, presence of lipomas and comorbid painful disorders in DD patients may help differentiate from lipedema.

A New Double Digestion Ligation Mediated Suppression PCR Method for Simultaneous Bacteria DNA-Typing and Confirmation of Species: An Acinetobacter sp. Model

PubMed Central

Stojowska, Karolina; Krawczyk, Beata

2014-01-01

We have designed a new ddLMS PCR (double digestion Ligation Mediated Suppression PCR) method based on restriction site polymorphism upstream from the specific target sequence for the simultaneous identification and differentiation of bacterial strains. The ddLMS PCR combines a simple PCR used for species or genus identification and the LM PCR strategy for strain differentiation. The bacterial identification is confirmed in the form of the PCR product(s), while the length of the PCR product makes it possible to differentiate between bacterial strains. If there is a single copy of the target sequence within genomic DNA, one specific PCR product is created (simplex ddLMS PCR), whereas for multiple copies of the gene the fingerprinting patterns can be obtained (multiplex ddLMS PCR). The described ddLMS PCR method is designed for rapid and specific strain differentiation in medical and microbiological studies. In comparison to other LM PCR it has substantial advantages: enables specific species' DNA-typing without the need for pure bacterial culture selection, is not sensitive to contamination with other cells or genomic DNA, and gives univocal “band-based” results, which are easy to interpret. The utility of ddLMS PCR was shown for Acinetobacter calcoaceticus-baumannii (Acb) complex, the genetically closely related and phenotypically similar species and also important nosocomial pathogens, for which currently, there are no recommended methods for screening, typing and identification. In this article two models are proposed: 3′ recA-ddLMS PCR-MaeII/RsaI for Acb complex interspecific typing and 5′ rrn-ddLMS PCR-HindIII/ApaI for Acinetobacter baumannii intraspecific typing. ddLMS PCR allows not only for DNA-typing but also for confirmation of species in one reaction. Also, practical guidelines for designing a diagnostic test based on ddLMS PCR for genotyping different species of bacteria are provided. PMID:25522278

Walleye recruitment success is less resilient to warming water temperatures in lakes with abundant largemouth bass populations

USGS Publications Warehouse

Hansen, Gretchen J. A.; Midway, Stephen R.; Wagner, Tyler

2018-01-01

Lakes respond heterogeneously to climate, with implications for fisheries management. We analyzed walleye (Sander vitreus) recruitment to age-0 in 359 lakes in Wisconsin, USA, to (i) quantify the relationship between annual water temperature degree days (DD) and walleye recruitment success and (ii) identify the influence of lake characteristics — area, conductivity, largemouth bass (Micropterus salmoides) catch rates, and mean DD — on this relationship. The relationship between walleye recruitment and annual DD varied among lakes and was not distinguishable from zero overall (posterior mean = −0.11, 90% CI = −0.34, 0.15). DD effects on recruitment were negative in 198 lakes (55%) and positive in 161 (45%). The effect of annual DD was most negative in lakes with high largemouth bass densities, and, on average, the probability of recruitment was highest in large lakes with low largemouth bass densities. Conductivity and mean DD influenced neither recruitment nor the effect of annual DD. Walleye recruitment was most resilient to warming in lakes with few largemouth bass, suggesting that the effects of climate change depend on lake-specific food-web and habitat contexts.

Relationship between drug dreams, affect, and craving during treatment for substance dependence.

PubMed

Tanguay, Hélène; Zadra, Antonio; Good, Daniel; Leri, Francesco

2015-01-01

To explore the relationship between occurrence of drug dreams (DDs) and daytime negative affect and drug craving during the course of a 5-week treatment program for substance dependence. Using the dream journal methodology, 86 participants reported occurrence of dreams, dream content, and ratings of affect and drug craving. The relationships between the experience of DD, dream content ("active" vs "passive"), and affect and craving were analyzed using mixed model methods. The experience of DD was associated with higher levels of negative affect (P < 0.001) and craving (P < 0.001). The occurrence of DD did not decrease significantly over the 5 weeks of the study. Cocaine/crack users reported a higher occurrence of DD (P < 0.05) than the other drug groups (opiates and alcohol), and DD involving "active" drug use was associated with larger (P < 0.05) changes in negative affect. These results are consistent with the hypothesis that DD can act as drug-conditioned stimuli to elevate negative affect and craving in abstaining individuals. Although correlational, such findings support the implementation of psychological and pharmacological interventions aimed at minimizing the impact of DD on individuals in recovery from drug addiction.

[Association between depression and glycemic control disorder in patients with diabetes mellitus 2].

PubMed

Castro-Aké, Gilberto Alejandro; Tovar-Espinosa, José Antonio; Mendoza-Cruz, Ulises

2009-01-01

Depression is associated with type 2 diabetes mellitus (DM2), physically affecting the general condition of the patient. It also has repercussions with a poor glycemic control, as found when nutrition is not adequate and there is little adherence to the therapeutic plan. Our objective was to identify the association between depression disorders (DD) in patients with DM2 and their glycemic control. A case and control study was carried out in 186 patients with DM2, aged 30 to 60 years, selected by simple random sampling. The MINI International Neuropsychiatric Interview was applied. The glycemic control was documented. There were 54 males and 132 females. Fifty three (28.4 %) were found with controlled glycemia and 135 (72.6 %) were not controlled. Fifty one (27.4 %) of the patients with DM2 suffered DD. There were 45 patients (24.1 %) controlled without DD, 8 (4.3 %) were controlled with DD; 90 (48.3 %) were uncontrolled without DD and 43 (23.1 %) were uncontrolled with DD. The chi(2) was p = 0.03. The presence of DD is associated with an uncontrolled glycemia in the DM2 patients.

Credit BG. View looking northeast down from the tower onto ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Credit BG. View looking northeast down from the tower onto the two horizontal test stations at Test Stand "D." Station Dy is at the far left (Dy vacuum cell out of view), with in-line exhaust gas cooling sections and steam-driven "air ejector" (or evacuator) discharging engine exhausts to the east. The Dd cell is visible at the lower left, and the Dd exhaust train has the same functions as at Dy. The spherical tank is an electrically heated "accumulator" which supplies steam to the ejectors at Dv, Dd, and Dy stations. Other large piping delivered cooling water to the horizontal train cooling sections. The horizontal duct at the "Y" branch in the Dd train connects the Dd ejector to the Dv and Cv vacuum duct system (a blank can be bolted into this duct to isolate the Dd system). The shed roof for the Dpond test station appears at bottom center of this image. The open steel frame to the lower left of the image supports a hoist and crane for installing or removing test engines from the Dd test cell - Jet Propulsion Laboratory Edwards Facility, Test Stand D, Edwards Air Force Base, Boron, Kern County, CA

Optimization of Diamond Nucleic Acid Dye for quantitative PCR.

PubMed

Haines, Alicia M; Tobe, Shanan S; Linacre, Adrian

2016-10-01

Here, we evaluate Diamond Nucleic Acid Dye (DD) for use in quantitative PCR (qPCR) applications. Although DD is a commercially available stain for detection of DNA separated by gel electrophoresis, its use as a detection dye in qPCR has yet to be described. To determine if DD can be used in qPCR, we investigated its inhibitory effects on qPCR at concentrations ranging 0.1-2.5×. Serial dilution of DNA was used to determine the efficiency, sensitivity, and linearity of DD-generated qPCR data in comparison to other commonly used fluorescent dyes such as SYBR Green (SG), EvaGreen (EG), and BRYT Green (BG). DD was found to be comparable with other dyes for qPCR applications, with an R2 value >0.9 and an efficiency of 0.83. Mitochondrial DNA (mtDNA) target signals were successfully produced by DD over a DNA dilution range of ~28 ng- 0.28 pg, demonstrating comparable sensitivity to the other dyes investigated. Cq values obtained using DD were lower than those using EG by almost 7 cycles. We conclude that Diamond Nucleic Acid Dye is a cheaper, less toxic alternative for qPCR applications.

Characterisation, analysis of expression and localisation of circadian clock genes from the perspective of photoperiodism in the aphid Acyrthosiphon pisum.

PubMed

Barberà, Miquel; Collantes-Alegre, Jorge Mariano; Martínez-Torres, David

2017-04-01

Aphids are typical photoperiodic insects that switch from viviparous parthenogenetic reproduction typical of long day seasons to oviparous sexual reproduction triggered by the shortening of photoperiod in autumn yielding an overwintering egg in which an embryonic diapause takes place. While the involvement of the circadian clock genes in photoperiodism in mammals is well established, there is still some controversy on their participation in insects. The availability of the genome of the pea aphid Acyrthosiphon pisum places this species as an excellent model to investigate the involvement of the circadian system in the aphid seasonal response. In the present report, we have advanced in the characterisation of the circadian clock genes and showed that these genes display extensive alternative splicing. Moreover, the expression of circadian clock genes, analysed at different moments of the day, showed a robust cycling of central clock genes period and timeless. Furthermore, the rhythmic expression of these genes was shown to be rapidly dampened under DD (continuous darkness conditions), thus supporting the model of a seasonal response based on a heavily dampened circadian oscillator. Additionally, increased expression of some of the circadian clock genes under short-day conditions suggest their involvement in the induction of the aphid seasonal response. Finally, in situ localisation of transcripts of genes period and timeless in the aphid brain revealed the site of clock neurons for the first time in aphids. Two groups of clock cells were identified: the Dorsal Neurons (DN) and the Lateral Neurons (LN), both in the protocerebrum. Copyright © 2017 Elsevier Ltd. All rights reserved.

Partially acoustic dark matter, interacting dark radiation, and large scale structure

NASA Astrophysics Data System (ADS)

Chacko, Zackaria; Cui, Yanou; Hong, Sungwoo; Okui, Takemichi; Tsai, Yuhsinz

2016-12-01

The standard paradigm of collisionless cold dark matter is in tension with measurements on large scales. In particular, the best fit values of the Hubble rate H 0 and the matter density perturbation σ 8 inferred from the cosmic microwave background seem inconsistent with the results from direct measurements. We show that both problems can be solved in a framework in which dark matter consists of two distinct components, a dominant component and a subdominant component. The primary component is cold and collisionless. The secondary component is also cold, but interacts strongly with dark radiation, which itself forms a tightly coupled fluid. The growth of density perturbations in the subdominant component is inhibited by dark acoustic oscillations due to its coupling to the dark radiation, solving the σ 8 problem, while the presence of tightly coupled dark radiation ameliorates the H 0 problem. The subdominant component of dark matter and dark radiation continue to remain in thermal equilibrium until late times, inhibiting the formation of a dark disk. We present an example of a simple model that naturally realizes this scenario in which both constituents of dark matter are thermal WIMPs. Our scenario can be tested by future stage-IV experiments designed to probe the CMB and large scale structure.

Partially acoustic dark matter, interacting dark radiation, and large scale structure

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

Chacko, Zackaria; Cui, Yanou; Hong, Sungwoo

The standard paradigm of collisionless cold dark matter is in tension with measurements on large scales. In particular, the best fit values of the Hubble rate H 0 and the matter density perturbation σ 8 inferred from the cosmic microwave background seem inconsistent with the results from direct measurements. We show that both problems can be solved in a framework in which dark matter consists of two distinct components, a dominant component and a subdominant component. The primary component is cold and collisionless. The secondary component is also cold, but interacts strongly with dark radiation, which itself forms a tightlymore » coupled fluid. The growth of density perturbations in the subdominant component is inhibited by dark acoustic oscillations due to its coupling to the dark radiation, solving the σ 8 problem, while the presence of tightly coupled dark radiation ameliorates the H 0 problem. The subdominant component of dark matter and dark radiation continue to remain in thermal equilibrium until late times, inhibiting the formation of a dark disk. We present an example of a simple model that naturally realizes this scenario in which both constituents of dark matter are thermal WIMPs. Our scenario can be tested by future stage-IV experiments designed to probe the CMB and large scale structure.« less

Partially acoustic dark matter, interacting dark radiation, and large scale structure

DOE PAGES

Chacko, Zackaria; Cui, Yanou; Hong, Sungwoo; ...

2016-12-21

The standard paradigm of collisionless cold dark matter is in tension with measurements on large scales. In particular, the best fit values of the Hubble rate H 0 and the matter density perturbation σ 8 inferred from the cosmic microwave background seem inconsistent with the results from direct measurements. We show that both problems can be solved in a framework in which dark matter consists of two distinct components, a dominant component and a subdominant component. The primary component is cold and collisionless. The secondary component is also cold, but interacts strongly with dark radiation, which itself forms a tightlymore » coupled fluid. The growth of density perturbations in the subdominant component is inhibited by dark acoustic oscillations due to its coupling to the dark radiation, solving the σ 8 problem, while the presence of tightly coupled dark radiation ameliorates the H 0 problem. The subdominant component of dark matter and dark radiation continue to remain in thermal equilibrium until late times, inhibiting the formation of a dark disk. We present an example of a simple model that naturally realizes this scenario in which both constituents of dark matter are thermal WIMPs. Our scenario can be tested by future stage-IV experiments designed to probe the CMB and large scale structure.« less

77 FR 6089 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-07

...) 767-6870. Title; Associated Form; and OMB Number: Certification of Qualified Products; DD Form 1718... (QMLs). DD Form 1718, ``Certification of Qualified Products'' records and certifies, from the... of the DD Form 1718 is essential in maintaining the integrity of the qualification program. Dated...

Re-ranking via User Feedback: Georgetown University at TREC 2015 DD Track

DTIC Science & Technology

2015-11-20

Re-ranking via User Feedback: Georgetown University at TREC 2015 DD Track Jiyun Luo and Hui Yang Department of Computer Science, Georgetown...involved in a search process, the user and the search engine. In TREC DD , the user is modeled by a simulator, called “jig”. The jig and the search engine...simulating user is provided by TREC 2015 DD Track organizer, and is called “jig”. There are 118 search topics in total. For each search topic, a short

40 CFR Table 3 to Subpart Dd of... - Tank Control Levels for Tanks at Existing Affected Sources as Required by 40 CFR 63.685(b)(1)

Code of Federal Regulations, 2010 CFR

2010-07-01

... Existing Affected Sources as Required by 40 CFR 63.685(b)(1) 3 Table 3 to Subpart DD of Part 63 Protection... Hazardous Air Pollutants from Off-Site Waste and Recovery Operations Pt. 63, Subpt. DD, Table 3 Table 3 to Subpart DD of Part 63—Tank Control Levels for Tanks at Existing Affected Sources as Required by 40 CFR 63...

40 CFR Table 4 to Subpart Dd of... - Tank Control Levels for Tanks at New Affected Sources as Required by 40 CFR 63.685(b)(2)

Code of Federal Regulations, 2010 CFR

2010-07-01

... Affected Sources as Required by 40 CFR 63.685(b)(2) 4 Table 4 to Subpart DD of Part 63 Protection of... Hazardous Air Pollutants from Off-Site Waste and Recovery Operations Pt. 63, Subpt. DD, Table 4 Table 4 to Subpart DD of Part 63—Tank Control Levels for Tanks at New Affected Sources as Required by 40 CFR 63.685(b...

Integration of progressive hedging and dual decomposition in stochastic integer programs

DOE PAGES

Watson, Jean -Paul; Guo, Ge; Hackebeil, Gabriel; ...

2015-04-07

We present a method for integrating the Progressive Hedging (PH) algorithm and the Dual Decomposition (DD) algorithm of Carøe and Schultz for stochastic mixed-integer programs. Based on the correspondence between lower bounds obtained with PH and DD, a method to transform weights from PH to Lagrange multipliers in DD is found. Fast progress in early iterations of PH speeds up convergence of DD to an exact solution. As a result, we report computational results on server location and unit commitment instances.

Site Environmental Report for Calendar Year 2013. DOE Operations at The Boeing Company, Santa Susana Field Laboratory, Area IV

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

None

2014-06-30

This Annual Site Environmental Report (ASER) for 2013 describes the environmental conditions related to work performed for the Department of Energy (DOE) at Area IV of the Santa Susana Field Laboratory (SSFL). The Energy Technology Engineering Center (ETEC), a government-owned, company-operated test facility, was located in Area IV. The operations in Area IV included development, fabrication, operation and disassembly of nuclear reactors, reactor fuel, and other radioactive materials. Other activities in the area involved the operation of large-scale liquid metal facilities that were used for testing non-nuclear liquid metal fast breeder reactor components. All nuclear work was terminated in 1988,more » and all subsequent radiological work has been directed toward environmental restoration and decontamination and decommissioning (D&D) of the former nuclear facilities and their associated sites. Liquid metal research and development ended in 2002. Since May 2007, the D&D operations in Area IV have been suspended by the DOE, but the environmental monitoring and characterization programs have continued. Results of the radiological monitoring program for the calendar year 2013 continue to indicate that there are no significant releases of radioactive material from Area IV of SSFL. All potential exposure pathways are sampled and/or monitored, including air, soil, surface water, groundwater, direct radiation, transfer of property (land, structures, waste), and recycling. Due to the suspension of D&D activities in Area IV, no effluents were released into the atmosphere during 2013. Therefore, the potential radiation dose to the general public through airborne release was zero. Similarly, the radiation dose to an offsite member of the public (maximally exposed individual) due to direct radiation from SSFL is indistinguishable from background. All radioactive wastes are processed for disposal at DOE disposal sites and/or other licensed sites approved by DOE for radioactive waste disposal. No liquid radioactive wastes were released into the environment in 2013.« less

Mast cells contribute to the mucosal adjuvant effect of CTA1-DD after IgG-complex formation.

PubMed

Fang, Yu; Larsson, Lisa; Mattsson, Johan; Lycke, Nils; Xiang, Zou

2010-09-01

Mast cell activation is one of the most dramatic immune-mediated responses the body can encounter. In the worst scenario (i.e., anaphylaxis), this response is fatal. However, the importance of mast cells as initiators and effectors of both innate and adaptive immunity in healthy individuals has recently been appreciated. It was reported that mast cell activation can be used as an adjuvant to promote Ag-specific humoral immune responses upon vaccination. In this study, we have used a clinically relevant mucosal adjuvant, cholera toxin A1 subunit (CTA1)-DD, which is a fusion protein composed of CTA1, the ADP-ribosylating part of cholera toxin, and DD, two Ig-binding domains derived from Staphylococcus aureus protein A. CTA1-DD in combination with polyclonal IgG induced degranulation and production of TNF-alpha from mouse mast cells. Furthermore, CTA1-DD and polyclonal IgG complex induced mast cell degranulation in mouse skin tissue and nasal mucosa. We also found that intranasal immunization with hapten (4-hydroxy-3-nitrophenyl) acetyl (NP) coupled to chicken gammaglobulin admixed with CTA1-DD complexed with polyclonal IgG greatly enhanced serum IgG anti-NP Ab responses and stimulated higher numbers of NP-specific plasma cells in the bone marrow as compared with that observed in mice immunized with NP-chicken gammaglobulin with CTA1-DD alone. This CTA1-DD/IgG complex-mediated enhancement was mast cell dependent because it was absent in mast cell-deficient Kit(W-sh/W-sh) mice. In conclusion, our data suggest that a clinically relevant adjuvant, CTA1-DD, exerts additional augmenting effects through activation of mucosal mast cells, clearly demonstrating that mast cells could be further exploited for improving the efficacy of mucosal vaccines.

Genome-Wide Analysis Using Exon Arrays Demonstrates an Important Role for Expression of Extra-Cellular Matrix, Fibrotic Control and Tissue Remodelling Genes in Dupuytren's Disease

PubMed Central

Ham, Seungmin; de Kretser, David; Southwick, Graeme; Sprung, Carl N.

2013-01-01

Dupuytren's disease (DD) is a classic example of pathological fibrosis which results in a debilitating disorder affecting a large sector of the human population. It is characterized by excessive local proliferation of fibroblasts and over-production of collagen and other components of extracellular matrix (ECM) in the palmar fascia. The fibrosis progressively results in contracture of elements between the palmar fascia and skin causing flexion deformity or clawing of the fingers and a severe reduction in hand function. While much is known about the pathogenesis and surgical treatment of DD, little is known about the factors that cause its onset and progression, despite many years of research. Gene expression patterns in DD patients now offers the potential to identify genes that direct the pathogenesis of DD. In this study we used primary cultures of fibroblasts derived from excisional biopsies of fibrotic tissue from DD patients to compare the gene expression profiles on a genome-wide basis with normal control fibroblasts. Our investigations have identified genes that may be involved with DD pathogenesis including some which are directly relevant to fibrosis. In particular, these include significantly reduced expression levels of three matrix metallopeptidases (MMP1, MMP3, MMP16), follistatin, and STAT1, and significantly increased expression levels of fibroblast growth factors (FGF9, FGF11), a number of collagen genes and other ECM genes in DD patient samples. Many of these gene products are known to be involved in fibrosis, tumour formation and in the normal processes of tissue remodelling. In addition, alternative splicing was identified in some DD associated genes. These highly sensitive genomic investigations provide new insight into the molecular mechanisms that may underpin the development and progression of DD. PMID:23554969

Differential effects of Denileukin Diftitox IL-2 immunotoxin on NK and regulatory T cells in non-human primates

PubMed Central

Yamada, Yohei; Aoyama, Akihiro; Tocco, Georges; Boskovic, Svjetlan; Nadazdin, Ognjenka; Alessandrini, Alessandro; Madsen, Joren C.; Cosimi, A. Benedict; Benichou, Gilles; Kawai, Tatsuo

2012-01-01

Denileukin Diftitox (DD), a fusion protein comprised of IL-2 and diphtheria toxin was initially expected to enhance anti-tumor immunity by selectively eliminating regulatory T cells (Tregs) displaying the high affinity IL-2R (α-β-γ trimers). While DD has been shown to deplete some Tregs in primates, its effects on NK cells (CD16+CD8+NKG2A+CD3−), which constitutively express the intermediate affinity IL-2R (β-γ dimers) and play a critical role in anti-tumor immunity, are still unknown. To address this question, cynomolgus monkeys were injected intravenously with two different doses of DD (8 or 18 μg/Kg). This treatment resulted in a rapid but short-term reduction in detectable peripheral blood resting Tregs (R-Tregs: CD4+CD45RA+Foxp3+) and a transient increase in the number of activated Tregs (A-Tregs: CD4+CD45RA−Foxp3high) followed by their partial depletion (50–60%). On the other hand, all NK cells were deleted immediately and durably after DD administration. This difference was not due to a higher binding or internalization of DD by NK cells as compared to Tregs. Co-administration of DD with IL-15, which binds to IL-2Rβ-γ, abrogated DD-induced NK cell deletion in vitro and in vivo while it did not affect Tregs elimination. Taken together, these results show that DD exerts a potent cytotoxic effect on NK cells, a phenomenon which might impair its anti-tumoral properties. However, co-administration of IL-15 with DD could alleviate this problem by selectively protecting potentially oncolytic NK cells while allowing the depletion of immunosuppressive regulatory T cells in cancer patients. PMID:22586034

Flexible Stoichiometry and Asymmetry of the PIDDosome Core Complex by Heteronuclear NMR Spectroscopy and Mass Spectrometry

PubMed Central

Nematollahi, Lily A.; Garza-Garcia, Acely; Bechara, Chérine; Esposito, Diego; Morgner, Nina; Robinson, Carol V.; Driscoll, Paul C.

2015-01-01

Homotypic death domain (DD)–DD interactions are important in the assembly of oligomeric signaling complexes such as the PIDDosome that acts as a platform for activation of caspase-2-dependent apoptotic signaling. The structure of the PIDDosome core complex exhibits an asymmetric three-layered arrangement containing five PIDD-DDs in one layer, five RAIDD-DDs in a second layer and an additional two RAIDD-DDs. We addressed complex formation between PIDD-DD and RAIDD-DD in solution using heteronuclear nuclear magnetic resonance (NMR) spectroscopy, nanoflow electrospray ionization mass spectrometry and size-exclusion chromatography with multi-angle light scattering. The DDs assemble into complexes displaying molecular masses in the range 130–158 kDa and RAIDD-DD:PIDD-DD stoichiometries of 5:5, 6:5 and 7:5. These data suggest that the crystal structure is representative of only the heaviest species in solution and that two RAIDD-DDs are loosely attached to the 5:5 core. Two-dimensional 1H,15N-NMR experiments exhibited signal loss upon complexation consistent with the formation of high-molecular-weight species. 13C-Methyl-transverse relaxation optimized spectroscopy measurements of the PIDDosome core exhibit signs of differential line broadening, cross-peak splitting and chemical shift heterogeneity that reflect the presence of non-equivalent sites at interfaces within an asymmetric complex. Experiments using a mutant RAIDD-DD that forms a monodisperse 5:5 complex with PIDD-DD show that the spectroscopic signature derives from the quasi- but non-exact equivalent environments of each DD. Since this characteristic was previously demonstrated for the complex between the DDs of CD95 and FADD, the NMR data for this system are consistent with the formation of a structure homologous to the PIDDosome core. PMID:25528640

Health-Related Quality of Life Among Young Children With Cochlear Implants and Developmental Disabilities.

PubMed

Zaidman-Zait, Anat; Curle, Deirdre; Jamieson, Janet R; Chia, Ruth; Kozak, Frederick K

The present study examined differences in health-related quality of life (HRQoL) between deaf children with cochlear implants (CI) with and without developmental disabilities (DD) and differences across HRQoL domains within both groups of children. Ninety-two parents of children with CI aged 3-7 years participated in this cross-sectional study. Of these children, 43 had DD (i.e., CI-DD group) and 49 had no DD or chronic illness, demonstrating overall typical development (i.e., CI-TD group). Parents of children in both groups completed the KINDL, a generic HRQoL questionnaire. Parents also provided anecdotal comments to open-ended questions, and parent comments were evaluated on a CI benefits scale to assess parent-perceived benefits of CI for the deaf children with and without disabilities. Children in the CI-DD group had significantly lower HRQoL compared to children in the CI-TD group, including lower scores on the self-esteem, friend, school, and family HRQoL subscales. No significant differences among groups were found on the physical well-being and emotional well-being subscales. For the CI-TD group, age at implantation correlated negatively with self-esteem and school HRQoL subscales. In the CI-DD group, children's current age correlated negatively with family and with the total HRQoL scores. Parent anecdotal comments and scores on the CI-benefits scale indicated strong parent perceptions of benefits of implantation for children in both groups. Based on parents' proxy report, findings suggest that having DD affects multiple domains of HRQoL among young children with CIs above and beyond that of the CI itself. Parents of deaf children with DD may need greater support through the CI process and follow-up than parents of deaf children without DD.

Sequence of the cDNA of a human dihydrodiol dehydrogenase isoform (AKR1C2) and tissue distribution of its mRNA.

PubMed Central

Shiraishi, H; Ishikura, S; Matsuura, K; Deyashiki, Y; Ninomiya, M; Sakai, S; Hara, A

1998-01-01

Human liver contains three isoforms (DD1, DD2 and DD4) of dihydrodiol dehydrogenase with 20alpha- or 3alpha-hydroxysteroid dehydrogenase activity; the dehydrogenases belong to the aldo-oxo reductase (AKR) superfamily. cDNA species encoding DD1 and DD4 have been identified. However, four cDNA species with more than 99% sequence identity have been cloned and are compatible with a partial amino acid sequence of DD2. In this study we have isolated a cDNA clone encoding DD2, which was confirmed by comparison of the properties of the recombinant and hepatic enzymes. This cDNA showed differences of one, two, four and five nucleotides from the previously reported four cDNA species for a dehydrogenase of human colon carcinoma HT29 cells, human prostatic 3alpha-hydroxysteroid dehydrogenase, a human liver 3alpha-hydroxysteroid dehydrogenase-like protein and chlordecone reductase-like protein respectively. Expression of mRNA species for the five similar cDNA species in 20 liver samples and 10 other different tissue samples was examined by reverse transcriptase-mediated PCR with specific primers followed by diagnostic restriction with endonucleases. All the tissues expressed only one mRNA species corresponding to the newly identified cDNA for DD2: mRNA transcripts corresponding to the other cDNA species were not detected. We suggest that the new cDNA is derived from the principal gene for DD2, which has been named AKR1C2 by a new nomenclature for the AKR superfamily. It is possible that some of the other cDNA species previously reported are rare allelic variants of this gene. PMID:9716498

The impact of Dupuytren disease on patient activity and quality of life.

PubMed

Wilburn, J; McKenna, S P; Perry-Hinsley, D; Bayat, A

2013-06-01

To explore the impact of Dupuytren disease (DD) from the patients' perspective. Audio-recorded interviews were conducted for patients with Dupuytren disease (DD) attending outpatient clinics. The interviews were transcribed and subjected to content analysis. This analysis highlighted key impact areas and common themes in individuals' personal experiences. These were then allocated to categories specified by the World Health Organization International Classification of Functioning, Disability, and Health (impairments and activity limitations) and the needs-based model of quality of life (QoL). Qualitative unstructured interviews were conducted with 34 patients (74% men; age, 41-80 y; mean [SD], 64 [13] y). The sample had a wide range of severity and duration of DD (range, 0.5-40; mean [SD], 13 [10] y). Nine hundred fifty-three statements relating to the impact of DD were identified from the interview transcripts. These statements fell into 2 major categories of impact: activity limitations (10 themes including problems with dressing, gripping, and personal care) and QoL (6 need categories: physiological, safety and security, social, affection, esteem, and cognitive needs). Findings from the interviews suggest that DD affects both performance of activities and QoL. To determine accurately the effectiveness of DD interventions from the patients' perspective, it is important to determine their impacts on both activity limitations and QoL. We intend to develop valid, reproducible, and responsive DD-specific scales for this purpose. The study identifies key issues specific to DD that influence patients' functioning and QoL. The information reported will form the basis of DD-specific patient-reported outcomes measures for use in clinical practice and evaluations of interventions. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Deliberative Assessment of Surrogate Consent in Dementia Research

PubMed Central

Kim, Scott Y. H.; Uhlmann, Rebecca A.; Appelbaum, Paul S.; Knopman, David S.; Kim, H. Myra; Damschroder, Laura; Beattie, Elizabeth; Struble, Laura; De Vries, Raymond

2009-01-01

Background Research involving incapacitated persons with dementia involves complex scientific, legal, and ethical issues, making traditional surveys of layperson views regarding the ethics of such research challenging. We therefore assessed the impact of democratic deliberation (DD)—involving balanced, detailed education and peer deliberation—on the views of those responsible for persons with dementia. Methods 178 community-recruited caregivers or primary decision-makers for persons with dementia were randomly assigned to either an all-day DD session group or a control group. Educational materials used for the DD session were vetted for balance and accuracy by an interdisciplinary advisory panel. We assessed the acceptability of family surrogate consent for dementia research (‘surrogate-based research’ or SBR) from a societal policy perspective as well as from the more personal perspectives of deciding for a loved one or for oneself (surrogate and self perspectives), assessed at baseline, immediately post-DD session, and a month after DD date, for 4 research scenarios of varying risk-benefit profiles. Results At baseline, a majority in both DD and control groups supported a policy of family consent for dementia research for all research scenarios. The support for a policy of family consent for SBR increased for the DD group, but not for the control group; the change in the DD group was maintained one month later. In the DD group, there were transient changes in attitudes from surrogate or self perspectives; in the control group, there were no changes from baseline in attitude toward surrogate consent from any perspective. Conclusions Intensive, balanced, and accurate education along with peer deliberation provided by democratic deliberation leads to a sustained increase in support for a societal policy of family consent for dementia research among those responsible for dementia patients. PMID:20188635

P2Y12 receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2',3'-dideoxycytidine.

PubMed

Yi, Zhihua; Xie, Lihui; Zhou, Congfa; Yuan, Huilong; Ouyang, Shuai; Fang, Zhi; Zhao, Shanhong; Jia, Tianyu; Zou, Lifang; Wang, Shouyu; Xue, Yun; Wu, Bing; Gao, Yun; Li, Guilin; Liu, Shuangmei; Xu, Hong; Xu, Changshui; Zhang, Chunping; Liang, Shangdong

2018-03-01

The direct neurotoxicity of HIV and neurotoxicity of combination antiretroviral therapy medications both contribute to the development of neuropathic pain. Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in mechanical and thermal hyperalgesia. The P2Y 12 receptor expressed in SGCs of the DRG is involved in pain transmission. In this study, we explored the role of the P2Y 12 receptor in neuropathic pain induced by HIV envelope glycoprotein 120 (gp120) combined with ddC (2',3'-dideoxycytidine). A rat model of gp120+ddC-induced neuropathic pain was used. Peripheral nerve exposure to HIV-gp120+ddC increased mechanical and thermal hyperalgesia in gp120+ddC-treated model rats. The gp120+ddC treatment increased expression of P2Y 12 receptor mRNA and protein in DRG SGCs. In primary cultured DRG SGCs treated with gp120+ddC, the levels of [Ca 2+ ] i activated by the P2Y 12 receptor agonist 2-(Methylthio) adenosine 5'-diphosphate trisodium salt (2-MeSADP) were significantly increased. P2Y 12 receptor shRNA treatment inhibited 2-MeSADP-induced [Ca 2+ ] i in primary cultured DRG SGCs treated with gp120+ddC. Intrathecal treatment with a shRNA against P2Y 12 receptor in DRG SGCs reduced the release of pro-inflammatory cytokines, decreased phosphorylation of p38 MAPK in the DRG of gp120+ddC-treated rats. Thus, downregulating the P2Y 12 receptor relieved mechanical and thermal hyperalgesia in gp120+ddC-treated rats.

Deliberative assessment of surrogate consent in dementia research.

PubMed

Kim, Scott Y H; Uhlmann, Rebecca A; Appelbaum, Paul S; Knopman, David S; Kim, H Myra; Damschroder, Laura; Beattie, Elizabeth; Struble, Laura; De Vries, Raymond

2010-07-01

Research involving incapacitated persons with dementia entails complex scientific, legal, and ethical issues, making traditional surveys of layperson views on the ethics of such research challenging. We therefore assessed the impact of democratic deliberation (DD), involving balanced, detailed education and peer deliberation, on the views of those responsible for persons with dementia. One hundred and seventy-eight community-recruited caregivers or primary decision-makers for persons with dementia were randomly assigned to either an all-day DD session group or a control group. Educational materials used for the DD session were vetted for balance and accuracy by an interdisciplinary advisory panel. We assessed the acceptability of family-surrogate consent for dementia research ("surrogate-based research") from a societal policy perspective as well as from the more personal perspectives of deciding for a loved one or for oneself (surrogate and self-perspectives), assessed at baseline, immediately post-DD session, and 1 month after DD date, for four research scenarios of varying risk-benefit profiles. At baseline, a majority in both the DD and control groups supported a policy of family consent for dementia research in all research scenarios. The support for a policy of family consent for surrogate-based research increased in the DD group, but not in the control group. The change in the DD group was maintained 1 month later. In the DD group, there were transient changes in attitudes from surrogate or self-perspectives. In the control group, there were no changes from baseline in attitude toward surrogate consent from any perspective. Intensive, balanced, and accurate education, along with peer deliberation provided by democratic deliberation, led to a sustained increase in support for a societal policy of family consent in dementia research among those responsible for dementia patients. Copyright 2010 The Alzheimer

Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2'3'-dideoxycytidine (ddC).

PubMed

Dalakas, M C; Semino-Mora, C; Leon-Monzon, M

2001-11-01

The 2'3'-dideoxycytidine (ddC), a nonazylated dideoxynucleoside analog used for the treatment of AIDS, causes a dose-dependent, painful, sensorimotor axonal peripheral neuropathy in up to 30% of the patients. To investigate the cause of the neuropathy, we performed morphological and molecular studies on nerve biopsy specimens from well-selected patients with ddC-neuropathy and from control subjects with disease, including patients with AIDS-related neuropathy never treated with ddC. Because ddC, in vitro, inhibits the replication of mitochondrial DNA (mtDNA), we counted the number of normal and abnormal mitochondria in a 0.04 mm(2) cross-sectional area of the nerves and quantified the copy numbers of mtDNA by competitive PCR in all specimens. A varying degree of axonal degeneration was present in all nerves. Abnormal mitochondria with enlarged size, excessive vacuolization, electron-dense concentric inclusions and degenerative myelin structures were prominent in the ddC-neuropathy and accounted for 55% +/- 2.5% of all counted mitochondria in the axon and Schwann cells, compared with 9% +/- 0.7% of the controls (p < 0.001). Significantly (p < 0.005) reduced copy numbers, with as high as 80% depletion, of the mtDNA was demonstrated in the nerves of the ddC-treated patients compared with the controls. We conclude that ddC induces a mitochondrial neuropathy with depletion of the nerve's mtDNA. The findings are consistent with the ability of ddC to selectively inhibit the gamma-DNA polymerase in neuronal cell lines. Toxicity to mitochondria of the peripheral nerve is a new cause of acquired neuropathy induced by exogenous toxins and may be the cause of neuropathy associated with the other neurotoxic antiretroviral drugs or toxic-metabolic conditions.

Association between the location of diverticular disease and the irritable bowel syndrome: a multicenter study in Japan.

PubMed

Yamada, Eiji; Inamori, Masahiko; Uchida, Eri; Tanida, Emiko; Izumi, Motoyoshi; Takeshita, Kimiya; Fujii, Tetsuro; Komatsu, Kazuto; Hamanaka, Jun; Maeda, Shin; Kanesaki, Akira; Matsuhashi, Nobuyuki; Nakajima, Atsushi

2014-12-01

No previous reports have shown an association between location of diverticular disease (DD) and the irritable bowel syndrome (IBS). We included 1,009 consecutive patients undergoing total colonoscopy in seven centers in Japan from June 2013 to September 2013. IBS was diagnosed using Rome III criteria, and diverticulosis was diagnosed by colonoscopy with transparent soft-short-hood. Left-sided colon was defined as sigmoid colon, descending colon, and rectum. Right-sided colon was defined as cecum, ascending colon, and transverse colon. We divided the patients into IBS and non-IBS groups and compared characteristics. Patient characteristics included mean age, 64.2±12.9 years and male:female ratio, 1.62:1. Right-sided DD was identified in 21.6% of subjects. Left-sided and bilateral DD was identified in 6.6 and 12.0% of subjects, respectively. IBS was observed in 7.5% of subjects. Multiple logistic regression analysis showed left-sided DD (odds ratio, 3.1; 95% confidence interval (CI): 1.4-7.1; P=0.0060) and bilateral DD (odds ratio, 2.6; 95% CI, 1.3-5.2; P=0.0070) were independent risk factors for IBS. Right-sided DD was not a risk factor for IBS. Our data showed that the presence of left-sided and bilateral DD, but not right-sided disease, was associated with a higher risk of IBS, indicating that differences in pathological factors caused by the location of the DD are important in the development of IBS. Clarifying the specific changes associated with left-sided DD could provide a better understanding of the pathogenic mechanisms of IBS (Trial registration # R000012739).

IGF-II and IGFBP-6 regulate cellular contractility and proliferation in Dupuytren's disease.

PubMed

Raykha, Christina; Crawford, Justin; Gan, Bing Siang; Fu, Ping; Bach, Leon A; O'Gorman, David B

2013-10-01

Dupuytren's disease (DD) is a common and heritable fibrosis of the palmar fascia that typically manifests as permanent finger contractures. The molecular interactions that induce the development of hyper-contractile fibroblasts, or myofibroblasts, in DD are poorly understood. We have identified IGF2 and IGFBP6, encoding insulin-like growth factor (IGF)-II and IGF binding protein (IGFBP)-6 respectively, as reciprocally dysregulated genes and proteins in primary cells derived from contracture tissues (DD cells). Recombinant IGFBP-6 inhibited the proliferation of DD cells, patient-matched control (PF) cells and normal palmar fascia (CT) cells. Co-treatments with IGF-II, a high affinity IGFBP-6 ligand, were unable to rescue these effects. A non-IGF-II binding analog of IGFBP-6 also inhibited cellular proliferation, implicating IGF-II-independent roles for IGFBP-6 in this process. IGF-II enhanced the proliferation of CT cells, but not DD or PF cells, and significantly enhanced DD and PF cell contractility in stressed collagen lattices. While IGFBP-6 treatment did not affect cellular contractility, it abrogated the IGF-II-induced contractility of DD and PF cells in stressed collagen lattices. IGF-II also significantly increased the contraction of DD cells in relaxed lattices, however this effect was not evident in relaxed collagen lattices containing PF cells. The disparate effects of IGF-II on DD and PF cells in relaxed and stressed contraction models suggest that IGF-II can enhance lattice contractility through more than one mechanism. This is the first report to implicate IGFBP-6 as a suppressor of cellular proliferation and IGF-II as an inducer of cellular contractility in this connective tissue disease. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

The enteric serotonergic system is altered in patients with diverticular disease.

PubMed

Böttner, Martina; Barrenschee, Martina; Hellwig, Ines; Harde, Jonas; Egberts, Jan-Hendrik; Becker, Thomas; Zorenkov, Dimitri; Wedel, Thilo

2013-12-01

Disturbances of the enteric serotonergic system have been implicated in several intestinal motility disorders. Patients with diverticular disease (DD) have been reported to exhibit abnormal intestinal motility and innervation patterns. Gene expression profiles of the serotonergic system and distribution of the serotonin type 4 receptor (5HT-4R) were thus studied in patients with DD. Colonic specimens from patients with DD and controls were subjected to quantitative PCR for serotonin receptors 2B, 3A, 4, serotonin transporter and synthesising enzyme tryptophan hydroxylase. Localisation of 5HT-4R was determined by dual-label immunocytochemistry using smooth muscle actin (α-SMA) and pan-neuronal markers (PGP 9.5) and quantitative analysis was carried out. Site-specific gene expression analysis of 5HT-4R was assessed within myenteric ganglia and muscle layers. Correlation of 5HT-4R with muscarinic receptors 2 and 3 (M2R, M3R) messenger RNA expression was determined. 5HT-4R mRNA expression was downregulated in the tunica muscularis and upregulated in the mucosa of patients with DD, whereas the other components of the serotonergic system remained unchanged. 5HT-4R was detected in ganglia and muscle layers, but was decreased in the circular muscle layer and myenteric ganglia of patients with DD. 5HT-4R mRNA expression correlated with M2R/M3R mRNA expression in controls, but not in patients with DD. The serotonergic system is compromised in DD. Altered expression of 5HT-4R at mRNA and protein levels may contribute to intestinal motor disturbances reported in patients with DD. The findings support the hypothesis that DD is associated and possibly promoted by an enteric neuromuscular pathology.

Impact of gender, work, and clinical presentation on diagnostic delay in Italian patients with primary ankylosing spondylitis.

PubMed

Bandinelli, F; Salvadorini, G; Delle Sedie, A; Riente, L; Bombardieri, S; Matucci-Cerinic, M

2016-02-01

The variability of demographic, social, genetic, and clinical factors might influence the time between the onset of symptoms and the diagnosis [diagnostic delay (DD)] of ankylosing spondylitis (AS) in different geographic areas. Different clinical manifestations in men and women affected by AS might indicate a possible role of gender in DD. The aim of the present study was to investigate the influence of demographic, social, genetic, and clinical factors on DD and the differences of DD between men and women related to the presence of different demographic, social, clinical, and genetic parameters in an Italian cohort of primary AS patients. A total of 135 Italian primary AS patients (45 female and 90 male, 27.9 ± 0.89 years old at onset) were studied. The DD, gender, education and work (manual or non-manual) levels, and type of first clinical presentation (inflammatory back pain, arthritis, enthesitis) at onset, family history of AS, and HLA B27 presence were analyzed. The DD (8.744 mean ±0.6869) was significantly higher in men (p = 0.0023), in axial presentation (p = 0.0021), and in manual work (even if with low significance, p = 0.047). The lower DD in women in comparison to that in men was likely related to higher education (p = 0.0045) and work (p = 0.0186) levels, peripheral involvement (p = 0.0009), and HLA B27 positivity (p = 0.0231). DD was higher in AS patients: male, employed in manual jobs, and with axial symptoms at onset. In men, DD seemed to be negatively influenced by lower level of education and work, axial clinical presentation, and HLA B27.

Identification of new modes of Dd-STATa regulation of gene expression in Dictyostelium by in situ hybridisation.

PubMed

Shimada, Nao; Maeda, Mineko; Urushihara, Hideko; Kawata, Takefumi

2004-09-01

Signal Transducers and Activators of Transcription (STATs) are transcription factors which lie at the end of cytokine and growth signal transduction pathways. Dictyostelium Dd-STATa is a functional homologue of metazoan STATs. It is activated by cAMP and, at the slug stage, it translocates into the nuclei of the tip cells, which are a subset of the anterior, prestalk A (pstA) cells. Here we searched for novel Dd-STATa regulated genes by in situ hybridisation. A set of 54 cDNA clones whose gene expression patterns are known to be prestalk-specific (Maeda et al., 2003), were chosen as probes and we compared their expression patterns in parental and Dd-STATa-null strains. We identified 13 genes which are candidates for direct induction by Dd-STATa. In the parental strain, most of these genes are expressed in the cone shaped mass of pstAB cells which is located within the prestalk region. These cDNAs show little or no expression in the Dd-STATa-null strain. This contrasts markedly with the paradigmatic ecmB gene which is expressed in pstAB cells in parental cells, but which is expressed throughout the prestalk zone in the Dd-STATa-null strain. We also identified several genes which are normally expressed in pstA cells, or throughout the prestalk region, but whose expression is markedly down-regulated in the null mutant. Again, this contrasts with markers derived from the paradigmatic, ecmA gene which are expressed normally in the Dd-STATa-null strain. The identification of these novel genes provides valuable tools to investigate the role of Dd-STATa.

Psychometric validation of the dysmenorrhea daily diary (DysDD): a patient-reported outcome for dysmenorrhea.

PubMed

Nguyen, Allison M; Arbuckle, Rob; Korver, Tjeerd; Chen, Fang; Taylor, Beverley; Turnbull, Alice; Norquist, Josephine M

2017-08-01

The objective of this study was to evaluate the psychometric properties of the Dysmenorrhea Daily Diary (DysDD), an electronic patient-reported outcome, in a sample of 355 women with primary dysmenorrhea enrolled in a phase IIb, multicenter, randomized, partially blinded, placebo-controlled trial for treatment of dysmenorrhea. Subjects completed the DysDD over three menstrual cycles, one pre-treatment baseline cycle and two treatment cycles. The DysDD was administered alongside the Menstrual Distress Questionnaire (MDQ), the Short-Form 36 Version 2.0 (SF-36v2), and a Global Assessment of Change (GAC). Item response distributions, test-retest reliability, concurrent and known groups validity, responsiveness, and minimally important difference (MID) were evaluated for the DysDD. As expected, item response distributions varied throughout the menstrual period for all items, with the response scales fully utilized. Within-cycle test-retest reliability was adequate (weighted kappa: 0.5-0.7), although between-cycle test-retest was poor (weighted kappa: 0.1-0.5), most likely due to the highly variable nature of dysmenorrhea between cycles rather than limitations of the measure. Correlations with the MDQ and SF-36v2 were low-moderate, but in the predicted direction, supporting concurrent validity. There were significant differences in DysDD scores across severity groups based on pain medication use. The DysDD was responsive to changes in patients' dysmenorrhea with significantly different changes in scores between change groups (p < 0.0001). MID analyses suggest changes on the DysDD 0-10 pelvic pain score of three points can be considered clinically meaningful. Overall, findings indicate that the DysDD has acceptable reliability and is a valid and responsive instrument for assessing dysmenorrhea.

Racial Disparity, Depression, and Birth Outcomes Among Pregnant Teens.

PubMed

Abdelaal, Hala; Mohamed, Mohamed A; Aly, Hany

2018-03-20

Objectives To examine the risk of premature delivery (PD) and small for gestational age (SGA) among pregnant teens with depressive disorders (DD), and the impact of race/ethnicity on these birth outcomes. Design/Methods We examined the hospital discharge records of pregnant mothers between the age of 13-18 year old who gave birth in the years 1994, 2000, 2006, and 2012 in the National Inpatient Sample database. We calculated the risk for PD and SGA among pregnant teens with and without DD in the overall population and within each race/ethnicity. Results Weighted sample included 1,023,586 pregnant teenage women. Prevalence of DD among teens was 0.93%, with a significantly increasing trend from 0.29% in 1994 to 2.01% in 2012 (p < 0.001). Declining trend was observed in the proportion of pregnant younger teens from 1994 to 2012. Prevalence of depression among teenage mothers was highest among Caucasians compared to other races. Prevalence of SGA among pregnant teens was 2.23% that significantly increased from 1.63% in 1994 to 3.44% in 2012 (p < 0.001). African American teens with DD had decreased risk for PD compared to AA without DD (OR 0.70; CI 0.57 - 0.387, p < 0.001). Hispanic teens with DD had increased risk for SGA compared to Hispanics without DD (adjusted OR 1.53; CI 1.10-2.13, p < 0.001). Conclusions for Practice There is an increasing trend for diagnosing DD among pregnant teens. Less young teenage girls are giving birth in recent years. The impact of DD on PD and SGA differs according to race. More studies are warranted to examine underlining factors responsible for these findings.

Evaluation of Lunar Dark Mantle Deposits as Key to Future Human Missions

NASA Technical Reports Server (NTRS)

Coombs, Cassandra

1997-01-01

I proposed to continue detailed mapping, analysis and assessment of the lunar pyroclastic dark mantle deposits in support of the Human Exploration and Development of Space (HEDS) initiative. Specifically: (1) I continued gathering data via the Internet and mailable media, and a variety of other digital lunar images including; high resolution digital images of the new Apollo masters from JSC, images from Clementine and Galileo, and recent telescopic images from Hawaii; (2) continued analyses on these images using sophisticated hardware and software at JSC and the College of Charleston to determine and map composition using returned sample data for calibration; (3) worked closely with Dr. David McKay and others at JSC to relate sample data to image data using laboratory spectra from JSC and Brown University; (4) mapped the extent, thickness, and composition of important dark mantle deposits in selected study areas; and (5) began composing a geographically referenced database of lunar pyroclastic materials in the Apollo 17 area. The results have been used to identify and evaluate several candidate landing sites in dark mantle terrains. Additional work spawned from this effort includes the development of an educational CD-Rom on exploring the Moon: Contact Light. Throughout the whole process I have been in contact with the JSC HEDS personnel.

Impaired Statistical Learning in Developmental Dyslexia

ERIC Educational Resources Information Center

Gabay, Yafit; Thiessen, Erik D.; Holt, Lori L.

2015-01-01

Purpose: Developmental dyslexia (DD) is commonly thought to arise from phonological impairments. However, an emerging perspective is that a more general procedural learning deficit, not specific to phonological processing, may underlie DD. The current study examined if individuals with DD are capable of extracting statistical regularities across…

Structural Study of the RIPoptosome Core Reveals a Helical Assembly for Kinase Recruitment

PubMed Central

2015-01-01

Receptor interaction protein kinase 1 (RIP1) is a molecular cell-fate switch. RIP1, together with Fas-associated protein with death domain (FADD) and caspase-8, forms the RIPoptosome that activates apoptosis. RIP1 also associates with RIP3 to form the necrosome that triggers necroptosis. The RIPoptosome assembles through interactions between the death domains (DDs) of RIP1 and FADD and between death effector domains (DEDs) of FADD and caspase-8. In this study, we analyzed the overall structure of the RIP1 DD/FADD DD complex, the core of the RIPoptosome, by negative-stain electron microscopy and modeling. The results show that RIP1 DD and FADD DD form a stable complex in vitro similar to the previously described Fas DD/FADD DD complex, suggesting that the RIPoptosome and the Fas death-inducing signaling complex share a common assembly mechanism. Both complexes adopt a helical conformation that requires type I, II, and III interactions between the death domains. PMID:25119434

Pigmented and hyperkeratotic napkin dermatitis: a liquid detergent irritant dermatitis.

PubMed

Patrizi, A; Neri, I; Marzaduri, S; Fiorillo, L

1996-01-01

Napkin or diaper dermatitis (DD) is an inflammatory cutaneous eruption limited to the diaper area and common in the first 2 years of life. A number of clinical variants of DD have been identified. We report a new variant of DD characterized by papyraceous skin, brownish discoloration and predilection for the depth of folds. 15 infants and toddlers affected by this peculiar type of DD were evaluated regarding duration, localization, morphology and evolution of their dermatosis. This variant of DD was mainly confined to the depth of inguinal and gluteal folds and invariably associated with severe xerosis with papyraceous and glazed skin. The patients were healthy and asymptomatic and all laboratory investigations performed were normal. All patients were frequently changed and thoroughly washed with synthetic detergents with acid pH. DD improved rapidly with reduced frequency of washing and discontinuation of liquid detergents. We conclude that this condition is a type of irritant contact dermatitis from excessive use of lipid acid detergents.

Delay discounting, impulsiveness, and addiction severity in opioid-dependent patients.

PubMed

Robles, Elias; Huang, B Emma; Simpson, Pippa M; McMillan, Donald E

2011-12-01

Individuals who abuse drugs show higher delay discounting (DD) rate and impulsiveness scores compared with controls; however, it is unclear if DD rate covaries with severity of the addiction or if an individual's discounting rate can be changed by effective substance abuse treatment. This study compared methadone maintenance treatment (MMT) patients (n = 30) who had not used illegal drugs for 2 years with drug-using MMT patients (n = 30) and controls (n = 25) in terms of addiction severity, DD rate, and impulsiveness. Methadone patients abstinent from illegal drugs scored significantly lower on a number of addiction severity measures than the drug-using methadone patients. In addition, both groups of MMT patients showed significantly higher rates of DD and impulsiveness than the control group; however, no differences in DD rate or impulsiveness were found between the groups of patients. Results suggest that DD rate and impulsiveness may not covary with indicators of addiction severity in MMT patients. Published by Elsevier Inc.

Droplet Digital PCR-Based Chimerism Analysis for Primary Immunodeficiency Diseases.

PubMed

Okano, Tsubasa; Tsujita, Yuki; Kanegane, Hirokazu; Mitsui-Sekinaka, Kanako; Tanita, Kay; Miyamoto, Satoshi; Yeh, Tzu-Wen; Yamashita, Motoi; Terada, Naomi; Ogura, Yumi; Takagi, Masatoshi; Imai, Kohsuke; Nonoyama, Shigeaki; Morio, Tomohiro

2018-04-01

In the current study, we aimed to accurately evaluate donor/recipient or male/female chimerism in samples from patients who underwent hematopoietic stem cell transplantation (HSCT). We designed the droplet digital polymerase chain reaction (ddPCR) for SRY and RPP30 to detect the male/female chimerism. We also developed mutation-specific ddPCR for four primary immunodeficiency diseases. The accuracy of the male/female chimerism analysis using ddPCR was confirmed by comparing the results with those of conventional methods (fluorescence in situ hybridization and short tandem repeat-PCR) and evaluating dilution assays. In particular, we found that this method was useful for analyzing small samples. Thus, this method could be used with patient samples, especially to sorted leukocyte subpopulations, during the early post-transplant period. Four mutation-specific ddPCR accurately detected post-transplant chimerism. ddPCR-based male/female chimerism analysis and mutation-specific ddPCR were useful for all HSCT, and these simple methods contribute to following the post-transplant chimerism, especially in disease-specific small leukocyte fractions.

Psychopathology in the adolescent and young adult offspring of parents with dysthymic disorder and major depressive disorder.

PubMed

Lizardi, Humberto; Klein, Daniel N; Shankman, Stewart A

2004-03-01

This study addressed the following question: are the adolescent and young adult offspring of parents with early-onset dysthymic disorder (DD) at increased risk for psychopathology? Participants included 41 offspring of 21 outpatients with early-onset DD, 19 offspring of nine outpatients with episodic major depressive disorder (MDD), and 32 offspring of 11 normal controls (NCs). Lifetime best-estimate diagnoses were determined for each offspring using a team consensus method. Diagnoses were derived blind to all information about the index parents. The offspring of outpatients with early-onset DD exhibited significantly higher lifetime rates of a broad range of psychiatric disorders than the offspring of NCs. In addition, the offspring of outpatients with early-onset DD exhibited significantly higher lifetime rates of DD, anxiety disorders, and phobia than the offspring of outpatients with episodic MDD. These results support the importance of early-onset DD in parents as a risk factor for psychopathology in their offspring.

Spectroscopic studies on [(DD18C6H 2)(HPA) 2](PA) 2 and [(DD18C6H 2)(DDQ) 2](DDQH) 2 formed in the reaction of N, N'-dibenzyl-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane with HPA and DDQ

NASA Astrophysics Data System (ADS)

Teleb, Said M.; Gaballa, Akmal S.; Elmosallamy, M. A. F.; Nour, El-Metwally

2005-09-01

The interaction of the mixed oxygen-nitrogen cyclic base, N, N'-dibenzyl-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane (DD18C6) with π-acceptors such as picric acid (HPA) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) has been studied spectrophotometrically in chloroform at 25 °C. The results obtained indicate the formation of 1:4 charge-transfer complexes with the general formula (DD18C6)(acceptor) 4. The electronic and infrared spectra of charge-transfer complexes along with the 1H NMR spectra were recorded and discussed. Based on the data obtained, the complexes were formulated as [(DD18C6H 2)(HPA) 2](PA) 2 and [(DD18C6H 2)(DDQ) 2](DDQH) 2. A general mechanism explaining the formation of the DDQ complex has been suggested.

Appropriate use of D-dimer testing can minimize over-utilization of venous duplex ultrasound in a contemporary high-volume hospital.

PubMed

Mousa, Albeir Y; Broce, Mike; Gill, Gurpreet; Kali, Maher; Yacoub, Michael; AbuRahma, Ali F

2015-02-01

The sensitivity of d-dimer (DD) in detecting deep venous thrombosis (DVT) is remarkably high; however, many institutions send patients immediately for a venous duplex ultrasound (VDU). This study was designed to examine the appropriate utilization of DD and VDU in a high-volume hospital. A retrospective study was conducted on consecutive patients who presented to a high-volume emergency department (ED) with lower extremity limb swelling/pain over a 30-day period, who were sent for VDU during an evaluation for DVT. VDU data were merged with electronic DD laboratory results. The enzyme-linked immunosorbent assay method was used to provide DD values and thresholds. Values above 0.60 mg/fibrinogen equivalent unit (FEU) were considered abnormal. We reviewed the medical records of 517 ED patients in the month of June 2013. After applying the Wells criteria, 157 patients (30.4%) were excluded because of a history of DVT or pulmonary embolism, having been screened for shortness of breath, or sent for surveillance-leaving 360 for analysis. The average age was 59.3 ± 16.5 years with more women (210, 58.3%) and the majority reported limb pain or swelling (73.9%). DD was performed on 51 patients with an average value of 3.6 ± 5.4 mg/FEU, of which 43 (84.3%) were positive. DD identified all positive and negative DVT patients (100% sensitivity and negative predictive value), but also included 40 false positives (16.7% specificity). On the other hand, 309 patients were sent directly to VDU without DD; of those, 43 (13.9%) were positive for DVT. However, 266 (86.1%) patients were negative for DVT by VDU without DD and these were deemed improper by our current study protocol. Potential charge savings were calculated as VDU for all (360 × $1000 = $360,000), DD for all (360 × $145 = $52,200), and VDU for both true and false positives (estimated to be about 25% of the cases; 90 × $1000 = $90,000); this equals a charge savings of $217,800 and would avoid unnecessary VDUs. Based on the results of our study, we suggest that the DD test be utilized during the initial work-up for patients with limb swelling/pain in the emergency room. Appropriate utilization of DD, as well as other clinical criteria, may limit the over-utilization and added cost of VDU, without a negative impact on patient care. The results of DD tests should be utilized to limit the number of patients sent for VDU to only those patients with a positive DD or other significant underlying concerns. Copyright © 2015 Elsevier Inc. All rights reserved.

Diagnostic Accuracy of the Aortic Dissection Detection Risk Score Plus D-Dimer for Acute Aortic Syndromes: The ADvISED Prospective Multicenter Study.

PubMed

Nazerian, Peiman; Mueller, Christian; Soeiro, Alexandre de Matos; Leidel, Bernd A; Salvadeo, Sibilla Anna Teresa; Giachino, Francesca; Vanni, Simone; Grimm, Karin; Oliveira, Múcio Tavares; Pivetta, Emanuele; Lupia, Enrico; Grifoni, Stefano; Morello, Fulvio

2018-01-16

Acute aortic syndromes (AASs) are rare and severe cardiovascular emergencies with unspecific symptoms. For AASs, both misdiagnosis and overtesting are key concerns, and standardized diagnostic strategies may help physicians to balance these risks. D-dimer (DD) is highly sensitive for AAS but is inadequate as a stand-alone test. Integration of pretest probability assessment with DD testing is feasible, but the safety and efficiency of such a diagnostic strategy are currently unknown. In a multicenter prospective observational study involving 6 hospitals in 4 countries from 2014 to 2016, consecutive outpatients were eligible if they had ≥1 of the following: chest/abdominal/back pain, syncope, perfusion deficit, and if AAS was in the differential diagnosis. The tool for pretest probability assessment was the aortic dissection detection risk score (ADD-RS, 0-3) per current guidelines. DD was considered negative (DD-) if <500 ng/mL. Final case adjudication was based on conclusive diagnostic imaging, autopsy, surgery, or 14-day follow-up. Outcomes were the failure rate and efficiency of a diagnostic strategy for ruling out AAS in patients with ADD-RS=0/DD- or ADD-RS ≤1/DD-. A total of 1850 patients were analyzed. Of these, 438 patients (24%) had ADD-RS=0, 1071 patients (58%) had ADD-RS=1, and 341 patients (18%) had ADD-RS >1. Two hundred forty-one patients (13%) had AAS: 125 had type A aortic dissection, 53 had type B aortic dissection, 35 had intramural aortic hematoma, 18 had aortic rupture, and 10 had penetrating aortic ulcer. A positive DD test result had an overall sensitivity of 96.7% (95% confidence interval [CI], 93.6-98.6) and a specificity of 64% (95% CI, 61.6-66.4) for the diagnosis of AAS; 8 patients with AAS had DD-. In 294 patients with ADD-RS=0/DD-, 1 case of AAS was observed. This yielded a failure rate of 0.3% (95% CI, 0.1-1.9) and an efficiency of 15.9% (95% CI, 14.3-17.6) for the ADD-RS=0/DD- strategy. In 924 patients with ADD-RS ≤1/DD-, 3 cases of AAS were observed. This yielded a failure rate of 0.3% (95% CI, 0.1-1) and an efficiency of 49.9% (95% CI, 47.7-52.2) for the ADD-RS ≤1/DD- strategy. Integration of ADD-RS (either ADD-RS=0 or ADD-RS ≤1) with DD may be considered to standardize diagnostic rule out of AAS. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02086136. © 2017 American Heart Association, Inc.

Network control principles predict neuron function in the Caenorhabditis elegans connectome

PubMed Central

Chew, Yee Lian; Walker, Denise S.; Schafer, William R.; Barabási, Albert-László

2017-01-01

Recent studies on the controllability of complex systems offer a powerful mathematical framework to systematically explore the structure-function relationship in biological, social and technological networks1–3. Despite theoretical advances, we lack direct experimental proof of the validity of these widely used control principles. Here we fill this gap by applying a control framework to the connectome of the nematode C. elegans4–6, allowing us to predict the involvement of each C. elegans neuron in locomotor behaviours. We predict that control of the muscles or motor neurons requires twelve neuronal classes, which include neuronal groups previously implicated in locomotion by laser ablation7–13, as well as one previously uncharacterised neuron, PDB. We validate this prediction experimentally, finding that the ablation of PDB leads to a significant loss of dorsoventral polarity in large body bends. Importantly, control principles also allow us to investigate the involvement of individual neurons within each neuronal class. For example, we predict that, within the class of DD motor neurons, only three (DD04, DD05, or DD06) should affect locomotion when ablated individually. This prediction is also confirmed, with single-cell ablations of DD04 or DD05, but not DD02 or DD03, specifically affecting posterior body movements. Our predictions are robust to deletions of weak connections, missing connections, and rewired connections in the current connectome, indicating the potential applicability of this analytical framework to larger and less well-characterised connectomes. PMID:29045391

Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD.

PubMed

Cortez, Eliane; Gladh, Hanna; Braun, Sebastian; Bocci, Matteo; Cordero, Eugenia; Björkström, Niklas K; Miyazaki, Hideki; Michael, Iacovos P; Eriksson, Ulf; Folestad, Erika; Pietras, Kristian

2016-02-16

Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. Aberrant platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer has motivated the development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib. The discovery of a novel ligand for PDGFRβ, platelet-derived growth factor (PDGF)-DD, opened the possibility of a previously unidentified signaling pathway involved in tumor development. However, the precise function of PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly, ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous malignant cell clones, some of which expressed PDGFRβ. The presence of a subclonal population of tumor cells characterized by PDGFRβ expression was further validated in a cohort of human PanNET. In conclusion, we demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the PDGF-DD/PDGFRβ axis.

Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD

PubMed Central

Cortez, Eliane; Gladh, Hanna; Braun, Sebastian; Bocci, Matteo; Cordero, Eugenia; Björkström, Niklas K.; Miyazaki, Hideki; Michael, Iacovos P.; Eriksson, Ulf; Folestad, Erika; Pietras, Kristian

2016-01-01

Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. Aberrant platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer has motivated the development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib. The discovery of a novel ligand for PDGFRβ, platelet-derived growth factor (PDGF)-DD, opened the possibility of a previously unidentified signaling pathway involved in tumor development. However, the precise function of PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly, ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous malignant cell clones, some of which expressed PDGFRβ. The presence of a subclonal population of tumor cells characterized by PDGFRβ expression was further validated in a cohort of human PanNET. In conclusion, we demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the PDGF-DD/PDGFRβ axis. PMID:26831065

A combined event-related potential and neuropsychological investigation of developmental dyscalculia.

PubMed

Soltész, Fruzsina; Szucs, Dénes; Dékány, Judit; Márkus, Attila; Csépe, Valéria

2007-05-01

Adolescents with developmental dyscalculia (DD) but no other impairments were examined with neuropsychological tests and with event-related brain potentials (ERPs). A matched control group and an adult control group were tested as well. Behavioural and ERP markers of the magnitude representation were examined in a task where subjects decided whether visually presented Hindu-Arabic digits were smaller or larger than 5. There was a normal behavioural numerical distance effect (better performance for digits closer to the reference number than for digits further away from it) in DD. This suggests that semantic magnitude relations depend on a phenomenologically (nearly) normal magnitude representation in DD, at least in the range of single-digit numbers. However, minor discrepancies between DD subjects and controls suggest that the perception of the magnitude of single digits may be slightly impaired in DD. Early ERP distance effects were similar in DD and in control subjects. In contrast, between 400 and 440 ms there was a focused right-parietal ERP distance effect in controls, but not in DD. This suggests that early, more automatic processing of digits was similar in both groups, and between-group processing differences arose later, during more complex controlled processing. This view is supported by signs of decelerated executive functioning in developmental dyscalculia. Further, DD subjects did not differ from controls in general mental rotation and in body parts knowledge, but were markedly impaired in mental finger rotation, finger knowledge, and tactile performance.

Depression in patients with chronic kidney disease on dialysis in Saudi Arabia.

PubMed

Al Zaben, Faten; Khalifa, Doaa Ahmed; Sehlo, Mohammad Gamal; Al Shohaib, Saad; Shaheen, Faisul; Alhozali, Hanadi; Hariri, Alferdose Osama; Ahmad, Riyadh Ghazi; Kabli, Moayad Reda; Koenig, Harold G

2014-12-01

Patients with chronic kidney disease on hemodialysis experience considerable psychological stress due to physical and social changes brought on by illness, increasing the risk of depressive disorder (DD). We examined the prevalence of DD and depressive symptoms, identified treatments for depression, and determined baseline demographic, social/behavioral, physical, and psychological correlates. A convenience sample of 310 dialysis patients in Jeddah, Saudi Arabia, was screened for DD using the Structured Clinical Interview for Depression and for depressive symptoms using the Hamilton Depression Rating Scale (HDRS). Established measures of psychosocial and physical health characteristics were administered, along with questions about current and past treatments. Bivariate and multivariate analyses identified independent correlates of DD and symptoms. The prevalence of DD was 6.8 % (major depression 3.2 %, minor depression 3.6 %), and significant depressive symptoms were present in 24.2 % (HDRS 8 or higher). No patients with DD were being treated with antidepressant medication, whereas 28.6 % (6 of 21) were receiving counseling. Being a Saudi national, married, in counseling, or having a history of antidepressant were associated with DD in bivariate analyses. Correlates of depressive symptoms HDRS in multivariate analyses were Saudi nationality, marital status, stressful life events, poor physical functioning, cognitive impairment, overall severity of medical illness, and history of family psychiatric problems. The prevalence of DD and depressive symptoms is lower in Saudi dialysis patients than in the rest of the world, largely untreated, and is associated with a distinct set of demographic, psychosocial, and physical health characteristics.

Network control principles predict neuron function in the Caenorhabditis elegans connectome

NASA Astrophysics Data System (ADS)

Yan, Gang; Vértes, Petra E.; Towlson, Emma K.; Chew, Yee Lian; Walker, Denise S.; Schafer, William R.; Barabási, Albert-László

2017-10-01

Recent studies on the controllability of complex systems offer a powerful mathematical framework to systematically explore the structure-function relationship in biological, social, and technological networks. Despite theoretical advances, we lack direct experimental proof of the validity of these widely used control principles. Here we fill this gap by applying a control framework to the connectome of the nematode Caenorhabditis elegans, allowing us to predict the involvement of each C. elegans neuron in locomotor behaviours. We predict that control of the muscles or motor neurons requires 12 neuronal classes, which include neuronal groups previously implicated in locomotion by laser ablation, as well as one previously uncharacterized neuron, PDB. We validate this prediction experimentally, finding that the ablation of PDB leads to a significant loss of dorsoventral polarity in large body bends. Importantly, control principles also allow us to investigate the involvement of individual neurons within each neuronal class. For example, we predict that, within the class of DD motor neurons, only three (DD04, DD05, or DD06) should affect locomotion when ablated individually. This prediction is also confirmed; single cell ablations of DD04 or DD05 specifically affect posterior body movements, whereas ablations of DD02 or DD03 do not. Our predictions are robust to deletions of weak connections, missing connections, and rewired connections in the current connectome, indicating the potential applicability of this analytical framework to larger and less well-characterized connectomes.

Formal Uncertainty and Dispersion of Single and Double Difference Models for GNSS-Based Attitude Determination.

PubMed

Chen, Wen; Yu, Chao; Dong, Danan; Cai, Miaomiao; Zhou, Feng; Wang, Zhiren; Zhang, Lei; Zheng, Zhengqi

2017-02-20

With multi-antenna synchronized global navigation satellite system (GNSS) receivers, the single difference (SD) between two antennas is able to eliminate both satellite and receiver clock error, thus it becomes necessary to reconsider the equivalency problem between the SD and double difference (DD) models. In this paper, we quantitatively compared the formal uncertainties and dispersions between multiple SD models and the DD model, and also carried out static and kinematic short baseline experiments. The theoretical and experimental results show that under a non-common clock scheme the SD and DD model are equivalent. Under a common clock scheme, if we estimate stochastic uncalibrated phase delay (UPD) parameters every epoch, this SD model is still equivalent to the DD model, but if we estimate only one UPD parameter for all epochs or take it as a known constant, the SD (here called SD2) and DD models are no longer equivalent. For the vertical component of baseline solutions, the formal uncertainties of the SD2 model are two times smaller than those of the DD model, and the dispersions of the SD2 model are even more than twice smaller than those of the DD model. In addition, to obtain baseline solutions, the SD2 model requires a minimum of three satellites, while the DD model requires a minimum of four satellites, which makes the SD2 more advantageous in attitude determination under sheltered environments.

Formal Uncertainty and Dispersion of Single and Double Difference Models for GNSS-Based Attitude Determination

PubMed Central

Chen, Wen; Yu, Chao; Dong, Danan; Cai, Miaomiao; Zhou, Feng; Wang, Zhiren; Zhang, Lei; Zheng, Zhengqi

2017-01-01

With multi-antenna synchronized global navigation satellite system (GNSS) receivers, the single difference (SD) between two antennas is able to eliminate both satellite and receiver clock error, thus it becomes necessary to reconsider the equivalency problem between the SD and double difference (DD) models. In this paper, we quantitatively compared the formal uncertainties and dispersions between multiple SD models and the DD model, and also carried out static and kinematic short baseline experiments. The theoretical and experimental results show that under a non-common clock scheme the SD and DD model are equivalent. Under a common clock scheme, if we estimate stochastic uncalibrated phase delay (UPD) parameters every epoch, this SD model is still equivalent to the DD model, but if we estimate only one UPD parameter for all epochs or take it as a known constant, the SD (here called SD2) and DD models are no longer equivalent. For the vertical component of baseline solutions, the formal uncertainties of the SD2 model are two times smaller than those of the DD model, and the dispersions of the SD2 model are even more than twice smaller than those of the DD model. In addition, to obtain baseline solutions, the SD2 model requires a minimum of three satellites, while the DD model requires a minimum of four satellites, which makes the SD2 more advantageous in attitude determination under sheltered environments. PMID:28230753

How the visual aspects can be crucial in reading acquisition? The intriguing case of crowding and developmental dyslexia.

PubMed

Gori, Simone; Facoetti, Andrea

2015-01-14

Developmental dyslexia (DD) is the most common neurodevelopmental disorder (about 10% of children across cultures) characterized by severe difficulties in learning to read. According to the dominant view, DD is considered a phonological processing impairment that might be linked to a cross-modal, letter-to-speech sound integration deficit. However, new theories-supported by consistent data-suggest that mild deficits in low-level visual and auditory processing can lead to DD. This evidence supports the probabilistic and multifactorial approach for DD. Among others, an interesting visual deficit that is often associated with DD is excessive visual crowding. Crowding is defined as difficulty in the ability to recognize objects when surrounded by similar items. Crowding, typically observed in peripheral vision, could be modulated by attentional processes. The direct consequence of stronger crowding on reading is the inability to recognize letters when they are surrounded by other letters. This problem directly translates to reading at a slower speed and being more prone to making errors while reading. Our aim is to review the literature supporting the important role of crowding in DD. Moreover, we are interested in proposing new possible studies in order to clarify whether the observed excessive crowding could be a cause rather than an effect of DD. Finally, we also suggest possible remediation and even prevention programs that could be based on reducing the crowding in children with or at risk for DD without involving any phonological or orthographic training. © 2015 ARVO.

Network control principles predict neuron function in the Caenorhabditis elegans connectome.

PubMed

Yan, Gang; Vértes, Petra E; Towlson, Emma K; Chew, Yee Lian; Walker, Denise S; Schafer, William R; Barabási, Albert-László

2017-10-26

Recent studies on the controllability of complex systems offer a powerful mathematical framework to systematically explore the structure-function relationship in biological, social, and technological networks. Despite theoretical advances, we lack direct experimental proof of the validity of these widely used control principles. Here we fill this gap by applying a control framework to the connectome of the nematode Caenorhabditis elegans, allowing us to predict the involvement of each C. elegans neuron in locomotor behaviours. We predict that control of the muscles or motor neurons requires 12 neuronal classes, which include neuronal groups previously implicated in locomotion by laser ablation, as well as one previously uncharacterized neuron, PDB. We validate this prediction experimentally, finding that the ablation of PDB leads to a significant loss of dorsoventral polarity in large body bends. Importantly, control principles also allow us to investigate the involvement of individual neurons within each neuronal class. For example, we predict that, within the class of DD motor neurons, only three (DD04, DD05, or DD06) should affect locomotion when ablated individually. This prediction is also confirmed; single cell ablations of DD04 or DD05 specifically affect posterior body movements, whereas ablations of DD02 or DD03 do not. Our predictions are robust to deletions of weak connections, missing connections, and rewired connections in the current connectome, indicating the potential applicability of this analytical framework to larger and less well-characterized connectomes.

Interrelationships between marijuana demand and discounting of delayed rewards: Convergence in behavioral economic methods.

PubMed

Aston, Elizabeth R; Metrik, Jane; Amlung, Michael; Kahler, Christopher W; MacKillop, James

2016-12-01

Distinct behavioral economic domains, including high perceived drug value (demand) and delay discounting (DD), have been implicated in the initiation of drug use and the progression to dependence. However, it is unclear whether frequent marijuana users conform to a "reinforcer pathology" addiction model wherein marijuana demand and DD jointly increase risk for problematic marijuana use and cannabis dependence (CD). Participants (n=88, 34% female, 14% cannabis dependent) completed a marijuana purchase task at baseline. A delay discounting task was completed following placebo marijuana cigarette (0% THC) administration during a separate experimental session. Marijuana demand and DD were quantified using area under the curve (AUC). In multiple regression models, demand uniquely predicted frequency of marijuana use while DD did not. In contrast, DD uniquely predicted CD symptom count while demand did not. There were no significant interactions between demand and DD in either model. These findings suggest that frequent marijuana users exhibit key constituents of the reinforcer pathology model: high marijuana demand and steep discounting of delayed rewards. However, demand and DD appear to be independent rather than synergistic risk factors for elevated marijuana use and risk for progression to CD. Findings also provide support for using AUC as a singular marijuana demand metric, particularly when also examining other behavioral economic constructs that apply similar statistical approaches, such as DD, to support analytic methodological convergence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Designer Drug (DD) abuse in Poland; a review of the psychoactive and toxic properties of substances found from seizures of illegal drug products and the legal consequences thereof. Part II--piperazines/piperidines, phenylethylamines, tryptamines and miscellaneous 'others'.

PubMed

Biliński, Przemysław; Hołownia, Piotr; Kapka-Skrzypczak, Lucyna; Wojtyła, Andrzej

2012-01-01

As the second and concluding part, this paper continues the summary review of the scientific evidence obtained from the literature and focuses on the remaining 4/6 groupings of DDs identified in illegal products found in the huge drug seizures made recently in Poland. They consist of piperazines/piperidines, phenylethylamines, tryptamines, (briefly mentioned), and a miscellaneous 'others' category; cannabinoids and cathinones derivatives having being reviewed in the first part. Also included in the introduction and discussion sections, in both reviews, are some legal aspects variously interwoven with the science. It is thus intended that these two articles may help suitable legislation to be rapidly devised to make the prohibition of DDs permanent whenever deemed necessary, as well as providing an up-to-date reference source for those engaged in the DD issue; whether scientists or regulatory bodies.

Environmental assessment for the construction, operation, and decommissioning of the Waste Segregation Facility at the Savannah River Site

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

NONE

1998-01-01

This Environmental Assessment (EA) has been prepared by the Department of Energy (DOE) to assess the potential environmental impacts associated with the construction, operation and decontamination and decommissioning (D&D) of the Waste Segregation Facility (WSF) for the sorting, shredding, and compaction of low-level radioactive waste (LLW) at the Savannah River Site (SRS) located near Aiken, South Carolina. The LLW to be processed consists of two waste streams: legacy waste which is currently stored in E-Area Vaults of SRS and new waste generated from continuing operations. The proposed action is to construct, operate, and D&D a facility to process low-activity job-controlmore » and equipment waste for volume reduction. The LLW would be processed to make more efficient use of low-level waste disposal capacity (E-Area Vaults) or to meet the waste acceptance criteria for treatment at the Consolidated Incineration Facility (CIF) at SRS.« less

Dark Energy and the Fate of the Universe

NASA Astrophysics Data System (ADS)

Linde, A.

2002-12-01

The present stage of acceleration of the universe may continue forever. However, we have found a broad class of theories of dark energy that lead to a global collapse of the universe 10-30 billion years from now. I will discuss the possibility to find our destiny using cosmological observations.

77 FR 22764 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-17

... (Regulation DD) 12 CFR 1030. OMB Number: 3170-0004. Abstract: Federal agencies use the records to ascertain... actions brought by the CFPB and other agencies. Without the Regulation DD recordkeeping requirement, the... required by TISA and Regulation DD to facilitate informed decision making regarding deposit accounts...

Recent Additions for 1998

EPA Science Inventory

December 22, 1998

Benchmark Dose Software

December 16, 1998

Recent Additions for 1997

EPA Science Inventory

December 15, 1997

Minutes of the Stakeholder Meetings on the Report of the JSA Shrimp Virus Work Group

November 21, 1997

Droplet digital PCR as a novel detection method for quantifying microRNAs in acute myocardial infarction.

PubMed

Robinson, S; Follo, M; Haenel, D; Mauler, M; Stallmann, D; Tewari, M; Duerschmied, D; Peter, K; Bode, C; Ahrens, I; Hortmann, M

2018-04-15

micro-RNAs have shown promise as potential biomarkers for acute myocardial infarction and ischemia-reperfusion injury (I/R). Most recently droplet digital polymerase chain reaction (ddPCR) has been introduced as a more reliable and reproducible method for detecting micro-RNAs. We aimed to demonstrate the improved technical performance and diagnostic potential of ddPCR by measuring micro-RNAs in ST-elevation myocardial infarction (STEMI). A dilution series was performed in duplicate on synthetic Caenorrhabditis elegans-miR-39, comparing quantitative real-time PCR (qRT-PCR) and ddPCR. We used ddPCR and qRT-PCR to quantify the serum levels of miR-21, miR-208a and miR-499 between STEMI patients (n=24) and stable coronary artery disease (CAD) patients (n=20). In STEMI, I/R injury was assessed via measurement of ST-segment resolution. In the dilution series, ddPCR demonstrated superior coefficient of variation (12.1%vs.32.9%) and limit of detection (0.9325 vs.2.425copies/μl). In the patient cohort, ddPCR demonstrated greater differences in miR-21 levels (2190.5 vs. 484.7copies/μl; p=0.0004 for ddPCR and 136.4 vs. 122.8copies/μl; p=0.2273 for qRT-PCR) and in miR-208a (0 vs. 24.1copies/μl, p=0.0013 for ddPCR and 0 vs. 0copies/μl, p=0.0032 for qRT-PCR), with similar differences observed in miR-499 levels (9.4 vs. 81.5copies/μl, p<0.0001 for ddPCR and 0 vs. 19.41copies/μl, p<0.0001 for qRT-PCR). ddPCR also more accurately defined STEMI for all miRNAs (area under the curve (AUC) of 0.8021/0.7740/0.9063 for miR-21/208a/499 with ddPCR vs. AUC of 0.6083/0.6917/0.8417 with qRT-PCR). However, there was no association between miR-21/208a/499 levels and ischemia-reperfusion injury. ddPCR demonstrates superiority in both technical performance and diagnostic potential compared to qRT-PCR. Ultimately, this supports its use as a diagnostic method for quantifying micro-RNAs, particularly in large multi-center trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Using Dialogic Methods as a Participatory Knowledge Translation Approach to Promote Integration of Nurse Practitioners in Primary Healthcare Settings.

PubMed

Oelke, Nelly D; Plamondon, Katrina M; Mendel, Donna

2016-01-01

Background: Nurse practitioners (NPs) were introduced in British Columbia (BC) in 2005 as a new category of health provider. Given the newness of NPs in our health system, it is not unexpected that continued work is required to better integrate NPs in healthcare in BC. Aim: This paper will focus on a research study using dialogic methods as a participatory knowledge translation approach to facilitate integration of NPs in primary healthcare (PHC) settings. Methods: Deliberative dialogue (DD) is a useful knowledge translation tool in health services delivery. Through facilitated conversations with stakeholders, invited to consider research evidence in the context of their experience and tacit knowledge, collective data are generated. DD is a powerful tool to engage stakeholders in the development and implementation of evidence-informed policies and services through discussion of issues, consideration of priorities and development of concrete actions that can be implemented by policy makers and decision-makers. Two DD sessions were held with stakeholders involved in supporting NP integration in a health authority in southern interior BC. Stakeholders were provided syntheses of a literature review and interview results. The first session resulted in the collective development of 10 actions to promote NP integration in PHC settings. The second session was conducted six months later to discuss progress and revisions to actions. Discussion: The use of the dialogic methods used in studying NP integration in PHC settings proved useful in promoting real conversation about the implications of research evidence in living contexts, enabling diverse stakeholders to co-create collaborative actions for further NP integration. The conversations and actions were used to support further NP integration during the study and beyond. Conclusion: DD is a useful approach for transforming health services policy and delivery. It has the potential to move change forward with co-created solutions by the stakeholders involved.

Eliciting perceptions of satisfaction with services and supports from persons with intellectual disability and developmental disabilities: a review of the literature.

PubMed

Copeland, S R; Luckasson, R; Shauger, R

2014-12-01

Assessing the perceptions of individuals with intellectual disability (ID) and developmental disabilities (DD) is an essential part of evaluating and planning services and an important component of respect for self-direction and autonomy. It can be difficult, however, to assess satisfaction in such a way that individuals with disabilities' actual perceptions of satisfaction are accurately represented because of intellectual and communication difficulties they may have, the restricted range and nature of service systems, and the limitations of strategies used by some researchers. The purpose of this literature review was to systematically examine research studies designed to solicit personal satisfaction information from individuals with ID and DD. We reviewed 29 studies that met inclusion criteria to determine (1) who were participants in the studies, (2) what processes researchers used to obtain opinions and perspectives of persons with ID and DD, and (3) how researchers ensured the credibility, accuracy and voluntariness of participants' responses. Findings revealed that most of the research participants had ID with higher IQs and limited needs for supports. Researchers utilised a variety of processes to elicit perceptions of satisfaction. Most studies employed individual interviews; researchers addressed comprehensibility of questions in a number of ways (e.g. use of visuals, adjusting wording of questions, providing clear examples). Few studies reported training interviewers or taking into account participants' primary language or cultural background. No studies reported educating participants about how to understand the satisfaction information data or how to use it in advocating for more appropriate supports. Assessing the satisfaction with supports and services of individuals with ID and DD is complex particularly for persons with extensive support needs. Continued research using varied conceptual frameworks and new technologies is needed. Also helpful will be teaching persons with disabilities about the assessment process and how to use its results. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Anomalous DD and TT yields relative to the DT yield in inertial-confinement-fusion implosions

NASA Astrophysics Data System (ADS)

Casey, Daniel T.

2011-10-01

Measurements of the D(d,p)T (DD), T(t,2n)4He (TT) and D(t,n)4He (DT) reactions have been conducted using deuterium-tritium gas-filled inertial confinement fusion (ICF) implosions. In these experiments, which were carried out at the OMEGA laser facility, absolute spectral measurements of the DD protons and TT neutrons were conducted and compared to neutron-time-of-flight measured DT-neutron yields. From these measurements, it is concluded that the DD yield is anomalously low and the TT yield is anomalously high relative to the DT yield, an effect that is enhanced with increasing ion temperature. These results can be explained by an enrichment of tritium in the core of an ICF implosion, which may be present in ignition experiments planned on the National Ignition Facility. In addition, the spectral measurements of the TT-neutron spectrum were conducted for the first time at reactant central-mass energies in the range of 15-30 keV. The results from these measurements indicate that the TT reaction proceeds primarily through the direct three-body reaction channel, producing a continuous TT-neutron spectrum in the range 0 - 9.5 MeV. This work was conducted in collaboration with J. A. Frenje, M. Gatu Johnson, M. J.-E. Manuel, H. G. Rinderknecht, N. Sinenian, F. H. Seguin, C. K. Li, R. D. Petrasso, P. B. Radha, J. A. Delettrez, V. Yu Glebov, D. D. Meyerhofer, T. C. Sangster, D. P. McNabb, P. A. Amendt, R. N. Boyd, J. R. Rygg, H. W. Herrmann, Y. H. Kim, G. P. Grim and A. D. Bacher. This work was supported in part by the U.S. Department of Energy (Grant No. DE-FG03-03SF22691), LLE (subcontract Grant No. 412160-001G), LLNL (subcontract Grant No. B504974).

The effects of chloroquine and verapamil on digestive vacuolar pH of P. falciparum either sensitive or resistant to chloroquine.

PubMed

Ursos, L M; Dzekunov, S M; Roepe, P D

2000-09-01

In the preceding paper, we present a novel method for measuring the digestive vacuolar pH (pH(vac)) of the malarial parasite Plasmodium falciparum, and show that, surprisingly, pH(vac) is lower for chloroquine resistant (CQR) Dd2 parasites relative to chloroquine sensitive (CQS) HB3. These data may have important consequences for elucidating mechanisms of antimalarial drug resistance and for developing new antimalarial therapy. Additional issues central to a better understanding of antimalarial pharmacology and antimalarial drug resistance require detailed comparative data on the effects of key drugs and other compounds on parasite biophysical parameters such as pH(vac), measured under close-to-physiologic conditions. Since the methods we develop in the previous paper allow us to record fluorescence signals from spatially well-defined regions of the living parasite while they are under continuous perfusion, it is relatively straightforward for us to test how antimalarial drugs (e. g. chloroquine, CQ) and other compounds (e.g. the chemoreversal agent verapamil [VPL]) affect pH(vac). In this paper, we measure both short term (i.e. initial perfusion conditions) and longer-term effects of CQ and VPL for living, intraerythrocytic CQS (HB3) and CQR (Dd2) malarial parasites under constant perfusion with physiologically relevant buffers. We find that VPL normalizes pH(vac) for Dd2 to a value near that measured for HB3, but has no effect on pH(vac) for HB3. Longer term CQ exposure is found to alter pH(vac) for HB3 but not Dd2, and short-term exposure to the drug has no significant effect in either strain. The results may help resolve longstanding debate regarding the effects of CQ and VPL on parasite physiology, and further support our evolving hypothesis for the mechanism of CQ resistance.

Dissolved Pesticide Concentrations Detected in Storm-Water Runoff at Selected Sites in the San Joaquin River Basin, California, 2000-2001

DTIC Science & Technology

2003-01-01

near Vernalis, California, 2000–2001—Continued Date (mm/dd/yy) Time Napropamide Pendimethalin Phosmet Oxyfluorfen Piperonyl butoxide Simazine...Napropamide 10.9 7.2 Oxyfluorfen — 4.2 Pebulate1 3.4 0.6 Pendimethalin 12.4 2.4 Phosmet 5.9 4.2 Piperonyl butoxide — 3.3 Simazine 5.2 6.9 Sulfotep1 2.0 1.2

Systems Analysis Directorate Activities Summary - September 1977. Volume 1

DTIC Science & Technology

1977-10-01

Identify by block number) Chemical agent Censor criteria Purity of the agent Statistical samples 20. ABSTRACT (Continue on reverse side U... chemical agent lots. Volume II (CONF) contains an analysis fo the operational capability as the 105rom MIOIAI and M102 Hpwltzej^g, DD , FORM JAN 73...Data Entered) CONTENTS Page Procedure for Determining the Serviceability Category of Chemical Agent Lots •• 5 User’s Guide to the Computer

Ion-Selective Electrodes for Basic Drugs.

DTIC Science & Technology

1981-01-01

coated wire ion selective electrodes for methadone , methylamphetamine, J cocaine, protriptyline i 20. ABSTRACT (Continue on reverse side If neeeeary...end Identify by block number) Coated-wire ion-selective electrodes based on dinonylnaphthalene u-i sulfonic acid (DNNS) are prepared for methadone ...range from 10- 5.5M for cocaine and methylamphetamine electrodes to 10Ś.0M for methadone , and 10-6.5M for DD I 󈨍 1473 EDITION OF I NOV 5 IS OBSOLETE

Microcomputer Polling Improvements for AFSATCOM.

DTIC Science & Technology

1981-06-01

AGENCY NAME A AODRESS(il differ~,.ru C~ntrolling Office) IS. SECURITY CLASS. (of this report) 2/’ .iUNCLASSI FIED 1/ 5a. DECLASSIFICATION DOWNGRADING...enhance (over) DD I1JAN 73 1473, UNCLASSIFIED - ~~~ SECURITY CLASSIFICATION OF THIS PAGE (When Dots Enterd’I.. SECURITY CLASSIaICATION OF THIS PAGE(ahnm...Data Entered) 20. ABSTRACT (Continued) /7 hetting capabilities for the satellite-user community /V 4. UNCLASSIFIED SECURITY CLASSIFICATION OF THIS PAGE